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Sample records for afferent neurons cans

  1. Anatomy and physiology of phrenic afferent neurons.

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    Nair, Jayakrishnan; Streeter, Kristi A; Turner, Sara M F; Sunshine, Michael D; Bolser, Donald C; Fox, Emily J; Davenport, Paul W; Fuller, David D

    2017-12-01

    Large-diameter myelinated phrenic afferents discharge in phase with diaphragm contraction, and smaller diameter fibers discharge across the respiratory cycle. In this article, we review the phrenic afferent literature and highlight areas in need of further study. We conclude that 1 ) activation of both myelinated and nonmyelinated phrenic sensory afferents can influence respiratory motor output on a breath-by-breath basis; 2 ) the relative impact of phrenic afferents substantially increases with diaphragm work and fatigue; 3 ) activation of phrenic afferents has a powerful impact on sympathetic motor outflow, and 4 ) phrenic afferents contribute to diaphragm somatosensation and the conscious perception of breathing. Much remains to be learned regarding the spinal and supraspinal distribution and synaptic contacts of myelinated and nonmyelinated phrenic afferents. Similarly, very little is known regarding the potential role of phrenic afferent neurons in triggering or modulating expression of respiratory neuroplasticity. Copyright © 2017 the American Physiological Society.

  2. Age-related changes of neurochemically different subpopulations of cardiac spinal afferent neurons in rats.

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    Guić, Maja Marinović; Runtić, Branka; Košta, Vana; Aljinović, Jure; Grković, Ivica

    2013-08-01

    This study investigated the effect of aging on cardiac spinal afferent neurons in the rat. A patch loaded with retrograde tracer Fast Blue (FB) was applied to all chambers of the rat heart. Morphological and neurochemical characteristics of labeled cardiac spinal afferent neurons were assessed in young (2 months) and old (2 years) rats using markers for likely unmyelinated (isolectin B4; IB4) and myelinated (neurofilament 200; N52) neurons. The number of cardiac spinal afferent neurons decreased in senescence to 15% of that found in young rats (1604 vs. 248). The size of neuronal soma as well as proportion of IB4+ neurons increased significantly, whereas the proportion of N52+ neurons decreased significantly in senescence. Unlike somatic spinal afferents, neurochemically different populations of cardiac spinal afferent neurons experience morphological and neurochemical changes related to aging. A major decrease in total number of cardiac spinal afferent neurons occurs in senescence. The proportion of N52+ neurons decreased in senescence, but it seems that nociceptive innervation is preserved due to increased proportion and size of IB4+ unmyelinated neurons. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Spinal afferent neurons projecting to the rat lung and pleura express acid sensitive channels

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    Kummer Wolfgang

    2006-07-01

    Full Text Available Abstract Background The acid sensitive ion channels TRPV1 (transient receptor potential vanilloid receptor-1 and ASIC3 (acid sensing ion channel-3 respond to tissue acidification in the range that occurs during painful conditions such as inflammation and ischemia. Here, we investigated to which extent they are expressed by rat dorsal root ganglion neurons projecting to lung and pleura, respectively. Methods The tracer DiI was either injected into the left lung or applied to the costal pleura. Retrogradely labelled dorsal root ganglion neurons were subjected to triple-labelling immunohistochemistry using antisera against TRPV1, ASIC3 and neurofilament 68 (marker for myelinated neurons, and their soma diameter was measured. Results Whereas 22% of pulmonary spinal afferents contained neither channel-immunoreactivity, at least one is expressed by 97% of pleural afferents. TRPV1+/ASIC3- neurons with probably slow conduction velocity (small soma, neurofilament 68-negative were significantly more frequent among pleural (35% than pulmonary afferents (20%. TRPV1+/ASIC3+ neurons amounted to 14 and 10% respectively. TRPV1-/ASIC3+ neurons made up between 44% (lung and 48% (pleura of neurons, and half of them presumably conducted in the A-fibre range (larger soma, neurofilament 68-positive. Conclusion Rat pleural and pulmonary spinal afferents express at least two different acid-sensitive channels that make them suitable to monitor tissue acidification. Patterns of co-expression and structural markers define neuronal subgroups that can be inferred to subserve different functions and may initiate specific reflex responses. The higher prevalence of TRPV1+/ASIC3- neurons among pleural afferents probably reflects the high sensitivity of the parietal pleura to painful stimuli.

  4. Glucose-dependent trafficking of 5-HT3 receptors in rat gastrointestinal vagal afferent neurons

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    Babic, Tanja; Troy, Amanda E; Fortna, Samuel R; Browning, Kirsteen N

    2012-01-01

    Background Intestinal glucose induces gastric relaxation via vagally mediated sensory-motor reflexes. Glucose can alter the activity of gastrointestinal (GI) vagal afferent (sensory) neurons directly, via closure of ATP-sensitive potassium channels, as well as indirectly, via the release of 5-hydroxytryptamine (5-HT) from mucosal enteroendocrine cells. We hypothesized that glucose may also be able to modulate the ability of GI vagal afferent neurons to respond to the released 5-HT, via regulation of neuronal 5-HT3 receptors. Methods Whole cell patch clamp recordings were made from acutely dissociated GI-projecting vagal afferent neurons exposed to equiosmolar Krebs’ solution containing different concentrations of D-glucose (1.25–20mM) and the response to picospritz application of 5-HT assessed. The distribution of 5-HT3 receptors in neurons exposed to different glucose concentrations was also assessed immunohistochemically. Key Results Increasing or decreasing extracellular D-glucose concentration increased or decreased, respectively, the 5-HT-induced inward current as well as the proportion of 5-HT3 receptors associated with the neuronal membrane. These responses were blocked by the Golgi-disrupting agent Brefeldin-A (5µM) suggesting involvement of a protein trafficking pathway. Furthermore, L-glucose did not mimic the response of D-glucose implying that metabolic events downstream of neuronal glucose uptake are required in order to observe the modulation of 5-HT3 receptor mediated responses. Conclusions & Inferences These results suggest that, in addition to inducing the release of 5-HT from enterochromaffin cells, glucose may also increase the ability of GI vagal sensory neurons to respond to the released 5-HT, providing a means by which the vagal afferent signal can be amplified or prolonged. PMID:22845622

  5. Afferent neuronal control of type-I gonadotropin releasing hormone (GnRH neurons in the human

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    Erik eHrabovszky

    2013-09-01

    Full Text Available Understanding the regulation of the human menstrual cycle represents an important ultimate challenge of reproductive neuroendocrine research. However, direct translation of information from laboratory animal experiments to the human is often complicated by strikingly different and unique reproductive strategies and central regulatory mechanisms that can be present in even closely related animal species. In all mammals studied so far, type-I gonadotropin releasing hormone (GnRH synthesizing neurons form the final common output way from the hypothalamus in the neuroendocrine control of the adenohypophysis. Under various physiological and pathological conditions, hormonal and metabolic signals either regulate GnRH neurons directly or act on upstream neuronal circuitries to influence the pattern of pulsatile GnRH secretion into the hypophysial portal circulation. Neuronal afferents to GnRH cells convey important metabolic-, stress-, sex steroid-, lactational- and circadian signals to the reproductive axis, among other effects. This article gives an overview of the available neuroanatomical literature that described the afferent regulation of human GnRH neurons by peptidergic, monoaminergic and amino acidergic neuronal systems. Recent studies of human genetics provided evidence that central peptidergic signaling by kisspeptins and neurokinin B play particularly important roles in puberty onset and later, in the sex steroid-dependent feedback regulation of GnRH neurons. This review article places special emphasis on the topographic distribution, sexual dimorphism, aging-dependent neuroanatomical changes and plastic connectivity to GnRH neurons of the critically important human hypothalamic kisspeptin and neurokinin B systems.

  6. Neuronal thresholds and choice-related activity of otolith afferent fibers during heading perception.

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    Yu, Xiong-jie; Dickman, J David; DeAngelis, Gregory C; Angelaki, Dora E

    2015-05-19

    How activity of sensory neurons leads to perceptual decisions remains a challenge to understand. Correlations between choices and single neuron firing rates have been found early in vestibular processing, in the brainstem and cerebellum. To investigate the origins of choice-related activity, we have recorded from otolith afferent fibers while animals performed a fine heading discrimination task. We find that afferent fibers have similar discrimination thresholds as central cells, and the most sensitive fibers have thresholds that are only twofold or threefold greater than perceptual thresholds. Unlike brainstem and cerebellar nuclei neurons, spike counts from afferent fibers do not exhibit trial-by-trial correlations with perceptual decisions. This finding may reflect the fact that otolith afferent responses are poorly suited for driving heading perception because they fail to discriminate self-motion from changes in orientation relative to gravity. Alternatively, if choice probabilities reflect top-down inference signals, they are not relayed to the vestibular periphery.

  7. Heat pulse excitability of vestibular hair cells and afferent neurons.

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    Rabbitt, Richard D; Brichta, Alan M; Tabatabaee, Hessam; Boutros, Peter J; Ahn, JoongHo; Della Santina, Charles C; Poppi, Lauren A; Lim, Rebecca

    2016-08-01

    In the present study we combined electrophysiology with optical heat pulse stimuli to examine thermodynamics of membrane electrical excitability in mammalian vestibular hair cells and afferent neurons. We recorded whole cell currents in mammalian type II vestibular hair cells using an excised preparation (mouse) and action potentials (APs) in afferent neurons in vivo (chinchilla) in response to optical heat pulses applied to the crista (ΔT ≈ 0.25°C per pulse). Afferent spike trains evoked by heat pulse stimuli were diverse and included asynchronous inhibition, asynchronous excitation, and/or phase-locked APs synchronized to each infrared heat pulse. Thermal responses of membrane currents responsible for APs in ganglion neurons were strictly excitatory, with Q10 ≈ 2. In contrast, hair cells responded with a mix of excitatory and inhibitory currents. Excitatory hair cell membrane currents included a thermoelectric capacitive current proportional to the rate of temperature rise (dT/dt) and an inward conduction current driven by ΔT An iberiotoxin-sensitive inhibitory conduction current was also evoked by ΔT, rising in protein biophysics and manipulate cellular excitability. Copyright © 2016 the American Physiological Society.

  8. Expression of the transient receptor potential channels TRPV1, TRPA1 and TRPM8 in mouse trigeminal primary afferent neurons innervating the dura

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    2012-01-01

    Background Migraine and other headache disorders affect a large percentage of the population and cause debilitating pain. Activation and sensitization of the trigeminal primary afferent neurons innervating the dura and cerebral vessels is a crucial step in the “headache circuit”. Many dural afferent neurons respond to algesic and inflammatory agents. Given the clear role of the transient receptor potential (TRP) family of channels in both sensing chemical stimulants and mediating inflammatory pain, we investigated the expression of TRP channels in dural afferent neurons. Methods We used two fluorescent tracers to retrogradely label dural afferent neurons in adult mice and quantified the abundance of peptidergic and non-peptidergic neuron populations using calcitonin gene-related peptide immunoreactivity (CGRP-ir) and isolectin B4 (IB4) binding as markers, respectively. Using immunohistochemistry, we compared the expression of TRPV1 and TRPA1 channels in dural afferent neurons with the expression in total trigeminal ganglion (TG) neurons. To examine the distribution of TRPM8 channels, we labeled dural afferent neurons in mice expressing farnesylated enhanced green fluorescent protein (EGFPf) from a TRPM8 locus. We used nearest-neighbor measurement to predict the spatial association between dural afferent neurons and neurons expressing TRPA1 or TRPM8 channels in the TG. Results and conclusions We report that the size of dural afferent neurons is significantly larger than that of total TG neurons and facial skin afferents. Approximately 40% of dural afferent neurons exhibit IB4 binding. Surprisingly, the percentage of dural afferent neurons containing CGRP-ir is significantly lower than those of total TG neurons and facial skin afferents. Both TRPV1 and TRPA1 channels are expressed in dural afferent neurons. Furthermore, nearest-neighbor measurement indicates that TRPA1-expressing neurons are clustered around a subset of dural afferent neurons. Interestingly, TRPM

  9. Heat pulse excitability of vestibular hair cells and afferent neurons

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    Brichta, Alan M.; Tabatabaee, Hessam; Boutros, Peter J.; Ahn, JoongHo; Della Santina, Charles C.; Poppi, Lauren A.; Lim, Rebecca

    2016-01-01

    In the present study we combined electrophysiology with optical heat pulse stimuli to examine thermodynamics of membrane electrical excitability in mammalian vestibular hair cells and afferent neurons. We recorded whole cell currents in mammalian type II vestibular hair cells using an excised preparation (mouse) and action potentials (APs) in afferent neurons in vivo (chinchilla) in response to optical heat pulses applied to the crista (ΔT ≈ 0.25°C per pulse). Afferent spike trains evoked by heat pulse stimuli were diverse and included asynchronous inhibition, asynchronous excitation, and/or phase-locked APs synchronized to each infrared heat pulse. Thermal responses of membrane currents responsible for APs in ganglion neurons were strictly excitatory, with Q10 ≈ 2. In contrast, hair cells responded with a mix of excitatory and inhibitory currents. Excitatory hair cell membrane currents included a thermoelectric capacitive current proportional to the rate of temperature rise (dT/dt) and an inward conduction current driven by ΔT. An iberiotoxin-sensitive inhibitory conduction current was also evoked by ΔT, rising in heat pulse excitability in vestibular sensory organs and provide quantitative methods for rational application of optical heat pulses to examine protein biophysics and manipulate cellular excitability. PMID:27226448

  10. Characterization of spinal afferent neurons projecting to different chambers of the rat heart.

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    Guić, Maja Marinović; Kosta, Vana; Aljinović, Jure; Sapunar, Damir; Grković, Ivica

    2010-01-29

    The pattern of distribution of spinal afferent neurons (among dorsal root ganglia-DRGs) that project to anatomically and functionally different chambers of the rat heart, as well as their morphological and neurochemical characteristics were investigated. Retrograde tracing using a patch loaded with Fast blue (FB) was applied to all four chambers of the rat heart and labeled cardiac spinal afferents were characterized by using three neurochemical markers. The majority of cardiac projecting neurons were found from T1 to T4 DRGs, whereas the peak was at T2 DRG. There was no difference in the total number of FB-labeled neurons located in ipsilateral and contralateral DRGs regardless of the chambers marked with the patch. However, significantly more FB-labeled neurons projected to the ventricles compared to the atria (859 vs. 715). The proportion of isolectin B(4) binding in FB-labeled neurons was equal among all neurons projecting to different heart chambers (2.4%). Neurofilament 200 positivity was found in greater proportions in DRG neurons projecting to the left side of the heart, whereas calretinin-immunoreactivity was mostly represented in neurons projecting to the left atrium. Spinal afferent neurons projecting to different chambers of the rat heart exhibit a variety of neurochemical phenotypes depending on binding capacity for isolectin B(4) and immunoreactivity for neurofilament 200 and calretinin, and thus represent important baseline data for future studies. (c) 2009 Elsevier Ireland Ltd. All rights reserved.

  11. Activation of afferent renal nerves modulates RVLM-projecting PVN neurons.

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    Xu, Bo; Zheng, Hong; Liu, Xuefei; Patel, Kaushik P

    2015-05-01

    Renal denervation for the treatment of hypertension has proven to be successful; however, the underlying mechanism/s are not entirely clear. To determine if preautonomic neurons in the paraventricular nucleus (PVN) respond to afferent renal nerve (ARN) stimulation, extracellular single-unit recording was used to investigate the contribution of the rostral ventrolateral medulla (RVLM)-projecting PVN (PVN-RVLM) neurons to the response elicited during stimulation of ARN. In 109 spontaneously active neurons recorded in the PVN of anesthetized rats, 25 units were antidromically activated from the RVLM. Among these PVN-RVLM neurons, 84% (21/25) were activated by ARN stimulation. The baseline discharge rate was significantly higher in these neurons than those PVN-RVLM neurons not activated by ARN stimulation (16%, 4/25). The responsiveness of these neurons to baroreflex activation induced by phenylephrine and activation of cardiac sympathetic afferent reflex (CSAR) was also examined. Almost all of the PVN neurons that responded to ARN stimulation were sensitive to baroreflex (95%) and CSAR (100%). The discharge characteristics for nonevoked neurons (not activated by RVLM antidromic stimulation) showed that 23% of these PVN neurons responded to ARN stimulation. All the PVN neurons that responded to ARN stimulation were activated by N-methyl-D-aspartate, and these responses were attenuated by the glutamate receptor blocker AP5. These experiments demonstrated that sensory information originating in the kidney is integrated at the level of preautonomic neurons within the PVN, providing a novel mechanistic insight for use of renal denervation in the modulation of sympathetic outflow in disease states such as hypertension and heart failure. Copyright © 2015 the American Physiological Society.

  12. Monosynaptic connections between primary afferents and giant neurons in the turtle spinal dorsal horn

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    Fernández, A; Radmilovich, M; Russo, R E

    1996-01-01

    This paper reports the occurrence of monosynaptic connections between dorsal root afferents and a distinct cell type-the giant neuron-deep in the dorsal horn of the turtle spinal cord. Light microscope studies combining Nissl stain and transganglionic HRP-labeling of the primary afferents have...

  13. The projection and synaptic organisation of NTS afferent connections with presympathetic neurons, GABA and nNOS neurons in the paraventricular nucleus of the hypothalamus

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    Affleck, V.S.; Coote, J.H.; Pyner, S.

    2012-01-01

    Elevated sympathetic nerve activity, strongly associated with cardiovascular disease, is partly generated from the presympathetic neurons of the paraventricular nucleus of the hypothalamus (PVN). The PVN-presympathetic neurons regulating cardiac and vasomotor sympathetic activity receive information about cardiovascular status from receptors in the heart and circulation. These receptors signal changes via afferent neurons terminating in the nucleus tractus solitarius (NTS), some of which may result in excitation or inhibition of PVN-presympathetic neurons. Understanding the anatomy and neurochemistry of NTS afferent connections within the PVN could provide important clues to the impairment in homeostasis cardiovascular control associated with disease. Transynaptic labelling has shown the presence of neuronal nitric oxide synthase (nNOS)-containing neurons and GABA interneurons that terminate on presympathetic PVN neurons any of which may be the target for NTS afferents. So far NTS connections to these diverse neuronal pools have not been demonstrated and were investigated in this study. Anterograde (biotin dextran amine – BDA) labelling of the ascending projection from the NTS and retrograde (fluorogold – FG or cholera toxin B subunit – CTB) labelling of PVN presympathetic neurons combined with immunohistochemistry for GABA and nNOS was used to identify the terminal neuronal targets of the ascending projection from the NTS. It was shown that NTS afferent terminals are apposed to either PVN-GABA interneurons or to nitric oxide producing neurons or even directly to presympathetic neurons. Furthermore, there was evidence that some NTS axons were positive for vesicular glutamate transporter 2 (vGLUT2). The data provide an anatomical basis for the different functions of cardiovascular receptors that mediate their actions via the NTS–PVN pathways. PMID:22698695

  14. Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons

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    Kim, Sojin; Jin, Zhenhua; Lee, Goeun [Department of Physiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Park, Yong Seek; Park, Cheung-Seog [Department of Microbiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Jin, Young-Ho, E-mail: jinyh@khu.ac.kr [Department of Physiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of)

    2015-01-02

    Highlights: • Prostaglandin E2 (PGE{sub 2}) effect was tested on visceral afferent neurons. • PGE{sub 2} did not evoke response but potentiated serotonin (5-HT) currents up to 167%. • PGE{sub 2}-induced potentiation was blocked by E-prostanoid type 4 receptors antagonist. • PGE{sub 2} effect on 5-HT response was also blocked by protein kinase A inhibitor KT5720. • Thus, PGE{sub 2} modulate visceral afferent neurons via synergistic signaling with 5-HT. - Abstract: Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E{sub 2} (PGE{sub 2}) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE{sub 2} induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE{sub 2} effect on visceral afferent sensory neurons of the rat. Interestingly, PGE{sub 2} itself did not evoked any response but enhanced serotonin (5-HT)-evoked currents up to 167% of the control level. The augmented 5-HT responses were completely inhibited by a 5-HT type 3 receptor antagonist, ondansetron. The PGE{sub 2}-induced potentiation were blocked by a selective E-prostanoid type4 (EP{sub 4}) receptors antagonist, L-161,982, but type1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE{sub 2} effects. PGE{sub 2} induced 5-HT current augmentation was observed on 15% and 21% of the stomach and ileum projecting neurons, respectively. Current results suggest a synergistic signaling in visceral afferent neurons underlying gastrointestinal disorder involving PGE{sub 2} potentiation of 5-HT currents. Our findings may open a possibility for screen a new type drugs with lower side effects than currently using steroidal prostaglandin

  15. Convergence of cranial visceral afferents within the solitary tract nucleus.

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    McDougall, Stuart J; Peters, James H; Andresen, Michael C

    2009-10-14

    Primary afferent axons within the solitary tract (ST) relay homeostatic information via glutamatergic synapses directly to second-order neurons within the nucleus of the solitary tract (NTS). These primary afferents arise from multiple organ systems and relay multiple sensory modalities. How this compact network organizes the flow of primary afferent information will shape central homeostatic control. To assess afferent convergence and divergence, we recorded ST-evoked synaptic responses in pairs of medial NTS neurons in horizontal brainstem slices. ST shocks activated EPSCs along monosynaptic or polysynaptic pathways. Gradations in shock intensity discriminated multiple inputs and stimulus recruitment profiles indicated that each EPSC was unitary. In 24 pairs, 75% were second-order neurons with 64% receiving one direct ST input with the remainder receiving additional convergent ST afferent inputs (22% two; 14% three monosynaptic ST-EPSCs). Some (34%) second-order neurons received polysynaptic EPSCs. Neurons receiving only higher-order inputs were uncommon (13%). Most ST-EPSCs were completely independent, but 4 EPSCs of a total of 81 had equal thresholds, highly correlated latencies, and synchronized synaptic failures consistent with divergence from a single source ST axon or from a common interneuron producing a pair of polysynaptic EPSCs. We conclude that ST afferent inputs are remarkably independent with little evidence of substantial shared information. Individual cells receive highly focused information from the viscera. Thus, afferent excitation of second-order NTS neurons is generally dominated by single visceral afferents and therefore focused on a single afferent modality and/or organ region.

  16. Effects of drugs of abuse on putative rostromedial tegmental neurons, inhibitory afferents to midbrain dopamine cells.

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    Lecca, Salvatore; Melis, Miriam; Luchicchi, Antonio; Ennas, Maria Grazia; Castelli, Maria Paola; Muntoni, Anna Lisa; Pistis, Marco

    2011-02-01

    Recent findings have underlined the rostromedial tegmental nucleus (RMTg), a structure located caudally to the ventral tegmental area, as an important site involved in the mechanisms of aversion. RMTg contains γ-aminobutyric acid neurons responding to noxious stimuli, densely innervated by the lateral habenula and providing a major inhibitory projection to reward-encoding midbrain dopamine (DA) neurons. One of the key features of drug addiction is the perseverance of drug seeking in spite of negative and unpleasant consequences, likely mediated by response suppression within neural pathways mediating aversion. To investigate whether the RMTg has a function in the mechanisms of addicting drugs, we studied acute effects of morphine, cocaine, the cannabinoid agonist WIN55212-2 (WIN), and nicotine on putative RMTg neurons. We utilized single unit extracellular recordings in anesthetized rats and whole-cell patch-clamp recordings in brain slices to identify and characterize putative RMTg neurons and their responses to drugs of abuse. Morphine and WIN inhibited both firing rate in vivo and excitatory postsynaptic currents (EPSCs) evoked by stimulation of rostral afferents in vitro, whereas cocaine inhibited discharge activity without affecting EPSC amplitude. Conversely, nicotine robustly excited putative RMTg neurons and enhanced EPSCs, an effect mediated by α7-containing nicotinic acetylcholine receptors. Our results suggest that activity of RMTg neurons is profoundly influenced by drugs of abuse and, as important inhibitory afferents to midbrain DA neurons, they might take place in the complex interplay between the neural circuits mediating aversion and reward.

  17. Stimulation of renal afferent fibers leads to activation of catecholaminergic and non-catecholaminergic neurons in the medulla oblongata.

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    Nishi, Erika E; Martins, Beatriz S; Milanez, Maycon I O; Lopes, Nathalia R; de Melo, Jose F; Pontes, Roberto B; Girardi, Adriana C; Campos, Ruy R; Bergamaschi, Cássia T

    2017-05-01

    Presympathetic neurons in the rostral ventrolateral medulla (RVLM) including the adrenergic cell groups play a major role in the modulation of several reflexes required for the control of sympathetic vasomotor tone and blood pressure (BP). Moreover, sympathetic vasomotor drive to the kidneys influence natriuresis and diuresis by inhibiting the cAMP/PKA pathway and redistributing the Na + /H + exchanger isoform 3 (NHE3) to the body of the microvilli in the proximal tubules. In this study we aimed to evaluate the effects of renal afferents stimulation on (1) the neurochemical phenotype of Fos expressing neurons in the medulla oblongata and (2) the level of abundance and phosphorylation of NHE3 in the renal cortex. We found that electrical stimulation of renal afferents increased heart rate and BP transiently and caused activation of tyrosine hydroxylase (TH)-containing neurons in the RVLM and non-TH neurons in the NTS. Additionally, activation of the inhibitory renorenal reflex over a 30-min period resulted in increased natriuresis and diuresis associated with increased phosphorylation of NHE3 at serine 552, a surrogate for reduced activity of this exchanger, in the contralateral kidney. This effect was not dependent of BP changes considering that no effects on natriuresis or diuresis were found in the ipsilateral-stimulated kidney. Therefore, our data show that renal afferents leads to activation of catecholaminergic and non-catecholaminergic neurons in the medulla oblongata. When renorenal reflex is induced, NHE3 exchanger activity appears to be decreased, resulting in decreased sodium and water reabsorption in the contralateral kidney. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Thyroid hormone is required for the pruning of afferent type II spiral ganglion neurons in the mouse cochlea

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    Sundaresan, Srividya; Balasubbu, Suganthalakshmi; Mustapha, Mirna

    2015-01-01

    Afferent connections to the sensory inner and outer hair cells in the cochlea refine and functionally mature during the thyroid hormone (TH)- critical period of inner ear development that occurs perinatally in rodents. In this study, we investigated the effects of hypothyroidism on afferent type II innervation to outer hair cells (OHCs) using the Snell dwarf mouse (Pit1dw). Using a transgenic approach to specifically label type II spiral ganglion neurons, we found that a lack of TH causes persistence of excess type II SGN connections to the OHCs, as well as continued expression of the hair cell functional marker, otoferlin, in the OHCs beyond the maturation period. We also observed a concurrent delay in efferent attachment to the OHCs. Supplementing with TH during the early postnatal period from postnatal day (P) 3 to P4 reversed the defect in type II SGN pruning but did not alter otoferlin expression. Our results show that hypothyroidism causes a defect in the large-scale pruning of afferent type II spiral ganglion neurons in the cochlea, and a delay in efferent attachment and the maturation of otoferlin expression. Our data suggest that the state of maturation of hair cells, as determined by otoferlin expression, may not regulate the pruning of their afferent innervation. PMID:26592716

  19. Immunomodulation of afferent neurons in guinea-pig isolated airway.

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    Riccio, M M; Myers, A C; Undem, B J

    1996-03-01

    1. The trachea, larynx and main bronchi with the right vagus nerve and nodose ganglion were isolated from guinea-pigs passively immunized 24 h previously with serum containing anti-ovalbumin antibody. 2. The airways were placed in one compartment of a Perspex chamber for recording of isometric tension while the nodose ganglion and attached vagus nerve were pulled into another compartment. Action potentials arriving from single airway afferent nerve endings were monitored extracellularly using a glass microelectrode positioned near neuronal cell bodies in the ganglion. Mechanosensitivity of the nerve endings was quantified using calibrated von Frey filaments immediately before and after exposure to antigen (10 micrograms ml-1 ovalbumin). 3. Ten endings responded to the force exerted by the lowest filament (0.078 mN) and were not further investigated. In airways from thirteen immunized guinea-pigs, the mechanical sensitivity of A delta afferent fibres (conduction velocity = 4.3 +/- 0.6 m s-1) was enhanced 4.1 +/- 0.9-fold following airway exposure to antigen (P action potential generation except in one instance when the receptive field was located over the smooth muscle. This ending also responded to methacholine suggesting that spatial changes in the receptive field, induced by muscle contraction, were responsible for the activation. 5. The mediators responsible for these effects are unknown, although histamine, prostaglandins, leukotrienes and tachykinins do not appear to be essential. The increase in mechanical responsiveness was not associated with the smooth muscle contraction since leukotriene C4, histamine and tachykinins, which all caused a similar contraction to antigen, did not affect mechanical thresholds. Moreover, the antigen-induced increases in excitability persisted beyond the duration of the smooth muscle contraction. 6. These results demonstrate that antigen-antibody-mediated inflammatory processes may enhance the excitability of vagal afferent

  20. Structure of the afferent terminals in terminal ganglion of a cricket and persistent homology.

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    Jacob Brown

    Full Text Available We use topological data analysis to investigate the three dimensional spatial structure of the locus of afferent neuron terminals in crickets Acheta domesticus. Each afferent neuron innervates a filiform hair positioned on a cercus: a protruding appendage at the rear of the animal. The hairs transduce air motion to the neuron signal that is used by a cricket to respond to the environment. We stratify the hairs (and the corresponding afferent terminals into classes depending on hair length, along with position. Our analysis uncovers significant structure in the relative position of these terminal classes and suggests the functional relevance of this structure. Our method is very robust to the presence of significant experimental and developmental noise. It can be used to analyze a wide range of other point cloud data sets.

  1. Morphological changes in different populations of bladder afferent neurons detected by herpes simplex virus (HSV) vectors with cell-type-specific promoters in mice with spinal cord injury.

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    Shimizu, Nobutaka; Doyal, Mark F; Goins, William F; Kadekawa, Katsumi; Wada, Naoki; Kanai, Anthony J; de Groat, William C; Hirayama, Akihide; Uemura, Hirotsugu; Glorioso, Joseph C; Yoshimura, Naoki

    2017-11-19

    Functional and morphological changes in C-fiber bladder afferent pathways are reportedly involved in neurogenic detrusor overactivity (NDO) after spinal cord injury (SCI). This study examined the morphological changes in different populations of bladder afferent neurons after SCI using replication-defective herpes simplex virus (HSV) vectors encoding the mCherry reporter driven by neuronal cell-type-specific promoters. Spinal intact (SI) and SCI mice were injected into the bladder wall with HSV mCherry vectors driven by the cytomegalovirus (CMV) promoter, CGRP promoter, TRPV1 promoter or neurofilament 200 (NF200) promoter. Two weeks after vector inoculation into the bladder wall, L1 and L6 dorsal root ganglia (DRG) were removed bilaterally for immunofluorescent staining using anti-mCherry antibody. The number of CMV promoter vector-labeled neurons was not altered after SCI. The number of CGRP and TRPV1 promoter vector-labeled neurons was significantly increased whereas the number of NF200 vector-labeled neurons was decreased in L6 DRG after SCI. The median size of CGRP promoter-labeled C-fiber neurons was increased from 247.0 in SI mice to 271.3μm 2 in SCI mice whereas the median cell size of TRPV1 promoter vector-labeled neurons was decreased from 245.2 in SI mice to 216.5μm 2 in SCI mice. CGRP and TRPV1 mRNA levels of laser-captured bladder afferent neurons labeled with Fast Blue were significantly increased in SCI mice compared to SI mice. Thus, using a novel HSV vector-mediated neuronal labeling technique, we found that SCI induces expansion of the CGRP- and TRPV1-expressing C-fiber cell population, which could contribute to C-fiber afferent hyperexcitability and NDO after SCI. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. A new model of strabismic amblyopia: Loss of spatial acuity due to increased temporal dispersion of geniculate X-cell afferents on to cortical neurons.

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    Crewther, D P; Crewther, S G

    2015-09-01

    Although the neural locus of strabismic amblyopia has been shown to lie at the first site of binocular integration, first in cat and then in primate, an adequate mechanism is still lacking. Here we hypothesise that increased temporal dispersion of LGN X-cell afferents driven by the deviating eye onto single cortical neurons may provide a neural mechanism for strabismic amblyopia. This idea was investigated via single cell extracellular recordings of 93 X and 50 Y type LGN neurons from strabismic and normal cats. Both X and Y neurons driven by the non-deviating eye showed shorter latencies than those driven by either the strabismic or normal eyes. Also the mean latency difference between X and Y neurons was much greater for the strabismic cells compared with the other two groups. The incidence of lagged X-cells driven by the deviating eye of the strabismic cats was higher than that of LGN X-cells from normal animals. Remarkably, none of the cells recorded from the laminae driven by the non-deviating eye were of the lagged class. A simple computational model was constructed in which a mixture of lagged and non-lagged afferents converge on to single cortical neurons. Model cut-off spatial frequencies to a moving grating stimulus were sensitive to the temporal dispersion of the geniculate afferents. Thus strabismic amblyopia could be viewed as a lack of developmental tuning of geniculate lags for neurons driven by the amblyopic eye. Monocular control of fixation by the non-deviating eye is associated with reduced incidence of lagged neurons, suggesting that in normal vision, lagged neurons might play a role in maintaining binocular connections for cortical neurons. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Tuning of spinal networks to frequency components of spike trains in individual afferents.

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    Koerber, H R; Seymour, A W; Mendell, L M

    1991-10-01

    Cord dorsum potentials (CDPs) evoked by primary afferent fiber stimulation reflect the response of postsynaptic dorsal horn neurons. The properties of these CDPs have been shown to vary in accordance with the type of primary afferent fiber stimulated. The purpose of the present study was to determine the relationships between frequency modulation of the afferent input trains, the amplitude modulation of the evoked CDPs, and the type of primary afferent stimulated. The somata of individual primary afferent fibers were impaled in the L7 dorsal root ganglion of alpha-chloralose-anesthetized cats. Action potentials (APs) were evoked in single identified afferents via the intracellular microelectrode while simultaneously recording the response of dorsal horn neurons as CDPs, or activity of individual target interneurons recorded extracellularly or intracellularly. APs were evoked in afferents using temporal patterns identical to the responses of selected afferents to natural stimulation of their receptive fields. Two such physiologically realistic trains, one recorded from a hair follicle and the other from a slowly adapting type 1 receptor, were chosen as standard test trains. Modulation of CDP amplitude in response to this frequency-modulated afferent activity varied according to the type of peripheral mechanoreceptor innervated. Dorsal horn networks driven by A beta afferents innervating hair follicles, rapidly adapting pad (Krause end bulb), and field receptors seemed "tuned" to amplify the onset of activity in single afferents. Networks driven by afferents innervating down hair follicles and pacinian corpuscles required more high-frequency activity to elicit their peak response. Dorsal horn networks driven by afferents innervating slowly adapting receptors including high-threshold mechanoreceptors exhibited some sensitivity to the instantaneous frequency, but in general they reproduced the activity in the afferent fiber much more faithfully. Responses of

  4. Detection thresholds of macaque otolith afferents.

    Science.gov (United States)

    Yu, Xiong-Jie; Dickman, J David; Angelaki, Dora E

    2012-06-13

    The vestibular system is our sixth sense and is important for spatial perception functions, yet the sensory detection and discrimination properties of vestibular neurons remain relatively unexplored. Here we have used signal detection theory to measure detection thresholds of otolith afferents using 1 Hz linear accelerations delivered along three cardinal axes. Direction detection thresholds were measured by comparing mean firing rates centered on response peak and trough (full-cycle thresholds) or by comparing peak/trough firing rates with spontaneous activity (half-cycle thresholds). Thresholds were similar for utricular and saccular afferents, as well as for lateral, fore/aft, and vertical motion directions. When computed along the preferred direction, full-cycle direction detection thresholds were 7.54 and 3.01 cm/s(2) for regular and irregular firing otolith afferents, respectively. Half-cycle thresholds were approximately double, with excitatory thresholds being half as large as inhibitory thresholds. The variability in threshold among afferents was directly related to neuronal gain and did not depend on spike count variance. The exact threshold values depended on both the time window used for spike count analysis and the filtering method used to calculate mean firing rate, although differences between regular and irregular afferent thresholds were independent of analysis parameters. The fact that minimum thresholds measured in macaque otolith afferents are of the same order of magnitude as human behavioral thresholds suggests that the vestibular periphery might determine the limit on our ability to detect or discriminate small differences in head movement, with little noise added during downstream processing.

  5. Afferent activity to necklace glomeruli is dependent on external stimuli

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    Munger Steven D

    2009-03-01

    Full Text Available Abstract Background The main olfactory epithelium (MOE is a complex organ containing several functionally distinct subpopulations of sensory neurons. One such subpopulation is distinguished by its expression of the guanylyl cyclase GC-D. The axons of GC-D-expressing (GC-D+ neurons innervate 9–15 "necklace" glomeruli encircling the caudal main olfactory bulb (MOB. Chemosensory stimuli for GC-D+ neurons include two natriuretic peptides, uroguanylin and guanylin, and CO2. However, the biologically-relevant source of these chemostimuli is unclear: uroguanylin is both excreted in urine, a rich source of olfactory stimuli for rodents, and expressed in human nasal epithelium; CO2 is present in both inspired and expired air. Findings To determine whether the principal source of chemostimuli for GC-D+ neurons is external or internal to the nose, we assessed the consequences of removing external chemostimuli for afferent activity to the necklace glomeruli. To do so, we performed unilateral naris occlusions in Gucy2d-Mapt-lacZ +/- mice [which express a β-galactosidase (β-gal reporter specifically in GC-D+ neurons] followed by immunohistochemistry for β-gal and a glomerular marker of afferent activity, tyrosine hydroxylase (TH. We observed a dramatic decrease in TH immunostaining, consistent with reduced or absent afferent activity, in both necklace and non-necklace glomeruli ipsilateral to the occluded naris. Conclusion Like other MOB glomeruli, necklace glomeruli exhibit a large decrease in afferent activity upon removal of external stimuli. Thus, we conclude that activity in GC-D+ neurons, which specifically innervate necklace glomeruli, is not dependent on internal stimuli. Instead, GC-D+ neurons, like other OSNs in the MOE, primarily sense the external world.

  6. TRPV1 marks synaptic segregation of multiple convergent afferents at the rat medial solitary tract nucleus.

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    James H Peters

    Full Text Available TRPV1 receptors are expressed on most but not all central terminals of cranial visceral afferents in the caudal solitary tract nucleus (NTS. TRPV1 is associated with unmyelinated C-fiber afferents. Both TRPV1+ and TRPV1- afferents enter NTS but their precise organization remains poorly understood. In horizontal brainstem slices, we activated solitary tract (ST afferents and recorded ST-evoked glutamatergic excitatory synaptic currents (ST-EPSCs under whole cell voltage clamp conditions from neurons of the medial subnucleus. Electrical shocks to the ST produced fixed latency EPSCs (jitter<200 µs that identified direct ST afferent innervation. Graded increases in shock intensity often recruited more than one ST afferent and ST-EPSCs had consistent threshold intensity, latency to onset, and unique EPSC waveforms that characterized each unitary ST afferent contact. The TRPV1 agonist capsaicin (100 nM blocked the evoked TRPV1+ ST-EPSCs and defined them as either TRPV1+ or TRPV1- inputs. No partial responses to capsaicin were observed so that in NTS neurons that received one or multiple (2-5 direct ST afferent inputs--all were either blocked by capsaicin or were unaltered. Since TRPV1 mediates asynchronous release following TRPV1+ ST-evoked EPSCs, we likewise found that recruiting more than one ST afferent further augmented the asynchronous response and was eliminated by capsaicin. Thus, TRPV1+ and TRPV1- afferents are completely segregated to separate NTS neurons. As a result, the TRPV1 receptor augments glutamate release only within unmyelinated afferent pathways in caudal medial NTS and our work indicates a complete separation of C-type from A-type afferent information at these first central neurons.

  7. Peptide and lipid modulation of glutamatergic afferent synaptic transmission in the solitary tract nucleus

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    Michael C. Andresen

    2013-01-01

    Full Text Available The brainstem nucleus of the solitary tract (NTS holds the first central neurons in major homeostatic reflex pathways. These homeostatic reflexes regulate and coordinate multiple organ systems from gastrointestinal to cardiopulmonary functions. The core of many of these pathways arise from cranial visceral afferent neurons that enter the brain as the solitary tract (ST with more than two-thirds arising from the gastrointestinal system. About one quarter of ST afferents have myelinated axons but the majority are classed as unmyelinated C-fibers. All ST afferents release the fast neurotransmitter glutamate with remarkably similar, high-probability release characteristics. Second order NTS neurons receive surprisingly limited primary afferent information with one or two individual inputs converging on single second order NTS neurons. A- and C-fiber afferents never mix at NTS second order neurons. Many transmitters modify the basic glutamatergic excitatory postsynaptic current (EPSC often by reducing glutamate release or interrupting terminal depolarization. Thus, a distinguishing feature of ST transmission is presynaptic expression of G-protein coupled receptors for peptides common to peripheral or forebrain (e.g. hypothalamus neuron sources. Presynaptic receptors for angiotensin (AT1, vasopressin (V1a, oxytocin (OT, opioid (MOR, ghrelin (GHSR1 and cholecystokinin (CCK differentially control glutamate release on particular subsets of neurons with most other ST afferents unaffected. Lastly, lipid-like signals are transduced by two key ST presynaptic receptors, the transient receptor potential vanilloid type 1 (TRPV1 and the cannabinoid receptor (CB1 that oppositely control glutamate release. Increasing evidence suggests that peripheral nervous signaling mechanisms are repurposed at central terminals to control excitation and are major sites of signal integration of peripheral and central inputs particularly from the hypothalamus.

  8. Light and electron microscopy of contacts between primary afferent fibres and neurones with axons ascending the dorsal columns of the feline spinal cord.

    Science.gov (United States)

    Maxwell, D J; Koerber, H R; Bannatyne, B A

    1985-10-01

    In addition to primary afferent fibres, the dorsal columns of the cat spinal cord contain ascending second-order axons which project to the dorsal column nuclei. The aim of the present study was to obtain morphological evidence that certain primary afferent axons form monosynaptic contacts with cells of origin of this postsynaptic dorsal column pathway. In ten adult cats, neurones with axons ascending the dorsal columns were retrogradely labelled with horseradish peroxidase using a pellet implantation method in the thoracic dorsal columns. In the lumbosacral regions of the same animals, primary afferent fibres were labelled intra-axonally with ionophoretic application of horseradish peroxidase. Tissue containing labelled axons was prepared for light and combined light and electron microscopy. Ultrastructural examination demonstrated that slowly adapting (Type I), hair follicle, Pacinian corpuscle and group Ia muscle spindle afferents formed monosynaptic contacts with labelled cells and light microscopical analysis suggested that they also received monosynaptic input from rapidly adapting (Krause) afferents. This evidence suggests that sensory information from large-diameter cutaneous and muscle spindle afferent fibres is conveyed disynaptically via the postsynaptic dorsal column pathway to the dorsal column nuclei. Some of the input to this pathway is probably modified in the spinal cord as the majority of primary afferent boutons forming monosynaptic contacts were postsynaptic to other axon terminals. The postsynaptic dorsal column system appears to constitute a major somatosensory pathway in the cat.

  9. elPBN neurons regulate rVLM activity through elPBN-rVLM projections during activation of cardiac sympathetic afferent nerves

    Science.gov (United States)

    Longhurst, John C.; Tjen-A-Looi, Stephanie C.; Fu, Liang-Wu

    2016-01-01

    The external lateral parabrachial nucleus (elPBN) within the pons and rostral ventrolateral medulla (rVLM) contributes to central processing of excitatory cardiovascular reflexes during stimulation of cardiac sympathetic afferent nerves (CSAN). However, the importance of elPBN cardiovascular neurons in regulation of rVLM activity during CSAN activation remains unclear. We hypothesized that CSAN stimulation excites the elPBN cardiovascular neurons and, in turn, increases rVLM activity through elPBN-rVLM projections. Compared with controls, in rats subjected to microinjection of retrograde tracer into the rVLM, the numbers of elPBN neurons double-labeled with c-Fos (an immediate early gene) and the tracer were increased after CSAN stimulation (P < 0.05). The majority of these elPBN neurons contain vesicular glutamate transporter 3. In cats, epicardial bradykinin and electrical stimulation of CSAN increased the activity of elPBN cardiovascular neurons, which was attenuated (n = 6, P < 0.05) after blockade of glutamate receptors with iontophoresis of kynurenic acid (Kyn, 25 mM). In separate cats, microinjection of Kyn (1.25 nmol/50 nl) into the elPBN reduced rVLM activity evoked by both bradykinin and electrical stimulation (n = 5, P < 0.05). Excitation of the elPBN with microinjection of dl-homocysteic acid (2 nmol/50 nl) significantly increased basal and CSAN-evoked rVLM activity. However, the enhanced rVLM activity induced by dl-homocysteic acid injected into the elPBN was reversed following iontophoresis of Kyn into the rVLM (n = 7, P < 0.05). These data suggest that cardiac sympathetic afferent stimulation activates cardiovascular neurons in the elPBN and rVLM sequentially through a monosynaptic (glutamatergic) excitatory elPBN-rVLM pathway. PMID:27225950

  10. Development of fusimotor innervation correlates with group Ia afferents but is independent of neurotrophin-3

    NARCIS (Netherlands)

    Ringstedt, T; Copray, S; Walro, J; Kucera, J

    1998-01-01

    Fusimotor neurons, group Ia afferents and muscle spindles are absent in mutant mice lacking the gene for neurotrophin-3 (NT3). To partition the effect of Ia afferent or spindle absence from that of NT3 deprivation on fusimotor neuron development, we examined the fusimotor system in a mutant mouse

  11. Modulation of jaw muscle spindle afferent activity following intramuscular injections with hypertonic saline.

    Science.gov (United States)

    Ro, J Y; Capra, N F

    2001-05-01

    Transient noxious chemical stimulation of small diameter muscle afferents modulates jaw movement-related responses of caudal brainstem neurons. While it is likely that the effect is mediated from the spindle afferents in the mesencephalic nucleus (Vmes) via the caudally projecting Probst's tract, the mechanisms of pain induced modulations of jaw muscle spindle afferents is not known. In the present study, we tested the hypothesis that jaw muscle nociceptors gain access to muscle spindle afferents in the same muscle via central mechanisms and alter their sensitivity. Thirty-five neurons recorded from the Vmes were characterized as muscle spindle afferents based on their responses to passive jaw movements, muscle palpation, and electrical stimulation of the masseter nerve. Each cell was tested by injecting a small volume (250 microl) of either 5% hypertonic and/or isotonic saline into the receptor-bearing muscle. Twenty-nine units were tested with 5% hypertonic saline, of which 79% (23/29) showed significant modulation of mean firing rates (MFRs) during one or more phases of ramp-and-hold movements. Among the muscle spindle primary-like units (n = 12), MFRs of 4 units were facilitated, five reduced, two showed mixed responses and one unchanged. In secondary-like units (n = 17), MFRs of 9 were facilitated, three reduced and five unchanged. Thirteen units were tested with isotonic saline, of which 77% showed no significant changes of MFRs. Further analysis revealed that the hypertonic saline not only affected the overall output of muscle spindle afferents, but also increased the variability of firing and altered the relationship between afferent signal and muscle length. These results demonstrated that activation of muscle nociceptors significantly affects proprioceptive properties of jaw muscle spindles via central neural mechanisms. The changes can have deleterious effects on oral motor function as well as kinesthetic sensibility.

  12. elPBN neurons regulate rVLM activity through elPBN-rVLM projections during activation of cardiac sympathetic afferent nerves.

    Science.gov (United States)

    Guo, Zhi-Ling; Longhurst, John C; Tjen-A-Looi, Stephanie C; Fu, Liang-Wu

    2016-08-01

    The external lateral parabrachial nucleus (elPBN) within the pons and rostral ventrolateral medulla (rVLM) contributes to central processing of excitatory cardiovascular reflexes during stimulation of cardiac sympathetic afferent nerves (CSAN). However, the importance of elPBN cardiovascular neurons in regulation of rVLM activity during CSAN activation remains unclear. We hypothesized that CSAN stimulation excites the elPBN cardiovascular neurons and, in turn, increases rVLM activity through elPBN-rVLM projections. Compared with controls, in rats subjected to microinjection of retrograde tracer into the rVLM, the numbers of elPBN neurons double-labeled with c-Fos (an immediate early gene) and the tracer were increased after CSAN stimulation (P neurons contain vesicular glutamate transporter 3. In cats, epicardial bradykinin and electrical stimulation of CSAN increased the activity of elPBN cardiovascular neurons, which was attenuated (n = 6, P neurons in the elPBN and rVLM sequentially through a monosynaptic (glutamatergic) excitatory elPBN-rVLM pathway. Copyright © 2016 the American Physiological Society.

  13. Persistent pain after spinal cord injury is maintained by primary afferent activity.

    Science.gov (United States)

    Yang, Qing; Wu, Zizhen; Hadden, Julia K; Odem, Max A; Zuo, Yan; Crook, Robyn J; Frost, Jeffrey A; Walters, Edgar T

    2014-08-06

    Chronic pain caused by insults to the CNS (central neuropathic pain) is widely assumed to be maintained exclusively by central mechanisms. However, chronic hyperexcitablility occurs in primary nociceptors after spinal cord injury (SCI), suggesting that SCI pain also depends upon continuing activity of peripheral sensory neurons. The present study in rats (Rattus norvegicus) found persistent upregulation after SCI of protein, but not mRNA, for a voltage-gated Na(+) channel, Nav1.8, that is expressed almost exclusively in primary afferent neurons. Selectively knocking down Nav1.8 after SCI suppressed spontaneous activity in dissociated dorsal root ganglion neurons, reversed hypersensitivity of hindlimb withdrawal reflexes, and reduced ongoing pain assessed by a conditioned place preference test. These results show that activity in primary afferent neurons contributes to ongoing SCI pain. Copyright © 2014 the authors 0270-6474/14/3410765-05$15.00/0.

  14. In vivo analysis of the role of metabotropic glutamate receptors in the afferent regulation of chick cochlear nucleus neurons.

    Science.gov (United States)

    Carzoli, Kathryn L; Hyson, Richard L

    2011-02-01

    Cochlea removal results in the death of approximately 20-30% of neurons in the chick nucleus magnocellularis (NM). One early event in NM neuronal degradation is the disruption of their ribosomes. This can be visualized in the first few hours following cochlea removal using Y10B, an antibody that recognizes ribosomal RNA. Previous studies using a brain slice preparation suggest that maintenance of ribosomal integrity in NM neurons requires metabotropic glutamate receptor (mGluR) activation. Isolating the brain slice in vitro, however, may eliminate other potential sources of trophic support and only allows for evaluation of the early changes that occur in NM neurons following deafferentation. Consequently, it is not known if mGluR activation is truly required for the maintenance of NM neurons in the intact system. The current experiments evaluated the importance of mGluRs in vivo. The effects of short-term receptor blockade were assessed through Y10B labeling and the effects of long-term blockade were assessed through stereological counting of NM neurons in Nissl-stained tissue. mGluR antagonists or vehicle were administered intracerebroventricularly following unilateral cochlea removal. Vehicle-treated subjects replicated the previously reported effects of cochlea removal, showing lighter Y10B labeling and fewer Nissl-stained NM neurons on the deafened side of the brain. Blockade of mGluRs prevented the rapid activity-dependent difference in Y10B labeling, and in some cases, had the reverse effect, yielding lighter labeling of NM neurons on the intact side of the brain. Similarly, mGluR blockade over longer survival periods resulted in a reduction in number of cells on both intact and deafferented sides of the brain, and in some cases, yielded a reverse effect of fewer neurons on the intact side versus deafened side. These data are consistent with in vitro findings and suggest that mGluR activation plays a vital role in the afferent maintenance of NM neurons

  15. Cortical Presynaptic Control of Dorsal Horn C–Afferents in the Rat

    Science.gov (United States)

    Martínez-Lorenzana, Guadalupe; Condés-Lara, Miguel; Rojas-Piloni, Gerardo

    2013-01-01

    Lamina 5 sensorimotor cortex pyramidal neurons project to the spinal cord, participating in the modulation of several modalities of information transmission. A well-studied mechanism by which the corticospinal projection modulates sensory information is primary afferent depolarization, which has been characterized in fast muscular and cutaneous, but not in slow-conducting nociceptive skin afferents. Here we investigated whether the inhibition of nociceptive sensory information, produced by activation of the sensorimotor cortex, involves a direct presynaptic modulation of C primary afferents. In anaesthetized male Wistar rats, we analyzed the effects of sensorimotor cortex activation on post tetanic potentiation (PTP) and the paired pulse ratio (PPR) of dorsal horn field potentials evoked by C–fiber stimulation in the sural (SU) and sciatic (SC) nerves. We also explored the time course of the excitability changes in nociceptive afferents produced by cortical stimulation. We observed that the development of PTP was completely blocked when C-fiber tetanic stimulation was paired with cortex stimulation. In addition, sensorimotor cortex activation by topical administration of bicuculline (BIC) produced a reduction in the amplitude of C–fiber responses, as well as an increase in the PPR. Furthermore, increases in the intraspinal excitability of slow-conducting fiber terminals, produced by sensorimotor cortex stimulation, were indicative of primary afferent depolarization. Topical administration of BIC in the spinal cord blocked the inhibition of C–fiber neuronal responses produced by cortical stimulation. Dorsal horn neurons responding to sensorimotor cortex stimulation also exhibited a peripheral receptive field and responded to stimulation of fast cutaneous myelinated fibers. Our results suggest that corticospinal inhibition of nociceptive responses is due in part to a modulation of the excitability of primary C–fibers by means of GABAergic inhibitory

  16. Fine structure of primary afferent axon terminals projecting from rapidly adapting mechanoreceptors of the toe and foot pads of the cat.

    Science.gov (United States)

    Maxwell, D J; Bannatyne, B A; Fyffe, R E; Brown, A G

    1984-04-01

    Two Pacinian corpuscle afferents and two rapidly adapting afferents from Krause corpuscles were intra-axonally labelled with horseradish peroxidase in the lumbosacral enlargement of the cat's spinal cord. Tissue was prepared for combined light and electron microscopical analysis. Boutons from both classes of afferent had similar ultrastructural appearances. They both formed from one to three synaptic junctions with dendritic shafts and spines and received axo-axonic synapses. In addition, both categories of bouton were seen to be presynaptic to structures interpreted as vesicle-containing dendrites. It is concluded that both types of afferent fibre are subject to presynaptic control and that they synapse with dorsal horn neurones which are possibly interneurones involved in primary afferent depolarization and post-synaptic dorsal column neurones.

  17. Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency facilitation in vagal afferents.

    Science.gov (United States)

    Perez-Burgos, Azucena; Wang, Bingxian; Mao, Yu-Kang; Mistry, Bhavik; McVey Neufeld, Karen-Anne; Bienenstock, John; Kunze, Wolfgang

    2013-01-15

    Mounting evidence supports the influence of the gut microbiome on the local enteric nervous system and its effects on brain chemistry and relevant behavior. Vagal afferents are involved in some of these effects. We previously showed that ingestion of the probiotic bacterium Lactobacillus rhamnosus (JB-1) caused extensive neurochemical changes in the brain and behavior that were abrogated by prior vagotomy. Because information can be transmitted to the brain via primary afferents encoded as neuronal spike trains, our goal was to record those induced by JB-1 in vagal afferents in the mesenteric nerve bundle and thus determine the nature of the signals sent to the brain. Male Swiss Webster mice jejunal segments were cannulated ex vivo, and serosal and luminal compartments were perfused separately. Bacteria were added intraluminally. We found no evidence for translocation of labeled bacteria across the epithelium during the experiment. We recorded extracellular multi- and single-unit neuronal activity with glass suction pipettes. Within minutes of application, JB-1 increased the constitutive single- and multiunit firing rate of the mesenteric nerve bundle, but Lactobacillus salivarius (a negative control) or media alone were ineffective. JB-1 significantly augmented multiunit discharge responses to an intraluminal distension pressure of 31 hPa. Prior subdiaphragmatic vagotomy abolished all of the JB-1-evoked effects. This detailed exploration of the neuronal spike firing that encodes behavioral signaling to the brain may be useful to identify effective psychoactive bacteria and thereby offer an alternative new perspective in the field of psychiatry and comorbid conditions.

  18. Dynorphin-dependent reduction of excitability and attenuation of inhibitory afferents of NPS neurons in the pericoerulear region of mice

    Directory of Open Access Journals (Sweden)

    Kay eJuengling

    2016-03-01

    Full Text Available The Neuropeptide S system, consisting of the 20-amino acid peptide neuropeptide S (NPS and its G-protein coupled receptor (NPSR, modulates arousal, wakefulness, anxiety, and fear-extinction in mice. In addition, recent evidence indicates that the NPS system attenuates stress-dependent impairment of fear extinction, and that NPS-expressing neurons in close proximity to the locus coeruleus (pericoerulear, periLC region are activated by stress. Furthermore, periLC NPS neurons receive afferents from neurons of the centrolateral nucleus of the amygdala (CeL, of which a substantial population expresses the kappa opioid receptor (KOR ligand precursor prodynorphin. This study aims to identify the effect of the dynorphinergic system on NPS neurons in the periLC via pre- and postsynaptic mechanisms. Using electrophysiological recordings in mouse brain slices, we provide evidence that NPS neurons in the periLC region are directly inhibited by dynorphin A via activation of κ-opioid receptor 1 (KOR1 and a subsequent increase of potassium conductances. Thus, the dynorphinergic system is suited to inactivate NPS neurons in the periLC. In addition to this direct, somatic effect, dynorphin A reduces the efficacy of GABAergic synapses on NPS neurons via KOR1 and KOR2. In conclusion, the present study provides evidence for the interaction of the NPS and the kappa opioid system in the periLC. Therefore, the endogenous opioid dynorphin is suited to inhibit NPS neurons with a subsequent decrease in NPS release in putative target regions leading to a variety of physiological consequences such as increased anxiety or vulnerability to stress exposure.

  19. On the nature of the afferent fibers of oculomotor nerve.

    Science.gov (United States)

    Manni, E; Draicchio, F; Pettorossi, V E; Carobi, C; Grassi, S; Bortolami, R; Lucchi, M L

    1989-03-01

    The oculogyric nerves contain afferent fibers originating from the ophthalmic territory, the somata of which are located in the ipsilateral semilunar ganglion. These primary sensory neurons project to the Subnucleus Gelatinosus of the Nucleus Caudalis Trigemini, where they make presynaptic contact with the central endings of the primary trigeminal afferents running in the fifth cranial nerve. After complete section of the trigeminal root, the antidromic volleys elicited in the trunk of the third cranial nerve by stimulating SG of NCT consisted of two waves belonging to the A delta and C groups. The area of both components of the antidromic volleys decreased both after bradykinin and hystamine injection into the corresponding cutaneous region and after thermic stimulation of the ipsilateral trigeminal ophthalmic territory. The reduction of such potentials can be explained in terms of collision between the antidromic volleys and those elicited orthodromically by chemical and thermic stimulation. Also, capsaicin applied on the nerve induced an immediate increase, followed by a long lasting decrease, of orthodromic evoked response area. These findings bring further support to the nociceptive nature of the afferent fibers running into the oculomotor nerve.

  20. Group Ia afferents likely contribute to short-latency interlimb reflexes in the human biceps femoris muscle

    DEFF Research Database (Denmark)

    Stevenson, Andrew James Thomas; Kamavuako, Ernest Nlandu; Geertsen, Svend Sparre

    2017-01-01

    amplitudes (4 vs. 8°) at the same 150°/s velocity (p’s > 0.08). Conclusion: Because fast conducting group Ia muscle spindle afferents are sensitive to changes in muscle stretch velocity, while group II spindle afferents are sensitive to changes in amplitude (Grey et al., JPhysiol., 2001; Matthews, Trends...... Neurosci., 1991), group Ia velocity sensitive muscle spindle afferents likely contribute to the short-latency crossed spinal reflexes in the cBF muscle following iKnee joint rotations. This supports the findings for the short-latency crossed responses in the human soleus muscle (Stubbs & Mrachacz...... neurons in humans, with primary contributions from group Ia muscle spindle afferents....

  1. Dural afferents express acid-sensing ion channels: a role for decreased meningeal pH in migraine headache.

    Science.gov (United States)

    Yan, Jin; Edelmayer, Rebecca M; Wei, Xiaomei; De Felice, Milena; Porreca, Frank; Dussor, Gregory

    2011-01-01

    Migraine headache is one of the most common neurological disorders. The pathological conditions that directly initiate afferent pain signaling are poorly understood. In trigeminal neurons retrogradely labeled from the cranial meninges, we have recorded pH-evoked currents using whole-cell patch-clamp electrophysiology. Approximately 80% of dural-afferent neurons responded to a pH 6.0 application with a rapidly activating and rapidly desensitizing ASIC-like current that often exceeded 20nA in amplitude. Inward currents were observed in response to a wide range of pH values and 30% of the neurons exhibited inward currents at pH 7.1. These currents led to action potentials in 53%, 30% and 7% of the dural afferents at pH 6.8, 6.9 and 7.0, respectively. Small decreases in extracellular pH were also able to generate sustained window currents and sustained membrane depolarizations. Amiloride, a non-specific blocker of ASIC channels, inhibited the peak currents evoked upon application of decreased pH while no inhibition was observed upon application of TRPV1 antagonists. The desensitization time constant of pH 6.0-evoked currents in the majority of dural afferents was less than 500ms which is consistent with that reported for ASIC3 homomeric or heteromeric channels. Finally, application of pH 5.0 synthetic-interstitial fluid to the dura produced significant decreases in facial and hind-paw withdrawal threshold, an effect blocked by amiloride but not TRPV1 antagonists, suggesting that ASIC activation produces migraine-related behavior in vivo. These data provide a cellular mechanism by which decreased pH in the meninges following ischemic or inflammatory events directly excites afferent pain-sensing neurons potentially contributing to migraine headache. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  2. The mast cell degranulator compound 48/80 directly activates neurons.

    Directory of Open Access Journals (Sweden)

    Michael Schemann

    Full Text Available BACKGROUND: Compound 48/80 is widely used in animal and tissue models as a "selective" mast cell activator. With this study we demonstrate that compound 48/80 also directly activates enteric neurons and visceral afferents. METHODOLOGY/PRINCIPAL FINDINGS: We used in vivo recordings from extrinsic intestinal afferents together with Ca(++ imaging from primary cultures of DRG and nodose neurons. Enteric neuronal activation was examined by Ca(++ and voltage sensitive dye imaging in isolated gut preparations and primary cultures of enteric neurons. Intraluminal application of compound 48/80 evoked marked afferent firing which desensitized on subsequent administration. In egg albumen-sensitized animals, intraluminal antigen evoked a similar pattern of afferent activation which also desensitized on subsequent exposure to antigen. In cross-desensitization experiments prior administration of compound 48/80 failed to influence the mast cell mediated response. Application of 1 and 10 µg/ml compound 48/80 evoked spike discharge and Ca(++ transients in enteric neurons. The same nerve activating effect was observed in primary cultures of DRG and nodose ganglion cells. Enteric neuron cultures were devoid of mast cells confirmed by negative staining for c-kit or toluidine blue. In addition, in cultured enteric neurons the excitatory action of compound 48/80 was preserved in the presence of histamine H(1 and H(2 antagonists. The mast cell stabilizer cromolyn attenuated compound 48/80 and nicotine evoked Ca(++ transients in mast cell-free enteric neuron cultures. CONCLUSIONS/SIGNIFICANCE: The results showed direct excitatory action of compound 48/80 on enteric neurons and visceral afferents. Therefore, functional changes measured in tissue or animal models may involve a mast cell independent effect of compound 48/80 and cromolyn.

  3. Cervical vagus nerve stimulation augments spontaneous discharge in second- and higher-order sensory neurons in the rat nucleus of the solitary tract.

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    Beaumont, Eric; Campbell, Regenia P; Andresen, Michael C; Scofield, Stephanie; Singh, Krishna; Libbus, Imad; KenKnight, Bruce H; Snyder, Logan; Cantrell, Nathan

    2017-08-01

    Vagus nerve stimulation (VNS) currently treats patients with drug-resistant epilepsy, depression, and heart failure. The mild intensities used in chronic VNS suggest that primary visceral afferents and central nervous system activation are involved. Here, we measured the activity of neurons in the nucleus of the solitary tract (NTS) in anesthetized rats using clinically styled VNS. Our chief findings indicate that VNS at threshold bradycardic intensity activated NTS neuron discharge in one-third of NTS neurons. This VNS directly activated only myelinated vagal afferents projecting to second-order NTS neurons. Most VNS-induced activity in NTS, however, was unsynchronized to vagal stimuli. Thus, VNS activated unsynchronized activity in NTS neurons that were second order to vagal afferent C-fibers as well as higher-order NTS neurons only polysynaptically activated by the vagus. Overall, cardiovascular-sensitive and -insensitive NTS neurons were similarly activated by VNS: 3/4 neurons with monosynaptic vagal A-fiber afferents, 6/42 neurons with monosynaptic vagal C-fiber afferents, and 16/21 polysynaptic NTS neurons. Provocatively, vagal A-fibers indirectly activated C-fiber neurons during VNS. Elevated spontaneous spiking was quantitatively much higher than synchronized activity and extended well into the periods of nonstimulation. Surprisingly, many polysynaptic NTS neurons responded to half the bradycardic intensity used in clinical studies, indicating that a subset of myelinated vagal afferents is sufficient to evoke VNS indirect activation. Our study uncovered a myelinated vagal afferent drive that indirectly activates NTS neurons and thus central pathways beyond NTS and support reconsideration of brain contributions of vagal afferents underpinning of therapeutic impacts. NEW & NOTEWORTHY Acute vagus nerve stimulation elevated activity in neurons located in the medial nucleus of the solitary tract. Such stimuli directly activated only myelinated vagal afferents

  4. The role of trigeminal nasal TRPM8-expressing afferent neurons in the antitussive effects of menthol.

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    Plevkova, J; Kollarik, M; Poliacek, I; Brozmanova, M; Surdenikova, L; Tatar, M; Mori, N; Canning, B J

    2013-07-15

    The cold-sensitive cation channel TRPM8 is a target for menthol, which is used routinely as a cough suppressant and as an additive to tobacco and food products. Given that cold temperatures and menthol activate neurons through gating of TRPM8, it is unclear how menthol actively suppresses cough. In this study we describe the antitussive effects of (-)-menthol in conscious and anesthetized guinea pigs. In anesthetized guinea pigs, cough evoked by citric acid applied topically to the tracheal mucosa was suppressed by menthol only when it was selectively administered as vapors to the upper airways. Menthol applied topically to the tracheal mucosa prior to and during citric acid application or administered continuously as vapors or as an aerosol to the lower airways was without effect on cough. These actions of upper airway menthol treatment were mimicked by cold air delivered to the upper airways but not by (+)-menthol, the inactive isomer of menthol, or by the TRPM8/TRPA1 agonist icilin administered directly to the trachea. Subsequent molecular analyses confirmed the expression of TRPM8 in a subset of nasal trigeminal afferent neurons that do not coincidently express TRPA1 or TRPV1. We conclude that menthol suppresses cough evoked in the lower airways primarily through a reflex initiated from the nose.

  5. Inhibition of muscle spindle afferent activity during masseter muscle fatigue in the rat.

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    Brunetti, Orazio; Della Torre, Giovannella; Lucchi, Maria Luisa; Chiocchetti, Roberto; Bortolami, Ruggero; Pettorossi, Vito Enrico

    2003-09-01

    The influence of muscle fatigue on the jaw-closing muscle spindle activity has been investigated by analyzing: (1) the field potentials evoked in the trigeminal motor nucleus (Vmot) by trigeminal mesencephalic nucleus (Vmes) stimulation, (2) the orthodromic and antidromic responses evoked in the Vmes by stimulation of the peripheral and central axons of the muscle proprioceptive afferents, and (3) the extracellular unitary discharge of masseter muscle spindles recorded in the Vmes. The masseter muscle was fatigued by prolonged tetanic masseter nerve electrical stimulation. Pre- and postsynaptic components of the potentials evoked in the Vmot showed a significant reduction in amplitude following muscle fatigue. Orthodromic and antidromic potentials recorded in the Vmes also showed a similar amplitude decrease. Furthermore, muscle fatigue caused a decrease of the discharge frequency of masseter muscle spindle afferents in most of the examined units. The inhibition of the potential amplitude and discharge frequency was strictly correlated with the extent of muscle fatigue and was mediated by the group III and IV afferent muscle fibers activated by fatigue. In fact, the inhibitory effect was abolished by capsaicin injection in the masseter muscle that provokes selective degeneration of small afferent muscle fibers containing neurokinins. We concluded that fatigue signals originating from the muscle and traveling through capsaicin-sensitive fibers are able to diminish the proprioceptive input by a central presynaptic influence. In the second part of the study, we examined the central projection of the masseter small afferents sensitive to capsaicin at the electron-microscopic level. Fiber degeneration was induced by injecting capsaicin into the masseter muscle. Degenerating terminals were found on the soma and stem process in Vmes and on the dendritic tree of neurons in Vmot. This suggests that small muscle afferents may influence the muscle spindle activity through

  6. Modulation of long-latency afferent inhibition by the amplitude of sensory afferent volley.

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    Turco, Claudia V; El-Sayes, Jenin; Fassett, Hunter J; Chen, Robert; Nelson, Aimee J

    2017-07-01

    Long-latency afferent inhibition (LAI) is the inhibition of the transcranial magnetic stimulation (TMS) motor-evoked potentials (MEP) by the sensory afferent volley following electrical stimulation of a peripheral nerve. It is unknown how the activation of sensory afferent fibers relates to the magnitude of LAI. This study investigated the relationship between LAI and the sensory nerve action potentials (SNAP) from the median nerve (MN) and the digital nerves (DN) of the second digit. LAI was obtained by delivering nerve stimulation 200 ms before a TMS pulse delivered over the motor cortex. Experiment 1 assessed the magnitude of LAI following stimulation of the contralateral MN or DN using nerve stimulus intensities relative to the maximum SNAP (SNAP max ) of that nerve and two TMS intensities (0.5- and 1-mV MEP). Results indicate that MN LAI is maximal at ~50% SNAP max , when presumably all sensory afferents are recruited for TMS of 0.5-mV MEP. For DN, LAI appears at ~50% SNAP max and does not increase with further recruitment of sensory afferents. Experiment 2 investigated the magnitude of LAI following ipsilateral nerve stimulation at intensities relative to SNAP max Results show minimal LAI evoked by ipsilateral MN and no LAI following ipsilateral DN stimulation. Implications for future studies investigating LAI include adjusting nerve stimulation to 50% SNAP max to obtain maximal LAI. Additionally, MN LAI can be used as a marker for neurological disease or injury by using a nerve stimulation intensity that can evoke a depth of LAI capable of increasing or decreasing. NEW & NOTEWORTHY This is the first investigation of the relationship between long-latency afferent inhibition (LAI) and the sensory afferent volley. Differences exist between median and digital nerve LAI. For the median nerve, LAI increases until all sensory fibers are presumably recruited. In contrast, digital nerve LAI does not increase with the recruitment of additional sensory fibers but

  7. Population coding of forelimb joint kinematics by peripheral afferents in monkeys.

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    Tatsuya Umeda

    Full Text Available Various peripheral receptors provide information concerning position and movement to the central nervous system to achieve complex and dexterous movements of forelimbs in primates. The response properties of single afferent receptors to movements at a single joint have been examined in detail, but the population coding of peripheral afferents remains poorly defined. In this study, we obtained multichannel recordings from dorsal root ganglion (DRG neurons in cervical segments of monkeys. We applied the sparse linear regression (SLiR algorithm to the recordings, which selects useful input signals to reconstruct movement kinematics. Multichannel recordings of peripheral afferents were performed by inserting multi-electrode arrays into the DRGs of lower cervical segments in two anesthetized monkeys. A total of 112 and 92 units were responsive to the passive joint movements or the skin stimulation with a painting brush in Monkey 1 and Monkey 2, respectively. Using the SLiR algorithm, we reconstructed the temporal changes of joint angle, angular velocity, and acceleration at the elbow, wrist, and finger joints from temporal firing patterns of the DRG neurons. By automatically selecting a subset of recorded units, the SLiR achieved superior generalization performance compared with a regularized linear regression algorithm. The SLiR selected not only putative muscle units that were responsive to only the passive movements, but also a number of putative cutaneous units responsive to the skin stimulation. These results suggested that an ensemble of peripheral primary afferents that contains both putative muscle and cutaneous units encode forelimb joint kinematics of non-human primates.

  8. Electrosensory Midbrain Neurons Display Feature Invariant Responses to Natural Communication Stimuli.

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    Tristan Aumentado-Armstrong

    2015-10-01

    Full Text Available Neurons that respond selectively but in an invariant manner to a given feature of natural stimuli have been observed across species and systems. Such responses emerge in higher brain areas, thereby suggesting that they occur by integrating afferent input. However, the mechanisms by which such integration occurs are poorly understood. Here we show that midbrain electrosensory neurons can respond selectively and in an invariant manner to heterogeneity in behaviorally relevant stimulus waveforms. Such invariant responses were not seen in hindbrain electrosensory neurons providing afferent input to these midbrain neurons, suggesting that response invariance results from nonlinear integration of such input. To test this hypothesis, we built a model based on the Hodgkin-Huxley formalism that received realistic afferent input. We found that multiple combinations of parameter values could give rise to invariant responses matching those seen experimentally. Our model thus shows that there are multiple solutions towards achieving invariant responses and reveals how subthreshold membrane conductances help promote robust and invariant firing in response to heterogeneous stimulus waveforms associated with behaviorally relevant stimuli. We discuss the implications of our findings for the electrosensory and other systems.

  9. Electrosensory Midbrain Neurons Display Feature Invariant Responses to Natural Communication Stimuli.

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    Aumentado-Armstrong, Tristan; Metzen, Michael G; Sproule, Michael K J; Chacron, Maurice J

    2015-10-01

    Neurons that respond selectively but in an invariant manner to a given feature of natural stimuli have been observed across species and systems. Such responses emerge in higher brain areas, thereby suggesting that they occur by integrating afferent input. However, the mechanisms by which such integration occurs are poorly understood. Here we show that midbrain electrosensory neurons can respond selectively and in an invariant manner to heterogeneity in behaviorally relevant stimulus waveforms. Such invariant responses were not seen in hindbrain electrosensory neurons providing afferent input to these midbrain neurons, suggesting that response invariance results from nonlinear integration of such input. To test this hypothesis, we built a model based on the Hodgkin-Huxley formalism that received realistic afferent input. We found that multiple combinations of parameter values could give rise to invariant responses matching those seen experimentally. Our model thus shows that there are multiple solutions towards achieving invariant responses and reveals how subthreshold membrane conductances help promote robust and invariant firing in response to heterogeneous stimulus waveforms associated with behaviorally relevant stimuli. We discuss the implications of our findings for the electrosensory and other systems.

  10. Ablation of capsaicin sensitive afferent nerves impairs defence but not rapid repair of rat gastric mucosa.

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    Pabst, M A; Schöninkle, E; Holzer, P

    1993-07-01

    Capsaicin sensitive afferent neurones have previously been reported to play a part in gastric mucosal protection. The aim of this study was to investigate whether these nociceptive neurones strengthen mucosal defence against injury or promote rapid repair of the damaged mucosa, or both. This hypothesis was examined in anaesthetised rats whose stomachs were perfused with ethanol (25 or 50% in saline, wt/wt) for 30 minutes. The gastric mucosa was inspected 0 and 180 minutes after ethanol had been given at the macroscopic, light, and scanning electron microscopic level. Rapid repair of the ethanol injured gastric mucosa (reduction of deep injury, partial re-epithelialisation of the denuded surface) took place in rats anaesthetised with phenobarbital, but not in those anaesthetised with urethane. Afferent nerve ablation as a result of treating rats with a neurotoxic dose of capsaicin before the experiment significantly aggravated ethanol induced damage as shown by an increase in the area and depth of mucosal erosions. Rapid repair of the injured mucosa, however, as seen in rats anesthetised with phenobarbital 180 minutes after ethanol was given, was similar in capsaicin and vehicle pretreated animals. Ablation of capsaicin sensitive afferent neurones was verified by a depletion of calcitonin gene related peptide from the gastric corpus wall. These findings indicate that nociceptive neurones control mechanisms of defence against acute injury but are not required for rapid repair of injured mucosa.

  11. Glucagon-like peptide 1 interacts with ghrelin and leptin to regulate glucose metabolism and food intake through vagal afferent neuron signaling.

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    Ronveaux, Charlotte C; Tomé, Daniel; Raybould, Helen E

    2015-04-01

    Emerging evidence has suggested a possible physiologic role for peripheral glucagon-like peptide 1 (GLP-1) in regulating glucose metabolism and food intake. The likely site of action of GLP-1 is on vagal afferent neurons (VANs). The vagal afferent pathway is the major neural pathway by which information about ingested nutrients reaches the central nervous system and influences feeding behavior. Peripheral GLP-1 acts on VANs to inhibit food intake. The mechanism of the GLP-1 receptor (GLP-1R) is unlike other gut-derived receptors; GLP-1Rs change their cellular localization according to feeding status rather than their protein concentrations. It is possible that several gut peptides are involved in mediating GLP-1R translocation. The mechanism of peripheral GLP-1R translocation still needs to be elucidated. We review data supporting the role of peripheral GLP-1 acting on VANs in influencing glucose homeostasis and feeding behavior. We highlight evidence demonstrating that GLP-1 interacts with ghrelin and leptin to induce satiation. Our aim was to understand the mechanism of peripheral GLP-1 in the development of noninvasive antiobesity treatments. © 2015 American Society for Nutrition.

  12. Isolation of TRPV1 independent mechanisms of spontaneous and asynchronous glutamate release at primary afferent to NTS synapses.

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    Axel J. Fenwick

    2014-01-01

    Full Text Available Cranial visceral afferents contained within the solitary tract (ST contact second-order neurons in the nucleus of the solitary tract (NTS and release the excitatory amino acid glutamate via three distinct exocytosis pathways; synchronous, asynchronous, and spontaneous release. The presence of TRPV1 in the central terminals of a majority of ST afferents conveys activity-dependent asynchronous glutamate release and provides a temperature sensitive calcium conductance which largely determines the rate of spontaneous vesicle fusion. TRPV1 is present in unmyelinated C-fiber afferents and these facilitated forms of glutamate release may underlie the relative strength of C-fibers in activating autonomic reflex pathways. However, pharmacological blockade of TRPV1 signaling eliminates only ~50% of the asynchronous profile and attenuates the temperature sensitivity of spontaneous release indicating additional thermosensitive calcium influx pathways may exist which mediate these forms of vesicle release. In the present study we isolate the contribution of TRPV1 independent forms of glutamate release at ST-NTS synapses. We found ST afferent innervation at NTS neurons and synchronous vesicle release from TRPV1 KO mice was not different to control animals; however, only half of TRPV1 KO ST afferents completely lacked asynchronous glutamate release. Further, temperature driven spontaneous rates of vesicle release were not different from 33˚ - 37˚C between control and TRPV1 KO afferents. These findings suggest additional temperature dependent mechanisms controlling asynchronous and thermosensitive spontaneous release at physiological temperatures, possibly mediated by additional thermosensitive TRP channels in primary afferent terminals.

  13. The response of guinea pig primary utricular and saccular irregular neurons to bone-conducted vibration (BCV) and air-conducted sound (ACS).

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    Curthoys, Ian S; Vulovic, Vedran; Burgess, Ann M; Sokolic, Ljiljana; Goonetilleke, Samanthi C

    2016-01-01

    This study sought to characterize the response of mammalian primary otolithic neurons to sound and vibration by measuring the resting discharge rates, thresholds for increases in firing rate and supra-threshold sensitivity functions of guinea pig single primary utricular and saccular afferents. Neurons with irregular resting discharge were activated in response to bone conducted vibration (BCV) and air conducted sound (ACS) for frequencies between 100 Hz and 3000 Hz. The location of neurons was verified by labelling with neurobiotin. Many afferents from both maculae have very low or zero resting discharge, with saccular afferents having on average, higher resting rates than utricular afferents. Most irregular utricular and saccular afferents can be evoked by both BCV and ACS. For BCV stimulation: utricular and saccular neurons show similar low thresholds for increased firing rate (around 0.02 g on average) for frequencies from 100 Hz to 750 Hz. There is a steep increase in rate change threshold for BCV frequencies above 750 Hz. The suprathreshold sensitivity functions for BCV were similar for both utricular and saccular neurons, with, at low frequencies, very steep increases in firing rate as intensity increased. For ACS stimulation: utricular and saccular neurons can be activated by high intensity stimuli for frequencies from 250 Hz to 3000 Hz with similar flattened U-shaped tuning curves with lowest thresholds for frequencies around 1000-2000 Hz. The average ACS thresholds for saccular afferents across these frequencies is about 15-20 dB lower than for utricular neurons. The suprathreshold sensitivity functions for ACS were similar for both utricular and saccular neurons. Both utricular and saccular afferents showed phase-locking to BCV and ACS, extending up to frequencies of at least around 1500 Hz for BCV and 3000 Hz for ACS. Phase-locking at low frequencies (e.g. 100 Hz) imposes a limit on the neural firing rate evoked by the stimulus since the

  14. Anatomy and physiology of the afferent visual system.

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    Prasad, Sashank; Galetta, Steven L

    2011-01-01

    The efficient organization of the human afferent visual system meets enormous computational challenges. Once visual information is received by the eye, the signal is relayed by the retina, optic nerve, chiasm, tracts, lateral geniculate nucleus, and optic radiations to the striate cortex and extrastriate association cortices for final visual processing. At each stage, the functional organization of these circuits is derived from their anatomical and structural relationships. In the retina, photoreceptors convert photons of light to an electrochemical signal that is relayed to retinal ganglion cells. Ganglion cell axons course through the optic nerve, and their partial decussation in the chiasm brings together corresponding inputs from each eye. Some inputs follow pathways to mediate pupil light reflexes and circadian rhythms. However, the majority of inputs arrive at the lateral geniculate nucleus, which relays visual information via second-order neurons that course through the optic radiations to arrive in striate cortex. Feedback mechanisms from higher cortical areas shape the neuronal responses in early visual areas, supporting coherent visual perception. Detailed knowledge of the anatomy of the afferent visual system, in combination with skilled examination, allows precise localization of neuropathological processes and guides effective diagnosis and management of neuro-ophthalmic disorders. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Artificial spatiotemporal touch inputs reveal complementary decoding in neocortical neurons.

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    Oddo, Calogero M; Mazzoni, Alberto; Spanne, Anton; Enander, Jonas M D; Mogensen, Hannes; Bengtsson, Fredrik; Camboni, Domenico; Micera, Silvestro; Jörntell, Henrik

    2017-04-04

    Investigations of the mechanisms of touch perception and decoding has been hampered by difficulties in achieving invariant patterns of skin sensor activation. To obtain reproducible spatiotemporal patterns of activation of sensory afferents, we used an artificial fingertip equipped with an array of neuromorphic sensors. The artificial fingertip was used to transduce real-world haptic stimuli into spatiotemporal patterns of spikes. These spike patterns were delivered to the skin afferents of the second digit of rats via an array of stimulation electrodes. Combined with low-noise intra- and extracellular recordings from neocortical neurons in vivo, this approach provided a previously inaccessible high resolution analysis of the representation of tactile information in the neocortical neuronal circuitry. The results indicate high information content in individual neurons and reveal multiple novel neuronal tactile coding features such as heterogeneous and complementary spatiotemporal input selectivity also between neighboring neurons. Such neuronal heterogeneity and complementariness can potentially support a very high decoding capacity in a limited population of neurons. Our results also indicate a potential neuroprosthetic approach to communicate with the brain at a very high resolution and provide a potential novel solution for evaluating the degree or state of neurological disease in animal models.

  16. Failure of action potential propagation in sensory neurons: mechanisms and loss of afferent filtering in C-type units after painful nerve injury.

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    Gemes, Geza; Koopmeiners, Andrew; Rigaud, Marcel; Lirk, Philipp; Sapunar, Damir; Bangaru, Madhavi Latha; Vilceanu, Daniel; Garrison, Sheldon R; Ljubkovic, Marko; Mueller, Samantha J; Stucky, Cheryl L; Hogan, Quinn H

    2013-02-15

    The T-junction of sensory neurons in the dorsal root ganglion (DRG) is a potential impediment to action potential (AP) propagation towards the CNS. Using intracellular recordings from rat DRG neuronal somata during stimulation of the dorsal root, we determined that the maximal rate at which all of 20 APs in a train could successfully transit the T-junction (following frequency) was lowest in C-type units, followed by A-type units with inflected descending limbs of the AP, and highest in A-type units without inflections. In C-type units, following frequency was slower than the rate at which AP trains could be produced in either dorsal root axonal segments or in the soma alone, indicating that the T-junction is a site that acts as a low-pass filter for AP propagation. Following frequency was slower for a train of 20 APs than for two, indicating that a cumulative process leads to propagation failure. Propagation failure was accompanied by diminished somatic membrane input resistance, and was enhanced when Ca(2+)-sensitive K(+) currents were augmented or when Ca(2+)-sensitive Cl(-) currents were blocked. After peripheral nerve injury, following frequencies were increased in axotomized C-type neurons and decreased in axotomized non-inflected A-type neurons. These findings reveal that the T-junction in sensory neurons is a regulator of afferent impulse traffic. Diminished filtering of AP trains at the T-junction of C-type neurons with axotomized peripheral processes could enhance the transmission of activity that is ectopically triggered in a neuroma or the neuronal soma, possibly contributing to pain generation.

  17. Ventromedial hypothalamic expression of Bdnf is required to establish normal patterns of afferent GABAergic connectivity and responses to hypoglycemia

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    Anna Kamitakahara

    2016-02-01

    Full Text Available Objective: The ventromedial nucleus of the hypothalamus (VMH controls energy and glucose homeostasis through direct connections to a distributed network of nuclei in the hypothalamus, midbrain, and hindbrain. Structural changes in VMH circuit morphology have the potential to alter VMH function throughout life, however, molecular signals responsible for specifying its neural connections are not fully defined. The VMH contains a high density of neurons that express brain-derived neurotrophic factor (BDNF, a potent neurodevelopmental effector known to regulate neuronal survival, growth, differentiation, and connectivity in a number of neural systems. In the current study, we examined whether BDNF impacts the afferent and efferent connections of the VMH, as well as energy homeostatic function. Methods: To determine if BDNF is required for VMH circuit formation, a transgenic mouse model was used to conditionally delete Bdnf from steroidogenic factor 1 (SF1 expressing neurons of the VMH prior to the onset of establishing neural connections with other regions. Projections of SF1 expressing neurons were visualized with a genetically targeted fluorescent label and immunofluorescence was used to measure the density of afferents to SF1 neurons in the absence of BDNF. Physiological changes in body weight and circulating blood glucose were also evaluated in the mutant mice. Results: Our findings suggest that BDNF is required to establish normal densities of GABAergic afferents onto SF1 neurons located in the ventrolateral part of the VMH. Furthermore, loss of BDNF from VMH SF1 neurons results in impaired physiological responses to insulin-induced hypoglycemia. Conclusion: The results of this study indicate that BDNF is required for formation and/or maintenance of inhibitory inputs to SF1 neurons, with enduring effects on glycemic control. Author Video: Author Video Watch what authors say about their articles Keywords: Ventromedial nucleus of the hypothalamus

  18. Gut vagal afferents differentially modulate innate anxiety and learned fear.

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    Klarer, Melanie; Arnold, Myrtha; Günther, Lydia; Winter, Christine; Langhans, Wolfgang; Meyer, Urs

    2014-05-21

    Vagal afferents are an important neuronal component of the gut-brain axis allowing bottom-up information flow from the viscera to the CNS. In addition to its role in ingestive behavior, vagal afferent signaling has been implicated modulating mood and affect, including distinct forms of anxiety and fear. Here, we used a rat model of subdiaphragmatic vagal deafferentation (SDA), the most complete and selective vagal deafferentation method existing to date, to study the consequences of complete disconnection of abdominal vagal afferents on innate anxiety, conditioned fear, and neurochemical parameters in the limbic system. We found that compared with Sham controls, SDA rats consistently displayed reduced innate anxiety-like behavior in three procedures commonly used in preclinical rodent models of anxiety, namely the elevated plus maze test, open field test, and food neophobia test. On the other hand, SDA rats exhibited increased expression of auditory-cued fear conditioning, which specifically emerged as attenuated extinction of conditioned fear during the tone re-exposure test. The behavioral manifestations in SDA rats were associated with region-dependent changes in noradrenaline and GABA levels in key areas of the limbic system, but not with functional alterations in the hypothalamus-pituitary-adrenal grand stress. Our study demonstrates that innate anxiety and learned fear are both subjected to visceral modulation through abdominal vagal afferents, possibly via changing limbic neurotransmitter systems. These data add further weight to theories emphasizing an important role of afferent visceral signals in the regulation of emotional behavior. Copyright © 2014 the authors 0270-6474/14/347067-10$15.00/0.

  19. Chicken (Gallus domesticus) inner ear afferents

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    Hara, H.; Chen, X.; Hartsfield, J. F.; Hara, J.; Martin, D.; Fermin, C. D.

    1998-01-01

    Neurons from the vestibular (VG) and the statoacoustic (SAG) ganglion of the chick (Gallus domesticus) were evaluated histologically and morphometrically. Embryos at stages 34 (E8 days), 39 (E13 days) and 44 (E18 days) were sacrificed and temporal bones microdissected. Specimens were embedded in JB-4 methacrylate plastic, and stained with a mixture of 0.2% toluidine blue (TB) and 0.1% basic Fuschin in 25% ethanol or with a mixture of 2% TB and 1% paraphenylenediamine (PDA) for axon and myelin measurement study. Images of the VIIIth nerve were produced by a V150 (R) color imaging system and the contour of 200-300 neuronal bodies (perikarya) was traced directly on a video screen with a mouse in real time. The cross-sectional area of VG perikarya was 67.29 micrometers2 at stage 34 (E8), 128.46 micrometers2 at stage 39 (E13) and 275.85 micrometers2 at stage 44 (E18). The cross-sectional area of SAG perikarya was 62.44 micrometers2 at stage 34 (E8), 102.05 micrometers2 at stage 39 (E13) and 165.02 micrometers2 at stage 44 (E18). A significant cross-sectional area increase of the VG perikarya between stage 39 (E13) and stage 44 (E18) was determined. We randomly measured the cross-sectional area of myelin and axoplasm of hatchling afferent nerves, and found a correspondence between axoplasmic and myelin cross-sectional area in the utricular, saccular and semicircular canal nerve branches of the nerve. The results suggest that the period between stage 34 (E8) and 39 (E13) is a critical period for afferent neuronal development. Physiological and behavioral vestibular properties of developing and maturing hatchlings may change accordingly. The results compliment previous work by other investigators and provide valuable anatomical measures useful to correlate physiological data obtained from stimulation of the whole nerve or its parts.

  20. Physiological properties of afferents to the rat cerebellum during normal development and after postnatal x irradiation

    International Nuclear Information System (INIS)

    Puro, D.G.

    1975-01-01

    The consequences of an altered cerebellar cortical development on afferent transmission and terminal organization were analyzed in adult rats which had received x irradiation to the cerebellum postnatally. Rats, anesthetized with 0.5 percent halothane, were studied in various ages from day 3 to adult. The ascending mossy and climbing fiber systems were activated by electrical stimulation of the limbs with needle electrodes. Stimulation of the motor cortex activated the descending climbing fiber pathways. Extracellular responses from cerebellar Purkinje cells were observed on an oscilloscope as poststimulus time histograms were constructed ''on-line''. Conclusions and assertions include: (1) Synaptogenesis between incoming afferent fibers and target neurons takes place early in cerebellar cortical development. (2) Mossy fiber transmission is mature before the bulk of cerebellar synaptogenesis occurs. (3) The ascending and descending components of the climbing fiber system mature, with respect to latency, in synchrony. (4) The terminal synaptic organization has little effect on the development of transmission characteristics in these afferent systems. (5) One possible mechanism by which an adult neural structure can have an abnormal synaptic organization is to maintain immature synaptic relationships due to the neonatal loss of interneurons

  1. Primary afferent terminal sprouting after a cervical dorsal rootlet section in the macaque monkey.

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    Darian-Smith, Corinna

    2004-03-01

    We examined the role of primary afferent neurons in the somatosensory cortical "reactivation" that occurs after a localized cervical dorsal root lesion (Darian-Smith and Brown [2000] Nat. Neurosci. 3:476-481). After section of the dorsal rootlets that enervate the macaque's thumb and index finger (segments C6-C8), the cortical representation of these digits was initially silenced but then re-emerged for these same digits over 2-4 postlesion months. Cortical reactivation was accompanied by the emergence of physiologically detectable input from these same digits within dorsal rootlets bordering the lesion site. We investigated whether central axonal sprouting of primary afferents spared by the rhizotomy could mediate this cortical reactivation. The cortical representation of the hand was mapped electrophysiologically 15-25 weeks after the dorsal rootlet section to define this reactivation. Cholera toxin subunit B conjugated to horseradish peroxidase was then injected into the thumb and index finger pads bilaterally to label the central terminals of any neurons that innervated these digits. Primary afferent terminal proliferation was assessed in the spinal dorsal horn and cuneate nucleus at 7 days and 15-25 postlesion weeks. Labeled terminal bouton distributions were reconstructed and the "lesion" and control sides compared within each monkey. Distributions were significantly larger on the side of the lesion in the dorsal horn and cuneate nucleus at 15-25 weeks after the dorsal rootlet section, than those mapped only 7 days postlesion. Our results provide direct evidence for localized sprouting of spared (uninjured) primary afferent terminals in the dorsal horn and cuneate nucleus after a restricted dorsal root injury. Copyright 2004 Wiley-Liss, Inc.

  2. Profiling of G protein-coupled receptors in vagal afferents reveals novel gut-to-brain sensing mechanisms.

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    Egerod, Kristoffer L; Petersen, Natalia; Timshel, Pascal N; Rekling, Jens C; Wang, Yibing; Liu, Qinghua; Schwartz, Thue W; Gautron, Laurent

    2018-06-01

    G protein-coupled receptors (GPCRs) act as transmembrane molecular sensors of neurotransmitters, hormones, nutrients, and metabolites. Because unmyelinated vagal afferents richly innervate the gastrointestinal mucosa, gut-derived molecules may directly modulate the activity of vagal afferents through GPCRs. However, the types of GPCRs expressed in vagal afferents are largely unknown. Here, we determined the expression profile of all GPCRs expressed in vagal afferents of the mouse, with a special emphasis on those innervating the gastrointestinal tract. Using a combination of high-throughput quantitative PCR, RNA sequencing, and in situ hybridization, we systematically quantified GPCRs expressed in vagal unmyelinated Na v 1.8-expressing afferents. GPCRs for gut hormones that were the most enriched in Na v 1.8-expressing vagal unmyelinated afferents included NTSR1, NPY2R, CCK1R, and to a lesser extent, GLP1R, but not GHSR and GIPR. Interestingly, both GLP1R and NPY2R were coexpressed with CCK1R. In contrast, NTSR1 was coexpressed with GPR65, a marker preferentially enriched in intestinal mucosal afferents. Only few microbiome-derived metabolite sensors such as GPR35 and, to a lesser extent, GPR119 and CaSR were identified in the Na v 1.8-expressing vagal afferents. GPCRs involved in lipid sensing and inflammation (e.g. CB1R, CYSLTR2, PTGER4), and neurotransmitters signaling (CHRM4, DRD2, CRHR2) were also highly enriched in Na v 1.8-expressing neurons. Finally, we identified 21 orphan GPCRs with unknown functions in vagal afferents. Overall, this study provides a comprehensive description of GPCR-dependent sensing mechanisms in vagal afferents, including novel coexpression patterns, and conceivably coaction of key receptors for gut-derived molecules involved in gut-brain communication. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

  3. Protease-Mediated Suppression of DRG Neuron Excitability by Commensal Bacteria.

    Science.gov (United States)

    Sessenwein, Jessica L; Baker, Corey C; Pradhananga, Sabindra; Maitland, Megan E; Petrof, Elaine O; Allen-Vercoe, Emma; Noordhof, Curtis; Reed, David E; Vanner, Stephen J; Lomax, Alan E

    2017-11-29

    Peripheral pain signaling reflects a balance of pronociceptive and antinociceptive influences; the contribution by the gastrointestinal microbiota to this balance has received little attention. Disorders, such as inflammatory bowel disease and irritable bowel syndrome, are associated with exaggerated visceral nociceptive actions that may involve altered microbial signaling, particularly given the evidence for bacterial dysbiosis. Thus, we tested whether a community of commensal gastrointestinal bacteria derived from a healthy human donor (microbial ecosystem therapeutics; MET-1) can affect the excitability of male mouse DRG neurons. MET-1 reduced the excitability of DRG neurons by significantly increasing rheobase, decreasing responses to capsaicin (2 μm) and reducing action potential discharge from colonic afferent nerves. The increase in rheobase was accompanied by an increase in the amplitude of voltage-gated K + currents. A mixture of bacterial protease inhibitors abrogated the effect of MET-1 effects on DRG neuron rheobase. A serine protease inhibitor but not inhibitors of cysteine proteases, acid proteases, metalloproteases, or aminopeptidases abolished the effects of MET-1. The serine protease cathepsin G recapitulated the effects of MET-1 on DRG neurons. Inhibition of protease-activated receptor-4 (PAR-4), but not PAR-2, blocked the effects of MET-1. Furthermore, Faecalibacterium prausnitzii recapitulated the effects of MET-1 on excitability of DRG neurons. We conclude that serine proteases derived from commensal bacteria can directly impact the excitability of DRG neurons, through PAR-4 activation. The ability of microbiota-neuronal interactions to modulate afferent signaling suggests that therapies that induce or correct microbial dysbiosis may impact visceral pain. SIGNIFICANCE STATEMENT Commercially available probiotics have the potential to modify visceral pain. Here we show that secretory products from gastrointestinal microbiota derived from a human

  4. Combined genetic and pharmacological inhibition of TRPV1 and P2X3 attenuates colorectal hypersensitivity and afferent sensitization

    OpenAIRE

    Kiyatkin, Michael E.; Feng, Bin; Schwartz, Erica S.; Gebhart, G. F.

    2013-01-01

    The ligand-gated channels transient receptor potential vanilloid 1 (TRPV1) and P2X3 have been reported to facilitate colorectal afferent neuron sensitization, thus contributing to organ hypersensitivity and pain. In the present study, we hypothesized that TRPV1 and P2X3 cooperate to modulate colorectal nociception and afferent sensitivity. To test this hypothesis, we employed TRPV1-P2X3 double knockout (TPDKO) mice and channel-selective pharmacological antagonists and evaluated combined chann...

  5. Bone conducted vibration selectively activates irregular primary otolithic vestibular neurons in the guinea pig.

    Science.gov (United States)

    Curthoys, Ian S; Kim, Juno; McPhedran, Samara K; Camp, Aaron J

    2006-11-01

    The main objective of this study was to determine whether bone-conducted vibration (BCV) is equally effective in activating both semicircular canal and otolith afferents in the guinea pig or whether there is preferential activation of one of these classes of vestibular afferents. To answer this question a large number (346) of single primary vestibular neurons were recorded extracellularly in anesthetized guinea pigs and were identified by their location in the vestibular nerve and classed as regular or irregular on the basis of the variability of their spontaneous discharge. If a neuron responded to angular acceleration it was classed as a semicircular canal neuron, if it responded to maintained roll or pitch tilts it was classified as an otolith neuron. Each neuron was then tested by BCV stimuli-either clicks, continuous pure tones (200-1,500 Hz) or short tone bursts (500 Hz lasting 7 ms)-delivered by a B-71 clinical bone-conduction oscillator cemented to the guinea pig's skull. All stimulus intensities were referred to that animal's own auditory brainstem response (ABR) threshold to BCV clicks, and the maximum intensity used was within the animal's physiological range and was usually around 70 dB above BCV threshold. In addition two sensitive single axis linear accelerometers cemented to the skull gave absolute values of the stimulus acceleration in the rostro-caudal direction. The criterion for a neuron being classed as activated was an audible, stimulus-locked increase in firing rate (a 10% change was easily detectable) in response to the BCV stimulus. At the stimulus levels used in this study, semicircular canal neurons, both regular and irregular, were insensitive to BCV stimuli and very few responded: only nine of 189 semicircular canal neurons tested (4.7%) showed a detectable increase in firing in response to BCV stimuli up to the maximum 2 V peak-to-peak level we delivered to the B-71 oscillator (which produced a peak-to-peak skull acceleration of around

  6. Short-term plasticity in turtle dorsal horn neurons mediated by L-type Ca2+ channels

    DEFF Research Database (Denmark)

    Russo, R E; Hounsgaard, J

    1994-01-01

    Windup--the gradual increase of the response--of dorsal horn neurons to repeated activation of primary afferents is an elementary form of short-term plasticity that may mediate central sensitization to pain. In deep dorsal horn neurons of the turtle spinal cord in vitro we report windup of the re......Windup--the gradual increase of the response--of dorsal horn neurons to repeated activation of primary afferents is an elementary form of short-term plasticity that may mediate central sensitization to pain. In deep dorsal horn neurons of the turtle spinal cord in vitro we report windup...

  7. Gastric electrical stimulation decreases gastric distension-induced central nociception response through direct action on primary afferents.

    Directory of Open Access Journals (Sweden)

    Wassila Ouelaa

    Full Text Available BACKGROUND & AIMS: Gastric electrical stimulation (GES is an effective therapy to treat patients with chronic dyspepsia refractory to medical management. However, its mechanisms of action remain poorly understood. METHODS: Gastric pain was induced by performing gastric distension (GD in anesthetized rats. Pain response was monitored by measuring the pseudo-affective reflex (e.g., blood pressure variation, while neuronal activation was determined using c-fos immunochemistry in the central nervous system. Involvement of primary afferents was assessed by measuring phosphorylation of ERK1/2 in dorsal root ganglia. RESULTS: GES decreased blood pressure variation induced by GD, and prevented GD-induced neuronal activation in the dorsal horn of the spinal cord (T9-T10, the nucleus of the solitary tract and in CRF neurons of the hypothalamic paraventricular nucleus. This effect remained unaltered within the spinal cord when sectioning the medulla at the T5 level. Furthermore, GES prevented GD-induced phosphorylation of ERK1/2 in dorsal root ganglia. CONCLUSIONS: GES decreases GD-induced pain and/or discomfort likely through a direct modulation of gastric spinal afferents reducing central processing of visceral nociception.

  8. Continuous detection of weak sensory signals in afferent spike trains: the role of anti-correlated interspike intervals in detection performance.

    Science.gov (United States)

    Goense, J B M; Ratnam, R

    2003-10-01

    An important problem in sensory processing is deciding whether fluctuating neural activity encodes a stimulus or is due to variability in baseline activity. Neurons that subserve detection must examine incoming spike trains continuously, and quickly and reliably differentiate signals from baseline activity. Here we demonstrate that a neural integrator can perform continuous signal detection, with performance exceeding that of trial-based procedures, where spike counts in signal- and baseline windows are compared. The procedure was applied to data from electrosensory afferents of weakly electric fish (Apteronotus leptorhynchus), where weak perturbations generated by small prey add approximately 1 spike to a baseline of approximately 300 spikes s(-1). The hypothetical postsynaptic neuron, modeling an electrosensory lateral line lobe cell, could detect an added spike within 10-15 ms, achieving near ideal detection performance (80-95%) at false alarm rates of 1-2 Hz, while trial-based testing resulted in only 30-35% correct detections at that false alarm rate. The performance improvement was due to anti-correlations in the afferent spike train, which reduced both the amplitude and duration of fluctuations in postsynaptic membrane activity, and so decreased the number of false alarms. Anti-correlations can be exploited to improve detection performance only if there is memory of prior decisions.

  9. Fine structural survey of the intermediate subnucleus of the nucleus tractus solitarii and its glossopharyngeal afferent terminals.

    Science.gov (United States)

    Hayakawa, Tetsu; Maeda, Seishi; Tanaka, Koichi; Seki, Makoto

    2005-10-01

    The intermediate subnucleus of the nucleus tractus solitarii (imNTS) receives somatosensory inputs from the soft palate and pharynx, and projects onto the nucleus ambiguus, thus serving as a relay nucleus for swallowing. The ultrastructure and synaptology of the rat imNTS, and its glossopharyngeal afferent terminals, have been examined with cholera toxin-conjugated horseradish peroxidase (CT-HRP) as an anterograde tracer. The imNTS contained oval or ellipsoid-shaped, small to medium-sized neurons (18.2 x 11.4 microm) with little cytoplasm, few cell organelles and an irregularly shaped nucleus. The cytoplasm often contained one or two nucleolus-like stigmoid bodies. The average number of axosomatic terminals was 1.8 per profile. About 83% of them contained round vesicles and formed asymmetric synaptic contacts (Gray's type I), while about 17% contained pleomorphic vesicles and formed symmetric synaptic contacts (Gray's type II). The neuropil contained small or large axodendritic terminals, and about 92% of them were Gray's type I. When CT-HRP was injected into the nodose ganglion, many labeled terminals were found in the imNTS. All anterogradely labeled terminals contacted dendrites but not somata. The labeled terminals were usually large (2.69+/-0.09 mum) and exclusively of Gray's type I. They often contacted more than two dendrites, were covered with glial processes, and formed synaptic glomeruli. A small unlabeled terminal occasionally made an asymmetric synaptic contact with a large labeled terminal. The large glossopharyngeal afferent terminals and the neurons containing stigmoid bodies characterized the imNTS neurons that received pharyngeal afferents.

  10. Retrograde and transganglionic transport of horseradish peroxidase-conjugated cholera toxin B subunit, wheatgerm agglutinin and isolectin B4 from Griffonia simplicifolia I in primary afferent neurons innervating the rat urinary bladder.

    Science.gov (United States)

    Wang, H F; Shortland, P; Park, M J; Grant, G

    1998-11-01

    In the present study, we investigated and compared the ability of the cholera toxin B subunit, wheat germ agglutinin and isolectin B4 from Griffonia simplicifolia I conjugated to horseradish peroxidase, to retrogradely and transganglionically label visceral primary afferents after unilateral injections into the rat urinary bladder wall. Horseradish peroxidase histochemical or lectin-immunofluorescence histochemical labelling of bladder afferents was seen in the L6-S1 spinal cord segments and in the T13-L2 and L6-S1 dorsal root ganglia. In the lumbosacral spinal cord, the most intense and extensive labelling of bladder afferents was seen when cholera toxin B subunit-horseradish peroxidase was injected. Cholera toxin B subunit-horseradish peroxidase-labelled fibres were found in Lissauer's tract, its lateral and medial collateral projections, and laminae I and IV-VI of the spinal gray matter. Labelled fibres were numerous in the lateral collateral projection and extended into the spinal parasympathetic nucleus. Labelling from both the lateral and medial projections extended into the dorsal grey commissural region. Wheat germ agglutinin-horseradish peroxidase labelling produced a similar pattern but was not as dense and extensive as that of cholera toxin B subunit-horseradish peroxidase. The isolectin B4 from Griffonia simplicifolia I-horseradish peroxidase-labelled fibres, on the other hand, were fewer and only observed in the lateral collateral projection and occasionally in lamina I. Cell profile counts showed that a larger number of dorsal root ganglion cells were labelled with cholera toxin B subunit-horseradish peroxidase than with wheat germ agglutinin- or isolectin B4-horseradish peroxidase. In the L6-S1 dorsal root ganglia, the majority (81%) of the cholera toxin B subunit-, and almost all of the wheat germ agglutinin- and isolectin B4-immunoreactive cells were RT97-negative (an anti-neurofilament antibody that labels dorsal root ganglion neurons with

  11. The Role of Kiss1 Neurons As Integrators of Endocrine, Metabolic, and Environmental Factors in the Hypothalamic–Pituitary–Gonadal Axis

    Directory of Open Access Journals (Sweden)

    Shel-Hwa Yeo

    2018-04-01

    Full Text Available Kisspeptin–GPR54 signaling in the hypothalamus is required for reproduction and fertility in mammals. Kiss1 neurons are key regulators of gonadotropin-releasing hormone (GnRH release and modulation of the hypothalamic–pituitary–gonadal (HPG axis. Arcuate Kiss1 neurons project to GnRH nerve terminals in the median eminence, orchestrating the pulsatile secretion of luteinizing hormone (LH through the intricate interaction between GnRH pulse frequency and the pituitary gonadotrophs. Arcuate Kiss1 neurons, also known as KNDy neurons in rodents and ruminants because of their co-expression of neurokinin B and dynorphin represent an ideal hub to receive afferent inputs from other brain regions in response to physiological and environmental changes, which can regulate the HPG axis. This review will focus on studies performed primarily in rodent and ruminant species to explore potential afferent inputs to Kiss1 neurons with emphasis on the arcuate region but also considering the rostral periventricular region of the third ventricle (RP3V. Specifically, we will discuss how these inputs can be modulated by hormonal, metabolic, and environmental factors to control gonadotropin secretion and fertility. We also summarize the methods and techniques that can be used to study functional inputs into Kiss1 neurons.

  12. Synchronous spikes are necessary but not sufficient for a synchrony code in populations of spiking neurons.

    Science.gov (United States)

    Grewe, Jan; Kruscha, Alexandra; Lindner, Benjamin; Benda, Jan

    2017-03-07

    Synchronous activity in populations of neurons potentially encodes special stimulus features. Selective readout of either synchronous or asynchronous activity allows formation of two streams of information processing. Theoretical work predicts that such a synchrony code is a fundamental feature of populations of spiking neurons if they operate in specific noise and stimulus regimes. Here we experimentally test the theoretical predictions by quantifying and comparing neuronal response properties in tuberous and ampullary electroreceptor afferents of the weakly electric fish Apteronotus leptorhynchus These related systems show similar levels of synchronous activity, but only in the more irregularly firing tuberous afferents a synchrony code is established, whereas in the more regularly firing ampullary afferents it is not. The mere existence of synchronous activity is thus not sufficient for a synchrony code. Single-cell features such as the irregularity of spiking and the frequency dependence of the neuron's transfer function determine whether synchronous spikes possess a distinct meaning for the encoding of time-dependent signals.

  13. Afferent loop syndrome: Role of sonography and CT

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong Ho; Lim, Jae Hoon; Ko, Young Tae [Kyung Hee University Hospital, Seoul (Korea, Republic of)

    1992-03-15

    Afferent loop syndrome(ALS) is caused by obstruction of the afferent loop after subtotal gastrectomy with Billroth II gastrojejunostomy. Prompt diagnosis of ALS is important as perforation of the loop occurs. The aim of study is to ascertain the sonography and CT to diagnose ALS. We describe the radiologic findings in ten patients with ALS. The cause of ALS, established at surgery, included cancer recurrence (n=4), internal hernia (n=4), marginal ulcer (n=1), and development of cancer at the anastomosis site (n=1). Abdominal X-ray and sonography were performed in all cases, upper GI series in five cases and computed tomography in two cases. The dilated afferent loop was detected in only two cases out often patients in retrospective review of abdominal X-ray. ALS with recurrence of cancer was diagnosed in three cases by upper GI series. Of the cases that had sonography, the afferent loop was seen in the upper abdomen crossing transversely over the midline in all ten patients. The cause of ALS were predicated on the basis of the sonograms in three of the five patients. In two cases of computed tomography, the dilated afferent loop and recurrent cancer at the remnant stomach were seen.Our experience suggests that the diagnosis of afferent syndrome can be made on the basis of the typical anatomic location and shape of the dilated bowel loop in both sonography and computed tomography.

  14. Afferent projections to the deep mesencephalic nucleus in the rat

    International Nuclear Information System (INIS)

    Veazey, R.B.; Severin, C.M.

    1982-01-01

    Afferent projections to the deep mesencephalic nucleus (DMN) of the rat were demonstrated with axonal transport techniques. Potential sources for projections to the DMN were first identified by injecting the nucleus with HRP and examining the cervical spinal cord, brain stem, and cortex for retrogradely labeled neurons. Areas consistently labeled were then injected with a tritiated radioisotope, the tissue processed for autoradiography, and the DMN examined for anterograde labeling. Afferent projections to the medial and/or lateral parts of the DMN were found to originate from a number of spinal, bulbar, and cortical centers. Rostral brain centers projecting to both medial and lateral parts of the DMN include the ipsilateral motor and somatosensory cortex, the entopeduncular nucleus, and zona incerta. at the level of the midbrain, the ipsilateral substantia nigra and contralateral DMN likewise project to the DMN. Furthermore, the ipsilateral superior colliculus projects to the DMN, involving mainly the lateral part of the nucleus. Afferents from caudal centers include bilateral projections from the sensory nucleus of the trigeminal complex and the nucleus medulla oblongata centralis, as well as from the contralateral dentate nucleus. The projections from the trigeminal complex and nucleus medullae oblongatae centralis terminate in the intermediate and medial parts of the DMN, whereas projections from the contralateral dentate nucleus terminate mainly in its lateral part. In general, the afferent connections of the DMN arise from diverse areas of the brain. Although most of these projections distribute throughout the entire extent of the DMN, some of them project mainly to either medial or lateral parts of the nucleus, thus suggesting that the organization of the DMN is comparable, at least in part, to that of the reticular formation of the pons and medulla, a region in which hodological differences between medial and lateral subdivisions are known to exist

  15. Rhythmic activity of feline dorsal and ventral spinocerebellar tract neurons during fictive motor actions

    DEFF Research Database (Denmark)

    Fedirchuk, Brent; Stecina, Katinka; Kristensen, Kasper Kyhl

    2013-01-01

    (without phasic afferent feedback). In this study, we compared the activity of DSCT and VSCT neurons during fictive rhythmic motor behaviors. We used decerebrate cat preparations in which fictive motor tasks can be evoked while the animal is paralyzed and there is no rhythmic sensory input from hindlimb......Neurons of the dorsal spinocerebellar tracts (DSCT) have been described to be rhythmically active during walking on a treadmill in decerebrate cats, but this activity ceased following deafferentation of the hindlimb. This observation supported the hypothesis that DSCT neurons primarily relay...

  16. Role of neuronal activity in regulating the structure and function of auditory neurons

    International Nuclear Information System (INIS)

    Born, D.E.

    1986-01-01

    The role of afferent activity in maintaining neuronal structure and function was investigated in second order auditory neurons in nucleus magnocellularis (NM) of the chicken. The cochlea provides the major excitatory input to NM neurons via the eighth nerve. Removal of the cochlea causes dramatic changes in NM neurons. To determine if the elimination of neuronal activity is responsible for the changes in NM seen after cochlea removal, tetrodotoxin was used block action potentials in the cochlear ganglion cells. Tetrodotoxin injections into the perilymph reliably blocked neuronal activity in the cochlear nerve and NM. Far field recordings of sound-evoked potentials revealed that responses returned within 6 hours. Changes in amino acid incorporation in NM neurons were measured by giving intracardiac injections of 3 H-leucine and preparing tissue for autoradiographic demonstration of incorporated amino acid. Grain counts over individual neurons revealed that a single injection of tetrodotoxin produced a 40% decrease in grain density in ipsilateral NM neurons. It is concluded that neuronal activity plays an important contribution to the maintenance of the normal properties of NM neurons

  17. Excitatory inputs to four types of spinocerebellar tract neurons in the cat and the rat thoraco-lumbar spinal cord

    Science.gov (United States)

    Shrestha, Sony Shakya; Bannatyne, B Anne; Jankowska, Elzbieta; Hammar, Ingela; Nilsson, Elin; Maxwell, David J

    2012-01-01

    The cerebellum receives information from the hindlimbs through several populations of spinocerebellar tract neurons. Although the role of these neurons has been established in electrophysiological experiments, the relative contribution of afferent fibres and central neurons to their excitatory input has only been estimated approximately so far. Taking advantage of differences in the immunohistochemistry of glutamatergic terminals of peripheral afferents and of central neurons (with vesicular glutamate transporters VGLUT1 or VGLUT2, respectively), we compared sources of excitatory input to four populations of spinocerebellar neurons in the thoraco-lumbar spinal cord: dorsal spinocerebellar tract neurons located in Clarke's column (ccDSCT) and in the dorsal horn (dhDSCT) and ventral spinocerebellar tract (VSCT) neurons including spinal border (SB) neurons. This was done on 22 electrophysiologically identified intracellularly labelled neurons in cats and on 80 neurons labelled by retrograde transport of cholera toxin b subunit injected into the cerebellum of rats. In both species distribution of antibodies against VGLUT1 and VGLUT2 on SB neurons (which have dominating inhibitory input from limb muscles), revealed very few VGLUT1 contacts and remarkably high numbers of VGLUT2 contacts. In VSCT neurons with excitatory afferent input, the number of VGLUT1 contacts was relatively high although VGLUT2 contacts likewise dominated, while the proportions of VGLUT1 and VGLUT2 immunoreactive terminals were the reverse on the two populations of DSCT neurons. These findings provide morphological evidence that SB neurons principally receive excitatory inputs from central neurons and provide the cerebellum with information regarding central neuronal activity. PMID:22371473

  18. Facilitation of the main generator source of earthworm muscle contraction by a peripheral neuron

    Directory of Open Access Journals (Sweden)

    Chang Y.C.

    1998-01-01

    Full Text Available A constant facilitation of responses evoked in the earthworm muscle contraction generator neurons by responses evoked in the neurons of its peripheral nervous system was demonstrated. It is based on the proposal that these two responses are bifurcations of an afferent response evoked by the same peripheral mechanical stimulus but converging again on this central neuron. A single-peaked generator response without facilitation was demonstrated by sectioning the afferent route of the peripheral facilitatory modulatory response, or conditioning response (CR. The multipeaked response could be restored by restimulating the sectioned modulatory neuron with an intracellular substitutive conditioning stimulus (SCS. These multi-peaked responses were proposed to be the result of reverberating the original single peaked unconditioned response (UR through a parallel (P neuronal circuit which receives the facilitation of the peripheral modulatory neuron. This peripheral modulatory neuron was named "Peri-Kästchen" (PK neuron because it has about 20 peripheral processes distributed on the surface of a Kästchen of longitudinal muscle cells on the body wall of this preparation as revealed by the Lucifer Yellow-CH-filling method.

  19. Combined genetic and pharmacological inhibition of TRPV1 and P2X3 attenuates colorectal hypersensitivity and afferent sensitization

    Science.gov (United States)

    Kiyatkin, Michael E.; Feng, Bin; Schwartz, Erica S.

    2013-01-01

    The ligand-gated channels transient receptor potential vanilloid 1 (TRPV1) and P2X3 have been reported to facilitate colorectal afferent neuron sensitization, thus contributing to organ hypersensitivity and pain. In the present study, we hypothesized that TRPV1 and P2X3 cooperate to modulate colorectal nociception and afferent sensitivity. To test this hypothesis, we employed TRPV1-P2X3 double knockout (TPDKO) mice and channel-selective pharmacological antagonists and evaluated combined channel contributions to behavioral responses to colorectal distension (CRD) and afferent fiber responses to colorectal stretch. Baseline responses to CRD were unexpectedly greater in TPDKO compared with control mice, but zymosan-produced CRD hypersensitivity was absent in TPDKO mice. Relative to control mice, proportions of mechanosensitive and -insensitive pelvic nerve afferent classes were not different in TPDKO mice. Responses of mucosal and serosal class afferents to mechanical probing were unaffected, whereas responses of muscular (but not muscular/mucosal) afferents to stretch were significantly attenuated in TPDKO mice; sensitization of both muscular and muscular/mucosal afferents by inflammatory soup was also significantly attenuated. In pharmacological studies, the TRPV1 antagonist A889425 and P2X3 antagonist TNP-ATP, alone and in combination, applied onto stretch-sensitive afferent endings attenuated responses to stretch; combined antagonism produced greater attenuation. In the aggregate, these observations suggest that 1) genetic manipulation of TRPV1 and P2X3 leads to reduction in colorectal mechanosensation peripherally and compensatory changes and/or disinhibition of other channels centrally, 2) combined pharmacological antagonism produces more robust attenuation of mechanosensation peripherally than does antagonism of either channel alone, and 3) the relative importance of these channels appears to be enhanced in colorectal hypersensitivity. PMID:23989007

  20. Pathological effects of chronic myocardial infarction on peripheral neurons mediating cardiac neurotransmission.

    Science.gov (United States)

    Nakamura, Keijiro; Ajijola, Olujimi A; Aliotta, Eric; Armour, J Andrew; Ardell, Jeffrey L; Shivkumar, Kalyanam

    2016-05-01

    To determine whether chronic myocardial infarction (MI) induces structural and neurochemical changes in neurons within afferent and efferent ganglia mediating cardiac neurotransmission. Neuronal somata in i) right atrial (RAGP) and ii) ventral interventricular ganglionated plexi (VIVGP), iii) stellate ganglia (SG) and iv) T1-2 dorsal root ganglia (DRG) bilaterally derived from normal (n=8) vs. chronic MI (n=8) porcine subjects were studied. We examined whether the morphology and neuronal nitric oxide synthase (nNOS) expression in soma of RAGP, VIVGP, DRG and SG neurons were altered as a consequence of chronic MI. In DRG, we also examined immunoreactivity of calcitonin gene related peptide (CGRP), a marker of afferent neurons. Chronic MI increased neuronal size and nNOS immunoreactivity in VIVGP (but not RAGP), as well as in the SG bilaterally. Across these ganglia, the increase in neuronal size was more pronounced in nNOS immunoreactive neurons. In the DRG, chronic MI also caused neuronal enlargement, and increased CGRP immunoreactivity. Further, DRG neurons expressing both nNOS and CGRP were increased in MI animals compared to controls, and represented a shift from double negative neurons. Chronic MI impacts diverse elements within the peripheral cardiac neuraxis. That chronic MI imposes such widespread, diverse remodeling of the peripheral cardiac neuraxis must be taken into consideration when contemplating neuronal regulation of the ischemic heart. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. PATHOLOGICAL EFFECTS OF CHRONIC MYOCARDIAL INFARCTION ON PERIPHERAL NEURONS MEDIATING CARDIAC NEUROTRANSMISSION

    Science.gov (United States)

    Nakamura, Keijiro; Ajijola, Olujimi A.; Aliotta, Eric; Armour, J. Andrew; Ardell, Jeffrey L.; Shivkumar, Kalyanam

    2016-01-01

    Objective To determine whether chronic myocardial infarction (MI) induces structural and neurochemical changes in neurons within afferent and efferent ganglia mediating cardiac neurotransmission. Methods Neuronal somata in i) right atrial (RAGP) and ii) ventral interventricular ganglionated plexi (VIVGP), iii) stellate ganglia (SG) and iv) T1-2 dorsal root ganglia (DRG) bilaterally derived from normal (n = 8) vs. chronic MI (n = 8) porcine subjects were studied. We examined whether the morphology and neuronal nitric oxide synthase (nNOS) expression in soma of RAGP, VIVGP, DRG and SG neurons were altered as a consequence of chronic MI. In DRG, we also examined immunoreactivity of calcitonin gene related peptide (CGRP), a marker of afferent neurons. Results Chronic MI increased neuronal size and nNOS immunoreactivity in VIVGP (but not RAGP), as well as in the SG bilaterally. Across these ganglia, the increase in neuronal size was more pronounced in nNOS immunoreacitive neurons. In the DRG, chronic MI also caused neuronal enlargement, and increased CGRP immunoreactivity. Further, DRG neurons expressing both nNOS and CGRP were increased in MI animals compared to controls, and represented a shift from double negative neurons. Conclusions Chronic MI impacts diverse elements within the peripheral cardiac neuraxis. That chronic MI imposes such widespread, diverse remodeling of the peripheral cardiac neuraxis must be taken into consideration when contemplating neuronal regulation of the ischemic heart. PMID:27209472

  2. Effects of cold temperatures on the excitability of rat trigeminal ganglion neurons that are not for cold-sensing

    Science.gov (United States)

    Kanda, Hirosato; Gu, Jianguo G.

    2016-01-01

    Except a small population of primary afferent neurons for sensing cold to generate the sensations of innocuous and noxious cold, it is generally believed that cold temperatures suppress the excitability of other primary afferent neurons that are not for cold-sensing. These not-for-cold-sensing neurons include the majority of non-nociceptive and nociceptive afferent neurons. In the present study we have found that not-for-cold-sensing neurons of rat trigeminal ganglia (TG) change their excitability in several ways at cooling temperatures. In nearly 70% of not-for-cold-sensing TG neurons, the cooling temperature of 15°C increases their membrane excitability. We regard these neurons as cold-active neurons. For the remaining 30% of not-for-cold-sensing TG neurons, the cooling temperature of 15°C either has no effect (regarded as cold-ineffective neurons) or suppress (regarded as cold-suppressive neurons) their membrane excitability. For cold-active neurons, the cold temperature of 15°C increases their excitability as is evidenced by the increases in action potential (AP) firing numbers and/or reduction of AP rheobase when these neurons are depolarized electrically. The cold temperature of 15°C significantly inhibits M-currents and increases membrane input resistance of cold-active neurons. Retigabine, an M-current activator, abolishes the effect of cold temperatures on AP firing but not the effect of cold temperature on AP rheobase levels. The inhibition of M-currents and the increases of membrane input resistance are likely two mechanisms by which cooling temperatures increase the excitability of not-for-cold-sensing TG neurons. PMID:26709732

  3. Duodenal activation of cAMP-dependent protein kinase induces vagal afferent firing and lowers glucose production in rats.

    Science.gov (United States)

    Rasmussen, Brittany A; Breen, Danna M; Luo, Ping; Cheung, Grace W C; Yang, Clair S; Sun, Biying; Kokorovic, Andrea; Rong, Weifang; Lam, Tony K T

    2012-04-01

    The duodenum senses nutrients to maintain energy and glucose homeostasis, but little is known about the signaling and neuronal mechanisms involved. We tested whether duodenal activation of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase A (PKA) is sufficient and necessary for cholecystokinin (CCK) signaling to trigger vagal afferent firing and regulate glucose production. In rats, we selectively activated duodenal PKA and evaluated changes in glucose kinetics during the pancreatic (basal insulin) pancreatic clamps and vagal afferent firing. The requirement of duodenal PKA signaling in glucose regulation was evaluated by inhibiting duodenal activation of PKA in the presence of infusion of the intraduodenal PKA agonist (Sp-cAMPS) or CCK1 receptor agonist (CCK-8). We also assessed the involvement of a neuronal network and the metabolic impact of duodenal PKA activation in rats placed on high-fat diets. Intraduodenal infusion of Sp-cAMPS activated duodenal PKA and lowered glucose production, in association with increased vagal afferent firing in control rats. The metabolic and neuronal effects of duodenal Sp-cAMPS were negated by coinfusion with either the PKA inhibitor H89 or Rp-CAMPS. The metabolic effect was also negated by coinfusion with tetracaine, molecular and pharmacologic inhibition of NR1-containing N-methyl-d-aspartate (NMDA) receptors within the dorsal vagal complex, or hepatic vagotomy in rats. Inhibition of duodenal PKA blocked the ability of duodenal CCK-8 to reduce glucose production in control rats, whereas duodenal Sp-cAMPS bypassed duodenal CCK resistance and activated duodenal PKA and lowered glucose production in rats on high-fat diets. We identified a neural glucoregulatory function of duodenal PKA signaling. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

  4. Partial Aminoglycoside Lesions in Vestibular Epithelia Reveal Broad Sensory Dysfunction Associated with Modest Hair Cell Loss and Afferent Calyx Retraction.

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    Sultemeier, David R; Hoffman, Larry F

    2017-01-01

    Although the effects of aminoglycoside antibiotics on hair cells have been investigated for decades, their influences on the dendrites of primary afferent neurons have not been widely studied. This is undoubtedly due to the difficulty in disassociating pathology to dendritic processes from that resulting from loss of the presynaptic hair cell. This was overcome in the present investigation through development of a preparation using Chinchilla laniger that enabled direct perilymphatic infusion. Through this strategy we unmasked gentamicin's potential effects on afferent calyces. The pathophysiology of the vestibular neuroepithelia after post-administration durations of 0.5 through 6 months was assessed using single-neuron electrophysiology, immunohistochemistry, and confocal microscopy. Hair cell densities within cristae central zones (0.5-, 1-, 2-, and 6-months) and utricle peri- and extrastriola (6-months) regions were determined, and damage to calretinin-immunoreactive calyces was quantified. Gentamicin-induced hair cell loss exhibited a profile that reflected elimination of a most-sensitive group by 0.5-months post-administration (18.2%), followed by loss of a second group (20.6%) over the subsequent 5.5 months. The total hair cell loss with this gentamicin dose (approximately 38.8%) was less than the estimated fraction of type I hair cells in the chinchilla's crista central zone (approximately 60%), indicating that viable type I hair cells remained. Extensive lesions to afferent calyces were observed at 0.5-months, though stimulus-evoked modulation was intact at this post-administration time. Widespread compromise to calyx morphology and severe attenuation of stimulus-evoked afferent discharge modulation was found at 1 month post-administration, a condition that persisted in preparations examined through the 6-month post-administration interval. Spontaneous discharge was robust at all post-administration intervals. All calretinin-positive calyces had retracted

  5. An excitatory paraventricular nucleus to AgRP neuron circuit that drives hunger.

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    Krashes, Michael J; Shah, Bhavik P; Madara, Joseph C; Olson, David P; Strochlic, David E; Garfield, Alastair S; Vong, Linh; Pei, Hongjuan; Watabe-Uchida, Mitsuko; Uchida, Naoshige; Liberles, Stephen D; Lowell, Bradford B

    2014-03-13

    Hunger is a hard-wired motivational state essential for survival. Agouti-related peptide (AgRP)-expressing neurons in the arcuate nucleus (ARC) at the base of the hypothalamus are crucial to the control of hunger. They are activated by caloric deficiency and, when naturally or artificially stimulated, they potently induce intense hunger and subsequent food intake. Consistent with their obligatory role in regulating appetite, genetic ablation or chemogenetic inhibition of AgRP neurons decreases feeding. Excitatory input to AgRP neurons is important in caloric-deficiency-induced activation, and is notable for its remarkable degree of caloric-state-dependent synaptic plasticity. Despite the important role of excitatory input, its source(s) has been unknown. Here, through the use of Cre-recombinase-enabled, cell-specific neuron mapping techniques in mice, we have discovered strong excitatory drive that, unexpectedly, emanates from the hypothalamic paraventricular nucleus, specifically from subsets of neurons expressing thyrotropin-releasing hormone (TRH) and pituitary adenylate cyclase-activating polypeptide (PACAP, also known as ADCYAP1). Chemogenetic stimulation of these afferent neurons in sated mice markedly activates AgRP neurons and induces intense feeding. Conversely, acute inhibition in mice with caloric-deficiency-induced hunger decreases feeding. Discovery of these afferent neurons capable of triggering hunger advances understanding of how this intense motivational state is regulated.

  6. Cholecystokinin enhances visceral pain-related affective memory via vagal afferent pathway in rats

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    Cao Bing

    2012-06-01

    the nociceptive response (visceral pain sensitivity and anterior cingulate cortex neuronal responses to CRD. Conclusion CCK activating vagal afferent C fibers enhances memory consolidation and retention involved in long-term visceral negative affective state. Thus, in a number of gastrointestinal disorders, such as irritable bowel syndrome, nutrient content may contribute to painful visceral perception by enhancing visceral aversive memory via acts on vagal afferent pathway.

  7. Cholecystokinin enhances visceral pain-related affective memory via vagal afferent pathway in rats.

    Science.gov (United States)

    Cao, Bing; Zhang, Xu; Yan, Ni; Chen, Shengliang; Li, Ying

    2012-06-09

    sensitivity) and anterior cingulate cortex neuronal responses to CRD. CCK activating vagal afferent C fibers enhances memory consolidation and retention involved in long-term visceral negative affective state. Thus, in a number of gastrointestinal disorders, such as irritable bowel syndrome, nutrient content may contribute to painful visceral perception by enhancing visceral aversive memory via acts on vagal afferent pathway.

  8. Microstimulation of the lumbar DRG recruits primary afferent neurons in localized regions of lower limb.

    Science.gov (United States)

    Ayers, Christopher A; Fisher, Lee E; Gaunt, Robert A; Weber, Douglas J

    2016-07-01

    Patterned microstimulation of the dorsal root ganglion (DRG) has been proposed as a method for delivering tactile and proprioceptive feedback to amputees. Previous studies demonstrated that large- and medium-diameter afferent neurons could be recruited separately, even several months after implantation. However, those studies did not examine the anatomical localization of sensory fibers recruited by microstimulation in the DRG. Achieving precise recruitment with respect to both modality and receptive field locations will likely be crucial to create a viable sensory neuroprosthesis. In this study, penetrating microelectrode arrays were implanted in the L5, L6, and L7 DRG of four isoflurane-anesthetized cats instrumented with nerve cuff electrodes around the proximal and distal branches of the sciatic and femoral nerves. A binary search was used to find the recruitment threshold for evoking a response in each nerve cuff. The selectivity of DRG stimulation was characterized by the ability to recruit individual distal branches to the exclusion of all others at threshold; 84.7% (n = 201) of the stimulation electrodes recruited a single nerve branch, with 9 of the 15 instrumented nerves recruited selectively. The median stimulation threshold was 0.68 nC/phase, and the median dynamic range (increase in charge while stimulation remained selective) was 0.36 nC/phase. These results demonstrate the ability of DRG microstimulation to achieve selective recruitment of the major nerve branches of the hindlimb, suggesting that this approach could be used to drive sensory input from localized regions of the limb. This sensory input might be useful for restoring tactile and proprioceptive feedback to a lower-limb amputee. Copyright © 2016 the American Physiological Society.

  9. Effects of cold temperatures on the excitability of rat trigeminal ganglion neurons that are not for cold sensing.

    Science.gov (United States)

    Kanda, Hirosato; Gu, Jianguo G

    2017-05-01

    Aside from a small population of primary afferent neurons for sensing cold, which generate sensations of innocuous and noxious cold, it is generally believed that cold temperatures suppress the excitability of primary afferent neurons not responsible for cold sensing. These not-for-cold-sensing neurons include the majority of non-nociceptive and nociceptive afferent neurons. In this study we have found that the not-for-cold-sensing neurons of rat trigeminal ganglia (TG) change their excitability in several ways at cooling temperatures. In nearly 70% of not-for-cold-sensing TG neurons, a cooling temperature of 15°C increases their membrane excitability. We regard these neurons as cold-active neurons. For the remaining 30% of not-for-cold-sensing TG neurons, the cooling temperature of 15°C either has no effect (cold-ineffective neurons) or suppress their membrane excitability (cold-suppressive neurons). For cold-active neurons, the cold temperature of 15°C increases their excitability as is evidenced by increases in action potential (AP) firing numbers and/or the reduction in AP rheobase when these neurons are depolarized electrically. The cold temperature of 15°C significantly inhibits M-currents and increases membrane input resistance of cold-active neurons. Retigabine, an M-current activator, abolishes the effect of cold temperatures on AP firing, but not the effect of cold temperature on AP rheobase levels. The inhibition of M-currents and the increases of membrane input resistance are likely two mechanisms by which cooling temperatures increase the excitability of not-for-cold-sensing TG neurons. This article is part of the special article series "Pain". © 2015 International Society for Neurochemistry.

  10. Afferent connectivity of the zebrafish habenulae

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    Katherine Jane Turner

    2016-04-01

    Full Text Available The habenulae are bilateral nuclei located in the dorsal diencephalon that are conserved across vertebrates.Here we describe the main afferents to the habenulae in larval and adult zebrafish.We observe afferents from the subpallium, nucleus rostrolateralis,posterior tuberculum, posterior hypothalamic lobe, median raphe, olfactory bulb to the right habenula and from the parapineal to the lefthabenula.In addition,we find afferents from a ventrolateral telencephalic nucleus that neurochemical and hodological data identify as the ventral entopeduncular nucleus(vENT,confirming and extending observations of Amo et al.(2014.Fate map and marker studies suggest that vENT originates from the diencephalic prethalamic eminence and extends into the lateral telencephalon from 48 to 120 hpf.No afferents to the habenula were observed from the dorsal entopeduncular nucleus(dENT.Consequently,we confirm that the vENT(and not the dENT should be considered as the entopeduncular nucleus proper in zebrafish.Furthermore,comparison with data in other vertebrates suggests that the vENT is a conserved basal ganglia nucleus,being homologous to the entopeduncular nucleus of mammals(internal segment of the globus pallidus of primates by both embryonic origin and projections,as previously suggested by Amo et al.(2014.Key words: habenula,connections,afferents,entopeduncular nucleus,posterior tuberculum,basal ganglia,zebrafish

  11. Afferent Connectivity of the Zebrafish Habenulae

    Science.gov (United States)

    Turner, Katherine J.; Hawkins, Thomas A.; Yáñez, Julián; Anadón, Ramón; Wilson, Stephen W.; Folgueira, Mónica

    2016-01-01

    The habenulae are bilateral nuclei located in the dorsal diencephalon that are conserved across vertebrates. Here we describe the main afferents to the habenulae in larval and adult zebrafish. We observe afferents from the subpallium, nucleus rostrolateralis, posterior tuberculum, posterior hypothalamic lobe, median raphe; we also see asymmetric afferents from olfactory bulb to the right habenula, and from the parapineal to the left habenula. In addition, we find afferents from a ventrolateral telencephalic nucleus that neurochemical and hodological data identify as the ventral entopeduncular nucleus (vENT), confirming and extending observations of Amo et al. (2014). Fate map and marker studies suggest that vENT originates from the diencephalic prethalamic eminence and extends into the lateral telencephalon from 48 to 120 hour post-fertilization (hpf). No afferents to the habenula were observed from the dorsal entopeduncular nucleus (dENT). Consequently, we confirm that the vENT (and not the dENT) should be considered as the entopeduncular nucleus “proper” in zebrafish. Furthermore, comparison with data in other vertebrates suggests that the vENT is a conserved basal ganglia nucleus, being homologous to the entopeduncular nucleus of mammals (internal segment of the globus pallidus of primates) by both embryonic origin and projections, as previously suggested by Amo et al. (2014). PMID:27199671

  12. Afferent innervation of the utricular macula in pigeons

    Science.gov (United States)

    Si, Xiaohong; Zakir, Mridha Md; Dickman, J. David

    2003-01-01

    Biotinylated dextran amine (BDA) was used to retrogradely label afferents innervating the utricular macula in adult pigeons. The pigeon utriclar macula consists of a large rectangular-shaped neuroepithelium with a dorsally curved anterior edge and an extended medioposterior tail. The macula could be demarcated into several regions based on cytoarchitectural differences. The striola occupied 30% of the macula and contained a large density of type I hair cells with fewer type II hair cells. Medial and lateral extrastriola zones were located outside the striola and contained only type II hair cells. A six- to eight-cell-wide band of type II hair cells existed near the center of the striola. The reversal line marked by the morphological polarization of hair cells coursed throughout the epithelium, near the peripheral margin, and through the center of the type II band. Calyx afferents innervated type I hair cells with calyceal terminals that contained between 2 and 15 receptor cells. Calyx afferents were located only in the striola region, exclusive of the type II band, had small total fiber innervation areas and low innervation densities. Dimorph afferents innervated both type I and type II hair cells with calyceal and bouton terminals and were primarily located in the striola region. Dimorph afferents had smaller calyceal terminals with few type I hair cells, extended fiber branches with bouton terminals and larger innervation areas. Bouton afferents innervated only type II hair cells in the extrastriola and type II band regions. Bouton afferents innervating the type II band had smaller terminal fields with fewer bouton terminals and smaller innervation areas than fibers located in the extrastriolar zones. Bouton afferents had the most bouton terminals on the longest fibers, the largest innervation areas with the highest innervation densities of all afferents. Among all afferents, smaller terminal innervation fields were observed in the striola and large fields were

  13. Response of spiking neurons to correlated inputs

    International Nuclear Information System (INIS)

    Moreno, Ruben; Rocha, Jaime de la; Renart, Alfonso; Parga, Nestor

    2002-01-01

    The effect of a temporally correlated afferent current on the firing rate of a leaky integrate-and-fire neuron is studied. This current is characterized in terms of rates, autocorrelations, and cross correlations, and correlation time scale τ c of excitatory and inhibitory inputs. The output rate ν out is calculated in the Fokker-Planck formalism in the limit of both small and large τ c compared to the membrane time constant τ of the neuron. By simulations we check the analytical results, provide an interpolation valid for all τ c , and study the neuron's response to rapid changes in the correlation magnitude

  14. [Acute pancreatitis and afferent loop syndrome. Case report].

    Science.gov (United States)

    Barajas-Fregoso, Elpidio Manuel; Romero-Hernández, Teodoro; Macías-Amezcua, Michel Dassaejv

    2013-01-01

    The afferent syndrome loop is a mechanic obstruction of the afferent limb before a Billroth II or Roux-Y reconstruction, secondary in most of case to distal or subtotal gastrectomy. Clinical case: Male 76 years old, with antecedent of cholecystectomy, gastric adenocarcinoma six years ago, with subtotal gastrectomy and Roux-Y reconstruction. Beginning a several abdominal pain, nausea and vomiting, abdominal distension, without peritoneal irritation sings. Amylase 1246 U/L, lipase 3381 U/L. Computed Tomography with thickness wall and dilatation of afferent loop, pancreas with diffuse enlargement diagnostic of acute pancreatitis secondary an afferent loop syndrome. The afferent loop syndrome is presented in 0.3%-1% in all cases with Billroth II reconstruction, with a mortality of up to 57%, the obstruction lead accumulation of bile, pancreatic and intestinal secretions, increasing the pressure and resulting in afferent limb, bile conduct and Wirsung conduct dilatation, triggering an inflammatory response that culminates in pancreatic inflammation. The severity of the presentation is related to the degree and duration of the blockage.

  15. Ultrastructure of the central subnucleus of the nucleus tractus solitarii and the esophageal afferent terminals in the rat.

    Science.gov (United States)

    Hayakawa, Tetsu; Takanaga, Akinori; Tanaka, Koichi; Maeda, Seishi; Seki, Makoto

    2003-03-01

    The central subnucleus of the nucleus tractus solitarii (ceNTS) receives afferent projections from the esophageal wall and projects to the nucleus ambiguus, thus serving as a relay nucleus for peristalsis of the esophagus. Here we examine the synaptic organization of the ceNTS, and its esophageal afferents by using transganglionic anterograde transport of cholera toxin-conjugated horseradish peroxidase (CT-HRP). When CT-HRP was injected into the subdiaphragmatic esophagus, many anterogradely labeled terminals were found only in the ceNTS. The ceNTS was composed of round or oval-shaped, small neurons (14.7x8.7 micro m) containing sparse organelles and an irregularly shaped nucleus. The average number of axosomatic terminals was only 1.3 per section cut through the nucleolus. Most of them (92%) contained round vesicles and formed asymmetric synaptic contacts (Gray's type I), and a few (8%) contained pleomorphic vesicles and formed symmetric synaptic contacts (Gray's type II). All anterogradely labeled terminals contacted dendrites but not the neuronal somata. The labeled terminals were large (2.55+/-0.07 micro m) and exclusively Gray's type I. More than half of them (60%) contacted small dendrites (less than 1 micro m in diameter), and contained dense-cored vesicles. More than 40% of the labeled terminals contacted two to four dendrites, thus forming a synaptic glomerulus. Sometimes a labeled terminal that contacted an unlabeled terminal by an adherent junction was found within the glomerulus. The large terminals and these complex synaptic relations appeared to characterize the esophageal afferent projections in the ceNTS.

  16. Bradykinin Contributes to Sympathetic and Pressor Responses Evoked by Activation of Skeletal Muscle Afferents P2X in Heart Failure

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    Jihong Xing

    2016-11-01

    Full Text Available Background/Aims: Published data suggest that purinergic P2X receptors of muscle afferent nerves contribute to the enhanced sympathetic nervous activity (SNA and blood pressure (BP responses during static exercise in heart failure (HF. In this study, we examined engagement of bradykinin (BK in regulating responses of SNA and BP evoked by P2X stimulation in rats with HF. We further examined cellular mechanisms responsible for BK. We hypothesized that BK potentiates P2X currents of muscle dorsal root ganglion (DRG neurons, and this effect is greater in HF due to upregulation of BK kinin B2 and P2X3 receptor. As a result, BK amplifies muscle afferents P2X-mediated SNA and BP responses. Methods: Renal SNA and BP responses were recorded in control rats and rats with HF. Western Blot analysis and patch-clamp methods were employed to examine the receptor expression and function of DRG neurons involved in the effects of BK. Results: BK injected into the arterial blood supply of the hindlimb muscles heightened the reflex SNA and BP responses induced by P2X activation with α,β-methylene ATP to a greater degree in HF rats. In addition, HF upregulated the protein expression of kinin B2 and P2X3 in DRG and the prior application of BK increased the magnitude of α,β-methylene ATP-induced currents in muscle DRG neurons from HF rats. Conclusion: BK plays a facilitating role in modulating muscle afferent P2X-engaged reflex sympathetic and pressor responses. In HF, P2X responsivness is augmented due to increases in expression of kinin B2 and P2X3 receptors and P2X current activity.

  17. Memory formation orchestrates the wiring of adult-born hippocampal neurons into brain circuits.

    Science.gov (United States)

    Petsophonsakul, Petnoi; Richetin, Kevin; Andraini, Trinovita; Roybon, Laurent; Rampon, Claire

    2017-08-01

    During memory formation, structural rearrangements of dendritic spines provide a mean to durably modulate synaptic connectivity within neuronal networks. New neurons generated throughout the adult life in the dentate gyrus of the hippocampus contribute to learning and memory. As these neurons become incorporated into the network, they generate huge numbers of new connections that modify hippocampal circuitry and functioning. However, it is yet unclear as to how the dynamic process of memory formation influences their synaptic integration into neuronal circuits. New memories are established according to a multistep process during which new information is first acquired and then consolidated to form a stable memory trace. Upon recall, memory is transiently destabilized and vulnerable to modification. Using contextual fear conditioning, we found that learning was associated with an acceleration of dendritic spines formation of adult-born neurons, and that spine connectivity becomes strengthened after memory consolidation. Moreover, we observed that afferent connectivity onto adult-born neurons is enhanced after memory retrieval, while extinction training induces a change of spine shapes. Together, these findings reveal that the neuronal activity supporting memory processes strongly influences the structural dendritic integration of adult-born neurons into pre-existing neuronal circuits. Such change of afferent connectivity is likely to impact the overall wiring of hippocampal network, and consequently, to regulate hippocampal function.

  18. Heart failure induces changes in acid-sensing ion channels in sensory neurons innervating skeletal muscle.

    Science.gov (United States)

    Gibbons, David D; Kutschke, William J; Weiss, Robert M; Benson, Christopher J

    2015-10-15

    Heart failure is associated with diminished exercise capacity, which is driven, in part, by alterations in exercise-induced autonomic reflexes triggered by skeletal muscle sensory neurons (afferents). These overactive reflexes may also contribute to the chronic state of sympathetic excitation, which is a major contributor to the morbidity and mortality of heart failure. Acid-sensing ion channels (ASICs) are highly expressed in muscle afferents where they sense metabolic changes associated with ischaemia and exercise, and contribute to the metabolic component of these reflexes. Therefore, we tested if ASICs within muscle afferents are altered in heart failure. We used whole-cell patch clamp to study the electrophysiological properties of acid-evoked currents in isolated, labelled muscle afferent neurons from control and heart failure (induced by myocardial infarction) mice. We found that the percentage of muscle afferents that displayed ASIC-like currents, the current amplitudes, and the pH dose-response relationships were not altered in mice with heart failure. On the other hand, the biophysical properties of ASIC-like currents were significantly different in a subpopulation of cells (40%) from heart failure mice. This population displayed diminished pH sensitivity, altered desensitization kinetics, and very fast recovery from desensitization. These unique properties define these channels within this subpopulation of muscle afferents as being heteromeric channels composed of ASIC2a and -3 subunits. Heart failure induced a shift in the subunit composition of ASICs within muscle afferents, which significantly altered their pH sensing characteristics. These results might, in part, contribute to the changes in exercise-mediated reflexes that are associated with heart failure. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  19. The role of the renal afferent and efferent nerve fibres in heart failure

    Directory of Open Access Journals (Sweden)

    Lindsea C Booth

    2015-10-01

    Full Text Available Renal nerves contain afferent, sensory and efferent, sympathetic nerve fibres. In heart failure (HF there is an increase in renal sympathetic nerve activity, which can lead to renal vasoconstriction, increased renin release and sodium retention. These changes are thought to contribute to renal dysfunction, which is predictive of poor outcome in patients with HF. In contrast, the role of the renal afferent nerves remains largely unexplored in HF. This is somewhat surprising as there are multiple triggers in HF that have the potential to increase afferent nerve activity, including increased venous pressure and reduced kidney perfusion. Some of the few studies investigating renal afferents in HF have suggested that at least the sympatho-inhibitory reno-renal reflex is blunted. In experimentally induced HF, renal denervation, both surgical and catheter-based, has been associated with some improvements in renal and cardiac function. It remains unknown whether the effects are due to removal of the efferent renal nerve fibres, afferent renal nerve fibres, or a combination of both. Here, we review the effects of HF on renal efferent and afferent nerve function and critically assess the latest evidence supporting renal denervation as a potential treatment in HF.

  20. The role of the renal afferent and efferent nerve fibers in heart failure

    Science.gov (United States)

    Booth, Lindsea C.; May, Clive N.; Yao, Song T.

    2015-01-01

    Renal nerves contain afferent, sensory and efferent, sympathetic nerve fibers. In heart failure (HF) there is an increase in renal sympathetic nerve activity (RSNA), which can lead to renal vasoconstriction, increased renin release and sodium retention. These changes are thought to contribute to renal dysfunction, which is predictive of poor outcome in patients with HF. In contrast, the role of the renal afferent nerves remains largely unexplored in HF. This is somewhat surprising as there are multiple triggers in HF that have the potential to increase afferent nerve activity, including increased venous pressure and reduced kidney perfusion. Some of the few studies investigating renal afferents in HF have suggested that at least the sympatho-inhibitory reno-renal reflex is blunted. In experimentally induced HF, renal denervation, both surgical and catheter-based, has been associated with some improvements in renal and cardiac function. It remains unknown whether the effects are due to removal of the efferent renal nerve fibers or afferent renal nerve fibers, or a combination of both. Here, we review the effects of HF on renal efferent and afferent nerve function and critically assess the latest evidence supporting renal denervation as a potential treatment in HF. PMID:26483699

  1. Reliable activation of immature neurons in the adult hippocampus.

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    Lucas A Mongiat

    Full Text Available Neurons born in the adult dentate gyrus develop, mature, and connect over a long interval that can last from six to eight weeks. It has been proposed that, during this period, developing neurons play a relevant role in hippocampal signal processing owing to their distinctive electrical properties. However, it has remained unknown whether immature neurons can be recruited into a network before synaptic and functional maturity have been achieved. To address this question, we used retroviral expression of green fluorescent protein to identify developing granule cells of the adult mouse hippocampus and investigate the balance of afferent excitation, intrinsic excitability, and firing behavior by patch clamp recordings in acute slices. We found that glutamatergic inputs onto young neurons are significantly weaker than those of mature cells, yet stimulation of cortical excitatory axons elicits a similar spiking probability in neurons at either developmental stage. Young neurons are highly efficient in transducing ionic currents into membrane depolarization due to their high input resistance, which decreases substantially in mature neurons as the inward rectifier potassium (Kir conductance increases. Pharmacological blockade of Kir channels in mature neurons mimics the high excitability characteristic of young neurons. Conversely, Kir overexpression induces mature-like firing properties in young neurons. Therefore, the differences in excitatory drive of young and mature neurons are compensated by changes in membrane excitability that render an equalized firing activity. These observations demonstrate that the adult hippocampus continuously generates a population of highly excitable young neurons capable of information processing.

  2. The Languages of Neurons: An Analysis of Coding Mechanisms by Which Neurons Communicate, Learn and Store Information

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    Morris H. Baslow

    2009-11-01

    Full Text Available In this paper evidence is provided that individual neurons possess language, and that the basic unit for communication consists of two neurons and their entire field of interacting dendritic and synaptic connections. While information processing in the brain is highly complex, each neuron uses a simple mechanism for transmitting information. This is in the form of temporal electrophysiological action potentials or spikes (S operating on a millisecond timescale that, along with pauses (P between spikes constitute a two letter “alphabet” that generates meaningful frequency-encoded signals or neuronal S/P “words” in a primary language. However, when a word from an afferent neuron enters the dendritic-synaptic-dendritic field between two neurons, it is translated into a new frequency-encoded word with the same meaning, but in a different spike-pause language, that is delivered to and understood by the efferent neuron. It is suggested that this unidirectional inter-neuronal language-based word translation step is of utmost importance to brain function in that it allows for variations in meaning to occur. Thus, structural or biochemical changes in dendrites or synapses can produce novel words in the second language that have changed meanings, allowing for a specific signaling experience, either external or internal, to modify the meaning of an original word (learning, and store the learned information of that experience (memory in the form of an altered dendritic-synaptic-dendritic field.

  3. Transposition and Intermingling of Galphai2 and Galphao afferences into single vomeronasal glomeruli in the Madagascan lesser Tenrec Echinops telfairi.

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    Rodrigo Suárez

    2009-11-01

    Full Text Available The vomeronasal system (VNS mediates pheromonal communication in mammals. From the vomeronasal organ, two populations of sensory neurons, expressing either Galphai2 or Galphao proteins, send projections that end in glomeruli distributed either at the rostral or caudal half of the accessory olfactory bulb (AOB, respectively. Neurons at the AOB contact glomeruli of a single subpopulation. The dichotomic segregation of AOB glomeruli has been described in opossums, rodents and rabbits, while Primates and Laurasiatheres present the Galphai2-pathway only, or none at all (such as apes, some bats and aquatic species. We studied the AOB of the Madagascan lesser tenrec Echinops telfairi (Afrotheria: Afrosoricida and found that Galphai2 and Galphao proteins are expressed in rostral and caudal glomeruli, respectively. However, the segregation of vomeronasal glomeruli at the AOB is not exclusive, as both pathways contained some glomeruli transposed into the adjoining subdomain. Moreover, some glomeruli seem to contain intermingled afferences from both pathways. Both the transposition and heterogeneity of vomeronasal afferences are features, to our knowledge, never reported before. The organization of AOB glomeruli suggests that synaptic integration might occur at the glomerular layer. Whether intrinsic AOB neurons may make synaptic contact with axon terminals of both subpopulations is an interesting possibility that would expand our understanding about the integration of vomeronasal pathways.

  4. Synaptic potentiation onto habenula neurons in the learned helplessness model of depression.

    Science.gov (United States)

    Li, Bo; Piriz, Joaquin; Mirrione, Martine; Chung, ChiHye; Proulx, Christophe D; Schulz, Daniela; Henn, Fritz; Malinow, Roberto

    2011-02-24

    The cellular basis of depressive disorders is poorly understood. Recent studies in monkeys indicate that neurons in the lateral habenula (LHb), a nucleus that mediates communication between forebrain and midbrain structures, can increase their activity when an animal fails to receive an expected positive reward or receives a stimulus that predicts aversive conditions (that is, disappointment or anticipation of a negative outcome). LHb neurons project to, and modulate, dopamine-rich regions, such as the ventral tegmental area (VTA), that control reward-seeking behaviour and participate in depressive disorders. Here we show that in two learned helplessness models of depression, excitatory synapses onto LHb neurons projecting to the VTA are potentiated. Synaptic potentiation correlates with an animal's helplessness behaviour and is due to an enhanced presynaptic release probability. Depleting transmitter release by repeated electrical stimulation of LHb afferents, using a protocol that can be effective for patients who are depressed, markedly suppresses synaptic drive onto VTA-projecting LHb neurons in brain slices and can significantly reduce learned helplessness behaviour in rats. Our results indicate that increased presynaptic action onto LHb neurons contributes to the rodent learned helplessness model of depression.

  5. Synaptic potentiation onto habenula neurons in the learned helplessness model of depression

    International Nuclear Information System (INIS)

    Li, B.; Schulz, D.; Piriz, J.; Mirrione, M.; Chung, C.H.; Proulx, C.D.; Schulz, D.; Henn, F.; Malinow, R.

    2011-01-01

    The cellular basis of depressive disorders is poorly understood. Recent studies in monkeys indicate that neurons in the lateral habenula (LHb), a nucleus that mediates communication between forebrain and midbrain structures, can increase their activity when an animal fails to receive an expected positive reward or receives a stimulus that predicts aversive conditions (that is, disappointment or anticipation of a negative outcome). LHb neurons project to, and modulate, dopamine-rich regions, such as the ventral tegmental area (VTA), that control reward-seeking behaviour and participate in depressive disorders. Here we show that in two learned helplessness models of depression, excitatory synapses onto LHb neurons projecting to the VTA are potentiated. Synaptic potentiation correlates with an animal's helplessness behaviour and is due to an enhanced presynaptic release probability. Depleting transmitter release by repeated electrical stimulation of LHb afferents, using a protocol that can be effective for patients who are depressed, markedly suppresses synaptic drive onto VTA-projecting LHb neurons in brain slices and can significantly reduce learned helplessness behaviour in rats. Our results indicate that increased presynaptic action onto LHb neurons contributes to the rodent learned helplessness model of depression.

  6. Emergent synchronous bursting of oxytocin neuronal network.

    Directory of Open Access Journals (Sweden)

    Enrico Rossoni

    2008-07-01

    Full Text Available When young suckle, they are rewarded intermittently with a let-down of milk that results from reflex secretion of the hormone oxytocin; without oxytocin, newly born young will die unless they are fostered. Oxytocin is made by magnocellular hypothalamic neurons, and is secreted from their nerve endings in the pituitary in response to action potentials (spikes that are generated in the cell bodies and which are propagated down their axons to the nerve endings. Normally, oxytocin cells discharge asynchronously at 1-3 spikes/s, but during suckling, every 5 min or so, each discharges a brief, intense burst of spikes that release a pulse of oxytocin into the circulation. This reflex was the first, and is perhaps the best, example of a physiological role for peptide-mediated communication within the brain: it is coordinated by the release of oxytocin from the dendrites of oxytocin cells; it can be facilitated by injection of tiny amounts of oxytocin into the hypothalamus, and it can be blocked by injection of tiny amounts of oxytocin antagonist. Here we show how synchronized bursting can arise in a neuronal network model that incorporates basic observations of the physiology of oxytocin cells. In our model, bursting is an emergent behaviour of a complex system, involving both positive and negative feedbacks, between many sparsely connected cells. The oxytocin cells are regulated by independent afferent inputs, but they interact by local release of oxytocin and endocannabinoids. Oxytocin released from the dendrites of these cells has a positive-feedback effect, while endocannabinoids have an inhibitory effect by suppressing the afferent input to the cells.

  7. Finite post synaptic potentials cause a fast neuronal response

    Directory of Open Access Journals (Sweden)

    Moritz eHelias

    2011-02-01

    Full Text Available A generic property of the communication between neurons is the exchange of pulsesat discrete time points, the action potentials. However, the prevalenttheory of spiking neuronal networks of integrate-and-fire model neuronsrelies on two assumptions: the superposition of many afferent synapticimpulses is approximated by Gaussian white noise, equivalent to avanishing magnitude of the synaptic impulses, and the transfer oftime varying signals by neurons is assessable by linearization. Goingbeyond both approximations, we find that in the presence of synapticimpulses the response to transient inputs differs qualitatively fromprevious predictions. It is instantaneous rather than exhibiting low-passcharacteristics, depends non-linearly on the amplitude of the impulse,is asymmetric for excitation and inhibition and is promoted by a characteristiclevel of synaptic background noise. These findings resolve contradictionsbetween the earlier theory and experimental observations. Here wereview the recent theoretical progress that enabled these insights.We explain why the membrane potential near threshold is sensitiveto properties of the afferent noise and show how this shapes the neuralresponse. A further extension of the theory to time evolution in discretesteps quantifies simulation artifacts and yields improved methodsto cross check results.

  8. Peripheral innervation patterns of vestibular nerve afferents in the bullfrog utriculus

    Science.gov (United States)

    Baird, Richard A.; Schuff, N. R.

    1994-01-01

    Vestibular nerve afferents innervating the bullfrog utriculus differ in their response dynamics and sensitivity to natural stimulation. They also supply hair cells that differ markedly in hair bundle morphology. To examine the peripheral innervation patterns of individual utricular afferents more closely, afferent fibers were labeled by the extracellular injection of horseradish peroxidase (HRP) into the vestibular nerve after sectioning the vestibular nerve medial to Scarpa's ganglion to allow the degeneration of sympathetic and efferent fibers. The peripheral arborizations of individual afferents were then correlated with the diameters of their parent axons, the regions of the macula they innervate, and the number and type of hair cells they supply. The utriculus is divided by the striola, a narrow zone of distinctive morphology, into media and lateral parts. Utiricular afferents were classified as striolar or extrastriolar according to the epithelial entrance of their parent axons and the location of their terminal fields. In general, striolar afferents had thicker parent axons, fewer subepithelial bifurcations, larger terminal fields, and more synaptic endings than afferents in extrstriolar regions. Afferents in a juxtastriolar zone, immediately adjacent to the medial striola, had innervation patterns transitional between those in the striola and more peripheral parts of the medial extrastriola. moast afferents innervated only a single macular zone. The terminal fields of striolar afferents, with the notable exception of a few afferents with thin parent axons, were generally confined to one side of the striola. Hair cells in the bullfrog utriculus have perviously been classified into four types based on hair bundle morphology. Afferents in the extrastriolar and juxtastriolar zones largely or exclusively innervated Type B hair cells, the predominant hair cell type in the utricular macula. Striolar afferents supplied a mixture of four hair cell types, but largely

  9. Long-term potentiation of synaptic response and intrinsic excitability in neurons of the rat medial vestibular nuclei.

    Science.gov (United States)

    Pettorossi, V E; Dieni, C V; Scarduzio, M; Grassi, S

    2011-07-28

    Using intracellular recordings, we investigated the effects of high frequency stimulation (HFS) of the primary vestibular afferents on the evoked excitatory postsynaptic potential (EPSP) and intrinsic excitability (IE) of type-A and type-B neurons of the medial vestibular nucleus (MVN), in male rat brainstem slices. HFS induces long-term potentiation (LTP) of both EPSP and IE, which may occur in combination or separately. Synaptic LTP is characterized by an increase in the amplitude, slope and decay time constant of EPSP and IE-LTP through enhancements of spontaneous and evoked neuron firing and of input resistance (Rin). Moreover, IE-LTP is associated with a decrease in action potential afterhyperpolarization (AHP) amplitude and an increase in interspike slope steepness (ISS). The more frequent effects of HFS are EPSP-LTP in type-B neurons and IE-LTP in type-A neurons. In addition, the development of EPSP-LTP is fast in type-B neurons but slow in type-A, whereas IE-LTP develops slowly in both types. We have demonstrated that activation of N-methyl-d aspartate receptors (NMDARs) is only required for EPSP-LTP induction, whereas metabotropic glutamate receptors type-1 (mGluR1) are necessary for IE-LTP induction as well as the full development and maintenance of EPSP-LTP. Taken together, these findings demonstrate that brief and intense activation of vestibular afferent input to the MVN neurons may provoke synaptic LTP and/or IE-LTP that, induced in combination or separately, may assure the different selectivity of the MVN neuron response enhancement to the afferent signals. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Targeted deletion of Sox10 by Wnt1-cre defects neuronal migration and projection in the mouse inner ear.

    Directory of Open Access Journals (Sweden)

    YanYan Mao

    Full Text Available Sensory nerves of the brainstem are mostly composed of placode-derived neurons, neural crest-derived neurons and neural crest-derived Schwann cells. This mixed origin of cells has made it difficult to dissect interdependence for fiber guidance. Inner ear-derived neurons are known to connect to the brain after delayed loss of Schwann cells in ErbB2 mutants. However, the ErbB2 mutant related alterations in the ear and the brain compound interpretation of the data. We present here a new model to evaluate exclusively the effect of Schwann cell loss on inner ear innervation. Conditional deletion of the neural crest specific transcription factor, Sox10, using the rhombic lip/neural crest specific Wnt1-cre driver spares Sox10 expression in the ear. We confirm that neural crest-derived cells provide a stop signal for migrating spiral ganglion neurons. In the absence of Schwann cells, spiral ganglion neurons migrate into the center of the cochlea and even out of the ear toward the brain. Spiral ganglion neuron afferent processes reach the organ of Corti, but many afferent fibers bypass the organ of Corti to enter the lateral wall of the cochlea. In contrast to this peripheral disorganization, the central projection to cochlear nuclei is normal. Compared to ErbB2 mutants, conditional Sox10 mutants have limited cell death in spiral ganglion neurons, indicating that the absence of Schwann cells alone contributes little to the embryonic survival of neurons. These data suggest that neural crest-derived cells are dispensable for all central and some peripheral targeting of inner ear neurons. However, Schwann cells provide a stop signal for migratory spiral ganglion neurons and facilitate proper targeting of the organ of Corti by spiral ganglion afferents.

  11. Targeted Deletion of Sox10 by Wnt1-cre Defects Neuronal Migration and Projection in the Mouse Inner Ear

    Science.gov (United States)

    Mao, YanYan; Reiprich, Simone; Wegner, Michael; Fritzsch, Bernd

    2014-01-01

    Sensory nerves of the brainstem are mostly composed of placode-derived neurons, neural crest-derived neurons and neural crest-derived Schwann cells. This mixed origin of cells has made it difficult to dissect interdependence for fiber guidance. Inner ear-derived neurons are known to connect to the brain after delayed loss of Schwann cells in ErbB2 mutants. However, the ErbB2 mutant related alterations in the ear and the brain compound interpretation of the data. We present here a new model to evaluate exclusively the effect of Schwann cell loss on inner ear innervation. Conditional deletion of the neural crest specific transcription factor, Sox10, using the rhombic lip/neural crest specific Wnt1-cre driver spares Sox10 expression in the ear. We confirm that neural crest-derived cells provide a stop signal for migrating spiral ganglion neurons. In the absence of Schwann cells, spiral ganglion neurons migrate into the center of the cochlea and even out of the ear toward the brain. Spiral ganglion neuron afferent processes reach the organ of Corti, but many afferent fibers bypass the organ of Corti to enter the lateral wall of the cochlea. In contrast to this peripheral disorganization, the central projection to cochlear nuclei is normal. Compared to ErbB2 mutants, conditional Sox10 mutants have limited cell death in spiral ganglion neurons, indicating that the absence of Schwann cells alone contributes little to the embryonic survival of neurons. These data suggest that neural crest-derived cells are dispensable for all central and some peripheral targeting of inner ear neurons. However, Schwann cells provide a stop signal for migratory spiral ganglion neurons and facilitate proper targeting of the organ of Corti by spiral ganglion afferents. PMID:24718611

  12. Plateau-generating neurones in the dorsal horn in an in vitro preparation of the turtle spinal cord

    DEFF Research Database (Denmark)

    Russo, R E; Hounsgaard, J

    1996-01-01

    1. In transverse slices of the spinal cord of the turtle, intracellular recordings were used to characterize and analyse the responses to injected current and activation of primary afferents in dorsal horn neurones. 2. A subpopulation of neurones, with cell bodies located laterally in the deep...

  13. Burst-generating neurones in the dorsal horn in an in vitro preparation of the turtle spinal cord

    DEFF Research Database (Denmark)

    Russo, R E; Hounsgaard, J

    1996-01-01

    1. In transverse slices of the spinal cord of the turtle, intracellular recordings were used to characterize and analyse the responses to injected current and activation of primary afferents in dorsal horn neurones. 2. A subpopulation of neurones, with cell bodies located centrally in the dorsal...

  14. Synaptic potentiation onto habenula neurons in learned helplessness model of depression

    Science.gov (United States)

    Li, Bo; Piriz, Joaquin; Mirrione, Martine; Chung, ChiHye; Proulx, Christophe D.; Schulz, Daniela; Henn, Fritz; Malinow, Roberto

    2010-01-01

    The cellular basis of depressive disorders is poorly understood1. Recent studies in monkeys indicate that neurons in the lateral habenula (LHb), a nucleus that mediates communication between forebrain and midbrain structures, can increase their activity when an animal fails to receive an expected positive reward or receives a stimulus that predicts aversive conditions (i.e. disappointment or anticipation of a negative outcome)2, 3, 4. LHb neurons project to and modulate dopamine-rich regions such as the ventral-tegmental area (VTA)2, 5 that control reward-seeking behavior6 and participate in depressive disorders7. Here we show in two learned helplessness models of depression that excitatory synapses onto LHb neurons projecting to the VTA are potentiated. Synaptic potentiation correlates with an animal’s helplessness behavior and is due to an enhanced presynaptic release probability. Depleting transmitter release by repeated electrical stimulation of LHb afferents, using a protocol that can be effective on depressed patients8, 9, dramatically suppresses synaptic drive onto VTA-projecting LHb neurons in brain slices and can significantly reduce learned helplessness behavior in rats. Our results indicate that increased presynaptic action onto LHb neurons contributes to the rodent learned helplessness model of depression. PMID:21350486

  15. Histological identification of phrenic afferent projections to the spinal cord.

    Science.gov (United States)

    Nair, Jayakrishnan; Bezdudnaya, Tatiana; Zholudeva, Lyandysha V; Detloff, Megan R; Reier, Paul J; Lane, Michael A; Fuller, David D

    2017-02-01

    Limited data are available regarding the spinal projections of afferent fibers in the phrenic nerve. We describe a method that robustly labels phrenic afferent spinal projections in adult rats. The proximal end of the cut phrenic nerve was secured in a microtube filled with a transganglionic tracer (cholera toxin β-subunit, CT-β, or Cascade Blue) and tissues harvested 96-h later. Robust CT-β labeling occurred in C3-C5 dorsal root ganglia cell bodies and phrenic afferent projections were identified in the mid-cervical dorsal horn (laminae I-III), intermediate grey matter (laminae IV, VII) and near the central canal (laminae X). Afferent fiber labeling was reduced or absent when CT-β was delivered to the intrapleural space or directly to the hemidiaphragm. Soaking the phrenic nerve with Cascade Blue also produced robust labeling of mid-cervical dorsal root ganglia cells bodies, and primary afferent fibers were observed in spinal grey matter and dorsal white matter. Our results show that the 'nerve soak' method effectively labels both phrenic motoneurons and phrenic afferent projections, and show that primary afferents project throughout the ipsilateral mid-cervical gray matter. Copyright © 2016. Published by Elsevier B.V.

  16. A combined Bodian-Nissl stain for improved network analysis in neuronal cell culture.

    Science.gov (United States)

    Hightower, M; Gross, G W

    1985-11-01

    Bodian and Nissl procedures were combined to stain dissociated mouse spinal cord cells cultured on coverslips. The Bodian technique stains fine neuronal processes in great detail as well as an intracellular fibrillar network concentrated around the nucleus and in proximal neurites. The Nissl stain clearly delimits neuronal cytoplasm in somata and in large dendrites. A combination of these techniques allows the simultaneous depiction of neuronal perikarya and all afferent and efferent processes. Costaining with little background staining by either procedure suggests high specificity for neurons. This procedure could be exploited for routine network analysis of cultured neurons.

  17. Cardinal features of involuntary force variability can arise from the closed-loop control of viscoelastic afferented muscles

    Science.gov (United States)

    Laine, Christopher M.; Valero-Cuevas, Francisco J.

    2018-01-01

    Involuntary force variability below 15 Hz arises from, and is influenced by, many factors including descending neural drive, proprioceptive feedback, and mechanical properties of muscles and tendons. However, their potential interactions that give rise to the well-structured spectrum of involuntary force variability are not well understood due to a lack of experimental techniques. Here, we investigated the generation, modulation, and interactions among different sources of force variability using a physiologically-grounded closed-loop simulation of an afferented muscle model. The closed-loop simulation included a musculotendon model, muscle spindle, Golgi tendon organ (GTO), and a tracking controller which enabled target-guided force tracking. We demonstrate that closed-loop control of an afferented musculotendon suffices to replicate and explain surprisingly many cardinal features of involuntary force variability. Specifically, we present 1) a potential origin of low-frequency force variability associated with co-modulation of motor unit firing rates (i.e.,‘common drive’), 2) an in-depth characterization of how proprioceptive feedback pathways suffice to generate 5-12 Hz physiological tremor, and 3) evidence that modulation of those feedback pathways (i.e., presynaptic inhibition of Ia and Ib afferents, and spindle sensitivity via fusimotor drive) influence the full spectrum of force variability. These results highlight the previously underestimated importance of closed-loop neuromechanical interactions in explaining involuntary force variability during voluntary ‘isometric’ force control. Furthermore, these results provide the basis for a unifying theory that relates spinal circuitry to various manifestations of altered involuntary force variability in fatigue, aging and neurological disease. PMID:29309405

  18. Cardinal features of involuntary force variability can arise from the closed-loop control of viscoelastic afferented muscles.

    Science.gov (United States)

    Nagamori, Akira; Laine, Christopher M; Valero-Cuevas, Francisco J

    2018-01-01

    Involuntary force variability below 15 Hz arises from, and is influenced by, many factors including descending neural drive, proprioceptive feedback, and mechanical properties of muscles and tendons. However, their potential interactions that give rise to the well-structured spectrum of involuntary force variability are not well understood due to a lack of experimental techniques. Here, we investigated the generation, modulation, and interactions among different sources of force variability using a physiologically-grounded closed-loop simulation of an afferented muscle model. The closed-loop simulation included a musculotendon model, muscle spindle, Golgi tendon organ (GTO), and a tracking controller which enabled target-guided force tracking. We demonstrate that closed-loop control of an afferented musculotendon suffices to replicate and explain surprisingly many cardinal features of involuntary force variability. Specifically, we present 1) a potential origin of low-frequency force variability associated with co-modulation of motor unit firing rates (i.e.,'common drive'), 2) an in-depth characterization of how proprioceptive feedback pathways suffice to generate 5-12 Hz physiological tremor, and 3) evidence that modulation of those feedback pathways (i.e., presynaptic inhibition of Ia and Ib afferents, and spindle sensitivity via fusimotor drive) influence the full spectrum of force variability. These results highlight the previously underestimated importance of closed-loop neuromechanical interactions in explaining involuntary force variability during voluntary 'isometric' force control. Furthermore, these results provide the basis for a unifying theory that relates spinal circuitry to various manifestations of altered involuntary force variability in fatigue, aging and neurological disease.

  19. A new function for ATP: activating cardiac sympathetic afferents during myocardial ischemia.

    Science.gov (United States)

    Fu, Liang-Wu; Longhurst, John C

    2010-12-01

    Myocardial ischemia activates cardiac sympathetic afferents leading to chest pain and reflex cardiovascular responses. Brief myocardial ischemia leads to ATP release in the interstitial space. Furthermore, exogenous ATP and α,β-methylene ATP (α,β-meATP), a P2X receptor agonist, stimulate cutaneous group III and IV sensory nerve fibers. The present study tested the hypothesis that endogenous ATP excites cardiac afferents during ischemia through activation of P2 receptors. Nerve activity of single unit cardiac sympathetic afferents was recorded from the left sympathetic chain or rami communicates (T(2)-T(5)) in anesthetized cats. Single fields of 45 afferents (conduction velocities = 0.25-4.92 m/s) were identified in the left ventricle with a stimulating electrode. Five minutes of myocardial ischemia stimulated 39 of 45 cardiac afferents (8 Aδ, 37 C fibers). Epicardial application of ATP (1-4 μmol) stimulated six ischemically sensitive cardiac afferents in a dose-dependent manner. Additionally, epicardial ATP (2 μmol), ADP (2 μmol), a P2Y agonist, and α,β-meATP (0.5 μmol) significantly activated eight other ischemically sensitive afferents. Third, pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid, a P2 receptor antagonist, abolished the responses of six afferents to epicardial ATP (2 μmol) and attenuated the ischemia-related increase in activity of seven other afferents by 37%. In the absence of P2 receptor blockade, cardiac afferents responded consistently to repeated application of ATP (n = 6) and to recurrent myocardial ischemia (n = 6). Finally, six ischemia-insensitive cardiac spinal afferents did not respond to epicardial ATP (2-4 μmol), although these afferents did respond to epicardial bradykinin. Taken together, these data indicate that, during ischemia, endogenously released ATP activates ischemia-sensitive, but not ischemia-insensitive, cardiac spinal afferents through stimulation of P2 receptors likely located on the cardiac sensory

  20. Afferent control of central pattern generators: experimental analysis of scratching in the decerebrate cat.

    Science.gov (United States)

    Baev, K V; Esipenko, V B; Shimansky, Y P

    1991-01-01

    Systematic quantitative analysis of changes in the spinal scratching generator motor activity evoked by tonic and phasic peripheral afferent signals during "fictitious" scratching was carried out in the cat. Correlations between the kinematics of hindlimb scratching movement, sensory inflow, and primary afferent depolarization were investigated. Reliable correlations between the parameters of generator motor activity during fictitious scratching were revealed: they depended on tonic peripheral afferent inflow. The functional role of these dependencies consists of providing stability for aiming the hindlimb to the itch site. It was shown that scratching generator reaction to a phasic sensory signal depended significantly on afferent input, signal intensity, and its arrival phase in the cycle of motor activity. Phase correction of "scratching" rhythm was performed by inhibition of the current stage of "scratching" cycle, the inhibition magnitude depending on the intensity of a sensory signal run along high threshold afferent fibers. The moments in the scratching cycle, in which the afferent signal caused no rearrangement in scratching generator activity, were discovered for all investigated afferent inputs. These moments corresponded to the transitions from one scratching cycle phase to another. Integral afferent activity was distributed unevenly in the cycle during real scratching. The main part of it was observed just in that scratching cycle part which included the above mentioned no rearrangement phase points. The data obtained allowed us to conclude that the scratching generator should be considered as a working program for the motor optimal control system containing the intrinsic model of the controlled object dynamics (e.g. hindlimb scratching movement dynamics), which produces an inner analog of peripheral flow. This inner flow interacts with peripheral afferent inflow just as one of the latter components. Centrally originated modulation of primary afferent

  1. CRF1 receptor activation increases the response of neurons in the basolateral nucleus of the amygdala to afferent stimulation

    Directory of Open Access Journals (Sweden)

    2008-07-01

    Full Text Available The basolateral nucleus (BLA of the amygdala contributes to the consolidation of memories for emotional or stressful events. The nucleus contains a high density of CRF1 receptors that are activated by corticotropin-releasing factor (CRF. Modulation of the excitability of neurons in the BLA by CRF may regulate the immediate response to stressful events and the formation of associated memories. In the present study, CRF was found to increase the amplitude of field potentials recorded in the BLA following excitatory afferent stimulation, in vitro. The increase was mediated by CRF1 receptors, since it could be blocked by the selective, non-peptide antagonists, NBI30775 and NBI35583, but not by the CRF2-selective antagonist, astressin 2B. Furthermore, the CRF2-selective agonist, urocortin II had no effect on field potential amplitude. The increase induced by CRF was long-lasting, could not be reversed by subsequent administration of NBI35583, and required the activation of protein kinase C. This effect of CRF in the BLA may be important for increasing the salience of aversive stimuli under stressful conditions, and for enhancing the consolidation of associated memories. The results provide further justification for studying the efficacy of selective antagonists of the CRF1 receptor to reduce memory formation linked to emotional or traumatic events, and suggest that these compounds might be useful as prophylactic treatment for stress-related illness such as post-traumatic stress disorder.

  2. Hebbian learning and predictive mirror neurons for actions, sensations and emotions

    OpenAIRE

    Keysers, C.; Gazzola, Valeria

    2014-01-01

    Spike-timing-dependent plasticity is considered the neurophysiological basis of Hebbian learning and has been shown to be sensitive to both contingency and contiguity between pre- and postsynaptic activity. Here, we will examine how applying this Hebbian learning rule to a system of interconnected neurons in the presence of direct or indirect re-afference (e.g. seeing/hearing one's own actions) predicts the emergence of mirror neurons with predictive properties. In this framework, we analyse ...

  3. AgRP Neurons Can Increase Food Intake during Conditions of Appetite Suppression and Inhibit Anorexigenic Parabrachial Neurons.

    Science.gov (United States)

    Essner, Rachel A; Smith, Alison G; Jamnik, Adam A; Ryba, Anna R; Trutner, Zoe D; Carter, Matthew E

    2017-09-06

    To maintain energy homeostasis, orexigenic (appetite-inducing) and anorexigenic (appetite suppressing) brain systems functionally interact to regulate food intake. Within the hypothalamus, neurons that express agouti-related protein (AgRP) sense orexigenic factors and orchestrate an increase in food-seeking behavior. In contrast, calcitonin gene-related peptide (CGRP)-expressing neurons in the parabrachial nucleus (PBN) suppress feeding. PBN CGRP neurons become active in response to anorexigenic hormones released following a meal, including amylin, secreted by the pancreas, and cholecystokinin (CCK), secreted by the small intestine. Additionally, exogenous compounds, such as lithium chloride (LiCl), a salt that creates gastric discomfort, and lipopolysaccharide (LPS), a bacterial cell wall component that induces inflammation, exert appetite-suppressing effects and activate PBN CGRP neurons. The effects of increasing the homeostatic drive to eat on feeding behavior during appetite suppressing conditions are unknown. Here, we show in mice that food deprivation or optogenetic activation of AgRP neurons induces feeding to overcome the appetite suppressing effects of amylin, CCK, and LiCl, but not LPS. AgRP neuron photostimulation can also increase feeding during chemogenetic-mediated stimulation of PBN CGRP neurons. AgRP neuron stimulation reduces Fos expression in PBN CGRP neurons across all conditions. Finally, stimulation of projections from AgRP neurons to the PBN increases feeding following administration of amylin, CCK, and LiCl, but not LPS. These results demonstrate that AgRP neurons are sufficient to increase feeding during noninflammatory-based appetite suppression and to decrease activity in anorexigenic PBN CGRP neurons, thereby increasing food intake during homeostatic need. SIGNIFICANCE STATEMENT The motivation to eat depends on the relative balance of activity in distinct brain regions that induce or suppress appetite. An abnormal amount of activity in

  4. Targeted deletion of neurokinin-1 receptor expressing nucleus tractus solitarii neurons precludes somatosensory depression of arterial baroreceptor-heart rate reflex.

    Science.gov (United States)

    Potts, J T; Fong, A Y; Anguelov, P I; Lee, S; McGovern, D; Grias, I

    2007-03-30

    Neurokinin-1 receptor (NK1-R) expressing neurons are densely distributed throughout the nucleus tractus solitarii (NTS). However, their fundamental role in arterial baroreflex function remains debated. Previously, our group has shown that activation of contraction-sensitive somatic afferents evoke substance P (SP) release in the NTS and resets the arterial baroreflex via activation of a GABAergic NTS circuit. Based on these findings, we hypothesized that modulation of arterial baroreflex function by somatic afferents is mediated by NK1-R dependent inhibition of barosensitive NTS circuits. In the present study, SP-conjugated saporin toxin (SP-SAP) was used to ablate NK1-R expressing NTS neurons. Contraction-sensitive somatic afferents were activated by electrically-evoked muscle contraction and the arterial baroreceptor-heart rate reflex was assessed by constructing reflex curves using a decerebrate, arterially-perfused preparation. Baseline baroreflex sensitivity was significantly attenuated in SP-SAP-treated rats compared with control rats receiving either unconjugated SAP or vehicle. Muscle contraction significantly attenuated baroslope in SAP and vehicle-treated animals and shifted the baroreflex curves to higher systemic pressure. In contrast, somatic afferent stimulation failed to alter baroslope or shift the baroreflex curves in SP-SAP-treated animals. Moreover, when reflex sensitivity was partially restored in SP-SAP animals, somatic stimulation failed to attenuate baroreflex bradycardia. In contrast, SP-SAP and somatic stimulation failed to blunt the reflex bradycardia evoked by the peripheral chemoreflex. Immunohistochemistry revealed that pretreatment with SP-SAP significantly reduced the number of NK1-R expressing neurons in the caudal NTS, while sparing NK1-R expressing neurons rostral to the injection site. This was accompanied by a significant reduction in the number of glutamic acid decarboxylase (GAD67) expressing neurons at equivalent levels of the

  5. Differential distribution of voltage-gated channels in myelinated and unmyelinated baroreceptor afferents.

    Science.gov (United States)

    Schild, John H; Kunze, Diana L

    2012-12-24

    hallmark of myelinated baroreceptors. Interestingly, HCN2 and HCN4 expression levels are comparable in both fiber types. Collectively, such apportion of VGC constrains the neural coding of myelinated A-type baroreceptors to low threshold, high frequency, high fidelity discharge but with a limited capacity for neuromodulation of afferent bandwidth. Unmyelinated C-type baroreceptors require greater depolarizing forces for spike initiation and have a low frequency discharge profile that is often poorly correlated with the physiological stimulus. But the complement of VGC in C-type neurons provides far greater capacity for neuromodulation of cell excitability than can be obtained from A-type baroreceptors. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Calyx and dimorphic neurons of mouse Scarpa's ganglion express histamine H3 receptors

    Directory of Open Access Journals (Sweden)

    Zucca Gianpiero

    2009-06-01

    Full Text Available Abstract Background Histamine-related drugs are commonly used in the treatment of vertigo and related vestibular disorders. The site of action of these drugs however has not been elucidated yet. Recent works on amphibians showed that histamine H3 receptor antagonists, e.g. betahistine, inhibit the afferent discharge recorded from the vestibular nerve. To assess the expression of H3 histamine receptors in vestibular neurons, we performed mRNA RT-PCR and immunofluorescence experiments in mouse Scarpa's ganglia. Results RT-PCR analysis showed the presence of H3 receptor mRNA in mouse ganglia tissue. H3 protein expression was found in vestibular neurons characterized by large and roundish soma, which labeled for calretinin and calbindin. Conclusion The present results are consistent with calyx and dimorphic, but not bouton, afferent vestibular neurons expressing H3 receptors. This study provides a molecular substrate for the effects of histamine-related antivertigo drugs acting on (or binding to H3 receptors, and suggest a potential target for the treatment of vestibular disorders of peripheral origin.

  7. Calyx and dimorphic neurons of mouse Scarpa's ganglion express histamine H3 receptors.

    Science.gov (United States)

    Tritto, Simona; Botta, Laura; Zampini, Valeria; Zucca, Gianpiero; Valli, Paolo; Masetto, Sergio

    2009-06-29

    Histamine-related drugs are commonly used in the treatment of vertigo and related vestibular disorders. The site of action of these drugs however has not been elucidated yet. Recent works on amphibians showed that histamine H3 receptor antagonists, e.g. betahistine, inhibit the afferent discharge recorded from the vestibular nerve. To assess the expression of H3 histamine receptors in vestibular neurons, we performed mRNA RT-PCR and immunofluorescence experiments in mouse Scarpa's ganglia. RT-PCR analysis showed the presence of H3 receptor mRNA in mouse ganglia tissue. H3 protein expression was found in vestibular neurons characterized by large and roundish soma, which labeled for calretinin and calbindin. The present results are consistent with calyx and dimorphic, but not bouton, afferent vestibular neurons expressing H3 receptors. This study provides a molecular substrate for the effects of histamine-related antivertigo drugs acting on (or binding to) H3 receptors, and suggest a potential target for the treatment of vestibular disorders of peripheral origin.

  8. Interactions between entorhinal axons and target hippocampal neurons: a role for glutamate in the development of hippocampal circuitry.

    Science.gov (United States)

    Mattson, M P; Lee, R E; Adams, M E; Guthrie, P B; Kater, S B

    1988-11-01

    A coculture system consisting of input axons from entorhinal cortex explants and target hippocampal pyramidal neurons was used to demonstrate that glutamate, released spontaneously from afferent axons, can influence both dendritic geometry of target neurons and formation of presumptive synaptic sites. Dendritic outgrowth was reduced in hippocampal neurons growing on entorhinal axons when compared with neurons growing off the axons. Presumptive presynaptic sites were observed in association with hippocampal neuron dendrites and somas. HPLC analysis showed that glutamate was released from the explants in an activity- and Ca2(+)-dependent manner. The general glutamate receptor antagonist D-glutamylglycine significantly increased dendritic outgrowth in pyramidal neurons associated with entorhinal axons and reduced presumptive presynaptic sites. Tetrodotoxin and reduction of extracellular Ca2+ also promoted dendritic outgrowth and reduced the formation of presumptive synaptic sites. The results suggest that the neurotransmitter glutamate may play important roles in the development of hippocampal circuitry.

  9. Modulation of the masseteric reflex by gastric vagal afferents.

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    Pettorossi, V E

    1983-04-01

    Several investigations have shown that the vagal nerve can affect the reflex responses of the masticatory muscles acting at level either of trigeminal motoneurons or of the mesencephalic trigeminal nucleus (MTN). The present experiments have been devoted to establish the origin of the vagal afferent fibres involved in modulating the masseteric reflex. In particular, the gastric vagal afferents were taken into consideration and selective stimulations of such fibres were performed in rabbit. Conditioning electrical stimulation of truncus vagalis ventralis (TVV) reduced the excitability of the MTN cells as shown by a decrease of the antidromic response recorded from the semilunar ganglion and elicited by MTN single-shock electrical stimulation. Sympathetic and cardiovascular influences were not involved in these responses. Mechanical stimulation of gastric receptors, by means of gastric distension, clearly diminished the amplitude of twitch tension of masseteric reflex and inhibited the discharge frequency of proprioceptive MTN units. The effect was phasic and depended upon the velocity of distension. Thus the sensory volleys originating from rapid adapting receptors reach the brain stem through vagal afferents and by means of a polysynaptic connection inhibits the masseteric reflex at level of MTN cells.

  10. Naftidrofuryl affects neurite regeneration by injured adult auditory neurons.

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    Lefebvre, P P; Staecker, H; Moonen, G; van de Water, T R

    1993-07-01

    Afferent auditory neurons are essential for the transmission of auditory information from Corti's organ to the central auditory pathway. Auditory neurons are very sensitive to acute insult and have a limited ability to regenerate injured neuronal processes. Therefore, these neurons appear to be a limiting factor in restoration of hearing function following an injury to the peripheral auditory receptor. In a previous study nerve growth factor (NGF) was shown to stimulate neurite repair but not survival of injured auditory neurons. In this study, we have demonstrated a neuritogenesis promoting effect of naftidrofuryl in an vitro model for injury to adult auditory neurons, i.e. dissociated cell cultures of adult rat spiral ganglia. Conversely, naftidrofuryl did not have any demonstrable survival promoting effect on these in vitro preparations of injured auditory neurons. The potential uses of this drug as a therapeutic agent in acute diseases of the inner ear are discussed in the light of these observations.

  11. Subpopulations of somatostatin-immunoreactive nonpyramidal neurons in the amygdala and adjacent external capsule project to the basal forebrain: evidence for the existence of GABAergic projection neurons in the cortical nuclei and basolateral nuclear complex

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    Alexander J. McDonald

    2012-07-01

    Full Text Available The hippocampus and amygdala are key structures of the limbic system whose connections include reciprocal interactions with the basal forebrain (BF. The hippocampus receives both cholinergic and GABAergic afferents from the medial septal area of the BF. Hippocampal projections back to the medial septal area arise from nonpyramidal GABAergic neurons that express somatostatin (SOM, calbindin (CB, and neuropeptide Y (NPY. Recent experiments in our lab have demonstrated that the basolateral amygdala, like the hippocampus, receives both cholinergic and GABAergic afferents from the BF. These projections arise from neurons in the substantia innominata and ventral pallidum. It remained to be determined, however, whether the amygdala has projections back to the BF that arise from GABAergic nonpyramidal neurons. This question was investigated in the present study by combining Fluorogold (FG retrograde tract tracing with immunohistochemistry for GABAergic nonpyramidal cell markers, including SOM, CB, NPY, parvalbumin, calretinin, and glutamic acid decarboxylase (GAD. FG injections into the basal forebrain produced a diffuse array of retrogradely labeled neurons in many nuclei of the amygdala. The great majority of amygdalar FG+ neurons did not express nonpyramidal cell markers. However, a subpopulation of nonpyramidal SOM+ neurons, termed long range nonpyramidal neurons (LRNP neurons, in the external capsule, basolateral amygdala, and cortical and medial amygdalar nuclei were FG+. About one-third of the SOM+ LRNP neurons were CB+ or NPY+, and one-half were GAD+. It remains to be determined if these inhibitory amygdalar projections to the BF, like those from the hippocampus, are important for regulating synchronous oscillations in the amygdalar-BF network.

  12. Retrograde axoplasmic flow of serotonin in central mono-aminergic neurons

    International Nuclear Information System (INIS)

    Leger, Lucienne; Pujol, J.-F.; Bobillier, Pierre; Jouvet, Michel

    1977-01-01

    Following an injection of 3 H-5 HT in the neostriatum of the Rat, the tracer is transported by axoplasmic retrograde flow to the cell groups containing mono-aminergic neurons which are known or thought to have afferences to this structure: substantia nigra, dopaminergic group A8 and n. raphe dorsalis [fr

  13. Selective plasticity of primary afferent innervation to the dorsal horn and autonomic nuclei following lumbosacral ventral root avulsion and reimplantation in long term studies.

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    Wu, Lisa; Wu, Jun; Chang, Huiyi H; Havton, Leif A

    2012-02-01

    Previous studies involving injuries to the nerves of the cauda equina and the conus medullaris have shown that lumbosacral ventral root avulsion in rat models results in denervation and dysfunction of the lower urinary tract, retrograde and progressive cell death of the axotomized motor and parasympathetic neurons, as well as the emergence of neuropathic pain. Root reimplantation has also been shown to ameliorate several of these responses, but experiments thus far have been limited to studying the effects of lesion and reimplantation local to the lumbosacral region. Here, we have expanded the region of investigation after lumbosacral ventral root avulsion and reimplantation to include the thoracolumbar sympathetic region of the spinal cord. Using a retrograde tracer injected into the major pelvic ganglion, we were able to define the levels of the spinal cord that contain sympathetic preganglionic neurons innervating the lower urinary tract. We have conducted studies on the effects of the lumbosacral ventral root avulsion and reimplantation models on the afferent innervation of the dorsal horn and autonomic nuclei at both thoracolumbar and lumbosacral levels through immunohistochemistry for the markers calcitonin gene-related peptide (CGRP) and vesicular glutamate transporter 1 (VGLUT1). Surprisingly, our experiments reveal a selective and significant decrease of CGRP-positive innervation in the dorsal horn at thoracolumbar levels that is partially restored with root reimplantation. However, no similar changes were detected at the lumbosacral levels despite the injury and repair targeting efferent neurons, and being performed at the lumbosacral levels. Despite the changes evident in the thoracolumbar dorsal horn, we find no changes in afferent innervation of the autonomic nuclei at either sympathetic or parasympathetic segmental levels by CGRP or VGLUT1. We conclude that even remote, efferent root injuries and repair procedures can have an effect on remote and non

  14. Wind-up of spinal cord neurones and pain sensation: much ado about something?

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    Herrero, J F; Laird, J M; López-García, J A

    2000-06-01

    Wind-up is a frequency-dependent increase in the excitability of spinal cord neurones, evoked by electrical stimulation of afferent C-fibres. Although it has been studied over the past thirty years, there are still uncertainties about its physiological meaning. Glutamate (NMDA) and tachykinin NK1 receptors are required to generate wind-up and therefore a positive modulation between these two receptor types has been suggested by some authors. However, most drugs capable of reducing the excitability of spinal cord neurones, including opioids and NSAIDs, can also reduce or even abolish wind-up. Thus, other theories involving synaptic efficacy, potassium channels, calcium channels, etc. have also been proposed for the generation of this phenomenon. Whatever the mechanisms involved in its generation, wind-up has been interpreted as a system for the amplification in the spinal cord of the nociceptive message that arrives from peripheral nociceptors connected to C-fibres. This probably reflects the physiological system activated in the spinal cord after an intense or persistent barrage of afferent nociceptive impulses. On the other hand, wind-up, central sensitisation and hyperalgesia are not the same phenomena, although they may share common properties. Wind-up can be an important tool to study the processing of nociceptive information in the spinal cord, and the central effects of drugs that modulate the nociceptive system. This paper reviews the physiological and pharmacological data on wind-up of spinal cord neurones, and the perceptual correlates of wind-up in human subjects, in the context of its possible relation to the triggering of hyperalgesic states, and also the multiple factors which contribute to the generation of wind-up.

  15. Acute cholangitis due to afferent loop syndrome after a Whipple procedure: a case report.

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    Spiliotis, John; Karnabatidis, Demetrios; Vaxevanidou, Archodoula; Datsis, Anastasios C; Rogdakis, Athanasios; Zacharis, Georgios; Siamblis, Demetrios

    2009-08-25

    Patients with resection of stomach and especially with Billroth II reconstruction (gastro jejunal anastomosis), are more likely to develop afferent loop syndrome which is a rare complication. When the afferent part is obstructed, biliary and pancreatic secretions accumulate and cause the distention of this part. In the case of a complete obstruction (rare), there is a high risk developing necrosis and perforation. This complication has been reported once in the literature. A 54-year-old Greek male had undergone a pancreato-duodenectomy (Whipple procedure) one year earlier due to a pancreatic adenocarcinoma. Approximately 10 months after the initial operation, the patient started having episodes of cholangitis (fever, jaundice) and abdominal pain. This condition progressively worsened and the suspicion of local recurrence or stenosis of the biliary-jejunal anastomosis was discussed. A few days before his admission the patient developed signs of septic cholangitis. Our case demonstrates a rare complication with serious clinical manifestation of the afferent loop syndrome. This advanced form of afferent loop syndrome led to the development of huge enterobiliary reflux, which had a serious clinical manifestation as cholangitis and systemic sepsis, due to bacterial overgrowth, which usually present in the afferent loop. The diagnosis is difficult and the interventional radiology gives all the details to support the therapeutic decision making. A variety of factors can contribute to its development including adhesions, kinking and angulation of the loop, stenosis of gastro-jejunal anastomosis and internal herniation. In order to decompress the afferent loop dilatation due to adhesions, a lateral-lateral jejunal anastomosis was performed between the afferent loop and a small bowel loop.

  16. Selective activation of primary afferent fibers evaluated by sine-wave electrical stimulation

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    Katafuchi Toshihiko

    2005-03-01

    Full Text Available Abstract Transcutaneous sine-wave stimuli at frequencies of 2000, 250 and 5 Hz (Neurometer are thought to selectively activate Aβ, Aδ and C afferent fibers, respectively. However, there are few reports to test the selectivity of these stimuli at the cellular level. In the present study, we analyzed action potentials (APs generated by sine-wave stimuli applied to the dorsal root in acutely isolated rat dorsal root ganglion (DRG preparations using intracellular recordings. We also measured excitatory synaptic responses evoked by transcutaneous stimuli in substantia gelatinosa (SG neurons of the spinal dorsal horn, which receive inputs predominantly from C and Aδ fibers, using in vivo patch-clamp recordings. In behavioral studies, escape or vocalization behavior of rats was observed with both 250 and 5 Hz stimuli at intensity of ~0.8 mA (T5/ T250, whereas with 2000 Hz stimulation, much higher intensity (2.14 mA, T2000 was required. In DRG neurons, APs were generated at T5/T250 by 2000 Hz stimulation in Aβ, by 250 Hz stimulation both in Aβ and Aδ, and by 5 Hz stimulation in all three classes of DRG neurons. However, the AP frequencies elicited in Aβ and Aδ by 5 Hz stimulation were much less than those reported previously in physiological condition. With in vivo experiments large amplitude of EPSCs in SG neurons were elicited by 250 and 5 Hz stimuli at T5/ T250. These results suggest that 2000 Hz stimulation excites selectively Aβ fibers and 5 Hz stimulation activates noxious transmission mediated mainly through C fibers. Although 250 Hz stimulation activates both Aδ and Aβ fibers, tactile sensation would not be perceived when painful sensation is produced at the same time. Therefore, 250 Hz was effective stimulus frequency for activation of Aδ fibers initiating noxious sensation. Thus, the transcutaneous sine-wave stimulation can be applied to evaluate functional changes of sensory transmission by comparing thresholds with the three

  17. Afferent connections of nervus facialis and nervus glossopharyngeus in the pigeon (Columba livia) and their role in feeding behavior.

    Science.gov (United States)

    Dubbeldam, J L

    1984-01-01

    The afferent connections of the facial nerve and glossopharyngeal nerve in the pigeon have been studied with the Fink-Heimer I method after ganglion lesions. The nucleus ventrolateralis anterior of the solitary complex and an indistinct cell group S VII medial to the nucleus interpolaris of the descending trigeminal tract are the terminal fields for facial afferents. The n. ventrolateralis anterior also receives an important projection from the distal glossopharyngeal ganglion. Other projection areas of this ganglion are the n. presulcalis , n. centralis anterior, n. intermedius anterior and the parasolitary nucleus. Both ganglia have only ipsilateral projections. A lesion in the jugular ganglion complex causes degeneration throughout the ipsilateral solitary complex, in the contralateral n. commissuralis and n. centralis posterior and in the n. cuneatus externus. The lack of a substantial contribution to the trigeminal system is ascribed to the absence of mechanoreceptors in the tongue. The implications for the organization of neuronal pathways related to the feeding behavior are discussed.

  18. Force sensor in simulated skin and neural model mimic tactile SAI afferent spiking response to ramp and hold stimuli.

    Science.gov (United States)

    Kim, Elmer K; Wellnitz, Scott A; Bourdon, Sarah M; Lumpkin, Ellen A; Gerling, Gregory J

    2012-07-23

    The next generation of prosthetic limbs will restore sensory feedback to the nervous system by mimicking how skin mechanoreceptors, innervated by afferents, produce trains of action potentials in response to compressive stimuli. Prior work has addressed building sensors within skin substitutes for robotics, modeling skin mechanics and neural dynamics of mechanotransduction, and predicting response timing of action potentials for vibration. The effort here is unique because it accounts for skin elasticity by measuring force within simulated skin, utilizes few free model parameters for parsimony, and separates parameter fitting and model validation. Additionally, the ramp-and-hold, sustained stimuli used in this work capture the essential features of the everyday task of contacting and holding an object. This systems integration effort computationally replicates the neural firing behavior for a slowly adapting type I (SAI) afferent in its temporally varying response to both intensity and rate of indentation force by combining a physical force sensor, housed in a skin-like substrate, with a mathematical model of neuronal spiking, the leaky integrate-and-fire. Comparison experiments were then conducted using ramp-and-hold stimuli on both the spiking-sensor model and mouse SAI afferents. The model parameters were iteratively fit against recorded SAI interspike intervals (ISI) before validating the model to assess its performance. Model-predicted spike firing compares favorably with that observed for single SAI afferents. As indentation magnitude increases (1.2, 1.3, to 1.4 mm), mean ISI decreases from 98.81 ± 24.73, 54.52 ± 6.94, to 41.11 ± 6.11 ms. Moreover, as rate of ramp-up increases, ISI during ramp-up decreases from 21.85 ± 5.33, 19.98 ± 3.10, to 15.42 ± 2.41 ms. Considering first spikes, the predicted latencies exhibited a decreasing trend as stimulus rate increased, as is observed in afferent recordings. Finally, the SAI afferent's characteristic response

  19. The expression profile of acid-sensing ion channel (ASIC) subunits ASIC1a, ASIC1b, ASIC2a, ASIC2b, and ASIC3 in the esophageal vagal afferent nerve subtypes.

    Science.gov (United States)

    Dusenkova, Svetlana; Ru, Fei; Surdenikova, Lenka; Nassenstein, Christina; Hatok, Jozef; Dusenka, Robert; Banovcin, Peter; Kliment, Jan; Tatar, Milos; Kollarik, Marian

    2014-11-01

    Acid-sensing ion channels (ASICs) have been implicated in esophageal acid sensing and mechanotransduction. However, insufficient knowledge of ASIC subunit expression profile in esophageal afferent nerves hampers the understanding of their role. This knowledge is essential because ASIC subunits form heteromultimeric channels with distinct functional properties. We hypothesized that the esophageal putative nociceptive C-fiber nerves (transient receptor potential vanilloid 1, TRPV1-positive) express multiple ASIC subunits and that the ASIC expression profile differs between the nodose TRPV1-positive subtype developmentally derived from placodes and the jugular TRPV1-positive subtype derived from neural crest. We performed single cell RT-PCR on the vagal afferent neurons retrogradely labeled from the esophagus. In the guinea pig, nearly all (90%-95%) nodose and jugular esophageal TRPV1-positive neurons expressed ASICs, most often in a combination (65-75%). ASIC1, ASIC2, and ASIC3 were expressed in 65-75%, 55-70%, and 70%, respectively, of both nodose and jugular TRPV1-positive neurons. The ASIC1 splice variants ASIC1a and ASIC1b and the ASIC2 splice variant ASIC2b were similarly expressed in both nodose and jugular TRPV1-positive neurons. However, ASIC2a was found exclusively in the nodose neurons. In contrast to guinea pig, ASIC3 was almost absent from the mouse vagal esophageal TRPV1-positive neurons. However, ASIC3 was similarly expressed in the nonnociceptive TRPV1-negative (tension mechanoreceptors) neurons in both species. We conclude that the majority of esophageal vagal nociceptive neurons express multiple ASIC subunits. The placode-derived nodose neurons selectively express ASIC2a, known to substantially reduce acid sensitivity of ASIC heteromultimers. ASIC3 is expressed in the guinea pig but not in the mouse vagal esophageal TRPV1-positive neurons, indicating species differences in ASIC expression. Copyright © 2014 the American Physiological Society.

  20. How the self-coupled neuron can affect the chaotic synchronization of network

    International Nuclear Information System (INIS)

    Jia Chenhui; Wang Jiang; Deng, Bin

    2009-01-01

    We have calculated 34 kinds of three-cell neuron networks' minimum coupling strength, from the result; we find that a self-coupled neuron can have some effect on the synchronization of the network. The reason is the self-coupled neurons make the number of neurons looks 'decrease', and they decrease the coupling strength of the other neurons which are coupled with them.

  1. Three-dimensional distribution of sensory stimulation-evoked neuronal activity of spinal dorsal horn neurons analyzed by in vivo calcium imaging.

    Science.gov (United States)

    Nishida, Kazuhiko; Matsumura, Shinji; Taniguchi, Wataru; Uta, Daisuke; Furue, Hidemasa; Ito, Seiji

    2014-01-01

    The spinal dorsal horn comprises heterogeneous populations of interneurons and projection neurons, which form neuronal circuits crucial for processing of primary sensory information. Although electrophysiological analyses have uncovered sensory stimulation-evoked neuronal activity of various spinal dorsal horn neurons, monitoring these activities from large ensembles of neurons is needed to obtain a comprehensive view of the spinal dorsal horn circuitry. In the present study, we established in vivo calcium imaging of multiple spinal dorsal horn neurons by using a two-photon microscope and extracted three-dimensional neuronal activity maps of these neurons in response to cutaneous sensory stimulation. For calcium imaging, a fluorescence resonance energy transfer (FRET)-based calcium indicator protein, Yellow Cameleon, which is insensitive to motion artifacts of living animals was introduced into spinal dorsal horn neurons by in utero electroporation. In vivo calcium imaging following pinch, brush, and heat stimulation suggests that laminar distribution of sensory stimulation-evoked neuronal activity in the spinal dorsal horn largely corresponds to that of primary afferent inputs. In addition, cutaneous pinch stimulation elicited activities of neurons in the spinal cord at least until 2 spinal segments away from the central projection field of primary sensory neurons responsible for the stimulated skin point. These results provide a clue to understand neuronal processing of sensory information in the spinal dorsal horn.

  2. Three-dimensional distribution of sensory stimulation-evoked neuronal activity of spinal dorsal horn neurons analyzed by in vivo calcium imaging.

    Directory of Open Access Journals (Sweden)

    Kazuhiko Nishida

    Full Text Available The spinal dorsal horn comprises heterogeneous populations of interneurons and projection neurons, which form neuronal circuits crucial for processing of primary sensory information. Although electrophysiological analyses have uncovered sensory stimulation-evoked neuronal activity of various spinal dorsal horn neurons, monitoring these activities from large ensembles of neurons is needed to obtain a comprehensive view of the spinal dorsal horn circuitry. In the present study, we established in vivo calcium imaging of multiple spinal dorsal horn neurons by using a two-photon microscope and extracted three-dimensional neuronal activity maps of these neurons in response to cutaneous sensory stimulation. For calcium imaging, a fluorescence resonance energy transfer (FRET-based calcium indicator protein, Yellow Cameleon, which is insensitive to motion artifacts of living animals was introduced into spinal dorsal horn neurons by in utero electroporation. In vivo calcium imaging following pinch, brush, and heat stimulation suggests that laminar distribution of sensory stimulation-evoked neuronal activity in the spinal dorsal horn largely corresponds to that of primary afferent inputs. In addition, cutaneous pinch stimulation elicited activities of neurons in the spinal cord at least until 2 spinal segments away from the central projection field of primary sensory neurons responsible for the stimulated skin point. These results provide a clue to understand neuronal processing of sensory information in the spinal dorsal horn.

  3. Vagal stimulation targets select populations of intrinsic cardiac neurons to control neurally induced atrial fibrillation.

    Science.gov (United States)

    Salavatian, Siamak; Beaumont, Eric; Longpré, Jean-Philippe; Armour, J Andrew; Vinet, Alain; Jacquemet, Vincent; Shivkumar, Kalyanam; Ardell, Jeffrey L

    2016-11-01

    Mediastinal nerve stimulation (MNS) reproducibly evokes atrial fibrillation (AF) by excessive and heterogeneous activation of intrinsic cardiac (IC) neurons. This study evaluated whether preemptive vagus nerve stimulation (VNS) impacts MNS-induced evoked changes in IC neural network activity to thereby alter susceptibility to AF. IC neuronal activity in the right atrial ganglionated plexus was directly recorded in anesthetized canines (n = 8) using a linear microelectrode array concomitant with right atrial electrical activity in response to: 1) epicardial touch or great vessel occlusion vs. 2) stellate or vagal stimulation. From these stressors, post hoc analysis (based on the Skellam distribution) defined IC neurons so recorded as afferent, efferent, or convergent (afferent and efferent inputs) local circuit neurons (LCN). The capacity of right-sided MNS to modify IC activity in the induction of AF was determined before and after preemptive right (RCV)- vs. left (LCV)-sided VNS (15 Hz, 500 μs; 1.2× bradycardia threshold). Neuronal (n = 89) activity at baseline (0.11 ± 0.29 Hz) increased during MNS-induced AF (0.51 ± 1.30 Hz; P neuronal synchrony increased during neurally induced AF, a local neural network response mitigated by preemptive VNS. These antiarrhythmic effects persisted post-VNS for, on average, 26 min. In conclusion, VNS preferentially targets convergent LCNs and their interactive coherence to mitigate the potential for neurally induced AF. The antiarrhythmic properties imposed by VNS exhibit memory. Copyright © 2016 the American Physiological Society.

  4. The Molecular Fingerprint of Dorsal Root and Trigeminal Ganglion Neurons

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    Douglas M. Lopes

    2017-09-01

    Full Text Available The dorsal root ganglia (DRG and trigeminal ganglia (TG are clusters of cell bodies of highly specialized sensory neurons which are responsible for relaying information about our environment to the central nervous system. Despite previous efforts to characterize sensory neurons at the molecular level, it is still unknown whether those present in DRG and TG have distinct expression profiles and therefore a unique molecular fingerprint. To address this question, we isolated lumbar DRG and TG neurons using fluorescence-activated cell sorting from Advillin-GFP transgenic mice and performed RNA sequencing. Our transcriptome analyses showed that, despite being overwhelmingly similar, a number of genes are differentially expressed in DRG and TG neurons. Importantly, we identified 24 genes which were uniquely expressed in either ganglia, including an arginine vasopressin receptor and several homeobox genes, giving each population a distinct molecular fingerprint. We compared our findings with published studies to reveal that many genes previously reported to be present in neurons are in fact likely to originate from other cell types in the ganglia. Additionally, our neuron-specific results aligned well with a dataset examining whole human TG and DRG. We propose that the data can both improve our understanding of primary afferent biology and help contribute to the development of drug treatments and gene therapies which seek targets with unique or restricted expression patterns.

  5. Mechanism for propagation of rate signals through a 10-layer feedforward neuronal network

    International Nuclear Information System (INIS)

    Jie, Li; Wan-Qing, Yu; Ding, Xu; Feng, Liu; Wei, Wang

    2009-01-01

    Using numerical simulations, we explore the mechanism for propagation of rate signals through a 10-layer feedforward network composed of Hodgkin–Huxley (HH) neurons with sparse connectivity. When white noise is afferent to the input layer, neuronal firing becomes progressively more synchronous in successive layers and synchrony is well developed in deeper layers owing to the feedforward connections between neighboring layers. The synchrony ensures the successful propagation of rate signals through the network when the synaptic conductance is weak. As the synaptic time constant τ syn varies, coherence resonance is observed in the network activity due to the intrinsic property of HH neurons. This makes the output firing rate single-peaked as a function of τ syn , suggesting that the signal propagation can be modulated by the synaptic time constant. These results are consistent with experimental results and advance our understanding of how information is processed in feedforward networks. (cross-disciplinary physics and related areas of science and technology)

  6. Neurokinin-1 Receptor Immunoreactive Neuronal Elements in the Superficial Dorsal Horn of the Chicken Spinal Cord: With Special Reference to Their Relationship with the Tachykinin-containing Central Axon Terminals in Synaptic Glomeruli

    International Nuclear Information System (INIS)

    Sakamoto, Hiroshi; Kawate, Toyoko; Li, Yongnan; Atsumi, Saoko

    2009-01-01

    Synaptic glomeruli that involve tachykinin-containing primary afferent central terminals are numerous in lamina II of the chicken spinal cord. Therefore, a certain amount of noxious information is likely to be modulated in these structures in chickens. In this study, we used immunohistochemistry with confocal and electron microscopy to investigate whether neurokinin-1 receptor (NK-1R)-expressing neuronal elements are in contact with the central primary afferent terminals in synaptic glomeruli of the chicken spinal cord. We also investigated which neuronal elements (axon terminals, dendrites, cell bodies) and which neurons in the spinal cord possess NK-1R, and are possibly influenced by tachykinin in the glomeruli. By confocal microscopy, NK-1R immunoreactivities were seen in a variety of neuronal cell bodies, their dendrites and smaller fibers of unknown origin. Some of the NK-1R immunoreactive profiles also expressed GABA immunoreactivities. A close association was observed between the NK-1R-immunoreactive neurons and tachykinin-immunoreactive axonal varicosities. By electron microscopy, NK-1R immunoreactivity was seen in cell bodies, conventional dendrites and vesicle-containing dendrites in laminae I and II. Among these elements, dendrites and vesicle-containing dendrites made contact with tachykinin-containing central terminals in the synaptic glomeruli. These results indicate that tachykinin-containing central terminals in the chicken spinal cord can modulate second-order neuronal elements in the synaptic glomeruli

  7. High glucose increases action potential firing of catecholamine neurons in the nucleus of the solitary tract by increasing spontaneous glutamate inputs.

    Science.gov (United States)

    Roberts, Brandon L; Zhu, Mingyan; Zhao, Huan; Dillon, Crystal; Appleyard, Suzanne M

    2017-09-01

    Glucose is a crucial substrate essential for cell survival and function. Changes in glucose levels impact neuronal activity and glucose deprivation increases feeding. Several brain regions have been shown to respond to glucoprivation, including the nucleus of the solitary tract (NTS) in the brain stem. The NTS is the primary site in the brain that receives visceral afferent information from the gastrointestinal tract. The catecholaminergic (CA) subpopulation within the NTS modulates many homeostatic functions including cardiovascular reflexes, respiration, food intake, arousal, and stress. However, it is not known if they respond to changes in glucose. Here we determined whether NTS-CA neurons respond to changes in glucose concentration and the mechanism involved. We found that decreasing glucose concentrations from 5 mM to 2 mM to 1 mM, significantly decreased action potential firing in a cell-attached preparation, whereas increasing it back to 5 mM increased the firing rate. This effect was dependent on glutamate release from afferent terminals and required presynaptic 5-HT 3 Rs. Decreasing the glucose concentration also decreased both basal and 5-HT 3 R agonist-induced increase in the frequency of spontaneous glutamate inputs onto NTS-CA neurons. Low glucose also blunted 5-HT-induced inward currents in nodose ganglia neurons, which are the cell bodies of vagal afferents. The effect of low glucose in both nodose ganglia cells and in NTS slices was mimicked by the glucokinase inhibitor glucosamine. This study suggests that NTS-CA neurons are glucosensing through a presynaptic mechanism that is dependent on vagal glutamate release, 5-HT 3 R activity, and glucokinase. Copyright © 2017 the American Physiological Society.

  8. Formalin-induced behavioural hypersensitivity and neuronal hyperexcitability are mediated by rapid protein synthesis at the spinal level

    Science.gov (United States)

    Asante, Curtis O; Wallace, Victoria C; Dickenson, Anthony H

    2009-01-01

    Background The mammalian target of rapamycin (mTOR) is a key regulator of mRNA translation whose action can be inhibited by the drug rapamycin. Forms of long-term plasticity require protein synthesis and evidence indicates that mRNA in dendrites, axon terminals and cell bodies is essential for long-term synaptic plasticity. Specific to pain, shifts in pain thresholds and responsiveness are an expression of neuronal plasticity and this likely contributes to persistent pain. We investigated this by inhibiting the activity of mTOR with rapamycin at the spinal level, of rats that were subjected to the formalin test, using both behavioural and electrophysiological techniques. Results For in vivo electrophysiology, Sprague Dawley rats were fully anaesthetised and single-unit extracellular recordings were obtained from lamina V wide dynamic range (WDR) dorsal horn spinal neurones at the region where input is received from the hind paw. Neuronal responses from naive rats showed that rapamycin-sensitive pathways were important in nociceptive-specific C-fibre mediated transmission onto WDR neurones as well mechanically-evoked responses since rapamycin was effective in attenuating these measures. Formalin solution was injected into the hind paw prior to which, rapamycin or vehicle was applied directly onto the exposed spinal cord. When rapamycin was applied to the spinal cord prior to hind paw formalin injection, there was a significant attenuation of the prolonged second phase of the formalin test, which comprises continuing afferent input to the spinal cord, neuronal hyperexcitability and an activated descending facilitatory drive from the brainstem acting on spinal neurones. In accordance with electrophysiological data, behavioural studies showed that rapamycin attenuated behavioural hypersensitivity elicited by formalin injection into the hind paw. Conclusion We conclude that mTOR has a role in maintaining persistent pain states via mRNA translation and thus protein

  9. Formalin-induced behavioural hypersensitivity and neuronal hyperexcitability are mediated by rapid protein synthesis at the spinal level

    Directory of Open Access Journals (Sweden)

    Wallace Victoria C

    2009-06-01

    Full Text Available Abstract Background The mammalian target of rapamycin (mTOR is a key regulator of mRNA translation whose action can be inhibited by the drug rapamycin. Forms of long-term plasticity require protein synthesis and evidence indicates that mRNA in dendrites, axon terminals and cell bodies is essential for long-term synaptic plasticity. Specific to pain, shifts in pain thresholds and responsiveness are an expression of neuronal plasticity and this likely contributes to persistent pain. We investigated this by inhibiting the activity of mTOR with rapamycin at the spinal level, of rats that were subjected to the formalin test, using both behavioural and electrophysiological techniques. Results For in vivo electrophysiology, Sprague Dawley rats were fully anaesthetised and single-unit extracellular recordings were obtained from lamina V wide dynamic range (WDR dorsal horn spinal neurones at the region where input is received from the hind paw. Neuronal responses from naive rats showed that rapamycin-sensitive pathways were important in nociceptive-specific C-fibre mediated transmission onto WDR neurones as well mechanically-evoked responses since rapamycin was effective in attenuating these measures. Formalin solution was injected into the hind paw prior to which, rapamycin or vehicle was applied directly onto the exposed spinal cord. When rapamycin was applied to the spinal cord prior to hind paw formalin injection, there was a significant attenuation of the prolonged second phase of the formalin test, which comprises continuing afferent input to the spinal cord, neuronal hyperexcitability and an activated descending facilitatory drive from the brainstem acting on spinal neurones. In accordance with electrophysiological data, behavioural studies showed that rapamycin attenuated behavioural hypersensitivity elicited by formalin injection into the hind paw. Conclusion We conclude that mTOR has a role in maintaining persistent pain states via m

  10. The modulation of visceral functions by somatic afferent activity.

    Science.gov (United States)

    Sato, A; Schmidt, R F

    1987-01-01

    We began by briefly reviewing the historical background of neurophysiological studies of the somato-autonomic reflexes and then discussed recent studies on somatic-visceral reflexes in combination with autonomic efferent nerve activity and effector organ responses. Most of the studies that have advanced our knowledge in this area have been carried out on anesthetized animals, thus eliminating emotional factors. We would like to emphasize again that the functions of many, or perhaps all visceral organs can be modulated by somato-sympathetic or somato-parasympathetic reflex activity induced by a appropriate somatic afferent stimulation in anesthetized animals. As mentioned previously, some autonomic nervous outflow, e.g. the adrenal sympathetic nerve activity, is involved in the control of hormonal secretion. John F. Fulton wrote in his famous textbook "Physiology of the Nervous System" (1949) that the posterior pituitary neurosecretion system (i.e. for oxytocin and vasopressin) could be considered a part of the parasympathetic nervous system. In the study of body homeostasis and environmental adaptation it would seem very important to further analyze the contribution of somatic afferent input to the autonomic nervous and hormonal regulation of visceral organ activity. Also, some immunological functions have been found to be influenced by autonomic nerves or hormones (e.g. adrenal cortical hormone and catecholamines). Finally, we must take into account, as we have briefly discussed, that visceral functions can be modulated by somatic afferent input via various degrees of integration of autonomic nerves, hormones, and immunological processes. We trust that such research will be expanded to higher species of mammals, and that ultimately this knowledge of somato-visceral reflexes obtained in the physiological laboratory will become clinically useful in influencing visceral functions.

  11. Afferent Endocrine Control of Eating

    DEFF Research Database (Denmark)

    Langhans, Wolfgang; Holst, Jens Juul

    2016-01-01

    The afferent endocrine factors that control eating can be separated into different categories. One obvious categorization is by the time course of their effects, with long-term factors that signal adiposity and short-term factors that operate within the time frame of single meals. The second...... obvious categorization is by the origin of the endocrine signalling molecules. The level of knowledge concerning the physiological mechanisms and relevance of the hormones that are implicated in the control of eating is clearly different. With the accumulating knowledge about the hormones' actions......, various criteria have been developed for when the effect of a hormone can be considered 'physiologic'. This chapter treats the hormones separately and categorizes them by origin. It discusses ALL hormones that are implicated in eating control such as Gastrointestinal (GI) hormone and glucagon-like peptide...

  12. Neuronal activation by mucosal biopsy supernatants from irritable bowel syndrome patients is linked to visceral sensitivity

    NARCIS (Netherlands)

    Buhner, Sabine; Braak, Breg; Li, Qin; Kugler, Eva Maria; Klooker, Tamira; Wouters, Mira; Donovan, Jemma; Vignali, Sheila; Mazzuoli-Weber, Gemma; Grundy, David; Boeckxstaens, Guy; Schemann, Michael

    2014-01-01

    Based on the discomfort/pain threshold during rectal distension, irritable bowel syndrome (IBS) patients may be subtyped as normo- or hypersensitive. We previously showed that mucosal biopsy supernatants from IBS patients activated enteric and visceral afferent neurons. We tested the hypothesis that

  13. Afferent Loop Syndrome after Roux-en-Y Total Gastrectomy Caused by Volvulus of the Roux-Limb

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    Hideki Katagiri

    2016-01-01

    Full Text Available Afferent loop syndrome is a rare complication of gastric surgery. An obstruction of the afferent limb can present in various ways. A 73-year-old man presented with one day of persistent abdominal pain, gradually radiating to the back. He had a history of total gastrectomy with a Roux-en-Y reconstruction. Abdominal computed tomography scan revealed dilation of the duodenum and small intestine in the left upper quadrant. Exploratory laparotomy showed volvulus of the biliopancreatic limb that caused afferent loop syndrome. In this patient, the 50 cm long limb was the cause of volvulus. It is important to fashion a Roux-limb of appropriate length to prevent this complication.

  14. Induction of hypertension blunts baroreflex inhibition of vasopressin neurons in the rat.

    Science.gov (United States)

    Han, Su Young; Bouwer, Gregory T; Seymour, Alexander J; Korpal, Aaron K; Schwenke, Daryl O; Brown, Colin H

    2015-11-01

    Vasopressin secretion from the posterior pituitary gland is determined by action potential discharge of hypothalamic magnocellular neurosecretory cells. Vasopressin is a potent vasoconstrictor, but vasopressin levels are paradoxically elevated in some patients with established hypertension. To determine whether vasopressin neurons are excited in hypertension, extracellular single-unit recordings of vasopressin neurons from urethane-anaesthetized Cyp1a1-Ren2 rats with inducible angiotensin-dependent hypertension were made. The basal firing rate of vasopressin neurons was higher in hypertensive Cyp1a1-Ren2 rats than in non-hypertensive Cyp1a1-Ren2 rats. The increase in firing rate was specific to vasopressin neurons because oxytocin neuron firing rate was unaffected by the induction of hypertension. Intravenous injection of the α1-adrenoreceptor agonist, phenylephrine (2.5 μg/kg), transiently increased mean arterial blood pressure to cause a baroreflex-induced inhibition of heart rate and vasopressin neuron firing rate (by 52 ± 9%) in non-hypertensive rats. By contrast, intravenous phenylephrine did not inhibit vasopressin neurons in hypertensive rats, despite a similar increase in mean arterial blood pressure and inhibition of heart rate. Circulating angiotensin II can excite vasopressin neurons via activation of afferent inputs from the subfornical organ. However, the increase in vasopressin neuron firing rate and the loss of inhibition by intravenous phenylephrine were not blocked by intra-subfornical organ infusion of the angiotensin AT1 receptor antagonist, losartan. It can be concluded that increased vasopressin neuron activity at the onset of hypertension is driven, at least in part, by reduced baroreflex inhibition of vasopressin neurons and that this might exacerbate the increase in blood pressure at the onset of hypertension. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  15. Afferent signalling from the acid-challenged rat stomach is inhibited and gastric acid elimination is enhanced by lafutidine

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    Holzer Peter

    2009-06-01

    Full Text Available Abstract Background Lafutidine is a histamine H2 receptor antagonist, the gastroprotective effect of which is related to its antisecretory activity and its ability to activate a sensory neuron-dependent mechanism of defence. The present study investigated whether intragastric administration of lafutidine (10 and 30 mg/kg modifies vagal afferent signalling, mucosal injury, intragastric acidity and gastric emptying after gastric acid challenge. Methods Adult rats were treated with vehicle, lafutidine (10 – 30 mg/kg or cimetidine (10 mg/kg, and 30 min later their stomachs were exposed to exogenous HCl (0.25 M. During the period of 2 h post-HCl, intragastric pH, gastric volume, gastric acidity and extent of macroscopic gastric mucosal injury were determined and the activation of neurons in the brainstem was visualized by c-Fos immunocytochemistry. Results Gastric acid challenge enhanced the expression of c-Fos in the nucleus tractus solitarii but caused only minimal damage to the gastric mucosa. Lafutidine reduced the HCl-evoked expression of c-Fos in the NTS and elevated the intragastric pH following intragastric administration of excess HCl. Further analysis showed that the gastroprotective effect of lafutidine against excess acid was delayed and went in parallel with facilitation of gastric emptying, measured indirectly via gastric volume changes, and a reduction of gastric acidity. The H2 receptor antagonist cimetidine had similar but weaker effects. Conclusion These observations indicate that lafutidine inhibits the vagal afferent signalling of a gastric acid insult, which may reflect an inhibitory action on acid-induced gastric pain. The ability of lafutidine to decrease intragastric acidity following exposure to excess HCl cannot be explained by its antisecretory activity but appears to reflect dilution and/or emptying of the acid load into the duodenum. This profile of actions emphasizes the notion that H2 receptor antagonists can protect

  16. Loss of Axon Bifurcation in Mesencephalic Trigeminal Neurons Impairs the Maximal Biting Force in Npr2-Deficient Mice

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    Gohar Ter-Avetisyan

    2018-06-01

    Full Text Available Bifurcation of axons from dorsal root ganglion (DRG and cranial sensory ganglion (CSG neurons is mediated by a cGMP-dependent signaling pathway composed of the ligand C-type natriuretic peptide (CNP, the receptor guanylyl cyclase Npr2 and the cGMP-dependent protein kinase I (cGKI. Here, we demonstrate that mesencephalic trigeminal neurons (MTN which are the only somatosensory neurons whose cell bodies are located within the CNS co-express Npr2 and cGKI. Afferents of MTNs form Y-shaped branches in rhombomere 2 where the ligand CNP is expressed. Analyzing mouse mutants deficient for CNP or Npr2 we found that in the absence of CNP-induced cGMP signaling MTN afferents no longer bifurcate and instead extend either into the trigeminal root or caudally in the hindbrain. Since MTNs provide sensory information from jaw closing muscles and periodontal ligaments we measured the bite force of conditional mouse mutants of Npr2 (Npr2flox/flox;Engr1Cre that lack bifurcation of MTN whereas the bifurcation of trigeminal afferents is normal. Our study revealed that the maximal biting force of both sexes is reduced in Npr2flox/flox;Engr1Cre mice as compared to their Npr2flox/flox littermate controls. In conclusion sensory feedback mechanisms from jaw closing muscles or periodontal ligaments might be impaired in the absence of MTN axon bifurcation.

  17. Functional recovery of anterior semicircular canal afferents following hair cell regeneration in birds

    Science.gov (United States)

    Boyle, Richard; Highstein, Stephen M.; Carey, John P.; Xu, Jinping

    2002-01-01

    Streptomycin sulfate (1.2 g/kg i.m.) was administered for 5 consecutive days to 5-7-day-old white Leghorn chicks; this causes damage to semicircular canal hair cells that ultimately regenerate to reform the sensory epithelium. During the recovery period, electrophysiological recordings were taken sequentially from anterior semicircular canal primary afferents using an indentation stimulus of the canal that has been shown to mimic rotational stimulation. Chicks were assigned to an early (14-18 days; n = 8), intermediate (28-34 days; n = 5), and late (38-58 days; n = 4) period based on days after treatment. Seven untreated chicks, 15-67 days old, provided control data. An absence of background and indent-induced discharge was the prominent feature of afferents in the early period: only "silent" afferents were encountered in 5/8 experiments. In several of these chicks, fascicles of afferent fibers were seen extending up to the epithelium that was void of hair cells, and intra- and extracellular biocytin labeling revealed afferent processes penetrating into the supporting cell layer of the crista. In 3/8 chicks 74 afferents could be characterized, and they significantly differed from controls (n = 130) by having a lower discharge rate and a negligible response to canal stimulation. In the intermediate period there was considerable variability in discharge properties of 121 afferents, but as a whole the number of "silent" fibers in the canal nerve diminished, the background rate increased, and a response to canal stimulation detected. Individually biocytin-labeled afferents had normal-appearing terminal specializations in the sensory epithelium by 28 days poststreptomycin. In the late period, afferents (n = 58) remained significantly different from controls in background discharge properties and response gain. The evidence suggests that a considerable amount of variability exists between chicks in the return of vestibular afferent function following ototoxic injury and

  18. Segregated populations of hippocampal principal CA1 neurons mediating conditioning and extinction of contextual fear.

    Science.gov (United States)

    Tronson, Natalie C; Schrick, Christina; Guzman, Yomayra F; Huh, Kyu Hwan; Srivastava, Deepak P; Penzes, Peter; Guedea, Anita L; Gao, Can; Radulovic, Jelena

    2009-03-18

    Learning processes mediating conditioning and extinction of contextual fear require activation of several key signaling pathways in the hippocampus. Principal hippocampal CA1 neurons respond to fear conditioning by a coordinated activation of multiple protein kinases and immediate early genes, such as cFos, enabling rapid and lasting consolidation of contextual fear memory. The extracellular signal-regulated kinase (Erk) additionally acts as a central mediator of fear extinction. It is not known however, whether these molecular events take place in overlapping or nonoverlapping neuronal populations. By using mouse models of conditioning and extinction of fear, we set out to determine the time course of cFos and Erk activity, their cellular overlap, and regulation by afferent cholinergic input from the medial septum. Analyses of cFos(+) and pErk(+) cells by immunofluorescence revealed predominant nuclear activation of either protein during conditioning and extinction of fear, respectively. Transgenic cFos-LacZ mice were further used to label in vivo Fos(+) hippocampal cells during conditioning followed by pErk immunostaining after extinction. The results showed that these signaling molecules were activated in segregated populations of hippocampal principal neurons. Furthermore, immunotoxin-induced lesions of medial septal neurons, providing cholinergic input into the hippocampus, selectively abolished Erk activation and extinction of fear without affecting cFos responses and conditioning. These results demonstrate that extinction mechanisms based on Erk signaling involve a specific population of CA1 principal neurons distinctively regulated by afferent cholinergic input from the medial septum.

  19. Neural input is critical for arcuate hypothalamic neurons to mount intracellular signaling responses to systemic insulin and deoxyglucose challenges in male rats: implications for communication within feeding and metabolic control networks.

    Science.gov (United States)

    Khan, Arshad M; Walker, Ellen M; Dominguez, Nicole; Watts, Alan G

    2014-02-01

    The hypothalamic arcuate nucleus (ARH) controls rat feeding behavior in part through peptidergic neurons projecting to the hypothalamic paraventricular nucleus (PVH). Hindbrain catecholaminergic (CA) neurons innervate both the PVH and ARH, and ablation of CA afferents to PVH neuroendocrine neurons prevents them from mounting cellular responses to systemic metabolic challenges such as insulin or 2-deoxy-d-glucose (2-DG). Here, we asked whether ablating CA afferents also limits their ARH responses to the same challenges or alters ARH connectivity with the PVH. We examined ARH neurons for three features: (1) CA afferents, visualized by dopamine-β-hydroxylase (DBH)- immunoreactivity; (2) activation by systemic metabolic challenge, as measured by increased numbers of neurons immunoreactive (ir) for phosphorylated ERK1/2 (pERK1/2); and (3) density of PVH-targeted axons immunoreactive for the feeding control peptides Agouti-related peptide and α-melanocyte-stimulating hormone (αMSH). Loss of PVH DBH immunoreactivity resulted in concomitant ARH reductions of DBH-ir and pERK1/2-ir neurons in the medial ARH, where AgRP neurons are enriched. In contrast, pERK1/2 immunoreactivity after systemic metabolic challenge was absent in αMSH-ir ARH neurons. Yet surprisingly, axonal αMSH immunoreactivity in the PVH was markedly increased in CA-ablated animals. These results indicate that (1) intrinsic ARH activity is insufficient to recruit pERK1/2-ir ARH neurons during systemic metabolic challenges (rather, hindbrain-originating CA neurons are required); and (2) rats may compensate for a loss of CA innervation to the ARH and PVH by increased expression of αMSH. These findings highlight the existence of a hierarchical dependence for ARH responses to neural and humoral signals that influence feeding behavior and metabolism.

  20. Proper development of relay somatic sensory neurons and D2/D4 interneurons requires homeobox genes Rnx/Tlx-3 and Tlx-1.

    Science.gov (United States)

    Qian, Ying; Shirasawa, Senji; Chen, Chih-Li; Cheng, Leping; Ma, Qiufu

    2002-05-15

    Trigeminal nuclei and the dorsal spinal cord are first-order relay stations for processing somatic sensory information such as touch, pain, and temperature. The origins and development of these neurons are poorly understood. Here we show that relay somatic sensory neurons and D2/D4 dorsal interneurons likely derive from Mash1-positive neural precursors, and depend on two related homeobox genes, Rnx and Tlx-1, for proper formation. Rnx and Tlx-1 maintain expression of Drg11, a homeobox gene critical for the development of pain circuitry, and are essential for the ingrowth of trkA+ nociceptive/thermoceptive sensory afferents to their central targets. We showed previously that Rnx is necessary for proper formation of the nucleus of solitary tract, the target for visceral sensory afferents. Together, our studies demonstrate a central role for Rnx and Tlx-1 in the development of two major classes of relay sensory neurons, somatic and visceral.

  1. Pain from intra-articular NGF or joint injury in the rat requires contributions from peptidergic joint afferents.

    Science.gov (United States)

    Kras, Jeffrey V; Weisshaar, Christine L; Pall, Parul S; Winkelstein, Beth A

    2015-09-14

    Non-physiological stretch of the cervical facet joint's capsular ligament induces persistent behavioral hypersensitivity and spinal neuronal hyperexcitability via an intra-articular NGF-dependent mechanism. Although that ligament is innervated by nociceptors, it is unknown if a subpopulation is exclusively responsible for the behavioral and spinal neuronal responses to intra-articular NGF and/or facet joint injury. This study ablated joint afferents using the neurotoxin saporin targeted to neurons involved in either peptidergic ([Sar(9),Met (O2)(11)]-substance P-saporin (SSP-Sap)) or non-peptidergic (isolectin B4-saporin (IB4-Sap)) signaling to investigate the contributions of those neuronal populations to facet-mediated pain. SSP-Sap, but not IB4-Sap, injected into the bilateral C6/C7 facet joints 14 days prior to an intra- articular NGF injection prevents NGF-induced mechanical and thermal hypersensitivity in the forepaws. Similarly, only SSP- Sap prevents the increase in mechanical forepaw stimulation- induced firing of spinal neurons after intra-articular NGF. In addition, intra-articular SSP-Sap prevents both behavioral hypersensitivity and upregulation of NGF in the dorsal root ganglion after a facet joint distraction that normally induces pain. These findings collectively suggest that disruption of peptidergic signaling within the joint may be a potential treatment for facet pain, as well as other painful joint conditions associated with elevated NGF, such as osteoarthritis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Central projections and entries of capsaicin-sensitive muscle afferents.

    Science.gov (United States)

    Della Torre, G; Lucchi, M L; Brunetti, O; Pettorossi, V E; Clavenzani, P; Bortolami, R

    1996-03-25

    The entry pathway and central distribution of A delta and C muscle afferents within the central nervous system (CNS) were investigated by combining electron microscopy and electrophysiological analysis after intramuscular injection of capsaicin. The drug was injected into the rat lateral gastrocnemius (LG) and extraocular (EO) muscles. The compound action potentials of LG nerve and the evoked field potentials recorded in semilunar ganglion showed an immediate and permanent reduction in A delta and C components. The morphological data revealed degenerating unmyelinated axons and terminals in the inner sublamina II and in the border of laminae I-II of the dorsal horn at L4-L5 and C1-C2 (subnucleus caudalis trigemini) spinal cord segments. Most degenerating terminals were the central bouton (C) of type I and II synaptic glomeruli. Furthermore, degenerating peripheral axonal endings (V2) presynaptic to normal C were found. Since V2 were previously found degenerated after cutting the oculomotor nerve (ON) or L4 ventral root, we conclude that some A delta and C afferents from LG and EO muscles entering the CNS by ON or ventral roots make axoaxonic synapses on other primary afferents to promote an afferent control of sensory input.

  3. Magnocellular Neurons and Posterior Pituitary Function.

    Science.gov (United States)

    Brown, Colin H

    2016-09-15

    The posterior pituitary gland secretes oxytocin and vasopressin (the antidiuretic hormone) into the blood system. Oxytocin is required for normal delivery of the young and for delivery of milk to the young during lactation. Vasopressin increases water reabsorption in the kidney to maintain body fluid balance and causes vasoconstriction to increase blood pressure. Oxytocin and vasopressin secretion occurs from the axon terminals of magnocellular neurons whose cell bodies are principally found in the hypothalamic supraoptic nucleus and paraventricular nucleus. The physiological functions of oxytocin and vasopressin depend on their secretion, which is principally determined by the pattern of action potentials initiated at the cell bodies. Appropriate secretion of oxytocin and vasopressin to meet the challenges of changing physiological conditions relies mainly on integration of afferent information on reproductive, osmotic, and cardiovascular status with local regulation of magnocellular neurons by glia as well as intrinsic regulation by the magnocellular neurons themselves. This review focuses on the control of magnocellular neuron activity with a particular emphasis on their regulation by reproductive function, body fluid balance, and cardiovascular status. © 2016 American Physiological Society. Compr Physiol 6:1701-1741, 2016. Copyright © 2016 John Wiley & Sons, Inc.

  4. Does metabosensitive afferent fibers activity differ from slow- and fast-twitch muscles?

    Science.gov (United States)

    Caron, Guillaume; Decherchi, Patrick; Marqueste, Tanguy

    2015-09-01

    This study was designed to investigate the metabosensitive afferent response evoked by electrically induced fatigue (EIF), lactic acid (LA) and potassium chloride (KCl) in three muscle types. We recorded the activity of groups III-IV afferents originating from soleus, gastrocnemius and tibialis anterior muscles. Our data showed a same pattern of response in the three muscles after chemical injections, i.e., a bell curve with maximal discharge rate at 1 mM for LA injections and a linear relationship between KCl concentrations and the afferent discharge rate. Furthermore, a stronger response was recorded after EIF in the gastrocnemius muscle compared to the two other muscles. The change in afferent discharge after 1 mM LA injection was higher for the gastrocnemius muscle compared to the response obtained with the corresponding concentration applied in the two other muscles, whereas changes to KCl injections did not dramatically differ between the three muscles. We conclude that anatomical (mass, phenotype, vascularization, receptor and afferent density…) and functional (flexor vs. extensor) differences between muscles could explain the amplitude of these responses.

  5. The changing roles of neurons in the cortical subplate

    Directory of Open Access Journals (Sweden)

    Michael J Friedlander

    2009-08-01

    Full Text Available Neurons may serve different functions over the course of an organism’s life. Recent evidence suggests that cortical subplate neurons including those that reside in the white matter may perform longitudinal multi-tasking at different stages of development. These cells play a key role in early cortical development in coordinating thalamocortical reciprocal innervation. At later stages of development, they become integrated within the cortical microcircuitry. This type of longitudinal multi-tasking can enhance the capacity for information processing by populations of cells serving different functions over the lifespan. Subplate cells are initially derived when cells from the ventricular zone underlying the cortex migrate to the cortical preplate that is subsequently split by the differentiating neurons of the cortical plate with some neurons locating in the marginal zone and others settling below in the subplate (SP. While the cortical plate neurons form most of the cortical layers (layers 2-6, the marginal zone neurons form layer 1 and the SP neurons become interstitial cells of the white matter as well as forming a compact sublayer along the bottom of layer 6. After serving as transient innervation targets for thalamocortical axons, most of these cells die and layer 4 neurons become innervated by thalamic axons. However, 10-20% survives, remaining into adulthood along the bottom of layer 6 and as a scattered population of interstitial neurons in the white matter. Surviving subplate cells’ axons project throughout the overlying laminae, reaching layer 1 and issuing axon collaterals within white matter and in lower layer 6. This suggests that they participate in local synaptic networks, as well. Moreover, they receive excitatory and inhibitory synaptic inputs, potentially monitoring outputs from axon collaterals of cortical efferents, from cortical afferents and/or from each other. We explore our understanding of the functional connectivity of

  6. The urodelean Mauthner cell. Morphology of the afferent synapses to the M-cell of larval Salamandra salamandra

    Energy Technology Data Exchange (ETDEWEB)

    Cioni, C.; De Palma, F.; De Vito, L.; Stefanelli, A. [Rome, Univ. (Italy). Dipt. di Biologia Animale e dell`Uomo

    1997-12-31

    In the present work the fine morphology and the distribution of the afferent synapses to the Mauthner cell of larval Salamandra salamandra are described. The aim of the study is to characterize the synaptic bed in the larvae of this terrestrial salamander in order to compare it with that of larval axolotl and larval anurans. Four main types of afferent endings have been identified: myelinated club endings, round-vesicle end bulbs, flattened-vesicle end bulbs and spiral fibers endings. The M-cell afferent synaptology of larval stages of terrestrial amphibians is quite similar to that previously observed in larval stages of aquatic species. This fact can be related to the fundamental similarities between the larval lifestyles.

  7. The urodelean Mauthner cell. Morphology of the afferent synapses to the M-cell of larval Salamandra salamandra

    Energy Technology Data Exchange (ETDEWEB)

    Cioni, C; De Palma, F; De Vito, L; Stefanelli, A [Rome, Univ. (Italy). Dipt. di Biologia Animale e dell` Uomo

    1998-12-31

    In the present work the fine morphology and the distribution of the afferent synapses to the Mauthner cell of larval Salamandra salamandra are described. The aim of the study is to characterize the synaptic bed in the larvae of this terrestrial salamander in order to compare it with that of larval axolotl and larval anurans. Four main types of afferent endings have been identified: myelinated club endings, round-vesicle end bulbs, flattened-vesicle end bulbs and spiral fibers endings. The M-cell afferent synaptology of larval stages of terrestrial amphibians is quite similar to that previously observed in larval stages of aquatic species. This fact can be related to the fundamental similarities between the larval lifestyles.

  8. Selective deletion of cochlear hair cells causes rapid age-dependent changes in spiral ganglion and cochlear nucleus neurons.

    Science.gov (United States)

    Tong, Ling; Strong, Melissa K; Kaur, Tejbeer; Juiz, Jose M; Oesterle, Elizabeth C; Hume, Clifford; Warchol, Mark E; Palmiter, Richard D; Rubel, Edwin W

    2015-05-20

    During nervous system development, critical periods are usually defined as early periods during which manipulations dramatically change neuronal structure or function, whereas the same manipulations in mature animals have little or no effect on the same property. Neurons in the ventral cochlear nucleus (CN) are dependent on excitatory afferent input for survival during a critical period of development. Cochlear removal in young mammals and birds results in rapid death of target neurons in the CN. Cochlear removal in older animals results in little or no neuron death. However, the extent to which hair-cell-specific afferent activity prevents neuronal death in the neonatal brain is unknown. We further explore this phenomenon using a new mouse model that allows temporal control of cochlear hair cell deletion. Hair cells express the human diphtheria toxin (DT) receptor behind the Pou4f3 promoter. Injections of DT resulted in nearly complete loss of organ of Corti hair cells within 1 week of injection regardless of the age of injection. Injection of DT did not influence surrounding supporting cells directly in the sensory epithelium or spiral ganglion neurons (SGNs). Loss of hair cells in neonates resulted in rapid and profound neuronal loss in the ventral CN, but not when hair cells were eliminated at a more mature age. In addition, normal survival of SGNs was dependent on hair cell integrity early in development and less so in mature animals. This defines a previously undocumented critical period for SGN survival. Copyright © 2015 the authors 0270-6474/15/357878-14$15.00/0.

  9. MR features of a case of afferent loop syndrome presenting as obstructive jaundice

    International Nuclear Information System (INIS)

    Chevallier, P.; Souci, J.; Oddo, F.; Diaine, B.; Padovani, B.; Gueyffier, C.

    2001-01-01

    The afferent loop syndrome corresponds to an acute or chronic obstruction of the afferent loop following a partial gastrectomy with Billroth II gastro-jejunal anastomosis. We describe the case of a 77-year-old man with history of partial gastrectomy for peptic ulcer disease performed 31 years ago and currently admitted for jaundice and poor general status. MR imaging showed dilatation of biliary and pancreatic ducts and showed a soft tissue mass between the afferent loop and the residual stomach. Endoscopy showed complete obstruction of the afferent loop by a biopsy-proven adenocarcinoma. The patient died of sepsis shortly after endoscopy of septicemia. (authors)

  10. Reciprocal inhibition between motor neurons of the tibialis anterior and triceps surae in humans.

    Science.gov (United States)

    Yavuz, Utku Ş; Negro, Francesco; Diedrichs, Robin; Farina, Dario

    2018-05-01

    Motor neurons innervating antagonist muscles receive reciprocal inhibitory afferent inputs to facilitate the joint movement in the two directions. The present study investigates the mutual transmission of reciprocal inhibitory afferent inputs between the tibialis anterior (TA) and triceps surae (soleus and medial gastrocnemius) motor units. We assessed this mutual mechanism in large populations of motor units for building a statistical distribution of the inhibition amplitudes during standardized input to the motor neuron pools to minimize the effect of modulatory pathways. Single motor unit activities were identified using high-density surface electromyography (HDsEMG) recorded from the TA, soleus (Sol), and medial gastrocnemius (GM) muscles during isometric dorsi- and plantarflexion. Reciprocal inhibition on the antagonist muscle was elicited by electrical stimulation of the tibial (TN) or common peroneal nerves (CPN). The probability density distributions of reflex strength for each muscle were estimated to examine the strength of mutual transmission of reciprocal inhibitory input. The results showed that the strength of reciprocal inhibition in the TA motor units was fourfold greater than for the GM and the Sol motor units. This suggests an asymmetric transmission of reciprocal inhibition between ankle extensor and flexor muscles. This asymmetry cannot be explained by differences in motor unit type composition between the investigated muscles since we sampled low-threshold motor units in all cases. Therefore, the differences observed for the strength of inhibition are presumably due to a differential reciprocal spindle afferent input and the relative contribution of nonreciprocal inhibitory pathways. NEW & NOTEWORTHY We investigated the mutual transmission of reciprocal inhibition in large samples of motor units using a standardized input (electrical stimulation) to the motor neurons. The results demonstrated that the disynaptic reciprocal inhibition exerted

  11. Vagal stimulation targets select populations of intrinsic cardiac neurons to control neurally induced atrial fibrillation

    Science.gov (United States)

    Salavatian, Siamak; Beaumont, Eric; Longpré, Jean-Philippe; Armour, J. Andrew; Vinet, Alain; Jacquemet, Vincent; Shivkumar, Kalyanam

    2016-01-01

    Mediastinal nerve stimulation (MNS) reproducibly evokes atrial fibrillation (AF) by excessive and heterogeneous activation of intrinsic cardiac (IC) neurons. This study evaluated whether preemptive vagus nerve stimulation (VNS) impacts MNS-induced evoked changes in IC neural network activity to thereby alter susceptibility to AF. IC neuronal activity in the right atrial ganglionated plexus was directly recorded in anesthetized canines (n = 8) using a linear microelectrode array concomitant with right atrial electrical activity in response to: 1) epicardial touch or great vessel occlusion vs. 2) stellate or vagal stimulation. From these stressors, post hoc analysis (based on the Skellam distribution) defined IC neurons so recorded as afferent, efferent, or convergent (afferent and efferent inputs) local circuit neurons (LCN). The capacity of right-sided MNS to modify IC activity in the induction of AF was determined before and after preemptive right (RCV)- vs. left (LCV)-sided VNS (15 Hz, 500 μs; 1.2× bradycardia threshold). Neuronal (n = 89) activity at baseline (0.11 ± 0.29 Hz) increased during MNS-induced AF (0.51 ± 1.30 Hz; P < 0.001). Convergent LCNs were preferentially activated by MNS. Preemptive RCV reduced MNS-induced changes in LCN activity (by 70%) while mitigating MNS-induced AF (by 75%). Preemptive LCV reduced LCN activity by 60% while mitigating AF potential by 40%. IC neuronal synchrony increased during neurally induced AF, a local neural network response mitigated by preemptive VNS. These antiarrhythmic effects persisted post-VNS for, on average, 26 min. In conclusion, VNS preferentially targets convergent LCNs and their interactive coherence to mitigate the potential for neurally induced AF. The antiarrhythmic properties imposed by VNS exhibit memory. PMID:27591222

  12. Intrinsic and integrative properties of substantia nigra pars reticulata neurons

    Science.gov (United States)

    Zhou, Fu-Ming; Lee, Christian R.

    2011-01-01

    The GABA projection neurons of the substantia nigra pars reticulata (SNr) are output neurons for the basal ganglia and thus critical for movement control. Their most striking neurophysiological feature is sustained, spontaneous high frequency spike firing. A fundamental question is: what are the key ion channels supporting the remarkable firing capability in these neurons? Recent studies indicate that these neurons express tonically active TRPC3 channels that conduct a Na-dependent inward current even at hyperpolarized membrane potentials. When the membrane potential reaches −60 mV, a voltage-gated persistent sodium current (INaP) starts to activate, further depolarizing the membrane potential. At or slightly below −50 mV, the large transient voltage-activated sodium current (INaT) starts to activate and eventually triggers the rapid rising phase of action potentials. SNr GABA neurons have a higher density of (INaT), contributing to the faster rise and larger amplitude of action potentials, compared with the slow-spiking dopamine neurons. INaT also recovers from inactivation more quickly in SNr GABA neurons than in nigral dopamine neurons. In SNr GABA neurons, the rising phase of the action potential triggers the activation of high-threshold, inactivation-resistant Kv3-like channels that can rapidly repolarize the membrane. These intrinsic ion channels provide SNr GABA neurons with the ability to fire spontaneous and sustained high frequency spikes. Additionally, robust GABA inputs from direct pathway medium spiny neurons in the striatum and GABA neurons in the globus pallidus may inhibit and silence SNr GABA neurons, whereas glutamate synaptic input from the subthalamic nucleus may induce burst firing in SNr GABA neurons. Thus, afferent GABA and glutamate synaptic inputs sculpt the tonic high frequency firing of SNr GABA neurons and the consequent inhibition of their targets into an integrated motor control signal that is further fine-tuned by neuromodulators

  13. Hebbian learning and predictive mirror neurons for actions, sensations and emotions.

    Science.gov (United States)

    Keysers, Christian; Gazzola, Valeria

    2014-01-01

    Spike-timing-dependent plasticity is considered the neurophysiological basis of Hebbian learning and has been shown to be sensitive to both contingency and contiguity between pre- and postsynaptic activity. Here, we will examine how applying this Hebbian learning rule to a system of interconnected neurons in the presence of direct or indirect re-afference (e.g. seeing/hearing one's own actions) predicts the emergence of mirror neurons with predictive properties. In this framework, we analyse how mirror neurons become a dynamic system that performs active inferences about the actions of others and allows joint actions despite sensorimotor delays. We explore how this system performs a projection of the self onto others, with egocentric biases to contribute to mind-reading. Finally, we argue that Hebbian learning predicts mirror-like neurons for sensations and emotions and review evidence for the presence of such vicarious activations outside the motor system.

  14. Reciprocal synapses between outer hair cells and their afferent terminals: evidence for a local neural network in the mammalian cochlea.

    Science.gov (United States)

    Thiers, Fabio A; Nadol, Joseph B; Liberman, M Charles

    2008-12-01

    Cochlear outer hair cells (OHCs) serve both as sensory receptors and biological motors. Their sensory function is poorly understood because their afferent innervation, the type-II spiral ganglion cell, has small unmyelinated axons and constitutes only 5% of the cochlear nerve. Reciprocal synapses between OHCs and their type-II terminals, consisting of paired afferent and efferent specialization, have been described in the primate cochlea. Here, we use serial and semi-serial-section transmission electron microscopy to quantify the nature and number of synaptic interactions in the OHC area of adult cats. Reciprocal synapses were found in all OHC rows and all cochlear frequency regions. They were more common among third-row OHCs and in the apical half of the cochlea, where 86% of synapses were reciprocal. The relative frequency of reciprocal synapses was unchanged following surgical transection of the olivocochlear bundle in one cat, confirming that reciprocal synapses were not formed by efferent fibers. In the normal ear, axo-dendritic synapses between olivocochlear terminals and type-II terminals and/or dendrites were as common as synapses between olivocochlear terminals and OHCs, especially in the first row, where, on average, almost 30 such synapses were seen in the region under a single OHC. The results suggest that a complex local neuronal circuitry in the OHC area, formed by the dendrites of type-II neurons and modulated by the olivocochlear system, may be a fundamental property of the mammalian cochlea, rather than a curiosity of the primate ear. This network may mediate local feedback control of, and bidirectional communication among, OHCs throughout the cochlear spiral.

  15. Afferent nerves regulating the cough reflex: Mechanisms and Mediators of Cough in Disease

    Science.gov (United States)

    Canning, Brendan J.

    2010-01-01

    Bronchopulmonary C-fibers and acid-sensitive, capsaicin-insensitive mechanoreceptors innervating the larynx, trachea and large bronchi regulate the cough reflex. These vagal afferent nerves may interact centrally with sensory input arising from afferent nerves innervating the intrapulmonary airways or even extrapulmonary afferents such as those innervating the nasal mucosa and esophagus to produce chronic cough or enhanced cough responsiveness. The mechanisms of cough initiation in health and in disease are briefly described. PMID:20172253

  16. Neurotensin enhances glutamatergic EPSCs in VTA neurons by acting on different neurotensin receptors.

    Science.gov (United States)

    Bose, Poulomee; Rompré, Pierre-Paul; Warren, Richard A

    2015-11-01

    Neurotensin (NT) is an endogenous neuropeptide that modulates dopamine and glutamate neurotransmission in several limbic regions innervated by neurons located in the ventral tegmental area (VTA). While several studies showed that NT exerted a direct modulation on VTA dopamine neurons less is known about its role in the modulation of glutamatergic neurotransmission in this region. The present study was aimed at characterising the effects of NT on glutamate-mediated responses in different populations of VTA neurons. Using whole cell patch clamp recording technique in horizontal rat brain slices, we measured the amplitude of glutamatergic excitatory post-synaptic currents (EPSCs) evoked by electrical stimulation of VTA afferents before and after application of different concentrations of NT1-13 or its C-terminal fragment, NT8-13. Neurons were classified as either Ih(+) or Ih(-) based on the presence or absence of a hyperpolarisation activated cationic current (Ih). We found that NT1-13 and NT8-13 produced comparable concentration dependent increase in the amplitude of EPSCs in both Ih(+) and Ih(-) neurons. In Ih(+) neurons, the enhancement effect of NT8-13 was blocked by both antagonists, while in Ih(-) neurons it was blocked by the NTS1/NTS2 antagonist, SR142948A, but not the preferred NTS1 antagonist, SR48692. In as much as Ih(-) neurons are non-dopaminergic neurons and Ih(+) neurons represent both dopamine and non-dopamine neurons, we can conclude that NT enhances glutamatergic mediated responses in dopamine, and in a subset of non-dopamine, neurons by acting respectively on NTS1 and an NT receptor other than NTS1. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Mechanosensitive enteric neurons in the guinea pig gastric corpus

    Directory of Open Access Journals (Sweden)

    Gemma eMazzuoli-Weber

    2015-11-01

    Full Text Available For long it was believed that a particular population of enteric neurons, referred to as intrinsic primary afferent neuron (IPANs, encodes mechanical stimulation. We recently proposed a new concept suggesting that there are in addition mechanosensitive enteric neurons (MEN that are multifunctional. Based on firing pattern MEN behaved as rapidly, slowly or ultra-slowly adapting RAMEN, SAMEN or USAMEN, respectively. We aimed to validate this concept in the myenteric plexus of the gastric corpus, a region where IPANs were not identified and existence of enteric sensory neurons was even questioned. The gastric corpus is characterized by a particularly dense extrinsic sensory innervation. Neuronal activity was recorded with voltage sensitive dye imaging after deformation of ganglia by compression (intraganglionic volume injection or von Fry hair or tension (ganglionic stretch. We demonstrated that 27% of the gastric neurons were MEN and responded to intraganglionic volume injection. Of these 73% were RAMEN, 25% SAMEN and 2% USAMEN with a firing frequency of 1.7 (1.1/ 2.2 Hz, 5.1 (2.2/7.7 Hz and of 5.4 (5.0/15.5 Hz, respectively. The responses were reproducible and stronger with increased stimulus strength. Even after adaptation another deformation evoked spike discharge again suggesting a resetting mode of the mechanoreceptors. All MEN received fast synaptic input. 55% of all MEN were cholinergic and 45% nitrergic. Responses in some MEN significantly decreased after perfusion of TTX, low Ca++/high Mg++ Krebs solution, capsaicin induced nerve defunctionalization and capsazepine indicating the involvement of TRPV1 expressing extrinsic mechanosensitive nerves. Half of gastric MEN responded to intraganglionic volume injection as well as to ganglionic stretch and 23% responded to stretch only. Tension-sensitive MEN were to a large proportion USAMEN (44%. In summary, we demonstrated for the first time compression and tension-sensitive MEN in the stomach

  18. Acylcarnitines as markers of exercise-associated fuel partitioning, xenometabolism, and potential signals to muscle afferent neurons.

    Science.gov (United States)

    Zhang, Jie; Light, Alan R; Hoppel, Charles L; Campbell, Caitlin; Chandler, Carol J; Burnett, Dustin J; Souza, Elaine C; Casazza, Gretchen A; Hughen, Ronald W; Keim, Nancy L; Newman, John W; Hunter, Gary R; Fernandez, Jose R; Garvey, W Timothy; Harper, Mary-Ellen; Fiehn, Oliver; Adams, Sean H

    2017-01-01

    that a weight-loss/fitness intervention alters plasma xenometabolites [i.e. cis-3,4-methylene-heptanoylcarnitine and γ-butyrobetaine (a co-metabolite possibly derived in part from gut bacteria)], suggesting that host metabolic health regulated gut microbe metabolism. Finally, we considered whether acylcarnitine metabolites signal to muscle-innervating afferents; palmitoylcarnitine at concentrations as low as 1-10 μm activated a subset (∼2.5-5%) of these neurons ex vivo. This supports the hypothesis that in addition to tracking exercise-associated shifts in fuel metabolism, muscle acylcarnitines act as signals of exertion to short-loop somatosensory-motor circuits or to the brain. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

  19. Some intrinsic neurons of the guinea-pig heart contain substance P.

    Science.gov (United States)

    Bałuk, P; Gabella, G

    1989-10-09

    Whole-mount preparations of the posterior wall of the atria of the guinea pig heart containing intrinsic ganglion cells and nerve plexuses were stained for substance P-like immunoreactivity by the peroxidase-antiperoxidase method. Substance P-like nerve fibres are present as pericellular baskets around most, but not all, of the neuronal cell bodies, and are also found in the connecting nerve bundles, as perivascular nerve plexuses and in the myocardium and pericardium. The majority of ganglion cell bodies are negative for substance P, as reported previously, but we describe for the first time, a small subpopulation of intrinsic neuronal cell bodies which show immunoreactivity for substance P. Therefore, not all cardiac substance P nerves are extrinsic afferent fibres. At present, the physiological role of intrinsic substance P neurones is not clear.

  20. VGLUTs and Glutamate Synthesis—Focus on DRG Neurons and Pain

    Directory of Open Access Journals (Sweden)

    Mariana Malet

    2015-12-01

    Full Text Available The amino acid glutamate is the principal excitatory transmitter in the nervous system, including in sensory neurons that convey pain sensation from the periphery to the brain. It is now well established that a family of membrane proteins, termed vesicular glutamate transporters (VGLUTs, serve a critical function in these neurons: they incorporate glutamate into synaptic vesicles. VGLUTs have a central role both under normal neurotransmission and pathological conditions, such as neuropathic or inflammatory pain. In the present short review, we will address VGLUTs in the context of primary afferent neurons. We will focus on the role of VGLUTs in pain triggered by noxious stimuli, peripheral nerve injury, and tissue inflammation, as mostly explored in transgenic mice. The possible interplay between glutamate biosynthesis and VGLUT-dependent packaging in synaptic vesicles, and its potential impact in various pain states will be presented.

  1. Rational modulation of neuronal processing with applied electric fields.

    Science.gov (United States)

    Bikson, Marom; Radman, Thomas; Datta, Abhishek

    2006-01-01

    Traditional approaches to electrical stimulation, using trains of supra-threshold pulses to trigger action potentials, may be replaced or augmented by using 'rational' sub-threshold stimulation protocols that incorporate knowledge of single neuron geometry, inhomogeneous tissue properties, and nervous system information coding. Sub-threshold stimulation, at intensities (well) below those sufficient to trigger action potentials, may none-the-less exert a profound effect on brain function through modulation of concomitant neuronal activity. For example, small DC fields may coherently polarize a network of neurons and thus modulate the simultaneous processing of afferent synaptic input as well as resulting changes in synaptic plasticity. Through 'activity-dependent plasticity', sub-threshold fields may allow specific targeting of pathological networks and are thus particularly suitable to overcome the poor anatomical focus of noninvasive (transcranial) electrical stimulation. Additional approaches to improve targeting in transcranial stimulation using novel electrode configurations are also introduced.

  2. [Nerve growth factor and the physiology of pain: the relationships among interoception, sympathetic neurons and the emotional response indicated by the molecular pathophysiology of congenital insensitivity to pain with anhidrosis].

    Science.gov (United States)

    Indo, Yasuhiro

    2015-05-01

    Nerve growth factor (NGF) is a neurotrophic factor essential for the survival and maintenance of neurons. Congenital insensitivity to pain with anhidrosis (CIPA) is caused by loss-of-function mutations in NTRK1, which encodes a receptor tyrosine kinase, TrkA, for NGF. Mutations in NTRK1 cause the selective loss of NGF-dependent neurons, including both NGF-dependent primary afferents and sympathetic postganglionic neurons, in otherwise intact systems. The NGF-dependent primary afferents are thinly myelinated AΔ or unmyelinated C-fibers that are dependent on the NGF-TrkA system during development. NGF-dependent primary afferents are not only nociceptive neurons that transmit pain and temperature sensation, but also are polymodal receptors that play essential roles for interoception by monitoring various changes in the physiological status of all tissues in the body. In addition, they contribute to various inflammatory processes in acute, chronic and allergic inflammation. Together with sympathetic postganglionic neurons, they maintain the homeostasis of the body and emotional responses via interactions with the brain, immune and endocrine systems. Pain is closely related to emotions that accompany physical responses induced by systemic activation of the sympathetic nervous system. In contrast to a negative image of emotions in daily life, Antonio Damasio proposed the 'Somatic Marker Hypothesis', wherein emotions play critical roles in the decision-making and reasoning processes. According to this hypothesis, reciprocal communication between the brain and the body-proper are essential for emotional responses. Using the pathophysiology of CIPA as a foundation, this article suggests that NGF-dependent neurons constitute a part of the neuronal network required for homeostasis and emotional responses, and indicates that this network plays important roles in mediating the reciprocal communication between the brain and the body-proper.

  3. Information analysis of posterior canal afferents in the turtle, Trachemys scripta elegans.

    Science.gov (United States)

    Rowe, Michael H; Neiman, Alexander B

    2012-01-24

    We have used sinusoidal and band-limited Gaussian noise stimuli along with information measures to characterize the linear and non-linear responses of morpho-physiologically identified posterior canal (PC) afferents and to examine the relationship between mutual information rate and other physiological parameters. Our major findings are: 1) spike generation in most PC afferents is effectively a stochastic renewal process, and spontaneous discharges are fully characterized by their first order statistics; 2) a regular discharge, as measured by normalized coefficient of variation (cv*), reduces intrinsic noise in afferent discharges at frequencies below the mean firing rate; 3) coherence and mutual information rates, calculated from responses to band-limited Gaussian noise, are jointly determined by gain and intrinsic noise (discharge regularity), the two major determinants of signal to noise ratio in the afferent response; 4) measures of optimal non-linear encoding were only moderately greater than optimal linear encoding, indicating that linear stimulus encoding is limited primarily by internal noise rather than by non-linearities; and 5) a leaky integrate and fire model reproduces these results and supports the suggestion that the combination of high discharge regularity and high discharge rates serves to extend the linear encoding range of afferents to higher frequencies. These results provide a framework for future assessments of afferent encoding of signals generated during natural head movements and for comparison with coding strategies used by other sensory systems. This article is part of a Special Issue entitled: Neural Coding. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Movement and afferent representations in human motor areas: a simultaneous neuroimaging and transcranial magnetic/peripheral nerve-stimulation study

    Directory of Open Access Journals (Sweden)

    Hitoshi eShitara

    2013-09-01

    Full Text Available Neuroimaging combined with transcranial magnetic stimulation (TMS to primary motor cortex (M1 is an emerging technique that can examine motor-system functionality through evoked activity. However, because sensory afferents from twitching muscles are widely represented in motor areas the amount of evoked activity directly resulting from TMS remains unclear. We delivered suprathreshold TMS to left M1 or electrically stimulated the right median nerve (MNS in 18 healthy volunteers while simultaneously conducting functional magnetic resonance imaging and monitoring with electromyography (EMG. We examined in detail the localization of TMS-, muscle afferent- and superficial afferent-induced activity in M1 subdivisions. Muscle afferent- and TMS-evoked activity occurred mainly in rostral M1, while superficial afferents generated a slightly different activation distribution. In 12 participants who yielded quantifiable EMG, differences in brain activity ascribed to differences in movement-size were adjusted using integrated information from the EMGs. Sensory components only explained 10-20% of the suprathreshold TMS-induced activity, indicating that locally and remotely evoked activity in motor areas mostly resulted from the recruitment of neural and synaptic activity. The present study appears to justify the use of fMRI combined with suprathreshold TMS to M1 for evoked motor network imaging.

  5. Effect of a muscle relaxant, chlorphenesin carbamate, on the spinal neurons of rats.

    Science.gov (United States)

    Kurachi, M; Aihara, H

    1984-09-01

    The effects of chlorphenesin carbamate (CPC) and mephenesin on spinal neurons were investigated in spinal rats. CPC (50 mg/kg i.v.) inhibited the mono-(MSR) and poly-synaptic reflex (PSR), the latter being more susceptible than the former to CPC depression. Mephenesin also inhibited MSR and PSR, though the effects were short in duration. CPC had no effect on the dorsal root potential evoked by the stimulation of the dorsal root, while mephenesin reduced the dorsal root-dorsal root reflex. The excitability of motoneuron was reduced by the administration of CPC or mephenesin. The excitability of primary afferent terminal was unchanged by CPC, while it was inhibited by mephenesin. Neither CPC nor mephenesin influenced the field potential evoked by the dorsal root stimulation. Both CPC and mephenesin had no effect on the synaptic recovery. These results suggest that both CPC and mephenesin inhibit the firing of motoneurons by stabilizing the neuronal membrane, while mephenesin additionally suppresses the dorsal root reflex and the excitability of the primary afferent terminal. These inhibitory actions of CPC on spinal activities may contribute, at least partly, to its muscle relaxing action.

  6. Long-term sensitization of mechanosensitive and -insensitive afferents in mice with persistent colorectal hypersensitivity

    OpenAIRE

    Feng, Bin; La, Jun-ho; Schwartz, Erica S.; Tanaka, Takahiro; McMurray, Timothy P.; Gebhart, G. F.

    2012-01-01

    Afferent input contributes significantly to the pain and colorectal hypersensitivity that characterize irritable bowel syndrome. In the present study, we investigated the contributions of mechanically sensitive and mechanically insensitive afferents (MIAs; or silent afferents) to colorectal hypersensitivity. The visceromotor response to colorectal distension (CRD; 15–60 mmHg) was recorded in mice before and for weeks after intracolonic treatment with zymosan or saline. After CRD tests, the di...

  7. Cutaneous TRPM8-expressing sensory afferents are a small population of neurons with unique firing properties.

    Science.gov (United States)

    Jankowski, Michael P; Rau, Kristofer K; Koerber, H Richard

    2017-04-01

    It has been well documented that the transient receptor potential melastatin 8 (TRPM8) receptor is involved in environmental cold detection. The role that this receptor plays in nociception however, has been somewhat controversial since conflicting reports have shown different neurochemical identities and responsiveness of TRPM8 neurons. In order to functionally characterize cutaneous TRMP8 fibers, we used two ex vivo somatosensory recording preparations to functionally characterize TRPM8 neurons that innervate the hairy skin in mice genetically engineered to express GFP from the TRPM8 locus. We found several types of cold-sensitive neurons that innervate the hairy skin of the mouse but the TRPM8-expressing neurons were found to be of two specific populations that responded with rapid firing to cool temperatures. The first group was mechanically insensitive but the other did respond to high threshold mechanical deformation of the skin. None of these fibers were found to contain calcitonin gene-related peptide, transient receptor potential vanilloid type 1 or bind isolectin B4. These results taken together with other reports suggest that TRPM8 containing sensory neurons are environmental cooling detectors that may be nociceptive or non-nociceptive depending on the sensitivity of individual fibers to different combinations of stimulus modalities. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  8. Capsaicin-sensitive intestinal mucosal afferent mechanism and body fat distribution.

    Science.gov (United States)

    Leung, Felix W

    2008-07-04

    This report summarizes clinical and experimental data in support of the hypothesis that capsaicin-sensitive intestinal mucosal afferent mechanism plays a role in regulating body fat distribution. Epidemiological data have revealed that the consumption of foods containing capsaicin is associated with a lower prevalence of obesity. Rural Thai people consume diets containing 0.014% capsaicin. Rodents fed a diet containing 0.014% capsaicin showed no change in caloric intake but a significant 24% and 29% reduction in the visceral (peri-renal) fat weight. Increase in intestinal blood flow facilitates nutrient energy absorption and decrease in adipose tissue blood flow facilitates storage of nutrient energy in adipose tissue. Stimulation of intestinal mucosal afferent nerves increases intestinal blood flow, but decreases visceral (mesenteric) adipost tissue blood flow. In in vitro cell studies capsaicin has a direct effect on adipocytes. Intravenous capsaicin produces measurable plasma level and subcutaneous capsaicin retards accumulation of adipose tissue. The data on a direct effect of oral capsaicin on adipose tissue at remote sites, however, are conflicting. Capsaicin absorbed from the gut lumen is almost completely metabolized before reaching the general circulation. Oral capsaicin significantly increases transient receptor potential vanilloid type-1 (TRPV1) channel expression as well as TRPV1 messenger ribonucleic acid (mRNA) in visceral adipose tissue. In TRPV1 knockout mice on a high fat diet the body weight was not significantly different in the absence or presence of oral capsaicin. In rodent experiments, daily intragastric administration of capsaicin for two weeks led to defunctionalization of intestinal mucosal afferent nerves, manifested by loss of acute mucosal capsaicin-induced effects; but not the corneal afferent nerves, with preservation of the paw wiping reflex of the eye exposed briefly to dilute capsaicin. The latter indicated the absence of an oral

  9. Dynamic Control of Synchronous Activity in Networks of Spiking Neurons.

    Directory of Open Access Journals (Sweden)

    Axel Hutt

    Full Text Available Oscillatory brain activity is believed to play a central role in neural coding. Accumulating evidence shows that features of these oscillations are highly dynamic: power, frequency and phase fluctuate alongside changes in behavior and task demands. The role and mechanism supporting this variability is however poorly understood. We here analyze a network of recurrently connected spiking neurons with time delay displaying stable synchronous dynamics. Using mean-field and stability analyses, we investigate the influence of dynamic inputs on the frequency of firing rate oscillations. We show that afferent noise, mimicking inputs to the neurons, causes smoothing of the system's response function, displacing equilibria and altering the stability of oscillatory states. Our analysis further shows that these noise-induced changes cause a shift of the peak frequency of synchronous oscillations that scales with input intensity, leading the network towards critical states. We lastly discuss the extension of these principles to periodic stimulation, in which externally applied driving signals can trigger analogous phenomena. Our results reveal one possible mechanism involved in shaping oscillatory activity in the brain and associated control principles.

  10. Dynamic Control of Synchronous Activity in Networks of Spiking Neurons.

    Science.gov (United States)

    Hutt, Axel; Mierau, Andreas; Lefebvre, Jérémie

    Oscillatory brain activity is believed to play a central role in neural coding. Accumulating evidence shows that features of these oscillations are highly dynamic: power, frequency and phase fluctuate alongside changes in behavior and task demands. The role and mechanism supporting this variability is however poorly understood. We here analyze a network of recurrently connected spiking neurons with time delay displaying stable synchronous dynamics. Using mean-field and stability analyses, we investigate the influence of dynamic inputs on the frequency of firing rate oscillations. We show that afferent noise, mimicking inputs to the neurons, causes smoothing of the system's response function, displacing equilibria and altering the stability of oscillatory states. Our analysis further shows that these noise-induced changes cause a shift of the peak frequency of synchronous oscillations that scales with input intensity, leading the network towards critical states. We lastly discuss the extension of these principles to periodic stimulation, in which externally applied driving signals can trigger analogous phenomena. Our results reveal one possible mechanism involved in shaping oscillatory activity in the brain and associated control principles.

  11. Giant renin secretory granules in beige mouse renal afferent arterioles

    DEFF Research Database (Denmark)

    Jensen, B L; Rasch, Ruth; Nyengaard, Jens Randel

    1997-01-01

    The mutant beige mouse (C57BL/6 bg) has a disease characterised by abnormally enlarged cytoplasmic granules in a variety of cells. With the purpose of establishing a suitable cellular model for studying renin secretion, the present study was undertaken to compare renin granule morphology in beige...... (average granular volume 0.681 microm3), whereas 1-2 large granules were present per cell in beige mice. The volume of afferent arteriole that contained secretory granules was lower in the beige mice. We conclude that the beige mouse synthesizes, stores and releases active renin. Renin secretory granules...... in beige mice are grossly enlarged with 1-2 granules per juxtaglomerular cell. Compared with control mice, a similar amount of total renin granule volume per afferent arteriole is contained in a smaller part of beige mouse afferent arteriole. Granular cells from beige mice could therefore be a valuable...

  12. ASIC3, an acid-sensing ion channel, is expressed in metaboreceptive sensory neurons

    Directory of Open Access Journals (Sweden)

    Fierro Leonardo

    2005-11-01

    Full Text Available Abstract Background ASIC3, the most sensitive of the acid-sensing ion channels, depolarizes certain rat sensory neurons when lactic acid appears in the extracellular medium. Two functions have been proposed for it: 1 ASIC3 might trigger ischemic pain in heart and muscle; 2 it might contribute to some forms of touch mechanosensation. Here, we used immunocytochemistry, retrograde labelling, and electrophysiology to ask whether the distribution of ASIC3 in rat sensory neurons is consistent with either of these hypotheses. Results Less than half (40% of dorsal root ganglion sensory neurons react with anti-ASIC3, and the population is heterogeneous. They vary widely in cell diameter and express different growth factor receptors: 68% express TrkA, the receptor for nerve growth factor, and 25% express TrkC, the NT3 growth factor receptor. Consistent with a role in muscle nociception, small ( Conclusion Our data indicates that: 1 ASIC3 is expressed in a restricted population of nociceptors and probably in some non-nociceptors; 2 co-expression of ASIC3 and CGRP, and the absence of P2X3, are distinguishing properties of a class of sensory neurons, some of which innervate blood vessels. We suggest that these latter afferents may be muscle metaboreceptors, neurons that sense the metabolic state of muscle and can trigger pain when there is insufficient oxygen.

  13. Rate response of neurons subject to fast or frozen noise: from stochastic and homogeneous to deterministic and heterogeneous populations.

    Science.gov (United States)

    Alijani, Azadeh Khajeh; Richardson, Magnus J E

    2011-07-01

    The response of a neuronal population to afferent drive can be expected to be sensitive to both the distribution and dynamics of membrane voltages within the population. Voltage fluctuations can be driven by synaptic noise, neuromodulators, or cellular inhomogeneities: processes ranging from millisecond autocorrelation times to effectively static or "frozen" noise. Here we extend previous studies of filtered fluctuations to the experimentally verified exponential integrate-and-fire model. How fast or frozen fluctuations affect the steady-state rate and firing-rate response are both examined using perturbative solutions and limits of a 1 + 2 dimensional Fokker-Planck equation. The central finding is that, under conditions of a more-or-less constant population voltage variance, the firing-rate response is only weakly dependent on the fluctuation filter constant: The voltage distribution is the principal determinant of the population response. This result is unexpected given the nature of the systems underlying the extreme limits of fast and frozen fluctuations; the first limit represents a homogeneous population of neurons firing stochastically, whereas the second limit is equivalent to a heterogeneous population of neurons firing deterministically.

  14. Neuronal plasticity in the hedgehog supraoptic nucleus during hibernation.

    Science.gov (United States)

    Sanchez-Toscano, F; Caminero, A A; Machin, C; Abella, G

    1989-01-01

    The purpose of the present study was to identify processes of plasticity in the receptive field of neurosecretory neurons of the supraoptic nucleus during hibernation in the hedgehog, in order to correlate them with the increased neurosecretory activity observed in this nucleus during this annual period. Using the Rapid Golgi method, a quantitative study was conducted in the receptive field of bipolar and multipolar neurons (the main components of the nucleus). Results indicate a generalized increase in the following characteristics: (1) number of dendritic spines per millimeter along the dendritic shafts; (2) degree of branching in the dendritic field; and (3) dendritic density around the neuronal soma. These data demonstrate modification of the dendritic field in the supraoptic nucleus during hibernation, a change undoubtedly related to functional conditions. Since the observed changes affect structures such as dendritic spines which are directly related to the arrival of neural afferences, the discussion is centered on the types of stimuli which may be responsible for the observed processes.

  15. Cochlear spike synchronization and neuron coincidence detection model

    Science.gov (United States)

    Bader, Rolf

    2018-02-01

    Coincidence detection of a spike pattern fed from the cochlea into a single neuron is investigated using a physical Finite-Difference model of the cochlea and a physiologically motivated neuron model. Previous studies have shown experimental evidence of increased spike synchronization in the nucleus cochlearis and the trapezoid body [Joris et al., J. Neurophysiol. 71(3), 1022-1036 and 1037-1051 (1994)] and models show tone partial phase synchronization at the transition from mechanical waves on the basilar membrane into spike patterns [Ch. F. Babbs, J. Biophys. 2011, 435135]. Still the traveling speed of waves on the basilar membrane cause a frequency-dependent time delay of simultaneously incoming sound wavefronts up to 10 ms. The present model shows nearly perfect synchronization of multiple spike inputs as neuron outputs with interspike intervals (ISI) at the periodicity of the incoming sound for frequencies from about 30 to 300 Hz for two different amounts of afferent nerve fiber neuron inputs. Coincidence detection serves here as a fusion of multiple inputs into one single event enhancing pitch periodicity detection for low frequencies, impulse detection, or increased sound or speech intelligibility due to dereverberation.

  16. Functional role of peripheral opioid receptors in the regulation of cardiac spinal afferent nerve activity during myocardial ischemia

    Science.gov (United States)

    Longhurst, John C.

    2013-01-01

    Thinly myelinated Aδ-fiber and unmyelinated C-fiber cardiac sympathetic (spinal) sensory nerve fibers are activated during myocardial ischemia to transmit the sensation of angina pectoris. Although recent observations showed that myocardial ischemia increases the concentrations of opioid peptides and that the stimulation of peripheral opioid receptors inhibits chemically induced visceral and somatic nociception, the role of opioids in cardiac spinal afferent signaling during myocardial ischemia has not been studied. The present study tested the hypothesis that peripheral opioid receptors modulate cardiac spinal afferent nerve activity during myocardial ischemia by suppressing the responses of cardiac afferent nerve to ischemic mediators like bradykinin and extracellular ATP. The nerve activity of single unit cardiac afferents was recorded from the left sympathetic chain (T2–T5) in anesthetized cats. Forty-three ischemically sensitive afferent nerves (conduction velocity: 0.32–3.90 m/s) with receptive fields in the left and right ventricles were identified. The responses of these afferent nerves to repeat ischemia or ischemic mediators were further studied in the following protocols. First, epicardial administration of naloxone (8 μmol), a nonselective opioid receptor antagonist, enhanced the responses of eight cardiac afferent nerves to recurrent myocardial ischemia by 62%, whereas epicardial application of vehicle (PBS) did not alter the responses of seven other cardiac afferent nerves to ischemia. Second, naloxone applied to the epicardial surface facilitated the responses of seven cardiac afferent nerves to epicardial ATP by 76%. Third, administration of naloxone enhanced the responses of seven other afferent nerves to bradykinin by 85%. In contrast, in the absence of naloxone, cardiac afferent nerves consistently responded to repeated application of ATP (n = 7) or bradykinin (n = 7). These data suggest that peripheral opioid peptides suppress the

  17. Afferent loop syndrome - a case report

    International Nuclear Information System (INIS)

    Borges, Ana Karina Nascimento; Pinheiro, Marco Antonio Lopes; Galvao, Cristine Norwig

    2000-01-01

    The afferent loop syndrome occurs in patients with previous gastric surgery for tumor, when there is anastomotic edema, use of inappropriate reconstruction technique for gastro jejunostomy or recurrent gastric cancer. Complaints such jaundice, intermittent abdominal distension associated with pain, and vomiting should be investigated in order to rule out this syndrome. (author)

  18. Functional Characterization of Lamina X Neurons in ex-Vivo Spinal Cord Preparation

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    Volodymyr Krotov

    2017-11-01

    Full Text Available Functional properties of lamina X neurons in the spinal cord remain unknown despite the established role of this area for somatosensory integration, visceral nociception, autonomic regulation and motoneuron output modulation. Investigations of neuronal functioning in the lamina X have been hampered by technical challenges. Here we introduce an ex-vivo spinal cord preparation with both dorsal and ventral roots still attached for functional studies of the lamina X neurons and their connectivity using an oblique LED illumination for resolved visualization of lamina X neurons in a thick tissue. With the elaborated approach, we demonstrate electrophysiological characteristics of lamina X neurons by their membrane properties, firing pattern discharge and fiber innervation (either afferent or efferent. The tissue preparation has been also probed using Ca2+ imaging with fluorescent Ca2+ dyes (membrane-impermeable or -permeable to demonstrate the depolarization-induced changes in intracellular calcium concentration in lamina X neurons. Finally, we performed visualization of subpopulations of lamina X neurons stained by retrograde labeling with aminostilbamidine dye to identify sympathetic preganglionic and projection neurons in the lamina X. Thus, the elaborated approach provides a reliable tool for investigation of functional properties and connectivity in specific neuronal subpopulations, boosting research of lamina X of the spinal cord.

  19. Bidirectional communication between sensory neurons and osteoblasts in an in vitro coculture system.

    Science.gov (United States)

    Kodama, Daisuke; Hirai, Takao; Kondo, Hisataka; Hamamura, Kazunori; Togari, Akifumi

    2017-02-01

    Recent studies have revealed that the sensory nervous system is involved in bone metabolism. However, the mechanism of communication between neurons and osteoblasts is yet to be elucidated. In this study, we investigated the signaling pathways between sensory neurons of the dorsal root ganglion (DRG) and the osteoblast-like MC3T3-E1 cells using an in vitro coculture system. Our findings indicate that signal transduction from DRG-derived neurons to MC3T3-E1 cells is suppressed by antagonists of the AMPA receptor and the NK 1 receptor. Conversely, signal transduction from MC3T3-E1 cells to DRG-derived neurons is suppressed by a P2X 7 receptor antagonist. Our results suggest that these cells communicate with each other by exocytosis of glutamate, substance P in the efferent signal, and ATP in the afferent signal. © 2017 Federation of European Biochemical Societies.

  20. Afferent control of central pattern generators: experimental analysis of locomotion in the decerebrate cat.

    Science.gov (United States)

    Baev, K V; Esipenko, V B; Shimansky YuP

    1991-01-01

    Changes in the motor activity of the spinal locomotor generator evoked by tonic and phasic peripheral afferent signals during fictitious locomotion of both slow and fast rhythms were analysed in the cat. The tonic afferent inflow was conditioned by the position of the hindlimb. The phasic afferent signals were imitated by electrical stimulation of hindlimb nerves. The correlation between the kinematics of hindlimb locomotor movement and sensory inflow was investigated during actual locomotion. Reliable correlations between motor activity parameters during fictitious locomotion were revealed in cases of both slow and fast "locomotor" rhythms. The main difference between these cases was that correlations "duration-intensity" were positive in the first and negative in the second case. The functional role of "locomotor" pattern dependence on tonic sensory inflow consisted of providing stability for planting the hindlimb on the ground. For any investigated afferent input the phase moments in the "locomotor" cycle were found, in which an afferent signal caused no rearrangement in locomotor generator activity. These moments corresponded to the transitions between "flexion" and "extension" phases and to the bursts of integral afferent activity observed during real locomotion. The data obtained are compared with the results previously described for the scratching generator. The character of changes in "locomotor" activity in response to tonic and phasic sensory signals was similar to that of such changes in "scratching" rhythm in the case of fast "locomotion". Intensification of the "flexion" phase caused by phasic high-intensity stimulation of cutaneous afferents during low "locomotor" rhythm was changed to inhibition (such as observed during "scratching") when this rhythm was fast. It is concluded that the main regularities of peripheral afferent control for both the locomotor and scratching generators are the same. Moreover, these central pattern generators are just

  1. Muscle afferent receptors engaged in augmented sympathetic responsiveness in peripheral artery disease

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    Jianhua eLi

    2012-07-01

    Full Text Available The exercise pressor reflex (EPR is a neural control mechanism responsible for the cardiovascular responses to exercise. As exercise is initiated, thin fiber muscle afferent nerves are activated by mechanical and metabolic stimuli arising in the contracting muscles. This leads to reflex increases in arterial blood pressure and heart rate primarily through activation of sympathetic nerve activity (SNA. Studies of humans and animals have indicated that the EPR is exaggerated in a number of cardiovascular diseases. For the last several years, studies have specifically employed a rodent model to examine the mechanisms at receptor and cellular levels by which responses of SNA and blood pressure to static exercise are heightened in peripheral artery disease (PAD, one of the most common cardiovascular disorders. A rat model of this disease has well been established. Specifically, femoral artery occlusion is used to study intermittent claudication that is observed in human PAD. The receptors on thin fiber muscle afferents that are engaged in this disease include transient receptor potential vanilloid type 1 (TRPV1, purinergic P2X and acid sensing ion channel (ASIC. The role played by nerve growth factor (NGF in regulating those sensory receptors in the processing of amplified EPR was also investigated. The purpose of this review is to focus on a theme namely that PAD accentuates autonomic reflex responses to exercise and further address regulatory mechanisms leading to abnormal sympathetic responsiveness. This review will present some of recent results in regard with several receptors in muscle sensory neurons in contribution to augmented autonomic reflex responses in PAD. Review of the findings from recent studies would lead to a better understanding in integrated processing of sympathetic nervous system in PAD.

  2. Exercise-induced neuronal plasticity in central autonomic networks: role in cardiovascular control.

    Science.gov (United States)

    Michelini, Lisete C; Stern, Javier E

    2009-09-01

    It is now well established that brain plasticity is an inherent property not only of the developing but also of the adult brain. Numerous beneficial effects of exercise, including improved memory, cognitive function and neuroprotection, have been shown to involve an important neuroplastic component. However, whether major adaptive cardiovascular adjustments during exercise, needed to ensure proper blood perfusion of peripheral tissues, also require brain neuroplasticity, is presently unknown. This review will critically evaluate current knowledge on proposed mechanisms that are likely to underlie the continuous resetting of baroreflex control of heart rate during/after exercise and following exercise training. Accumulating evidence indicates that not only somatosensory afferents (conveyed by skeletal muscle receptors, baroreceptors and/or cardiopulmonary receptors) but also projections arising from central command neurons (in particular, peptidergic hypothalamic pre-autonomic neurons) converge into the nucleus tractus solitarii (NTS) in the dorsal brainstem, to co-ordinate complex cardiovascular adaptations during dynamic exercise. This review focuses in particular on a reciprocally interconnected network between the NTS and the hypothalamic paraventricular nucleus (PVN), which is proposed to act as a pivotal anatomical and functional substrate underlying integrative feedforward and feedback cardiovascular adjustments during exercise. Recent findings supporting neuroplastic adaptive changes within the NTS-PVN reciprocal network (e.g. remodelling of afferent inputs, structural and functional neuronal plasticity and changes in neurotransmitter content) will be discussed within the context of their role as important underlying cellular mechanisms supporting the tonic activation and improved efficacy of these central pathways in response to circulatory demand at rest and during exercise, both in sedentary and in trained individuals. We hope this review will stimulate

  3. H2O2 INDUCES DELAYED HYPEREXCITABILITY IN NUCLEUS TRACTUS SOLITARII NEURONS

    Science.gov (United States)

    Ostrowski, Tim D.; Hasser, Eileen M.; Heesch, Cheryl M.; Kline, David D.

    2014-01-01

    Hydrogen peroxide (H2O2) is a stable reactive oxygen species and potent neuromodulator of cellular and synaptic activity. Centrally, endogenous H2O2 is elevated during bouts of hypoxia-reoxygenation, a variety of disease states, and aging. The nucleus tractus solitarii (nTS) is the central termination site of visceral afferents for homeostatic reflexes and contributes to reflex alterations during these conditions. We determined the extent to which H2O2 modulates synaptic and membrane properties in nTS neurons in rat brainstem slices. Stimulation of the tractus solitarii (which contains the sensory afferent fibers) evoked synaptic currents that were not altered by 10 – 500 μM H2O2. However, 500 μM H2O2 modulated several intrinsic membrane properties of nTS neurons, including a decrease in input resistance, hyperpolarization of resting membrane potential (RMP) and action potential (AP) threshold (THR), and an initial reduction in AP discharge to depolarizing current. H2O2 increased conductance of barium-sensitive potassium currents, and block of these currents ablated H2O2-induced changes in RMP, input resistance and AP discharge. Following washout of H2O2 AP discharge was enhanced due to depolarization of RMP and a partially maintained hyperpolarization of THR. Hyperexcitability persisted with repeated H2O2 exposure. H2O2 effects on RMP and THR were ablated by intracellular administration of the antioxidant catalase, which was immunohistochemically identified in neurons throughout the nTS. Thus, H2O2 initially reduces excitability of nTS neurons that is followed by sustained hyperexcitability, which may play a profound role in cardiorespiratory reflexes. PMID:24397952

  4. Inhibition of micturition reflex by activation of somatic afferents in posterior femoral cutaneous nerve.

    Science.gov (United States)

    Tai, Changfeng; Shen, Bing; Mally, Abhijith D; Zhang, Fan; Zhao, Shouguo; Wang, Jicheng; Roppolo, James R; de Groat, William C

    2012-10-01

    This study determined if activation of somatic afferents in posterior femoral cutaneous nerve (PFCN) could modulate the micturition reflex recorded under isovolumetric conditions in α-chloralose anaesthetized cats. PFCN stimulation inhibited reflex bladder activity and significantly (P acid (AA). The optimal frequency for PFCN stimulation-induced bladder inhibition was between 3 and 10 Hz, and a minimal stimulation intensity of half of the threshold for inducing anal twitching was required. Bilateral pudendal nerve transection eliminated PFCN stimulation-induced anal twitching but did not change the stimulation-induced bladder inhibition, excluding the involvement of pudendal afferent or efferent axons in PFCN afferent inhibition.Mechanical or electrical stimulation on the skin surface in the PFCN dermatome also inhibited bladder activity. Prolonged (2 × 30 min) PFCN stimulation induced a post-stimulation inhibition that persists for at least 2 h. This study revealed a new cutaneous-bladder reflex activated by PFCN afferents. Although the mechanisms and physiological functions of this cutaneous-bladder reflex need to be further studied, our data raise the possibility that stimulation of PFCN afferents might be useful clinically for the treatment of overactive bladder symptoms.

  5. Withdrawal and restoration of central vagal afferents within the dorsal vagal complex following subdiaphragmatic vagotomy.

    Science.gov (United States)

    Peters, James H; Gallaher, Zachary R; Ryu, Vitaly; Czaja, Krzysztof

    2013-10-15

    Vagotomy, a severing of the peripheral axons of the vagus nerve, has been extensively utilized to determine the role of vagal afferents in viscerosensory signaling. Vagotomy is also an unavoidable component of some bariatric surgeries. Although it is known that peripheral axons of the vagus nerve degenerate and then regenerate to a limited extent following vagotomy, very little is known about the response of central vagal afferents in the dorsal vagal complex to this type of damage. We tested the hypothesis that vagotomy results in the transient withdrawal of central vagal afferent terminals from their primary central target, the nucleus of the solitary tract (NTS). Sprague-Dawley rats underwent bilateral subdiaphragmatic vagotomy and were sacrificed 10, 30, or 60 days later. Plastic changes in vagal afferent fibers and synapses were investigated at the morphological and functional levels by using a combination of an anterograde tracer, synapse-specific markers, and patch-clamp electrophysiology in horizontal brain sections. Morphological data revealed that numbers of vagal afferent fibers and synapses in the NTS were significantly reduced 10 days following vagotomy and were restored to control levels by 30 days and 60 days, respectively. Electrophysiology revealed transient decreases in spontaneous glutamate release, glutamate release probability, and the number of primary afferent inputs. Our results demonstrate that subdiaphragmatic vagotomy triggers transient withdrawal and remodeling of central vagal afferent terminals in the NTS. The observed vagotomy-induced plasticity within this key feeding center of the brain may be partially responsible for the response of bariatric patients following gastric bypass surgery. Copyright © 2013 Wiley Periodicals, Inc.

  6. Coupling an aVLSI neuromorphic vision chip to a neurotrophic model of synaptic plasticity: the development of topography.

    Science.gov (United States)

    Elliott, Terry; Kramer, Jörg

    2002-10-01

    We couple a previously studied, biologically inspired neurotrophic model of activity-dependent competitive synaptic plasticity and neuronal development to a neuromorphic retina chip. Using this system, we examine the development and refinement of a topographic mapping between an array of afferent neurons (the retinal ganglion cells) and an array of target neurons. We find that the plasticity model can indeed drive topographic refinement in the presence of afferent activity patterns generated by a real-world device. We examine the resilience of the developing system to the presence of high levels of noise by adjusting the spontaneous firing rate of the silicon neurons.

  7. Morphological evidence for novel enteric neuronal circuitry in guinea pig distal colon.

    Science.gov (United States)

    Smolilo, D J; Costa, M; Hibberd, T J; Wattchow, D A; Spencer, Nick J

    2018-07-01

    The gastrointestinal (GI) tract is unique compared to all other internal organs; it is the only organ with its own nervous system and its own population of intrinsic sensory neurons, known as intrinsic primary afferent neurons (IPANs). How these IPANs form neuronal circuits with other functional classes of neurons in the enteric nervous system (ENS) is incompletely understood. We used a combination of light microscopy, immunohistochemistry and confocal microscopy to examine the topographical distribution of specific classes of neurons in the myenteric plexus of guinea-pig colon, including putative IPANs, with other classes of enteric neurons. These findings were based on immunoreactivity to the neuronal markers, calbindin, calretinin and nitric oxide synthase. We then correlated the varicose outputs formed by putative IPANs with subclasses of excitatory interneurons and motor neurons. We revealed that calbindin-immunoreactive varicosities form specialized structures resembling 'baskets' within the majority of myenteric ganglia, which were arranged in clusters around calretinin-immunoreactive neurons. These calbindin baskets directly arose from projections of putative IPANs and represent morphological evidence of preferential input from sensory neurons directly to a select group of calretinin neurons. Our findings uncovered that these neurons are likely to be ascending excitatory interneurons and excitatory motor neurons. Our study reveals for the first time in the colon, a novel enteric neural circuit, whereby calbindin-immunoreactive putative sensory neurons form specialized varicose structures that likely direct synaptic outputs to excitatory interneurons and motor neurons. This circuit likely forms the basis of polarized neuronal pathways underlying motility. © 2018 Wiley Periodicals, Inc.

  8. Ionic mechanisms of spinal neuronal cold hypersensitivity in ciguatera.

    Science.gov (United States)

    Patel, Ryan; Brice, Nicola L; Lewis, Richard J; Dickenson, Anthony H

    2015-12-01

    Cold hypersensitivity is evident in a range of neuropathies and can evoke sensations of paradoxical burning cold pain. Ciguatoxin poisoning is known to induce a pain syndrome caused by consumption of contaminated tropical fish that can persist for months and include pruritus and cold allodynia; at present no suitable treatment is available. This study examined, for the first time, the neural substrates and molecular components of Pacific ciguatoxin-2-induced cold hypersensitivity. Electrophysiological recordings of dorsal horn lamina V/VI wide dynamic range neurones were made in non-sentient rats. Subcutaneous injection of 10 nm ciguatoxin-2 into the receptive field increased neuronal responses to innocuous and noxious cooling. In addition, neuronal responses to low-threshold but not noxious punctate mechanical stimuli were also elevated. The resultant cold hypersensitivity was not reversed by 6-({2-[2-fluoro-6-(trifluoromethyl)phenoxy]-2-methylpropyl}carbamoyl)pyridine-3-carboxylic acid, an antagonist of transient receptor potential melastatin 8 (TRPM8). Both mechanical and cold hypersensitivity were completely prevented by co-injection with the Nav 1.8 antagonist A803467, whereas the transient receptor potential ankyrin 1 (TRPA1) antagonist A967079 only prevented hypersensitivity to innocuous cooling and partially prevented hypersensitivity to noxious cooling. In naive rats, neither innocuous nor noxious cold-evoked neuronal responses were inhibited by antagonists of Nav 1.8, TRPA1 or TRPM8 alone. Ciguatoxins may confer cold sensitivity to a subpopulation of cold-insensitive Nav 1.8/TRPA1-positive primary afferents, which could underlie the cold allodynia reported in ciguatera. These data expand the understanding of central spinal cold sensitivity under normal conditions and the role of these ion channels in this translational rat model of ciguatoxin-induced hypersensitivity. © 2015 The Authors. European Journal of Neuroscience published by Federation of

  9. Metabolic sensing neurons and the control of energy homeostasis.

    Science.gov (United States)

    Levin, Barry E

    2006-11-30

    The brain and periphery carry on a constant conversation; the periphery informs the brain about its metabolic needs and the brain provides for these needs through its control of somatomotor, autonomic and neurohumoral pathways involved in energy intake, expenditure and storage. Metabolic sensing neurons are the integrators of a variety of metabolic, humoral and neural inputs from the periphery. Such neurons, originally called "glucosensing", also respond to fatty acids, hormones and metabolites from the periphery. They are integrated within neural pathways involved in the regulation of energy homeostasis. Unlike most neurons, they utilize glucose and other metabolites as signaling molecules to regulate their membrane potential and firing rate. For glucosensing neurons, glucokinase acts as the rate-limiting step in glucosensing while the pathways that mediate responses to metabolites like lactate, ketone bodies and fatty acids are less well characterized. Many metabolic sensing neurons also respond to insulin and leptin and other peripheral hormones and receive neural inputs from peripheral organs. Each set of afferent signals arrives with different temporal profiles and by different routes and these inputs are summated at the level of the membrane potential to produce a given neural firing pattern. In some obese individuals, the relative sensitivity of metabolic sensing neurons to various peripheral inputs is genetically reduced. This may provide one mechanism underlying their propensity to become obese when exposed to diets high in fat and caloric density. Thus, metabolic sensing neurons may provide a potential therapeutic target for the treatment of obesity.

  10. TRPV1 Channels and Gastric Vagal Afferent Signalling in Lean and High Fat Diet Induced Obese Mice.

    Directory of Open Access Journals (Sweden)

    Stephen J Kentish

    Full Text Available Within the gastrointestinal tract vagal afferents play a role in control of food intake and satiety signalling. Activation of mechanosensitive gastric vagal afferents induces satiety. However, gastric vagal afferent responses to mechanical stretch are reduced in high fat diet mice. Transient receptor potential vanilloid 1 channels (TRPV1 are expressed in vagal afferents and knockout of TRPV1 reduces gastro-oesophageal vagal afferent responses to stretch. We aimed to determine the role of TRPV1 on gastric vagal afferent mechanosensitivity and food intake in lean and HFD-induced obese mice.TRPV1+/+ and -/- mice were fed either a standard laboratory diet or high fat diet for 20wks. Gastric emptying of a solid meal and gastric vagal afferent mechanosensitivity was determined.Gastric emptying was delayed in high fat diet mice but there was no difference between TRPV1+/+ and -/- mice on either diet. TRPV1 mRNA expression in whole nodose ganglia of TRPV1+/+ mice was similar in both dietary groups. The TRPV1 agonist N-oleoyldopamine potentiated the response of tension receptors in standard laboratory diet but not high fat diet mice. Food intake was greater in the standard laboratory diet TRPV1-/- compared to TRPV1+/+ mice. This was associated with reduced response of tension receptors to stretch in standard laboratory diet TRPV1-/- mice. Tension receptor responses to stretch were decreased in high fat diet compared to standard laboratory diet TRPV1+/+ mice; an effect not observed in TRPV1-/- mice. Disruption of TRPV1 had no effect on the response of mucosal receptors to mucosal stroking in mice on either diet.TRPV1 channels selectively modulate gastric vagal afferent tension receptor mechanosensitivity and may mediate the reduction in gastric vagal afferent mechanosensitivity in high fat diet-induced obesity.

  11. Plasticity of Select Primary Afferent Projections to the Dorsal Horn after a Lumbosacral Ventral Root Avulsion Injury and Root Replantation in Rats

    Directory of Open Access Journals (Sweden)

    Allison J. Bigbee

    2017-07-01

    Full Text Available Injuries to the conus medullaris and cauda equina portions of the spinal cord result in neurological impairments, including paralysis, autonomic dysfunction, and pain. In experimental studies, earlier investigations have shown that a lumbosacral ventral root avulsion (VRA injury results in allodynia, which may be ameliorated by surgical replantation of the avulsed ventral roots. Here, we investigated the long-term effects of an L6 + S1 VRA injury on the plasticity of three populations of afferent projections to the dorsal horn in rats. At 8 weeks after a unilateral L6 + S1 VRA injury, quantitative morphological studies of the adjacent L5 dorsal horn showed reduced immunoreactivity (IR for the vesicular glutamate transporter, VGLUT1 and isolectin B4 (IB4 binding, whereas IR for calcitonin gene-related peptide (CGRP was unchanged. The IR for VGLUT1 and CGRP as well as IB4 binding was at control levels in the L5 dorsal horn at 8 weeks following an acute surgical replantation of the avulsed L6 + S1 ventral roots. Quantitative morphological studies of the L5 dorsal root ganglia (DRGs showed unchanged neuronal numbers for both the VRA and replanted series compared to shams. The portions of L5 DRG neurons expressing IR for VGLUT1 and CGRP, and IB4 binding were also the same between the VRA, replanted, and sham-operated groups. We conclude that the L5 dorsal horn shows selective plasticity for VGLUT1 and IB4 primary afferent projections after an L6 + S1 VRA injury and surgical repair.

  12. Nociceptor sensory neurons suppress neutrophil and γδ T cell responses in bacterial lung infections and lethal pneumonia.

    Science.gov (United States)

    Baral, Pankaj; Umans, Benjamin D; Li, Lu; Wallrapp, Antonia; Bist, Meghna; Kirschbaum, Talia; Wei, Yibing; Zhou, Yan; Kuchroo, Vijay K; Burkett, Patrick R; Yipp, Bryan G; Liberles, Stephen D; Chiu, Isaac M

    2018-05-01

    Lung-innervating nociceptor sensory neurons detect noxious or harmful stimuli and consequently protect organisms by mediating coughing, pain, and bronchoconstriction. However, the role of sensory neurons in pulmonary host defense is unclear. Here, we found that TRPV1 + nociceptors suppressed protective immunity against lethal Staphylococcus aureus pneumonia. Targeted TRPV1 + -neuron ablation increased survival, cytokine induction, and lung bacterial clearance. Nociceptors suppressed the recruitment and surveillance of neutrophils, and altered lung γδ T cell numbers, which are necessary for immunity. Vagal ganglia TRPV1 + afferents mediated immunosuppression through release of the neuropeptide calcitonin gene-related peptide (CGRP). Targeting neuroimmunological signaling may be an effective approach to treat lung infections and bacterial pneumonia.

  13. Hyperbolic Plykin attractor can exist in neuron models

    DEFF Research Database (Denmark)

    Belykh, V.; Belykh, I.; Mosekilde, Erik

    2005-01-01

    Strange hyperbolic attractors are hard to find in real physical systems. This paper provides the first example of a realistic system, a canonical three-dimensional (3D) model of bursting neurons, that is likely to have a strange hyperbolic attractor. Using a geometrical approach to the study...... of the neuron model, we derive a flow-defined Poincare map giving ail accurate account of the system's dynamics. In a parameter region where the neuron system undergoes bifurcations causing transitions between tonic spiking and bursting, this two-dimensional map becomes a map of a disk with several periodic...... holes. A particular case is the map of a disk with three holes, matching the Plykin example of a planar hyperbolic attractor. The corresponding attractor of the 3D neuron model appears to be hyperbolic (this property is not verified in the present paper) and arises as a result of a two-loop (secondary...

  14. Control of somatic membrane potential in nociceptive neurons and its implications for peripheral nociceptive transmission

    Science.gov (United States)

    Du, Xiaona; Hao, Han; Gigout, Sylvain; Huang, Dongyang; Yang, Yuehui; Li, Li; Wang, Caixue; Sundt, Danielle; Jaffe, David B.; Zhang, Hailin; Gamper, Nikita

    2014-01-01

    Peripheral sensory ganglia contain somata of afferent fibres conveying somatosensory inputs to the central nervous system. Growing evidence suggests that the somatic/perisomatic region of sensory neurons can influence peripheral sensory transmission. Control of resting membrane potential (Erest) is an important mechanism regulating excitability, but surprisingly little is known about how Erest is regulated in sensory neuron somata or how changes in somatic/perisomatic Erest affect peripheral sensory transmission. We first evaluated the influence of several major ion channels on Erest in cultured small-diameter, mostly capsaicin-sensitive (presumed nociceptive) dorsal root ganglion (DRG) neurons. The strongest and most prevalent effect on Erest was achieved by modulating M channels, K2P and 4-aminopiridine-sensitive KV channels, while hyperpolarization-activated cyclic nucleotide-gated, voltage-gated Na+, and T-type Ca2+ channels to a lesser extent also contributed to Erest. Second, we investigated how varying somatic/perisomatic membrane potential, by manipulating ion channels of sensory neurons within the DRG, affected peripheral nociceptive transmission in vivo. Acute focal application of M or KATP channel enhancers or a hyperpolarization-activated cyclic nucleotide-gated channel blocker to L5 DRG in vivo significantly alleviated pain induced by hind paw injection of bradykinin. Finally, we show with computational modelling how somatic/perisomatic hyperpolarization, in concert with the low-pass filtering properties of the t-junction within the DRG, can interfere with action potential propagation. Our study deciphers a complement of ion channels that sets the somatic Erest of nociceptive neurons and provides strong evidence for a robust filtering role of the somatic and perisomatic compartments of peripheral nociceptive neuron. PMID:25168672

  15. Central projections of antennular chemosensory and mechanosensory afferents in the brain of the terrestrial hermit crab (Coenobita clypeatus; Coenobitidae, Anomura)

    Science.gov (United States)

    Tuchina, Oksana; Koczan, Stefan; Harzsch, Steffen; Rybak, Jürgen; Wolff, Gabriella; Strausfeld, Nicholas J.; Hansson, Bill S.

    2015-01-01

    The Coenobitidae (Decapoda, Anomura, Paguroidea) is a taxon of hermit crabs that includes two genera with a fully terrestrial life style as adults. Previous studies have shown that Coenobitidae have evolved a sense of spatial odor localization that is behaviorally highly relevant. Here, we examined the central olfactory pathway of these animals by analyzing central projections of the antennular nerve of Coenobita clypeatus, combining backfilling of the nerve with dextran-coupled dye, Golgi impregnations and three-dimensional reconstruction of the primary olfactory center, the antennular lobe. The principal pattern of putative olfactory sensory afferents in C. clypeatus is in many aspects similar to what have been established for aquatic decapod crustaceans, such as the spiny lobster Panulirus argus. However, there are also obvious differences that may, or may not represent adaptations related to a terrestrial lifestyle. In C. clypeatus, the antennular lobe dominates the deutocerebrum, having more than one thousand allantoid-shaped subunits. We observed two distinct patterns of sensory neuron innervation: putative olfactory afferents from the aesthetascs either supply the cap/subcap region of the subunits or they extend through its full depth. Our data also demonstrate that any one sensory axon can supply input to several subunits. Putative chemosensory (non-aesthetasc) and mechanosensory axons represent a different pathway and innervate the lateral and median antennular neuropils. Hence, we suggest that the chemosensory input in C. clypeatus might be represented via a dual pathway: aesthetascs target the antennular lobe, and bimodal sensilla target the lateral antennular neuropil and median antennular neuropil. The present data is compared to related findings in other decapod crustaceans. PMID:26236202

  16. Chemokines in neuron-glial cell interaction and pathogenesis of neuropathic pain.

    Science.gov (United States)

    Zhang, Zhi-Jun; Jiang, Bao-Chun; Gao, Yong-Jing

    2017-09-01

    Neuropathic pain resulting from damage or dysfunction of the nervous system is a highly debilitating chronic pain state and is often resistant to currently available treatments. It has become clear that neuroinflammation, mainly mediated by proinflammatory cytokines and chemokines, plays an important role in the establishment and maintenance of neuropathic pain. Chemokines were originally identified as regulators of peripheral immune cell trafficking and were also expressed in neurons and glial cells in the central nervous system. In recent years, accumulating studies have revealed the expression, distribution and function of chemokines in the spinal cord under chronic pain conditions. In this review, we provide evidence showing that several chemokines are upregulated after peripheral nerve injury and contribute to the pathogenesis of neuropathic pain via different forms of neuron-glia interaction in the spinal cord. First, chemokine CX3CL1 is expressed in primary afferents and spinal neurons and induces microglial activation via its microglial receptor CX3CR1 (neuron-to-microglia signaling). Second, CCL2 and CXCL1 are expressed in spinal astrocytes and act on CCR2 and CXCR2 in spinal neurons to increase excitatory synaptic transmission (astrocyte-to-neuron signaling). Third, we recently identified that CXCL13 is highly upregulated in spinal neurons after spinal nerve ligation and induces spinal astrocyte activation via receptor CXCR5 (neuron-to-astrocyte signaling). Strategies that target chemokine-mediated neuron-glia interactions may lead to novel therapies for the treatment of neuropathic pain.

  17. Role of local neurons in cerebrocortical vasodilation elicited from cerebellum

    International Nuclear Information System (INIS)

    Iadecola, C.; Arneric, S.P.; Baker, H.D.; Tucker, L.W.; Reis, D.J.

    1987-01-01

    The vasodilation elicited in cerebral cortex by stimulation of the cerebellar fastigial nucleus (FN) is mediated by input pathways coming from the basal forebrain. The authors studied whether these pathways mediate the cortical vasodilation via a direct action on local blood vessels or via interposed local neurons. Neurons were destroyed in the primary sensory cortex by local microinjection of the excitotoxin ibotenic acid (IBO). Five days later rats were anesthetized, paralyzed, and ventilated. Arterial pressure and blood gases were controlled, and FN was stimulated electrically. Local cerebral blood flow (LCBF) was measured using the [ 14 C]iodoantipyrine technique with autoradiography. Five days after IBO, neurons were destroyed in a restricted cortical area, and afferent fibers and terminals were preserved. The selectivity of the neuronal loss was established by histological and biochemical criteria and by transport of horseradish, peroxidase from or into the lesion. Within the lesion, resting LCBF was unaffected, but the increase in LCBF evoked from the FN was abolished. In contrast the vasodilation elicited by hypercapnia was preserved. In the rest of the brain the vasodilation elicited from FN was largely unaffected. The authors conclude that the vasodilation evoked from FN in cerebral cortex depends on the integrity of a restricted population of local neurons that interact with the local microvasculature

  18. Vascular smooth muscle cells express the alpha(1A) subunit of a P-/Q-type voltage-dependent Ca(2+)Channel, and It is functionally important in renal afferent arterioles

    DEFF Research Database (Denmark)

    Hansen, Pernille B. Lærkegaard; Jensen, Boye L.; Andreasen, D

    2000-01-01

    In the present study, we tested whether the alpha(1A) subunit, which encodes a neuronal isoform of voltage-dependent Ca(2+) channels (VDCCs) (P-/Q-type), was present and functional in vascular smooth muscle and renal resistance vessels. By reverse transcription-polymerase chain reaction...... preglomerular resistance vessels and aorta, as well as mesangial cells, and that P-type VDCCs contribute to Ca(2+) influx in aortic and renal VSMCs and are involved in depolarization-mediated contraction in renal afferent arterioles....

  19. Interdependency between mechanical parameters and afferent nerve discharge in remodeled diabetic Goto-Kakizaki rat intestine

    Directory of Open Access Journals (Sweden)

    Zhao J

    2017-12-01

    Full Text Available Jingbo Zhao,1 Jian Yang,1 Donghua Liao,1 Hans Gregersen2 1Giome Academia, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 2Giome Center, Department of Surgery, Chinese University of Hong Kong and Prince of Wales Hospital, Shatin, Hong Kong Background: Gastrointestinal disorders are very common in diabetic patients, but the pathogenesis is still not well understood. Peripheral afferent nerves may be involved due to the complex regulation of gastrointestinal function by the enteric nervous system. Objective: We aimed to characterize the stimulus–response function of afferent fibers innervating the jejunum in the Goto-Kakizaki (GK type 2 diabetic rat model. A key question is whether changes in afferent firing arise from remodeled tissue or from adaptive afferent processes. Design: Seven 32-week-old male GK rats and seven age-matched normal Wistar rats were studied. Firing from mesenteric afferent nerves was recorded in excised jejunal segments of seven GK rats and seven normal Wistar rats during ramp test, stress relaxation test, and creep test. The circumferential stress–strain, spike rate increase ratio (SRIR, and single unit firing rates were calculated for evaluation of interdependency of the mechanical stimulations and the afferent nerve discharge. Results: Elevated sensitivity to mechanical stimuli was found for diabetic nerve bundles and single unit activity (P<0.05. The stress relaxed less in the diabetic intestinal segment (P<0.05. Linear association between SRIR and the thickness of circumferential muscle layer was found at high stress levels as well as for SRIR and the glucose level. Conclusion: Altered viscoelastic properties and elevated mechanosensitivity were found in the GK rat intestine. The altered nerve signaling is related to muscle layer remodeling and glucose levels and may contribute to gastrointestinal symptoms experienced by diabetic patients. Keywords: afferents, spike rate, stress–strain, creep

  20. Interdependency between mechanical parameters and afferent nerve discharge in remodeled diabetic Goto-Kakizaki rat intestine.

    Science.gov (United States)

    Zhao, Jingbo; Yang, Jian; Liao, Donghua; Gregersen, Hans

    2017-01-01

    Gastrointestinal disorders are very common in diabetic patients, but the pathogenesis is still not well understood. Peripheral afferent nerves may be involved due to the complex regulation of gastrointestinal function by the enteric nervous system. We aimed to characterize the stimulus-response function of afferent fibers innervating the jejunum in the Goto-Kakizaki (GK) type 2 diabetic rat model. A key question is whether changes in afferent firing arise from remodeled tissue or from adaptive afferent processes. Seven 32-week-old male GK rats and seven age-matched normal Wistar rats were studied. Firing from mesenteric afferent nerves was recorded in excised jejunal segments of seven GK rats and seven normal Wistar rats during ramp test, stress relaxation test, and creep test. The circumferential stress-strain, spike rate increase ratio (SRIR), and single unit firing rates were calculated for evaluation of interdependency of the mechanical stimulations and the afferent nerve discharge. Elevated sensitivity to mechanical stimuli was found for diabetic nerve bundles and single unit activity ( P <0.05). The stress relaxed less in the diabetic intestinal segment ( P <0.05). Linear association between SRIR and the thickness of circumferential muscle layer was found at high stress levels as well as for SRIR and the glucose level. Altered viscoelastic properties and elevated mechanosensitivity were found in the GK rat intestine. The altered nerve signaling is related to muscle layer remodeling and glucose levels and may contribute to gastrointestinal symptoms experienced by diabetic patients.

  1. Somatic modulation of spinal reflex bladder activity mediated by nociceptive bladder afferent nerve fibers in cats.

    Science.gov (United States)

    Xiao, Zhiying; Rogers, Marc J; Shen, Bing; Wang, Jicheng; Schwen, Zeyad; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2014-09-15

    The goal of the present study was to determine if supraspinal pathways are necessary for inhibition of bladder reflex activity induced by activation of somatic afferents in the pudendal or tibial nerve. Cats anesthetized with α-chloralose were studied after acute spinal cord transection at the thoracic T9/T10 level. Dilute (0.25%) acetic acid was used to irritate the bladder, activate nociceptive afferent C-fibers, and trigger spinal reflex bladder contractions (amplitude: 19.3 ± 2.9 cmH2O). Hexamethonium (a ganglionic blocker, intravenously) significantly (P reflex bladder contractions to 8.5 ± 1.9 cmH2O. Injection of lidocaine (2%, 1-2 ml) into the sacral spinal cord or transection of the sacral spinal roots and spinal cord further reduced the contraction amplitude to 4.2 ± 1.3 cmH2O. Pudendal nerve stimulation (PNS) at frequencies of 0.5-5 Hz and 40 Hz but not at 10-20 Hz inhibited reflex bladder contractions, whereas tibial nerve stimulation (TNS) failed to inhibit bladder contractions at all tested frequencies (0.5-40 Hz). These results indicate that PNS inhibition of nociceptive afferent C-fiber-mediated spinal reflex bladder contractions can occur at the spinal level in the absence of supraspinal pathways, but TNS inhibition requires supraspinal pathways. In addition, this study shows, for the first time, that after acute spinal cord transection reflex bladder contractions can be triggered by activating nociceptive bladder afferent C-fibers using acetic acid irritation. Understanding the sites of action for PNS or TNS inhibition is important for the clinical application of pudendal or tibial neuromodulation to treat bladder dysfunctions. Copyright © 2014 the American Physiological Society.

  2. Illuminating the multifaceted roles of neurotransmission in shaping neuronal circuitry.

    Science.gov (United States)

    Okawa, Haruhisa; Hoon, Mrinalini; Yoshimatsu, Takeshi; Della Santina, Luca; Wong, Rachel O L

    2014-09-17

    Across the nervous system, neurons form highly stereotypic patterns of synaptic connections that are designed to serve specific functions. Mature wiring patterns are often attained upon the refinement of early, less precise connectivity. Much work has led to the prevailing view that many developing circuits are sculpted by activity-dependent competition among converging afferents, which results in the elimination of unwanted synapses and the maintenance and strengthening of desired connections. Studies of the vertebrate retina, however, have recently revealed that activity can play a role in shaping developing circuits without engaging competition among converging inputs that differ in their activity levels. Such neurotransmission-mediated processes can produce stereotypic wiring patterns by promoting selective synapse formation rather than elimination. We discuss how the influence of transmission may also be limited by circuit design and further highlight the importance of transmission beyond development in maintaining wiring specificity and synaptic organization of neural circuits. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. The visceromotor and somatic afferent nerves of the penis.

    Science.gov (United States)

    Diallo, Djibril; Zaitouna, Mazen; Alsaid, Bayan; Quillard, Jeanine; Ba, Nathalie; Allodji, Rodrigue Sètchéou; Benoit, Gérard; Bedretdinova, Dina; Bessede, Thomas

    2015-05-01

    Innervation of the penis supports erectile and sensory functions. This article aims to study the efferent autonomic (visceromotor) and afferent somatic (sensory) nervous systems of the penis and to investigate how these systems relate to vascular pathways. Penises obtained from five adult cadavers were studied via computer-assisted anatomic dissection (CAAD). The number of autonomic and somatic nerve fibers was compared using the Kruskal-Wallis test. Proximally, penile innervation was mainly somatic in the extra-albugineal sector and mainly autonomic in the intracavernosal sector. Distally, both sectors were almost exclusively supplied by somatic nerve fibers, except the intrapenile vascular anastomoses that accompanied both somatic and autonomic (nitrergic) fibers. From this point, the neural immunolabeling within perivascular nerve fibers was mixed (somatic labeling and autonomic labeling). Accessory afferent, extra-albugineal pathways supplied the outer layers of the penis. There is a major change in the functional type of innervation between the proximal and distal parts of the intracavernosal sector of the penis. In addition to the pelvis and the hilum of the penis, the intrapenile neurovascular routes are the third level where the efferent autonomic (visceromotor) and the afferent somatic (sensory) penile nerve fibers are close. Intrapenile neurovascular pathways define a proximal penile segment, which guarantees erectile rigidity, and a sensory distal segment. © 2015 International Society for Sexual Medicine.

  4. Cellular mechanisms for presynaptic inhibition of sensory afferents

    DEFF Research Database (Denmark)

    Perrier, Jean-Francois Marie; delgado-lezama, rodolfo; Christensen, Rasmus Kordt

    It is well established that presynaptic inhibition of primary afferents involves the activation of GABAA receptors located on presynaptic terminals. However, the source of GABA remains unknown. In an integrated preparation of the spinal cord of the adult turtle, we evoked dorsal root potentials...

  5. Afferent and efferent projections of the anterior cortical amygdaloid nucleus in the mouse.

    Science.gov (United States)

    Cádiz-Moretti, Bernardita; Abellán-Álvaro, María; Pardo-Bellver, Cecília; Martínez-García, Fernando; Lanuza, Enrique

    2017-09-01

    The anterior cortical amygdaloid nucleus (ACo) is a chemosensory area of the cortical amygdala that receives afferent projections from both the main and accessory olfactory bulbs. The role of this structure is unknown, partially due to a lack of knowledge of its connectivity. In this work, we describe the pattern of afferent and efferent projections of the ACo by using fluorogold and biotinylated dextranamines as retrograde and anterograde tracers, respectively. The results show that the ACo is reciprocally connected with the olfactory system and basal forebrain, as well as with the chemosensory and basomedial amygdala. In addition, it receives dense projections from the midline and posterior intralaminar thalamus, and moderate projections from the posterior bed nucleus of the stria terminalis, mesocortical structures and the hippocampal formation. Remarkably, the ACo projects moderately to the central nuclei of the amygdala and anterior bed nucleus of the stria terminalis, and densely to the lateral hypothalamus. Finally, minor connections are present with some midbrain and brainstem structures. The afferent projections of the ACo indicate that this nucleus might play a role in emotional learning involving chemosensory stimuli, such as olfactory fear conditioning. The efferent projections confirm this view and, given its direct output to the medial part of the central amygdala and the hypothalamic 'aggression area', suggest that the ACo can initiate defensive and aggressive responses elicited by olfactory or, to a lesser extent, vomeronasal stimuli. © 2017 Wiley Periodicals, Inc.

  6. Cells from the adult corneal stroma can be reprogrammed to a neuron-like cell using exogenous growth factors

    Energy Technology Data Exchange (ETDEWEB)

    Greene, Carol Ann, E-mail: carol.greene@auckland.ac.nz; Chang, Chuan-Yuan; Fraser, Cameron J.; Nelidova, Dasha E.; Chen, Jing A.; Lim, Angela; Brebner, Alex; McGhee, Jennifer; Sherwin, Trevor; Green, Colin R.

    2014-03-10

    Cells thought to be stem cells isolated from the cornea of the eye have been shown to exhibit neurogenic potential. We set out to uncover the identity and location of these cells within the cornea and to elucidate their neuronal protein and gene expression profile during the process of switching to a neuron-like cell. Here we report that every cell of the adult human and rat corneal stroma is capable of differentiating into a neuron-like cell when treated with neurogenic differentiation specifying growth factors. Furthermore, the expression of genes regulating neurogenesis and mature neuronal structure and function was increased. The switch from a corneal stromal cell to a neuron-like cell was also shown to occur in vivo in intact corneas of living rats. Our results clearly indicate that lineage specifying growth factors can affect changes in the protein and gene expression profiles of adult cells, suggesting that possibly many adult cell populations can be made to switch into another type of mature cell by simply modifying the growth factor environment. - Highlights: • Adult corneal stromal cells can differentiated into neuron-like cells. • Neuronal specification of the adult stromal cell population is stochastic. • Neuronal specification in an adult cell population can be brought about by growth factors.

  7. Cells from the adult corneal stroma can be reprogrammed to a neuron-like cell using exogenous growth factors

    International Nuclear Information System (INIS)

    Greene, Carol Ann; Chang, Chuan-Yuan; Fraser, Cameron J.; Nelidova, Dasha E.; Chen, Jing A.; Lim, Angela; Brebner, Alex; McGhee, Jennifer; Sherwin, Trevor; Green, Colin R.

    2014-01-01

    Cells thought to be stem cells isolated from the cornea of the eye have been shown to exhibit neurogenic potential. We set out to uncover the identity and location of these cells within the cornea and to elucidate their neuronal protein and gene expression profile during the process of switching to a neuron-like cell. Here we report that every cell of the adult human and rat corneal stroma is capable of differentiating into a neuron-like cell when treated with neurogenic differentiation specifying growth factors. Furthermore, the expression of genes regulating neurogenesis and mature neuronal structure and function was increased. The switch from a corneal stromal cell to a neuron-like cell was also shown to occur in vivo in intact corneas of living rats. Our results clearly indicate that lineage specifying growth factors can affect changes in the protein and gene expression profiles of adult cells, suggesting that possibly many adult cell populations can be made to switch into another type of mature cell by simply modifying the growth factor environment. - Highlights: • Adult corneal stromal cells can differentiated into neuron-like cells. • Neuronal specification of the adult stromal cell population is stochastic. • Neuronal specification in an adult cell population can be brought about by growth factors

  8. Sensitization of dural afferents underlies migraine-related behavior following meningeal application of interleukin-6 (IL-6

    Directory of Open Access Journals (Sweden)

    Yan Jin

    2012-01-01

    Full Text Available Abstract Background Migraine headache is one of the most common neurological disorders, but the pathophysiology contributing to migraine is poorly understood. Intracranial interleukin-6 (IL-6 levels have been shown to be elevated during migraine attacks, suggesting that this cytokine may facilitate pain signaling from the meninges and contribute to the development of headache. Methods Cutaneous allodynia was measured in rats following stimulation of the dura with IL-6 alone or in combination with the MEK inhibitor, U0126. The number of action potentials and latency to the first action potential peak in response to a ramp current stimulus as well as current threshold were measured in retrogradely-labeled dural afferents using patch-clamp electrophysiology. These recordings were performed in the presence of IL-6 alone or in combination with U0126. Association between ERK1 and Nav1.7 following IL-6 treatment was also measured by co-immunoprecipitation. Results Here we report that in awake animals, direct application of IL-6 to the dura produced dose-dependent facial and hindpaw allodynia. The MEK inhibitor U0126 blocked IL-6-induced allodynia indicating that IL-6 produced this behavioral effect through the MAP kinase pathway. In trigeminal neurons retrogradely labeled from the dura, IL-6 application decreased the current threshold for action potential firing. In response to a ramp current stimulus, cells treated with IL-6 showed an increase in the numbers of action potentials and a decrease in latency to the first spike, an effect consistent with phosphorylation of the sodium channel Nav1.7. Pretreatment with U0126 reversed hyperexcitability following IL-6 treatment. Moreover, co-immunoprecipitation experiments demonstrated an increased association between ERK1 and Nav1.7 following IL-6 treatment. Conclusions Our results indicate that IL-6 enhances the excitability of dural afferents likely via ERK-mediated modulation of Nav1.7 and these responses

  9. Unmasking of spiral ganglion neuron firing dynamics by membrane potential and neurotrophin-3.

    Science.gov (United States)

    Crozier, Robert A; Davis, Robin L

    2014-07-16

    Type I spiral ganglion neurons have a unique role relative to other sensory afferents because, as a single population, they must convey the richness, complexity, and precision of auditory information as they shape signals transmitted to the brain. To understand better the sophistication of spiral ganglion response properties, we compared somatic whole-cell current-clamp recordings from basal and apical neurons obtained during the first 2 postnatal weeks from CBA/CaJ mice. We found that during this developmental time period neuron response properties changed from uniformly excitable to differentially plastic. Low-frequency, apical and high-frequency basal neurons at postnatal day 1 (P1)-P3 were predominantly slowly accommodating (SA), firing at low thresholds with little alteration in accommodation response mode induced by changes in resting membrane potential (RMP) or added neurotrophin-3 (NT-3). In contrast, P10-P14 apical and basal neurons were predominately rapidly accommodating (RA), had higher firing thresholds, and responded to elevation of RMP and added NT-3 by transitioning to the SA category without affecting the instantaneous firing rate. Therefore, older neurons appeared to be uniformly less excitable under baseline conditions yet displayed a previously unrecognized capacity to change response modes dynamically within a remarkably stable accommodation framework. Because the soma is interposed in the signal conduction pathway, these specializations can potentially lead to shaping and filtering of the transmitted signal. These results suggest that spiral ganglion neurons possess electrophysiological mechanisms that enable them to adapt their response properties to the characteristics of incoming stimuli and thus have the capacity to encode a wide spectrum of auditory information. Copyright © 2014 the authors 0270-6474/14/349688-15$15.00/0.

  10. Afferent Innervation, Muscle Spindles, and Contractures Following Neonatal Brachial Plexus Injury in a Mouse Model.

    Science.gov (United States)

    Nikolaou, Sia; Hu, Liangjun; Cornwall, Roger

    2015-10-01

    We used an established mouse model of elbow flexion contracture after neonatal brachial plexus injury (NBPI) to test the hypothesis that preservation of afferent innervation protects against contractures and is associated with preservation of muscle spindles and ErbB signaling. A model of preganglionic C5 through C7 NBPI was first tested in mice with fluorescent axons using confocal imaging to confirm preserved afferent innervation of spindles despite motor end plate denervation. Preganglionic and postganglionic injuries were then created in wild-type mice. Four weeks later, we assessed total and afferent denervation of the elbow flexors by musculocutaneous nerve immunohistochemistry. Biceps muscle volume and cross-sectional area were measured by micro computed tomography. An observer who was blinded to the study protocol measured elbow flexion contractures. Biceps spindle and muscle fiber morphology and ErbB signaling pathway activity were assessed histologically and immunohistochemically. Preganglionic and postganglionic injuries caused similar total denervation and biceps muscle atrophy. However, after preganglionic injuries, afferent innervation was partially preserved and elbow flexion contractures were significantly less severe. Spindles degenerated after postganglionic injury but were preserved after preganglionic injury. ErbB signaling was inactivated in denervated spindles after postganglionic injury but ErbB signaling activity was preserved in spindles after preganglionic injury with retained afferent innervation. Preganglionic and postganglionic injuries were associated with upregulation of ErbB signaling in extrafusal muscle fibers. Contractures after NBPI are associated with muscle spindle degeneration and loss of spindle ErbB signaling activity. Preservation of afferent innervation maintained spindle development and ErbB signaling activity, and protected against contractures. Pharmacologic modulation of ErbB signaling, which is being investigated as a

  11. Prior Activation of Inositol 1,4,5-Trisphosphate Receptors Suppresses the Subsequent Induction of Long-Term Potentiation in Hippocampal CA1 Neurons

    Science.gov (United States)

    Fujii, Satoshi; Yamazaki, Yoshihiko; Goto, Jun-Ichi; Fujiwara, Hiroki; Mikoshiba, Katsuhiko

    2016-01-01

    We investigated the role of inositol 1,4,5-trisphosphate receptors (IP3Rs) activated by preconditioning low-frequency afferent stimulation (LFS) in the subsequent induction of long-term potentiation (LTP) in CA1 neurons in hippocampal slices from mature guinea pigs. Induction of LTP in the field excitatory postsynaptic potential or the population…

  12. Fatigue-induced changes in group IV muscle afferent activity: differences between high- and low-frequency electrically induced fatigues.

    Science.gov (United States)

    Darques, J L; Jammes, Y

    1997-03-07

    Recordings of group IV afferent activity of tibialis anterior muscle were performed in paralysed rabbits during runs of electrically induced fatigue produced by direct muscle stimulation at a high (100 Hz, high-frequency fatigue HFF) or a low rate (10 Hz, low-frequency fatigue LFF). In addition to analysis of afferent nerve action potentials, muscle force and compound muscle action potentials (M waves) elicited by direct muscle stimulation with single shocks were recorded. Changes in M wave configuration were used as an index of the altered propagation of membrane potentials and the associated efflux of potassium from muscle fibers. The data show that increased group IV afferent activity occurred during LFF as well as HFF trials and developed parallel with force failure. Enhanced afferent activity was significantly higher during LFF (maximal delta f(impulses) = 249 +/- 35%) than HFF (147 +/- 45%). No correlation was obtained between the responses of group IV afferents to LFF or to pressure exerted on tibialis anterior muscle. On the other hand, decreased M wave amplitude was minimal with LFF while it was pronounced with HFF. Close correlations were found between fatigue-induced activation of group IV afferents and decreases in force or M wave amplitude, but their strength was significantly higher with LFF compared to HFF. Thus, electrically induced fatigue activates group IV muscle afferents with a prominent effect of low-frequency stimulation. The mechanism of muscle afferent stimulation does not seem to be due to the sole increase in extracellular potassium concentration, but also by the efflux of muscle metabolites, present during fatiguing contractions at low rate of stimulation.

  13. Chloride regulates afferent arteriolar contraction in response to depolarization

    DEFF Research Database (Denmark)

    Hansen, P B; Jensen, B L; Skott, O

    1998-01-01

    -Renal vascular reactivity is influenced by the level of dietary salt intake. Recent in vitro data suggest that afferent arteriolar contractility is modulated by extracellular chloride. In the present study, we assessed the influence of chloride on K+-induced contraction in isolated perfused rabbit...... afferent arterioles. In 70% of vessels examined, K+-induced contraction was abolished by acute substitution of bath chloride. Consecutive addition of Cl- (30, 60, 80, 100, 110, and 117 mmol/L) restored the sensitivity to K+, and half-maximal response was observed at 82 mmol/L chloride. The calcium channel...... antagonist diltiazem (10(-6) mol/L) abolished K+-induced contractions. Bicarbonate did not modify the sensitivity to chloride. Norepinephrine (10(-6) mol/L) induced full contraction in depolarized vessels even in the absence of chloride. Iodide and nitrate were substituted for chloride with no inhibitory...

  14. Inflammatory mediators potentiate high affinity GABA(A) currents in rat dorsal root ganglion neurons.

    Science.gov (United States)

    Lee, Kwan Yeop; Gold, Michael S

    2012-06-19

    Following acute tissue injury action potentials may be initiated in afferent processes terminating in the dorsal horn of the spinal cord that are propagated back out to the periphery, a process referred to as a dorsal root reflex (DRR). The DRR is dependent on the activation of GABA(A) receptors. The prevailing hypothesis is that DRR is due to a depolarizing shift in the chloride equilibrium potential (E(Cl)) following an injury-induced activation of the Na(+)-K(+)-Cl(-)-cotransporter. Because inflammatory mediators (IM), such as prostaglandin E(2) are also released in the spinal cord following tissue injury, as well as evidence that E(Cl) is already depolarized in primary afferents, an alternative hypothesis is that an IM-induced increase in GABA(A) receptor mediated current (I(GABA)) could underlie the injury-induced increase in DRR. To test this hypothesis, we explored the impact of IM (prostaglandin E(2) (1 μM), bradykinin (10 μM), and histamine (1 μM)) on I(GABA) in dissociated rat dorsal root ganglion (DRG) neurons with standard whole cell patch clamp techniques. IM potentiated I(GABA) in a subpopulation of medium to large diameter capsaicin insensitive DRG neurons. This effect was dependent on the concentration of GABA, manifest only at low concentrations (emergence of injury-induced DRR. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  15. Short-term Synaptic Depression in the Feedforward Inhibitory Circuit in the Dorsal Lateral Geniculate Nucleus.

    Science.gov (United States)

    Augustinaite, Sigita; Heggelund, Paul

    2018-05-24

    Synaptic short-term plasticity (STP) regulates synaptic transmission in an activity-dependent manner and thereby has important roles in the signal processing in the brain. In some synapses, a presynaptic train of action potentials elicits post-synaptic potentials that gradually increase during the train (facilitation), but in other synapses, these potentials gradually decrease (depression). We studied STP in neurons in the visual thalamic relay, the dorsal lateral geniculate nucleus (dLGN). The dLGN contains two types of neurons: excitatory thalamocortical (TC) neurons, which transfer signals from retinal afferents to visual cortex, and local inhibitory interneurons, which form an inhibitory feedforward loop that regulates the thalamocortical signal transmission. The overall STP in the retino-thalamic relay is short-term depression, but the distinct kind and characteristics of the plasticity at the different types of synapses are unknown. We studied STP in the excitatory responses of interneurons to stimulation of retinal afferents, in the inhibitory responses of TC neurons to stimulation of afferents from interneurons, and in the disynaptic inhibitory responses of TC neurons to stimulation of retinal afferents. Moreover, we studied STP at the direct excitatory input to TC neurons from retinal afferents. The STP at all types of the synapses showed short-term depression. This depression can accentuate rapid changes in the stream of signals and thereby promote detectability of significant features in the sensory input. In vision, detection of edges and contours is essential for object perception, and the synaptic short-term depression in the early visual pathway provides important contributions to this detection process. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Connectivity of Pacemaker Neurons in the Neonatal Rat Superficial Dorsal Horn

    Science.gov (United States)

    Ford, Neil C.; Arbabi, Shahriar; Baccei, Mark L.

    2014-01-01

    Pacemaker neurons with an intrinsic ability to generate rhythmic burst-firing have been characterized in lamina I of the neonatal spinal cord, where they are innervated by high-threshold sensory afferents. However, little is known about the output of these pacemakers, as the neuronal populations which are targeted by pacemaker axons have yet to be identified. The present study combines patch clamp recordings in the intact neonatal rat spinal cord with tract-tracing to demonstrate that lamina I pacemaker neurons contact multiple spinal motor pathways during early life. Retrograde labeling of premotor interneurons with the trans-synaptic virus PRV-152 revealed the presence of burst-firing in PRV-infected lamina I neurons, thereby confirming that pacemakers are synaptically coupled to motor networks in the spinal ventral horn. Notably, two classes of pacemakers could be distinguished in lamina I based on cell size and the pattern of their axonal projections. While small pacemaker neurons possessed ramified axons which contacted ipsilateral motor circuits, large pacemaker neurons had unbranched axons which crossed the midline and ascended rostrally in the contralateral white matter. Recordings from identified spino-parabrachial and spino-PAG neurons indicated the presence of pacemaker activity within neonatal lamina I projection neurons. Overall, these results show that lamina I pacemakers are positioned to regulate both the level of activity in developing motor circuits as well as the ascending flow of nociceptive information to the brain, thus highlighting a potential role for pacemaker activity in the maturation of pain and sensorimotor networks in the CNS. PMID:25380417

  17. Merkel cells transduce and encode tactile stimuli to drive Aβ-afferent impulses

    Science.gov (United States)

    Ikeda, Ryo; Cha, Myeounghoon; Ling, Jennifer; Jia, Zhanfeng; Coyle, Dennis; Gu, Jianguo G.

    2014-01-01

    SUMMARY Sensory systems for detecting tactile stimuli have evolved from touch-sensing nerves in invertebrates to complicated tactile end-organs in mammals. Merkel discs are tactile end-organs consisting of Merkel cells and Aβ-afferent nerve endings, and are localized in fingertips, whisker hair follicles and other touch-sensitive spots. Merkel discs transduce touch into slowly adapting impulses to enable tactile discrimination, but their transduction and encoding mechanisms remain unknown. Using rat whisker hair follicles, we show that Merkel cells rather than Aβ-afferent nerve endings are primary sites of tactile transduction, and identify the Piezo2 ion channel as the Merkel cell mechanical transducer. Piezo2 transduces tactile stimuli into Ca2+-action potentials in Merkel cells, which drive Aβ-afferent nerve endings to fire slowly adapting impulses. We further demonstrate that Piezo2 and Ca2+-action potentials in Merkel cells are required for behavioral tactile responses. Our findings provide insights into how tactile end-organs function and have clinical implications for tactile dysfunctions. PMID:24746027

  18. Differential roles of stretch-sensitive pelvic nerve afferents innervating mouse distal colon and rectum

    OpenAIRE

    Feng, Bin; Brumovsky, Pablo R.; Gebhart, Gerald F.

    2010-01-01

    Information about colorectal distension (i.e., colorectal dilation by increased intraluminal pressure) is primarily encoded by stretch-sensitive colorectal afferents in the pelvic nerve (PN). Despite anatomic differences between rectum and distal colon, little is known about the functional roles of colonic vs. rectal afferents in the PN pathway or the quantitative nature of mechanosensory encoding. We utilized an in vitro mouse colorectum-PN preparation to investigate pressure-encoding charac...

  19. Collagen organization regulates stretch-initiated pain-related neuronal signals in vitro: Implications for structure-function relationships in innervated ligaments.

    Science.gov (United States)

    Zhang, Sijia; Singh, Sagar; Winkelstein, Beth A

    2018-02-01

    Injury to the spinal facet capsule, an innervated ligament with heterogeneous collagen organization, produces pain. Although mechanical facet joint trauma activates embedded afferents, it is unclear if, and how, the varied extracellular microstructure of its ligament affects sensory transduction for pain from mechanical inputs. To investigate the effects of macroscopic deformations on afferents in collagen matrices with different organizations, an in vitro neuron-collagen construct (NCC) model was used. NCCs with either randomly organized or parallel aligned collagen fibers were used to mimic the varied microstructure in the facet capsular ligament. Embryonic rat dorsal root ganglia (DRG) were encapsulated in the NCCs; axonal outgrowth was uniform and in all directions in random NCCs, but parallel in aligned NCCs. NCCs underwent uniaxial stretch (0.25 ± 0.06 strain) corresponding to sub-failure facet capsule strains that induce pain. Macroscopic NCC mechanics were measured and axonal expression of phosphorylated extracellular signal-regulated kinase (pERK) and the neurotransmitter substance P (SP) was assayed at 1 day to assess neuronal activation and nociception. Stretch significantly upregulated pERK expression in both random and aligned gels (p organization. These findings suggest that collagen organization differentially modulates pain-related neuronal signaling and support structural heterogeneity of ligament tissue as mediating sensory function. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:770-777, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  20. Sustained neurochemical plasticity in central terminals of mouse DRG neurons following colitis.

    Science.gov (United States)

    Benson, Jessica R; Xu, Jiameng; Moynes, Derek M; Lapointe, Tamia K; Altier, Christophe; Vanner, Stephen J; Lomax, Alan E

    2014-05-01

    Sensitization of dorsal root ganglia (DRG) neurons is an important mechanism underlying the expression of chronic abdominal pain caused by intestinal inflammation. Most studies have focused on changes in the peripheral terminals of DRG neurons in the inflamed intestine but recent evidence suggests that the sprouting of central nerve terminals in the dorsal horn is also important. Therefore, we examine the time course and reversibility of changes in the distribution of immunoreactivity for substance P (SP), a marker of the central terminals of DRG neurons, in the spinal cord during and following dextran sulphate sodium (DSS)-induced colitis in mice. Acute and chronic treatment with DSS significantly increased SP immunoreactivity in thoracic and lumbosacral spinal cord segments. This increase developed over several weeks and was evident in both the superficial laminae of the dorsal horn and in lamina X. These increases persisted for 5 weeks following cessation of both the acute and chronic models. The increase in SP immunoreactivity was not observed in segments of the cervical spinal cord, which were not innervated by the axons of colonic afferent neurons. DRG neurons dissociated following acute DSS-colitis exhibited increased neurite sprouting compared with neurons dissociated from control mice. These data suggest significant colitis-induced enhancements in neuropeptide expression in DRG neuron central terminals. Such neurotransmitter plasticity persists beyond the period of active inflammation and might contribute to a sustained increase in nociceptive signaling following the resolution of inflammation.

  1. Serotonin, dopamine and noradrenaline adjust actions of myelinated afferents via modulation of presynaptic inhibition in the mouse spinal cord.

    Directory of Open Access Journals (Sweden)

    David L García-Ramírez

    Full Text Available Gain control of primary afferent neurotransmission at their intraspinal terminals occurs by several mechanisms including primary afferent depolarization (PAD. PAD produces presynaptic inhibition via a reduction in transmitter release. While it is known that descending monoaminergic pathways complexly regulate sensory processing, the extent these actions include modulation of afferent-evoked PAD remains uncertain. We investigated the effects of serotonin (5HT, dopamine (DA and noradrenaline (NA on afferent transmission and PAD. Responses were evoked by stimulation of myelinated hindlimb cutaneous and muscle afferents in the isolated neonatal mouse spinal cord. Monosynaptic responses were examined in the deep dorsal horn either as population excitatory synaptic responses (recorded as extracellular field potentials; EFPs or intracellular excitatory postsynaptic currents (EPSCs. The magnitude of PAD generated intraspinally was estimated from electrotonically back-propagating dorsal root potentials (DRPs recorded on lumbar dorsal roots. 5HT depressed the DRP by 76%. Monosynaptic actions were similarly depressed by 5HT (EFPs 54%; EPSCs 75% but with a slower time course. This suggests that depression of monosynaptic EFPs and DRPs occurs by independent mechanisms. DA and NA had similar depressant actions on DRPs but weaker effects on EFPs. IC50 values for DRP depression were 0.6, 0.8 and 1.0 µM for 5HT, DA and NA, respectively. Depression of DRPs by monoamines was nearly-identical in both muscle and cutaneous afferent-evoked responses, supporting a global modulation of the multimodal afferents stimulated. 5HT, DA and NA produced no change in the compound antidromic potentials evoked by intraspinal microstimulation indicating that depression of the DRP is unrelated to direct changes in the excitability of intraspinal afferent fibers, but due to metabotropic receptor activation. In summary, both myelinated afferent-evoked DRPs and monosynaptic

  2. Influence of oculomotor nerve afferents on central endings of primary trigeminal fibers.

    Science.gov (United States)

    Manni, E; Bortolami, R; Pettorossi, V E; Lucchi, M L; Callegari, E; Draicchio, F

    1987-12-01

    Painful fibers running in the third nerve and originating from the ophthalmic trigeminal area send their central projections at level of substantia gelatinosa of nucleus caudalis trigemini. The central endings of these fibers form axoaxonic synapses with trigeminal fibers entering the brain stem through the trigeminal root. The effect of electrical stimulation of the third nerve central stump on the central endings of trigeminal afferent fibers consists in an increased excitability, possibly resulting in a presynaptic inhibition. This inhibitory influence is due to both direct and indirect connections of the third nerve afferent fibers with the trigeminal ones.

  3. Gaze-Stabilizing Central Vestibular Neurons Project Asymmetrically to Extraocular Motoneuron Pools.

    Science.gov (United States)

    Schoppik, David; Bianco, Isaac H; Prober, David A; Douglass, Adam D; Robson, Drew N; Li, Jennifer M B; Greenwood, Joel S F; Soucy, Edward; Engert, Florian; Schier, Alexander F

    2017-11-22

    Within reflex circuits, specific anatomical projections allow central neurons to relay sensations to effectors that generate movements. A major challenge is to relate anatomical features of central neural populations, such as asymmetric connectivity, to the computations the populations perform. To address this problem, we mapped the anatomy, modeled the function, and discovered a new behavioral role for a genetically defined population of central vestibular neurons in rhombomeres 5-7 of larval zebrafish. First, we found that neurons within this central population project preferentially to motoneurons that move the eyes downward. Concordantly, when the entire population of asymmetrically projecting neurons was stimulated collectively, only downward eye rotations were observed, demonstrating a functional correlate of the anatomical bias. When these neurons are ablated, fish failed to rotate their eyes following either nose-up or nose-down body tilts. This asymmetrically projecting central population thus participates in both upward and downward gaze stabilization. In addition to projecting to motoneurons, central vestibular neurons also receive direct sensory input from peripheral afferents. To infer whether asymmetric projections can facilitate sensory encoding or motor output, we modeled differentially projecting sets of central vestibular neurons. Whereas motor command strength was independent of projection allocation, asymmetric projections enabled more accurate representation of nose-up stimuli. The model shows how asymmetric connectivity could enhance the representation of imbalance during nose-up postures while preserving gaze stabilization performance. Finally, we found that central vestibular neurons were necessary for a vital behavior requiring maintenance of a nose-up posture: swim bladder inflation. These observations suggest that asymmetric connectivity in the vestibular system facilitates representation of ethologically relevant stimuli without

  4. Piezo Is Essential for Amiloride-Sensitive Stretch-Activated Mechanotransduction in Larval Drosophila Dorsal Bipolar Dendritic Sensory Neurons.

    Science.gov (United States)

    Suslak, Thomas J; Watson, Sonia; Thompson, Karen J; Shenton, Fiona C; Bewick, Guy S; Armstrong, J Douglas; Jarman, Andrew P

    2015-01-01

    Stretch-activated afferent neurons, such as those of mammalian muscle spindles, are essential for proprioception and motor co-ordination, but the underlying mechanisms of mechanotransduction are poorly understood. The dorsal bipolar dendritic (dbd) sensory neurons are putative stretch receptors in the Drosophila larval body wall. We have developed an in vivo protocol to obtain receptor potential recordings from intact dbd neurons in response to stretch. Receptor potential changes in dbd neurons in response to stretch showed a complex, dynamic profile with similar characteristics to those previously observed for mammalian muscle spindles. These profiles were reproduced by a general in silico model of stretch-activated neurons. This in silico model predicts an essential role for a mechanosensory cation channel (MSC) in all aspects of receptor potential generation. Using pharmacological and genetic techniques, we identified the mechanosensory channel, DmPiezo, in this functional role in dbd neurons, with TRPA1 playing a subsidiary role. We also show that rat muscle spindles exhibit a ruthenium red-sensitive current, but found no expression evidence to suggest that this corresponds to Piezo activity. In summary, we show that the dbd neuron is a stretch receptor and demonstrate that this neuron is a tractable model for investigating mechanisms of mechanotransduction.

  5. NeuronBank: a tool for cataloging neuronal circuitry

    Directory of Open Access Journals (Sweden)

    Paul S Katz

    2010-04-01

    Full Text Available The basic unit of any nervous system is the neuron. Therefore, understanding the operation of nervous systems ultimately requires an inventory of their constituent neurons and synaptic connectivity, which form neural circuits. The presence of uniquely identifiable neurons or classes of neurons in many invertebrates has facilitated the construction of cellular-level connectivity diagrams that can be generalized across individuals within a species. Homologous neurons can also be recognized across species. Here we describe NeuronBank.org, a web-based tool that we are developing for cataloging, searching, and analyzing neuronal circuitry within and across species. Information from a single species is represented in an individual branch of NeuronBank. Users can search within a branch or perform queries across branches to look for similarities in neuronal circuits across species. The branches allow for an extensible ontology so that additional characteristics can be added as knowledge grows. Each entry in NeuronBank generates a unique accession ID, allowing it to be easily cited. There is also an automatic link to a Wiki page allowing an encyclopedic explanation of the entry. All of the 44 previously published neurons plus one previously unpublished neuron from the mollusc, Tritonia diomedea, have been entered into a branch of NeuronBank as have 4 previously published neurons from the mollusc, Melibe leonina. The ability to organize information about neuronal circuits will make this information more accessible, ultimately aiding research on these important models.

  6. The Renal Nerves in Chronic Heart Failure: Afferent and Efferent Mechanisms

    Directory of Open Access Journals (Sweden)

    Alicia Marie Schiller

    2015-08-01

    Full Text Available The function of the renal nerves has been an area of scientific and medical interest for many years. The recent advent of a minimally invasive catheter-based method of renal denervation has renewed excitement in understanding the afferent and efferent actions of the renal nerves in multiple diseases. While hypertension has been the focus of much this work, less attention has been given to the role of the renal nerves in the development of chronic heart failure (CHF. Recent studies from our laboratory and those of others implicate an essential role for the renal nerves in the development and progression of CHF. Using a rabbit tachycardia model of CHF and surgical unilateral renal denervation, we provide evidence for both renal efferent and afferent mechanisms in the pathogenesis of CHF. Renal denervation prevented the decrease in renal blood flow observed in CHF while also preventing increases in Angiotensin-II receptor protein in the microvasculature of the renal cortex. Renal denervation in CHF also reduced physiological markers of autonomic dysfunction including an improvement in arterial baroreflex function, heart rate variability, and decreased resting cardiac sympathetic tone. Taken together, the renal sympathetic nerves are necessary in the pathogenesis of CHF via both efferent and afferent

  7. Neocortical inhibitory activities and long-range afferents contribute to the synchronous onset of silent states of the neocortical slow oscillation.

    Science.gov (United States)

    Lemieux, Maxime; Chauvette, Sylvain; Timofeev, Igor

    2015-02-01

    During slow-wave sleep, neurons of the thalamocortical network are engaged in a slow oscillation (<1 Hz), which consists of an alternation between the active and the silent states. Several studies have provided insights on the transition from the silent, which are essentially periods of disfacilitation, to the active states. However, the conditions leading to the synchronous onset of the silent state remain elusive. We hypothesized that a synchronous input to local inhibitory neurons could contribute to the transition to the silent state in the cat suprasylvian gyrus during natural sleep and under ketamine-xylazine anesthesia. After partial and complete deafferentation of the cortex, we found that the silent state onset was more variable among remote sites. We found that the transition to the silent state was preceded by a reduction in excitatory postsynaptic potentials and firing probability in cortical neurons. We tested the impact of chloride-mediated inhibition in the silent-state onset. We uncovered a long-duration (100-300 ms) inhibitory barrage occurring about 250 ms before the silent state onset in 3-6% of neurons during anesthesia and in 12-15% of cases during natural sleep. These inhibitory activities caused a decrease in cortical firing that reduced the excitatory drive in the neocortical network. That chain reaction of disfacilitation ends up on the silent state. Electrical stimuli could trigger a network silent state with a maximal efficacy in deep cortical layers. We conclude that long-range afferents to the neocortex and chloride-mediated inhibition play a role in the initiation of the silent state. Copyright © 2015 the American Physiological Society.

  8. GABA in Paraventricular Nucleus Regulates Adipose Afferent Reflex in Rats.

    Directory of Open Access Journals (Sweden)

    Lei Ding

    Full Text Available Chemical stimulation of white adipose tissue (WAT induces adipose afferent reflex (AAR, and thereby causes a general sympathetic activation. Paraventricular nucleus (PVN is important in control of sympathetic outflow. This study was designed to investigate the role of γ-aminobutyric acid (GABA in PVN in regulating the AAR.Experiments were carried out in anesthetized rats. Renal sympathetic nerve activity (RSNA and mean arterial pressure (MAP were continuously recorded. AAR was evaluated by the RSNA and MAP responses to electrical stimulation of the right epididymal WAT (eWAT afferent nerve. Electrical stimulation of eWAT afferent nerve increase RSNA. Bilateral microinjection of the GABAA receptor agonist isoguvacine or the GABAB receptor agonist baclofen attenuated the AAR. The effect of isoguvacine on the AAR was greater than that of baclofen. The GABAA receptor antagonist gabazine enhanced the AAR, while the GABAB receptor antagonist CGP-35348 had no significant effect on the AAR. Bilateral PVN microinjection of vigabatrin, a selective GABA-transaminase inhibitor, to increase endogenous GABA levels in the PVN abolished the AAR. The inhibitory effect of vigabatrin on the AAR was attenuated by the pretreatment with gabazine or CGP-35348. Pretreatment with combined gabazine and CGP-35348 abolished the effects of vigabatrin.Activation of GABAA or GABAB receptors in the PVN inhibits the AAR. Blockade of GABAA receptors in the PVN enhances the AAR. Endogenous GABA in the PVN plays an important role in regulating the AAR.

  9. How many neurons can we see with current spike sorting algorithms?

    Science.gov (United States)

    Pedreira, Carlos; Martinez, Juan; Ison, Matias J; Quian Quiroga, Rodrigo

    2012-10-15

    Recent studies highlighted the disagreement between the typical number of neurons observed with extracellular recordings and the ones to be expected based on anatomical and physiological considerations. This disagreement has been mainly attributed to the presence of sparsely firing neurons. However, it is also possible that this is due to limitations of the spike sorting algorithms used to process the data. To address this issue, we used realistic simulations of extracellular recordings and found a relatively poor spike sorting performance for simulations containing a large number of neurons. In fact, the number of correctly identified neurons for single-channel recordings showed an asymptotic behavior saturating at about 8-10 units, when up to 20 units were present in the data. This performance was significantly poorer for neurons with low firing rates, as these units were twice more likely to be missed than the ones with high firing rates in simulations containing many neurons. These results uncover one of the main reasons for the relatively low number of neurons found in extracellular recording and also stress the importance of further developments of spike sorting algorithms. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Cerebro-afferent vessel and pupillary basal diameter variation induced by stomatognathic trigeminal proprioception: a case report.

    Science.gov (United States)

    De Cicco, Vincenzo

    2012-09-03

    A patient affected by asymmetric hemodynamics of cerebro-afferent vessels underwent duplex color scanner investigations in occlusal proprioceptive un- and rebalance conditions. Pupillometric video-oculographic examinations were performed in order to spot connected trigeminal proprioceptive motor patterns able to interfere on sympathetic autonomic activity. The aim of this case report is to verify if involuntary jaw closing during swallowing, executed in unbalance and rebalance myoelectric activity, would be able to modify cerebral hemodynamics. A 56-year-old Caucasian Italian woman affected by asymmetric blood flow of cerebro-afferent vessels underwent an electromyographic investigation of her occlusal muscles in order to assess their occlusal functional balance. The extreme asymmetry of myoelectric activity in dental occlusion evidenced by electromyographic values suggested the rebalancing of the functions of occlusal muscles through concurrent transcutaneous stimulation of the trigeminal nerve supra- and submandibular motor branches. The above-mentioned method allowed the detection of a symmetric craniomandibular muscular relation that can be kept constant through the use of a cusp bite modeled on the inferior dental arch: called orthotic-syntropic bite for its peculiar use of electrostimulation. A few days later, the patient underwent a duplex color scanner investigation and pupillometric video-oculographic examinations in occlusal unbalance and rebalance conditions. A comparative data analysis showed that an unbalanced dental occlusal function may represent an interferential pattern on cerebral hemodynamics velocity and pupillometric evaluations have proved useful both in the analysis of locus coeruleus functional modalities and as a diagnostic tool in the assessment of pathologies involving locus coeruleus and autonomic systems. The inclusion of myoelectric masseter examinations can be useful in patients with asymmetric hemodynamics of cerebro-afferent

  11. Age-related Changes in Lateral Entorhinal and CA3 Neuron Allocation Predict Poor Performance on Object Discrimination

    Directory of Open Access Journals (Sweden)

    Andrew P. Maurer

    2017-06-01

    Full Text Available Age-related memory deficits correlate with dysfunction in the CA3 subregion of the hippocampus, which includes both hyperactivity and overly rigid activity patterns. While changes in intrinsic membrane currents and interneuron alterations are involved in this process, it is not known whether alterations in afferent input to CA3 also contribute. Neurons in layer II of the lateral entorhinal cortex (LEC project directly to CA3 through the perforant path, but no data are available regarding the effects of advanced age on LEC activity and whether these activity patterns update in response to environmental change. Furthermore, it is not known the extent to which age-related deficits in sensory discrimination relate to the inability of aged CA3 neurons to update in response to new environments. Young and aged rats were pre-characterized on a LEGO© object discrimination task, comparable to behavioral tests in humans in which CA3 hyperactivity has been linked to impairments. The cellular compartment analysis of temporal activity with fluorescence in situ hybridization for the immediate-early gene Arc was then used to identify the principal cell populations that were active during two distinct epochs of random foraging in different environments. This approach enabled the extent to which rats could discriminate two similar objects to be related to the ability of CA3 neurons to update across different environments. In both young and aged rats, there were animals that performed poorly on the LEGO object discrimination task. In the aged rats only, however, the poor performers had a higher percent of CA3 neurons that were active during random foraging in a novel environment, but this is not related to the ability of CA3 neurons to remap when the environment changed. Afferent neurons to CA3 in LEC, as identified with the retrograde tracer choleratoxin B (CTB, also showed a higher percentage of cells that were positive for Arc mRNA in aged poor performing rats

  12. Somatostatin receptors in rat hippocampus: localization to intrinsic neurons

    International Nuclear Information System (INIS)

    Palacios, J.M.; Reubi, J.C.; Maurer, R.

    1986-01-01

    The effect of neurotoxic chemical and electrolytical lesions on somatostatin (SS) receptor binding in the septo-hippocampal afferents, pyramidal and granule cells of the rat hippocampus was examined by autoradiography using the stable SS analogue 125 I-204-090 as radioligand. Electrolytical lesions of the septum did not result in modification of SS binding in the hippocampus. In contrast, both granule cell lesion with colchicine and pyramidal or pyramidal and granule cell lesions with increasing kainic acid doses did result in a specific decrease of binding in the dentate gyrus and hippocampus (CA 1 and CA 3 ). These results suggest that SS receptors in the hippocampus are probably associated with elements from intrinsic neurons. (Author)

  13. Neural Plasticity: Single Neuron Models for Discrimination and Generalization and AN Experimental Ensemble Approach.

    Science.gov (United States)

    Munro, Paul Wesley

    A special form for modification of neuronal response properties is described in which the change in the synaptic state vector is parallel to the vector of afferent activity. This process is termed "parallel modification" and its theoretical and experimental implications are examined. A theoretical framework has been devised to describe the complementary functions of generalization and discrimination by single neurons. This constitutes a basis for three models each describing processes for the development of maximum selectivity (discrimination) and minimum selectivity (generalization) by neurons. Strengthening and weakening of synapses is expressed as a product of the presynaptic activity and a nonlinear modulatory function of two postsynaptic variables--namely a measure of the spatially integrated activity of the cell and a temporal integration (time-average) of that activity. Some theorems are given for low-dimensional systems and computer simulation results from more complex systems are discussed. Model neurons that achieve high selectivity mimic the development of cat visual cortex neurons in a wide variety of rearing conditions. A role for low-selectivity neurons is proposed in which they provide inhibitory input to neurons of the opposite type, thereby suppressing the common component of a pattern class and enhancing their selective properties. Such contrast-enhancing circuits are analyzed and supported by computer simulation. To enable maximum selectivity, the net inhibition to a cell must become strong enough to offset whatever excitation is produced by the non-preferred patterns. Ramifications of parallel models for certain experimental paradigms are analyzed. A methodology is outlined for testing synaptic modification hypotheses in the laboratory. A plastic projection from one neuronal population to another will attain stable equilibrium under periodic electrical stimulation of constant intensity. The perturbative effect of shifting this intensity level

  14. Neonatal capsaicin causes compensatory adjustments to energy homeostasis in rats

    NARCIS (Netherlands)

    van de Wall, E. H. E. M.; Wielinga, P. Y.; Strubbe, J. H.; van Dijk, G.

    2006-01-01

    Several mechanisms involved in ingestive behavior and neuroendocrine activity rely on vagal afferent neuronal signaling. Seemingly contradictory to this idea are observations that vagal afferent neuronal ablation by neonatal capsaicin (CAP) treatment has relatively small effects on glucose

  15. A long noncoding RNA contributes to neuropathic pain by silencing Kcna2 in primary afferent neurons

    Science.gov (United States)

    Zhao, Xiuli; Tang, Zongxiang; Zhang, Hongkang; Atianjoh, Fidelis E.; Zhao, Jian-Yuan; Liang, Lingli; Wang, Wei; Guan, Xiaowei; Kao, Sheng-Chin; Tiwari, Vinod; Gao, Yong-Jing; Hoffman, Paul N.; Cui, Hengmi; Li, Min; Dong, Xinzhong; Tao, Yuan-Xiang

    2013-01-01

    Neuropathic pain is a refractory disease characterized by maladaptive changes in gene transcription and translation within the sensory pathway. Long noncoding RNAs (lncRNAs) are emerging as new players in gene regulation, but how lncRNAs operate in the development of neuropathic pain is unclear. Here we identify a conserved lncRNA for Kcna2 (named Kcna2 antisense RNA) in first-order sensory neurons of rat dorsal root ganglion (DRG). Peripheral nerve injury increases Kcna2 antisense RNA expression in injured DRG through activation of myeloid zinc finger protein 1, a transcription factor that binds to Kcna2 antisense RNA gene promoter. Mimicking this increase downregulates Kcna2, reduces total Kv current, increases excitability in DRG neurons, and produces neuropathic pain symptoms. Blocking this increase reverses nerve injury-induced downregulation of DRG Kcna2 and attenuates development and maintenance of neuropathic pain. These findings suggest native Kcna2 antisense RNA as a new therapeutic target for the treatment of neuropathic pain. PMID:23792947

  16. Two Pairs of Mushroom Body Efferent Neurons Are Required for Appetitive Long-Term Memory Retrieval in Drosophila

    Directory of Open Access Journals (Sweden)

    Pierre-Yves Plaçais

    2013-11-01

    Full Text Available One of the challenges facing memory research is to combine network- and cellular-level descriptions of memory encoding. In this context, Drosophila offers the opportunity to decipher, down to single-cell resolution, memory-relevant circuits in connection with the mushroom bodies (MBs, prominent structures for olfactory learning and memory. Although the MB-afferent circuits involved in appetitive learning were recently described, the circuits underlying appetitive memory retrieval remain unknown. We identified two pairs of cholinergic neurons efferent from the MB α vertical lobes, named MB-V3, that are necessary for the retrieval of appetitive long-term memory (LTM. Furthermore, LTM retrieval was correlated to an enhanced response to the rewarded odor in these neurons. Strikingly, though, silencing the MB-V3 neurons did not affect short-term memory (STM retrieval. This finding supports a scheme of parallel appetitive STM and LTM processing.

  17. The renal nerves in chronic heart failure: efferent and afferent mechanisms

    Science.gov (United States)

    Schiller, Alicia M.; Pellegrino, Peter R.; Zucker, Irving H.

    2015-01-01

    The function of the renal nerves has been an area of scientific and medical interest for many years. The recent advent of a minimally invasive catheter-based method of renal denervation has renewed excitement in understanding the afferent and efferent actions of the renal nerves in multiple diseases. While hypertension has been the focus of much this work, less attention has been given to the role of the renal nerves in the development of chronic heart failure (CHF). Recent studies from our laboratory and those of others implicate an essential role for the renal nerves in the development and progression of CHF. Using a rabbit tachycardia model of CHF and surgical unilateral renal denervation, we provide evidence for both renal efferent and afferent mechanisms in the pathogenesis of CHF. Renal denervation prevented the decrease in renal blood flow observed in CHF while also preventing increases in Angiotensin-II receptor protein in the microvasculature of the renal cortex. Renal denervation in CHF also reduced physiological markers of autonomic dysfunction including an improvement in arterial baroreflex function, heart rate variability, and decreased resting cardiac sympathetic tone. Taken together, the renal sympathetic nerves are necessary in the pathogenesis of CHF via both efferent and afferent mechanisms. Additional investigation is warranted to fully understand the role of these nerves and their role as a therapeutic target in CHF. PMID:26300788

  18. Measurement of the relative afferent pupillary defect in retinal detachment.

    Science.gov (United States)

    Bovino, J A; Burton, T C

    1980-07-01

    A swinging flashlight test and calibrated neutral density filters were used to quantitate the depth of relative afferent pupillary defects in ten patients with retinal detachment. Postoperatively, the pupillary responses returned to normal in seven of nine patients with anatomically successful surgery.

  19. Trafficking regulates the subcellular distribution of voltage-gated sodium channels in primary sensory neurons.

    Science.gov (United States)

    Bao, Lan

    2015-09-30

    Voltage-gated sodium channels (Navs) comprise at least nine pore-forming α subunits. Of these, Nav1.6, Nav1.7, Nav1.8 and Nav1.9 are the most frequently studied in primary sensory neurons located in the dorsal root ganglion and are mainly localized to the cytoplasm. A large pool of intracellular Navs raises the possibility that changes in Nav trafficking could alter channel function. The molecular mediators of Nav trafficking mainly consist of signals within the Navs themselves, interacting proteins and extracellular factors. The surface expression of Navs is achieved by escape from the endoplasmic reticulum and proteasome degradation, forward trafficking and plasma membrane anchoring, and it is also regulated by channel phosphorylation and ubiquitination in primary sensory neurons. Axonal transport and localization of Navs in afferent fibers involves the motor protein KIF5B and scaffold proteins, including contactin and PDZ domain containing 2. Localization of Nav1.6 to the nodes of Ranvier in myelinated fibers of primary sensory neurons requires node formation and the submembrane cytoskeletal protein complex. These findings inform our understanding of the molecular and cellular mechanisms underlying Nav trafficking in primary sensory neurons.

  20. [Myofibroblasts and afferent signalling in the urinary bladder. A concept].

    Science.gov (United States)

    Neuhaus, J; Scholler, U; Freick, K; Schwalenberg, T; Heinrich, M; Horn, L C; Stolzenburg, J U

    2008-09-01

    Afferent signal transduction in the urinary bladder is still not clearly understood. An increasing body of evidence supports the view of complex interactions between urothelium, suburothelial myofibroblasts, and sensory nerves. Bladder tissue from tumour patients was used in this study. Methods included confocal immunofluorescence, polymerase chain reaction, calcium imaging, and fluorescence recovery after photobleaching (FRAP).Myofibroblasts express muscarinic and purinergic receptors. They show constitutive spontaneous activity in calcium imaging, which completely depends on extracellular calcium. Stimulation with carbachol and ATP-evoked intracellular calcium transients also depend on extracellular calcium. The intensive coupling between the cells is significantly diminished by incubation with TGF-beta 1. Myofibroblasts form an important cellular element within the afferent signalling of the urinary bladder. They possess all features required to take part in the complex interactions with urothelial cells and sensory nerves. Modulation of their function by cytokines may provide a pathomechanism for bladder dysfunction.

  1. Afferent and Efferent Connections of the Cortex-Amygdala Transition Zone in Mice.

    Science.gov (United States)

    Cádiz-Moretti, Bernardita; Abellán-Álvaro, María; Pardo-Bellver, Cecília; Martínez-García, Fernando; Lanuza, Enrique

    2016-01-01

    The transitional zone between the ventral part of the piriform cortex and the anterior cortical nucleus of the amygdala, named the cortex-amygdala transition zone (CxA), shows two differential features that allow its identification as a particular structure. First, it receives dense cholinergic and dopaminergic innervations as compared to the adjacent piriform cortex and amygdala, and second, it receives projections from the main and accessory olfactory bulbs. In this work we have studied the pattern of afferent and efferent projections of the CxA, which are mainly unknown, by using the retrograde tracer Fluorogold and the anterograde tracer biotinylated dextranamine. The results show that the CxA receives a relatively restricted set of intratelencephalic connections, originated mainly by the olfactory system and basal forebrain, with minor afferents from the amygdala. The only relevant extratelencephalic afference originates in the ventral tegmental area (VTA). The efferent projections of the CxA reciprocate the inputs from the piriform cortex and olfactory amygdala. In addition, the CxA projects densely to the basolateral amygdaloid nucleus and the olfactory tubercle. The extratelencephalic projections of the CxA are very scarce, and target mainly hypothalamic structures. The pattern of connections of the CxA suggests that it is indeed a transitional area between the piriform cortex and the cortical amygdala. Double labeling with choline acetyltransferase indicates that the afferent projection from the basal forebrain is the origin of its distinctive cholinergic innervation, and double labeling with dopamine transporter shows that the projection from the VTA is the source of dopaminergic innervation. These connectivity and neurochemical features, together with the fact that it receives vomeronasal in addition to olfactory information, suggest that the CxA may be involved in processing olfactory information endowed with relevant biological meaning, such as odors

  2. Extrasynaptic neurotransmission in the modulation of brain function. Focus on the striatal neuronal-glial networks

    Directory of Open Access Journals (Sweden)

    Kjell eFuxe

    2012-06-01

    Full Text Available Extrasynaptic neurotransmission is an important short distance form of volume transmission (VT and describes the extracellular diffusion of transmitters and modulators after synaptic spillover or extrasynaptic release in the local circuit regions binding to and activating mainly extrasynaptic neuronal and glial receptors in the neuroglial networks of the brain. Receptor-receptor interactions in G protein-coupled receptor (GPCR heteromers play a major role, on dendritic spines and nerve terminals including glutamate synapses, in the integrative processes of the extrasynaptic signaling. Heteromeric complexes between GPCR and ion-channel receptors play a special role in the integration of the synaptic and extrasynaptic signals. Changes in extracellular concentrations of the classical synaptic neurotransmitters glutamate and GABA found with microdialysis is likely an expression of the activity of the neuron-astrocyte unit of the brain and can be used as an index of VT-mediated actions of these two neurotransmitters in the brain. Thus, the activity of neurons may be functionally linked to the activity of astrocytes, which may release glutamate and GABA to the extracellular space where extrasynaptic glutamate and GABA receptors do exist. Wiring transmission (WT and VT are fundamental properties of all neurons of the CNS but the balance between WT and VT varies from one nerve cell population to the other. The focus is on the striatal cellular networks, and the WT and VT and their integration via receptor heteromers are described in the GABA projection neurons, the glutamate, dopamine, 5-hydroxytryptamine (5-HT and histamine striatal afferents, the cholinergic interneurons and different types of GABA interneurons. In addition, the role in these networks of VT signaling of the energy-dependent modulator adenosine and of endocannabinoids mainly formed in the striatal projection neurons will be underlined to understand the communication in the striatal

  3. Preprotachykinin A is expressed by a distinct population of excitatory neurons in the mouse superficial spinal dorsal horn including cells that respond to noxious and pruritic stimuli.

    Science.gov (United States)

    Gutierrez-Mecinas, Maria; Bell, Andrew M; Marin, Alina; Taylor, Rebecca; Boyle, Kieran A; Furuta, Takahiro; Watanabe, Masahiko; Polgár, Erika; Todd, Andrew J

    2017-03-01

    The superficial dorsal horn, which is the main target for nociceptive and pruritoceptive primary afferents, contains a high density of excitatory interneurons. Our understanding of their roles in somatosensory processing has been restricted by the difficulty of distinguishing functional populations among these cells. We recently defined 3 nonoverlapping populations among the excitatory neurons, based on the expression of neurotensin, neurokinin B, and gastrin-releasing peptide. Here we identify and characterise another population: neurons that express the tachykinin peptide substance P. We show with immunocytochemistry that its precursor protein (preprotachykinin A, PPTA) can be detected in ∼14% of lamina I-II neurons, and these are concentrated in the outer part of lamina II. Over 80% of the PPTA-positive cells lack the transcription factor Pax2 (which determines an inhibitory phenotype), and these account for ∼15% of the excitatory neurons in this region. They are different from the neurotensin, neurokinin B, or gastrin-releasing peptide neurons, although many of them contain somatostatin, which is widely expressed among superficial dorsal horn excitatory interneurons. We show that many of these cells respond to noxious thermal and mechanical stimuli and to intradermal injection of pruritogens. Finally, we demonstrate that these cells can also be identified in a knock-in Cre mouse line (Tac1), although our findings suggest that there is an additional population of neurons that transiently express PPTA. This population of substance P-expressing excitatory neurons is likely to play an important role in the transmission of signals that are perceived as pain and itch.

  4. Kv1 channels and neural processing in vestibular calyx afferents

    Directory of Open Access Journals (Sweden)

    Frances L Meredith

    2015-06-01

    Full Text Available Potassium-selective ion channels are important for accurate transmission of signals from auditory and vestibular sensory end organs to their targets in the central nervous system. During different gravity conditions, astronauts experience altered input signals from the peripheral vestibular system resulting in sensorimotor dysfunction. Adaptation to altered sensory input occurs, but it is not explicitly known whether this involves synaptic modifications within the vestibular epithelia. Future investigations of such potential plasticity require a better understanding of the electrophysiological mechanisms underlying the known heterogeneity of afferent discharge under normal conditions. This study advances this understanding by examining the role of the Kv1 potassium channel family in mediating action potentials in specialized vestibular afferent calyx endings in the gerbil crista and utricle. Pharmacological agents selective for different sub-types of Kv1 channels were tested on membrane responses in whole cell recordings in the crista. Kv1 channels sensitive to α-dendrotoxin and dendrotoxin-K were found to prevail in the central regions, whereas K+ channels sensitive to margatoxin, which blocks Kv1.3 and 1.6 channels, were more prominent in peripheral regions. Margatoxin-sensitive currents showed voltage-dependent inactivation. Dendrotoxin-sensitive currents showed no inactivation and dampened excitability in calyces in central neuroepithelial regions. The differential distribution of Kv1 potassium channels in vestibular afferents supports their importance in accurately relaying gravitational and head movement signals through specialized lines to the central nervous system. Pharmacological modulation of specific groups of K+ channels could help alleviate vestibular dysfunction on earth and in space.

  5. Kv1 channels and neural processing in vestibular calyx afferents.

    Science.gov (United States)

    Meredith, Frances L; Kirk, Matthew E; Rennie, Katherine J

    2015-01-01

    Potassium-selective ion channels are important for accurate transmission of signals from auditory and vestibular sensory end organs to their targets in the central nervous system. During different gravity conditions, astronauts experience altered input signals from the peripheral vestibular system resulting in sensorimotor dysfunction. Adaptation to altered sensory input occurs, but it is not explicitly known whether this involves synaptic modifications within the vestibular epithelia. Future investigations of such potential plasticity require a better understanding of the electrophysiological mechanisms underlying the known heterogeneity of afferent discharge under normal conditions. This study advances this understanding by examining the role of the Kv1 potassium channel family in mediating action potentials in specialized vestibular afferent calyx endings in the gerbil crista and utricle. Pharmacological agents selective for different sub-types of Kv1 channels were tested on membrane responses in whole cell recordings in the crista. Kv1 channels sensitive to α-dendrotoxin and dendrotoxin-K were found to prevail in the central regions, whereas K(+) channels sensitive to margatoxin, which blocks Kv1.3 and 1.6 channels, were more prominent in peripheral regions. Margatoxin-sensitive currents showed voltage-dependent inactivation. Dendrotoxin-sensitive currents showed no inactivation and dampened excitability in calyces in central neuroepithelial regions. The differential distribution of Kv1 potassium channels in vestibular afferents supports their importance in accurately relaying gravitational and head movement signals through specialized lines to the central nervous system. Pharmacological modulation of specific groups of K(+) channels could help alleviate vestibular dysfunction on earth and in space.

  6. Afferent projections to the pontine micturition center in the cat

    NARCIS (Netherlands)

    Kuipers, R; Mouton, LJ; Holstege, G; Kuiper, Rutger

    2006-01-01

    The pontine micturition center (PMC) or Barrington's nucleus controls micturition by way of its descending projections to the sacral spinal cord. However, little is known about the afferents to the PMC that control its function and may be responsible for dysfunction in patients with

  7. Nociceptive afferents to the premotor neurons that send axons simultaneously to the facial and hypoglossal motoneurons by means of axon collaterals.

    Directory of Open Access Journals (Sweden)

    Yulin Dong

    Full Text Available It is well known that the brainstem premotor neurons of the facial nucleus and hypoglossal nucleus coordinate orofacial nociceptive reflex (ONR responses. However, whether the brainstem PNs receive the nociceptive projection directly from the caudal spinal trigeminal nucleus is still kept unclear. Our present study focuses on the distribution of premotor neurons in the ONR pathways of rats and the collateral projection of the premotor neurons which are involved in the brainstem local pathways of the orofacial nociceptive reflexes of rat. Retrograde tracer Fluoro-gold (FG or FG/tetramethylrhodamine-dextran amine (TMR-DA were injected into the VII or/and XII, and anterograde tracer biotinylated dextran amine (BDA was injected into the caudal spinal trigeminal nucleus (Vc. The tracing studies indicated that FG-labeled neurons receiving BDA-labeled fibers from the Vc were mainly distributed bilaterally in the parvicellular reticular formation (PCRt, dorsal and ventral medullary reticular formation (MdD, MdV, supratrigeminal nucleus (Vsup and parabrachial nucleus (PBN with an ipsilateral dominance. Some FG/TMR-DA double-labeled premotor neurons, which were observed bilaterally in the PCRt, MdD, dorsal part of the MdV, peri-motor nucleus regions, contacted with BDA-labeled axonal terminals and expressed c-fos protein-like immunoreactivity which induced by subcutaneous injection of formalin into the lip. After retrograde tracer wheat germ agglutinated horseradish peroxidase (WGA-HRP was injected into VII or XII and BDA into Vc, electron microscopic study revealed that some BDA-labeled axonal terminals made mainly asymmetric synapses on the dendritic and somatic profiles of WGA-HRP-labeled premotor neurons. These data indicate that some premotor neurons could integrate the orofacial nociceptive input from the Vc and transfer these signals simultaneously to different brainstem motonuclei by axonal collaterals.

  8. Daily changes in synaptic innervation of VIP neurons in the rat suprachiasmatic nucleus: contribution of glutamatergic afferents.

    Science.gov (United States)

    Girardet, Clémence; Blanchard, Marie-Pierre; Ferracci, Géraldine; Lévêque, Christian; Moreno, Mathias; François-Bellan, Anne-Marie; Becquet, Denis; Bosler, Olivier

    2010-01-01

    The daily temporal organization of rhythmic functions in mammals, which requires synchronization of the circadian clock to the 24-h light-dark cycle, is believed to involve adjustments of the mutual phasing of the cellular oscillators that comprise the time-keeper within the suprachiasmatic nucleus of the hypothalamus (SCN). Following from a previous study showing that the SCN undergoes day/night rearrangements of its neuronal-glial network that may be crucial for intercellular phasing, we investigated the contribution of glutamatergic synapses, known to play major roles in SCN functioning, to such rhythmic plastic events. Neither expression levels of the vesicular glutamate transporters nor numbers of glutamatergic terminals showed nycthemeral variations in the SCN. However, using quantitative imaging after combined immunolabelling, the density of synapses on neurons expressing vasoactive intestinal peptide, known as targets of the retinal input, increased during the day and both glutamatergic and non-glutamatergic synapses contributed to the increase (+36%). This was not the case for synapses made on vasopressin-containing neurons, the other major source of SCN efferents in the non-retinorecipient region. Together with electron microscope observations showing no differences in the morphometric features of glutamatergic terminals during the day and night, these data show that the light synchronization process in the SCN involves a selective remodelling of synapses at sites of photic integration. They provide a further illustration of how the adult brain may rapidly and reversibly adapt its synaptic architecture to functional needs.

  9. Muscle weakness, afferent sensory dysfunction and exercise in knee osteoarthritis

    DEFF Research Database (Denmark)

    Roos, Ewa M.; Herzog, Walter; Block, Joel A

    2011-01-01

    Lower-extremity muscle strength and afferent sensory dysfunction, such as reduced proprioceptive acuity, are potentially modifiable putative risk factors for knee osteoarthritis (OA). Findings from current studies suggest that muscle weakness is a predictor of knee OA onset, while there is confli...... with previous knee injuries) are easily identified, and may benefit from exercise interventions to prevent or delay OA onset....... there is conflicting evidence regarding the role of muscle weakness in OA progression. In contrast, the literature suggests a role for afferent sensory dysfunction in OA progression but not necessarily in OA onset. The few pilot exercise studies performed in patients who are at risk of incident OA indicate...... a possibility for achieving preventive structure or load modifications. In contrast, large randomized controlled trials of patients with established OA have failed to demonstrate beneficial effects of strengthening exercises. Subgroups of individuals who are at increased risk of knee OA (such as those...

  10. Thyroid hormone is required for pruning, functioning and long-term maintenance of afferent inner hair cell synapses.

    Science.gov (United States)

    Sundaresan, Srividya; Kong, Jee-Hyun; Fang, Qing; Salles, Felipe T; Wangsawihardja, Felix; Ricci, Anthony J; Mustapha, Mirna

    2016-01-01

    Functional maturation of afferent synaptic connections to inner hair cells (IHCs) involves pruning of excess synapses formed during development, as well as the strengthening and survival of the retained synapses. These events take place during the thyroid hormone (TH)-critical period of cochlear development, which is in the perinatal period for mice and in the third trimester for humans. Here, we used the hypothyroid Snell dwarf mouse (Pit1(dw)) as a model to study the role of TH in afferent type I synaptic refinement and functional maturation. We observed defects in afferent synaptic pruning and delays in calcium channel clustering in the IHCs of Pit1(dw) mice. Nevertheless, calcium currents and capacitance reached near normal levels in Pit1(dw) IHCs by the age of onset of hearing, despite the excess number of retained synapses. We restored normal synaptic pruning in Pit1(dw) IHCs by supplementing with TH from postnatal day (P)3 to P8, establishing this window as being critical for TH action on this process. Afferent terminals of older Pit1(dw) IHCs showed evidence of excitotoxic damage accompanied by a concomitant reduction in the levels of the glial glutamate transporter, GLAST. Our results indicate that a lack of TH during a critical period of inner ear development causes defects in pruning and long-term homeostatic maintenance of afferent synapses. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  11. Mechanoreceptor afferent activity compared with receptor field dimensions and pressure changes in feline urinary bladder.

    Science.gov (United States)

    Downie, J W; Armour, J A

    1992-11-01

    The relationship between vesical mechanoreceptor field dimensions and afferent nerve activity recorded in pelvic plexus nerve filaments was examined in chloralose-anesthetized cats. Orthogonal receptor field dimensions were monitored with piezoelectric ultrasonic crystals. Reflexly generated bladder contractile activity made measurements difficult, therefore data were collected from cats subjected to actual sacral rhizotomy. Afferent activity was episodic and was initiated at different pressure and receptor field dimension thresholds. Maximum afferent activity did not correlate with maximum volume or pressure. Furthermore, activity was not linearly related to intravesical pressure, receptor field dimensions, or calculated wall tension. Pressure-length hysteresis of the receptor fields occurred. The responses of identified afferent units and their associated receptor field dimensions to brief contractions elicited by the ganglion stimulant 1,1-dimethyl-4-phenylpiperazinium iodide (2.5-20 micrograms i.a.), studied under constant volume or constant pressure conditions, are compatible with bladder mechanoreceptors behaving as tension receptors. Because activity generated by bladder mechanoreceptors did not correlate in a simple fashion with intravesical pressure or receptor field dimensions, it is concluded that such receptors are influenced by the viscoelastic properties of the bladder wall. Furthermore, as a result of the heterogeneity of the bladder wall, receptor field tension appears to offer a more precise relationship with the activity of bladder wall mechanoreceptors than does intravesical pressure.

  12. Salsolinol facilitates glutamatergic transmission to dopamine neurons in the posterior ventral tegmental area of rats.

    Directory of Open Access Journals (Sweden)

    Guiqin Xie

    Full Text Available Although in vivo evidence indicates that salsolinol, the condensation product of acetaldehyde and dopamine, has properties that may contribute to alcohol abuse, the underlying mechanisms have not been fully elucidated. We have reported previously that salsolinol stimulates dopamine neurons in the posterior ventral tegmental area (p-VTA partly by reducing inhibitory GABAergic transmission, and that ethanol increases glutamatergic transmission to VTA-dopamine neurons via the activation of dopamine D(1 receptors (D(1Rs. In this study, we tested the hypothesis that salsolinol stimulates dopamine neurons involving activation of D(1Rs. By using whole-cell recordings on p-VTA-dopamine neurons in acute brain slices of rats, we found that salsolinol-induced increase in spike frequency of dopamine neurons was substantially attenuated by DL-2-amino-5-phosphono-valeric acid and 6, 7-dinitroquinoxaline-2, 3-dione, the antagonists of glutamatergic N-Methyl-D-aspartic acid and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Moreover, salsolinol increased the amplitude of evoked excitatory postsynaptic currents (EPSCs and the frequency but not the amplitude of spontaneous EPSCs. Additionally, SKF83566, a D(1R antagonist attenuated the salsolinol-induced facilitation of EPSCs and of spontaneous firing of dopamine neurons. Our data reveal that salsolinol enhances glutamatergic transmission onto dopamine neurons via activation of D(1Rs at the glutamatergic afferents in dopamine neurons, which contributes to salsolinol's stimulating effect on p-VTA dopamine neurons. This appears to be a novel mechanism which contributes toward rewarding properties of salsolinol.

  13. Effect of superficial radial nerve stimulation on the activity of nigro-striatal dopaminergic neurons in the cat: role of cutaneous sensory input

    International Nuclear Information System (INIS)

    Nieoullon, A.; Dusticier, N.

    1982-01-01

    The release of 3 H-dopamine (DA) continuously synthesized from 3 H-thyrosine was measured in the caudate nucleus (CN) and in the substantia nigra (SN) in both sides of the brain during electrical stimulation of the superficial radial nerve in cats lightly anaesthetized with halothane. Use of appropriate electrophysiologically controlled stimulation led to selective activation of low threshold afferent fibers whereas high stimulation activated all cutaneous afferents. Results showed that low threshold fiber activation induced a decreased dopaminergic activity in CN contralateral to nerve stimulation and a concomitant increase in dopaminergic activity on the ipsilateral side. Stimulation of group I and threshold stimulation of group II afferent fibers induced changes in the release of 3 H-DA mainly on the contralateral CN and SN and in the ipsilateral CN. High stimulation was followed by a general increase of the neurotransmitter release in the four structures. This shows that the nigro-striatal dopaminergic neurons are mainly-if not exclusively-controlled by cutaneous sensory inputs. This control, non-specific when high threshold cutaneous fibers are also activated. Such activations could contribute to restablish sufficient release of DA when the dopaminergic function is impaired as in Parkinson's disease. (Author)

  14. Effect of superficial radial nerve stimulation on the activity of nigro-striatal dopaminergic neurons in the cat: role of cutaneous sensory input

    Energy Technology Data Exchange (ETDEWEB)

    Nieoullon, A; Dusticier, N [Centre National de la Recherche Scientifique, 13 - Marseille (France). Inst. de Neurophysiologie et Psychophysiologie

    1982-01-01

    The release of /sup 3/H-dopamine (DA) continuously synthesized from /sup 3/H-thyrosine was measured in the caudate nucleus (CN) and in the substantia nigra (SN) in both sides of the brain during electrical stimulation of the superficial radial nerve in cats lightly anaesthetized with halothane. Use of appropriate electrophysiologically controlled stimulation led to selective activation of low threshold afferent fibers whereas high stimulation activated all cutaneous afferents. Results showed that low threshold fiber activation induced a decreased dopaminergic activity in CN contralateral to nerve stimulation and a concomitant increase in dopaminergic activity on the ipsilateral side. Stimulation of group I and threshold stimulation of group II afferent fibers induced changes in the release of /sup 3/H-DA mainly on the contralateral CN and SN and in the ipsilateral CN. High stimulation was followed by a general increase of the neurotransmitter release in the four structures. This shows that the nigro-striatal dopaminergic neurons are mainly-if not exclusively-controlled by cutaneous sensory inputs. This control, non-specific when high threshold cutaneous fibers are also activated. Such activations could contribute to reestablish sufficient release of DA when the dopaminergic function is impaired as in Parkinson's disease.

  15. Gamma motor neurons survive and exacerbate alpha motor neuron degeneration in ALS.

    Science.gov (United States)

    Lalancette-Hebert, Melanie; Sharma, Aarti; Lyashchenko, Alexander K; Shneider, Neil A

    2016-12-20

    The molecular and cellular basis of selective motor neuron (MN) vulnerability in amyotrophic lateral sclerosis (ALS) is not known. In genetically distinct mouse models of familial ALS expressing mutant superoxide dismutase-1 (SOD1), TAR DNA-binding protein 43 (TDP-43), and fused in sarcoma (FUS), we demonstrate selective degeneration of alpha MNs (α-MNs) and complete sparing of gamma MNs (γ-MNs), which selectively innervate muscle spindles. Resistant γ-MNs are distinct from vulnerable α-MNs in that they lack synaptic contacts from primary afferent (I A ) fibers. Elimination of these synapses protects α-MNs in the SOD1 mutant, implicating this excitatory input in MN degeneration. Moreover, reduced I A activation by targeted reduction of γ-MNs in SOD1 G93A mutants delays symptom onset and prolongs lifespan, demonstrating a pathogenic role of surviving γ-MNs in ALS. This study establishes the resistance of γ-MNs as a general feature of ALS mouse models and demonstrates that synaptic excitation of MNs within a complex circuit is an important determinant of relative vulnerability in ALS.

  16. Cultured Cortical Neurons Can Perform Blind Source Separation According to the Free-Energy Principle

    Science.gov (United States)

    Isomura, Takuya; Kotani, Kiyoshi; Jimbo, Yasuhiko

    2015-01-01

    Blind source separation is the computation underlying the cocktail party effect––a partygoer can distinguish a particular talker’s voice from the ambient noise. Early studies indicated that the brain might use blind source separation as a signal processing strategy for sensory perception and numerous mathematical models have been proposed; however, it remains unclear how the neural networks extract particular sources from a complex mixture of inputs. We discovered that neurons in cultures of dissociated rat cortical cells could learn to represent particular sources while filtering out other signals. Specifically, the distinct classes of neurons in the culture learned to respond to the distinct sources after repeating training stimulation. Moreover, the neural network structures changed to reduce free energy, as predicted by the free-energy principle, a candidate unified theory of learning and memory, and by Jaynes’ principle of maximum entropy. This implicit learning can only be explained by some form of Hebbian plasticity. These results are the first in vitro (as opposed to in silico) demonstration of neural networks performing blind source separation, and the first formal demonstration of neuronal self-organization under the free energy principle. PMID:26690814

  17. Cultured Cortical Neurons Can Perform Blind Source Separation According to the Free-Energy Principle.

    Directory of Open Access Journals (Sweden)

    Takuya Isomura

    2015-12-01

    Full Text Available Blind source separation is the computation underlying the cocktail party effect--a partygoer can distinguish a particular talker's voice from the ambient noise. Early studies indicated that the brain might use blind source separation as a signal processing strategy for sensory perception and numerous mathematical models have been proposed; however, it remains unclear how the neural networks extract particular sources from a complex mixture of inputs. We discovered that neurons in cultures of dissociated rat cortical cells could learn to represent particular sources while filtering out other signals. Specifically, the distinct classes of neurons in the culture learned to respond to the distinct sources after repeating training stimulation. Moreover, the neural network structures changed to reduce free energy, as predicted by the free-energy principle, a candidate unified theory of learning and memory, and by Jaynes' principle of maximum entropy. This implicit learning can only be explained by some form of Hebbian plasticity. These results are the first in vitro (as opposed to in silico demonstration of neural networks performing blind source separation, and the first formal demonstration of neuronal self-organization under the free energy principle.

  18. Gad1 mRNA as a reliable indicator of altered GABA release from orexigenic neurons in the hypothalamus.

    Science.gov (United States)

    Dicken, Matthew S; Hughes, Alexander R; Hentges, Shane T

    2015-11-01

    The strength of γ-aminobutyric acid (GABA)-mediated inhibitory synaptic input is a principle determinant of neuronal activity. However, because of differences in the number of GABA afferent inputs and the sites of synapses, it is difficult to directly assay for altered GABA transmission between specific cells. The present study tested the hypothesis that the level of mRNA for the GABA synthetic enzyme glutamate decarboxylase (GAD) can provide a reliable proxy for GABA release. This was tested in a mouse hypothalamic circuit important in the regulation of energy balance. Fluorescent in situ hybridization results show that the expression of Gad1 mRNA (encoding the GAD67 enzyme) was increased in hypothalamic neuropeptide Y/agouti-related peptide (NPY/AgRP) neurons after an overnight fast, consistent with the ability of GABA from these neurons to stimulate food intake. Optogenetic studies confirmed that the observed increase in Gad1 mRNA correlated with an increase in the probability of GABA release from NPY/AgRP neurons onto downstream proopiomelanocortin neurons. Likewise, there was an increase in the readily releasable pool of GABA in NPY/AgRP neurons. Selective inhibition of GAD activity in NPY/AgRP neurons decreased GABA release, indicating that GAD67 activity, which is largely dictated by expression level, is a key determinant of GABA release. Altogether, it appears that Gad expression may be a reliable proxy of altered GABAergic transmission. Examining changes in Gad mRNA as a proxy for GABA release may be particularly helpful when the downstream targets are not known or when limited tools exist for detecting GABA release at a particular synapse. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  19. Peripheral chemoreceptors tune inspiratory drive via tonic expiratory neuron hubs in the medullary ventral respiratory column network.

    Science.gov (United States)

    Segers, L S; Nuding, S C; Ott, M M; Dean, J B; Bolser, D C; O'Connor, R; Morris, K F; Lindsey, B G

    2015-01-01

    Models of brain stem ventral respiratory column (VRC) circuits typically emphasize populations of neurons, each active during a particular phase of the respiratory cycle. We have proposed that "tonic" pericolumnar expiratory (t-E) neurons tune breathing during baroreceptor-evoked reductions and central chemoreceptor-evoked enhancements of inspiratory (I) drive. The aims of this study were to further characterize the coordinated activity of t-E neurons and test the hypothesis that peripheral chemoreceptors also modulate drive via inhibition of t-E neurons and disinhibition of their inspiratory neuron targets. Spike trains of 828 VRC neurons were acquired by multielectrode arrays along with phrenic nerve signals from 22 decerebrate, vagotomized, neuromuscularly blocked, artificially ventilated adult cats. Forty-eight of 191 t-E neurons fired synchronously with another t-E neuron as indicated by cross-correlogram central peaks; 32 of the 39 synchronous pairs were elements of groups with mutual pairwise correlations. Gravitational clustering identified fluctuations in t-E neuron synchrony. A network model supported the prediction that inhibitory populations with spike synchrony reduce target neuron firing probabilities, resulting in offset or central correlogram troughs. In five animals, stimulation of carotid chemoreceptors evoked changes in the firing rates of 179 of 240 neurons. Thirty-two neuron pairs had correlogram troughs consistent with convergent and divergent t-E inhibition of I cells and disinhibitory enhancement of drive. Four of 10 t-E neurons that responded to sequential stimulation of peripheral and central chemoreceptors triggered 25 cross-correlograms with offset features. The results support the hypothesis that multiple afferent systems dynamically tune inspiratory drive in part via coordinated t-E neurons. Copyright © 2015 the American Physiological Society.

  20. Submucosal neurons and enteric glial cells expressing the P2X7 receptor in rat experimental colitis.

    Science.gov (United States)

    da Silva, Marcos Vinícius; Marosti, Aline Rosa; Mendes, Cristina Eusébio; Palombit, Kelly; Castelucci, Patricia

    2017-06-01

    The aim of this study was to evaluate the effect of ulcerative colitis on the submucosal neurons and glial cells of the submucosal ganglia of rats. 2,4,6-Trinitrobenzene sulfonic acid (TNBS; colitis group) was administered in the colon to induce ulcerative colitis, and distal colons were collected after 24h. The colitis rats were compared with those in the sham and control groups. Double labelling of the P2X7 receptor with calbindin (marker for intrinsic primary afferent neurons, IPANs, submucosal plexus), calretinin (marker for secretory and vasodilator neurons of the submucosal plexus), HuC/D and S100β was performed in the submucosal plexus. The density (neurons per area) of submucosal neurons positive for the P2X7 receptor, calbindin, calretinin and HuC/D decreased by 21%, 34%, 8.2% and 28%, respectively, in the treated group. In addition, the density of enteric glial cells in the submucosal plexus decreased by 33%. The profile areas of calbindin-immunoreactive neurons decreased by 25%. Histological analysis revealed increased lamina propria and decreased collagen in the colitis group. This study demonstrated that ulcerative colitis affected secretory and vasodilatory neurons, IPANs and enteric glia of the submucosal plexus expressing the P2X7 receptor. Copyright © 2017 Elsevier GmbH. All rights reserved.

  1. Evidence of the Primary Afferent Tracts Undergoing Neurodegeneration in Horses With Equine Degenerative Myeloencephalopathy Based on Calretinin Immunohistochemical Localization.

    Science.gov (United States)

    Finno, C J; Valberg, S J; Shivers, J; D'Almeida, E; Armién, A G

    2016-01-01

    Equine degenerative myeloencephalopathy (EDM) is characterized by a symmetric general proprioceptive ataxia in young horses, and is likely underdiagnosed for 2 reasons: first, clinical signs overlap those of cervical vertebral compressive myelopathy; second, histologic lesions--including axonal spheroids in specific tracts of the somatosensory and motor systems--may be subtle. The purpose of this study was (1) to utilize immunohistochemical (IHC) markers to trace axons in the spinocuneocerebellar, dorsal column-medial lemniscal, and dorsospinocerebellar tracts in healthy horses and (2) to determine the IHC staining characteristics of the neurons and degenerated axons along the somatosensory tracts in EDM-affected horses. Examination of brain, spinal cord, and nerves was performed on 2 age-matched control horses, 3 EDM-affected horses, and 2 age-matched disease-control horses via IHC for calbindin, vesicular glutamate transporter 2, parvalbumin, calretinin, glutamic acid decarboxylase, and glial fibrillary acidic protein. Primary afferent axons of the spinocuneocerebellar, dorsal column-medial lemniscal, and dorsospinocerebellar tracts were successfully traced with calretinin. Calretinin-positive cell bodies were identified in a subset of neurons in the dorsal root ganglia, suggesting that calretinin IHC could be used to trace axonal projections from these cell bodies. Calretinin-immunoreactive spheroids were present in EDM-affected horses within the nuclei cuneatus medialis, cuneatus lateralis, and thoracicus. Neurons within those nuclei were calretinin negative. Cell bodies of degenerated axons in EDM-affected horses are likely located in the dorsal root ganglia. These findings support the role of sensory axonal degeneration in the pathogenesis of EDM and provide a method to highlight tracts with axonal spheroids to aid in the diagnosis of this neurodegenerative disease. © The Author(s) 2015.

  2. Ghrelin is involved in the paracrine communication between neurons and glial cells.

    Science.gov (United States)

    Avau, B; De Smet, B; Thijs, T; Geuzens, A; Tack, J; Vanden Berghe, P; Depoortere, I

    2013-09-01

    Ghrelin is the only known peripherally active orexigenic hormone produced by the stomach that activates vagal afferents to stimulate food intake and to accelerate gastric emptying. Vagal sensory neurons within the nodose ganglia are surrounded by glial cells, which are able to receive and transmit chemical signals. We aimed to investigate whether ghrelin activates or influences the interaction between both types of cells. The effect of ghrelin was compared with that of leptin and cholecystokinin (CCK). Cultures of rat nodose ganglia were characterized by immunohistochemistry and the functional effects of peptides, neurotransmitters, and pharmacological blockers were measured by Ca(2+) imaging using Fluo-4-AM as an indicator. Neurons responded to KCl and were immunoreactive for PGP-9.5 whereas glial cells responded to lysophosphatidic acid and had the typical SOX-10-positive nuclear staining. Neurons were only responsive to CCK (31 ± 5%) whereas glial cells responded equally to the applied stimuli: ghrelin (27 ± 2%), leptin (21 ± 2%), and CCK (30 ± 2%). In contrast, neurons stained more intensively for the ghrelin receptor than glial cells. ATP induced [Ca(2+) ]i rises in 90% of the neurons whereas ACh and the NO donor, SIN-1, mainly induced [Ca(2+) ]i changes in glial cells (41 and 51%, respectively). The percentage of ghrelin-responsive glial cells was not affected by pretreatment with suramin, atropine, hexamethonium or 1400 W, but was reduced by l-NAME and by tetrodotoxin. Neurons were shown to be immunoreactive for neuronal NO-synthase (nNOS). Our data show that ghrelin induces Ca(2+) signaling in glial cells of the nodose ganglion via the release of NO originating from the neurons. © 2013 John Wiley & Sons Ltd.

  3. Glutamatergic synaptic currents of nigral dopaminergic neurons follow a postnatal developmental sequence

    Directory of Open Access Journals (Sweden)

    Edouard ePearlstein

    2015-05-01

    Full Text Available The spontaneous activity pattern of adult dopaminergic (DA neurons of the substantia nigra pars compacta (SNc results from interactions between intrinsic membrane conductances and afferent inputs. In adult SNc DA neurons, low-frequency tonic background activity is generated by intrinsic pacemaker mechanisms, whereas burst generation depends on intact synaptic inputs in particular the glutamatergic ones. Tonic DA release in the striatum during pacemaking is required to maintain motor activity, and burst firing evokes phasic DA release, necessary for cue-dependent learning tasks. However, it is still unknown how the firing properties of SNc DA neurons mature during postnatal development before reaching the adult state. We studied the postnatal developmental profile of spontaneous and evoked AMPA and NMDA receptor-mediated excitatory postsynaptic currents (EPSCs in SNc DA neurons in brain slices from immature (postnatal days P4-10 and young adult (P30-50 tyrosine hydroxylase (TH-GFP mice. We found that somato-dendritic fields of SNc DA neurons are already mature at P4-10. In contrast, spontaneous glutamatergic EPSCs show a developmental sequence. Spontaneous NMDA EPSCs in particular are larger and more frequent in immature SNc DA neurons than in young adult ones and have a bursty pattern. They are mediated by GluN2B and GluN2D subunit-containing NMDA receptors. The latter generate long-lasting, DQP1105-sensitive, spontaneous EPSCs, which are transiently recorded during this early period. Due to high NMDA activity, immature SNc DA neurons generate large and long lasting NMDA receptor-dependent (APV-sensitive bursts in response to the stimulation of the subthalamic nucleus. We conclude that the transient high NMDA activity allows calcium influx into the dendrites of developing SNc DA neurons.

  4. Percutaneous Transhepatic Duodenal Drainage as an Alternative Approach in Afferent Loop Obstruction with Secondary Obstructive Jaundice in Recurrent Gastric Cancer

    International Nuclear Information System (INIS)

    Yao, N.-S.; Wu, C.-W.; Tiu, Chui-Mei; Liu, Jacqueline M.; Whang-Peng, Jacqueline; Chen, L.-T.

    1998-01-01

    Two cases are reported of chronic, partial afferent loop obstruction with resultant obstructive jaundice in recurrent gastric cancer. The diagnosis was made by characteristic clinical presentations, abdominal computed tomography, and cholescintigraphy. Percutaneous transhepatic duodenal drainage (PTDD) provided effective palliation for both afferent loop obstruction and biliary stasis. We conclude that cholescintigraphy is of value in making the diagnosis of partial afferent loop obstruction and in differentiating the cause of obstructive jaundice in such patients, and PTDD provides palliation for those patients in whom surgical intervention is not feasible

  5. Cortical Regulation of Striatal Medium Spiny Neuron Dendritic Remodeling in Parkinsonism: Modulation of Glutamate Release Reverses Dopamine Depletion–Induced Dendritic Spine Loss

    OpenAIRE

    Garcia, Bonnie G.; Neely, M. Diana; Deutch, Ariel Y.

    2010-01-01

    Striatal medium spiny neurons (MSNs) receive glutamatergic afferents from the cerebral cortex and dopaminergic inputs from the substantia nigra (SN). Striatal dopamine loss decreases the number of MSN dendritic spines. This loss of spines has been suggested to reflect the removal of tonic dopamine inhibitory control over corticostriatal glutamatergic drive, with increased glutamate release culminating in MSN spine loss. We tested this hypothesis in two ways. We first determined in vivo if dec...

  6. Populations of subplate and interstitial neurons in fetal and adult human telencephalon.

    Science.gov (United States)

    Judaš, Miloš; Sedmak, Goran; Pletikos, Mihovil; Jovanov-Milošević, Nataša

    2010-10-01

    In the adult human telencephalon, subcortical (gyral) white matter contains a special population of interstitial neurons considered to be surviving descendants of fetal subplate neurons [Kostovic & Rakic (1980) Cytology and the time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon. J Neurocytol9, 219]. We designate this population of cells as superficial (gyral) interstitial neurons and describe their morphology and distribution in the postnatal and adult human cerebrum. Human fetal subplate neurons cannot be regarded as interstitial, because the subplate zone is an essential part of the fetal cortex, the major site of synaptogenesis and the 'waiting' compartment for growing cortical afferents, and contains both projection neurons and interneurons with distinct input-output connectivity. However, although the subplate zone is a transient fetal structure, many subplate neurons survive postnatally as superficial (gyral) interstitial neurons. The fetal white matter is represented by the intermediate zone and well-defined deep periventricular tracts of growing axons, such as the corpus callosum, anterior commissure, internal and external capsule, and the fountainhead of the corona radiata. These tracts gradually occupy the territory of transient fetal subventricular and ventricular zones.The human fetal white matter also contains distinct populations of deep fetal interstitial neurons, which, by virtue of their location, morphology, molecular phenotypes and advanced level of dendritic maturation, remain distinct from subplate neurons and neurons in adjacent structures (e.g. basal ganglia, basal forebrain). We describe the morphological, histochemical (nicotinamide-adenine dinucleotide phosphate-diaphorase) and immunocytochemical (neuron-specific nuclear protein, microtubule-associated protein-2, calbindin, calretinin, neuropeptide Y) features of both deep fetal interstitial neurons and deep (periventricular

  7. Chloride is essential for contraction of afferent arterioles after agonists and potassium

    DEFF Research Database (Denmark)

    Jensen, B L; Ellekvist, Peter; Skøtt, O

    1997-01-01

    to norepinephrine, angiotensin II (ANG II), and potassium were measured after chloride depletion and compared with controls. Chloride depletion did not change arteriolar diameters, but the response to norepinephrine was markedly reduced when chloride was substituted with gluconate (n = 6) or isethionate (n = 6......). Reintroduction of chloride fully restored the sensitivity to norepinephrine. Contractions after ANG II and potassium were totally abolished in the absence of chloride (n = 6). In additional experiments (n = 7), the arteriolar contraction to 100 mM potassium was abolished only 1 min after removal of extracellular......A depolarizing chloride efflux has been suggested to activate voltage-dependent calcium channels in renal afferent arteriolar smooth muscle cells in response to vasoconstrictors. To test this proposal, rabbit afferent arterioles were microperfused, and the contractile dose responses...

  8. Neuronal health - can culinary and medicinal mushrooms help?

    Science.gov (United States)

    Sabaratnam, Vikineswary; Kah-Hui, Wong; Naidu, Murali; Rosie David, Pamela

    2013-01-01

    Hericium erinaceus a culinary and medicinal mushroom is a well established candidate for brain and nerve health. Ganoderma lucidum, Grifola frondosa and Sarcodon scabrosus have been reported to have neurite outgrowth and neuronal health benefits. The number of mushrooms, however, studied for neurohealth activity are few compared to the more than 2 000 species of edible and / or medicinal mushrooms identified. In the on-going search for other potent culinary and / or medicinal mushrooms, indigenous mushrooms used in traditional medicines such as Lignosus rhinocerotis and Ganoderma neo-japonicum are also being investigated. Further, the edible mushroom, Pleurotus giganteus can be a potential candidate, too. Can these edible and medicinal mushrooms be tapped to tackle the health concerns of the aging population which is projected to be more than 80-90 million of people age 65 and above in 2050 who may be affected by age-related neurodegenerative disorders. Scientific validation is needed if these mushrooms are to be considered and this can be achieved by understanding the molecular and biochemical mechanisms involved in the stimulation of neurite outgrowth. Though it is difficult to extrapolate the in vitro studies to what may happen in the human brain, studies have shown that there can be improvement in cognitive abilities of the aged if the mushroom is incorporated in their daily diets.

  9. The repetition timing of high frequency afferent stimulation drives the bidirectional plasticity at central synapses in the rat medial vestibular nuclei.

    Science.gov (United States)

    Scarduzio, M; Panichi, R; Pettorossi, V E; Grassi, S

    2012-10-25

    In this study we show that high frequency stimulation (HFS, 100Hz) of afferent fibers to the medial vestibular nucleus (MVN) can induce opposite long-term modifications of synaptic responses in the type B neurons depending upon the stimulation pattern. Long burst stimulation (LBS: 2s) and short burst stimulation (SBS: 0.55s) were applied with different burst number (BN) and inter-burst intervals (IBI). It results that both LBS and SBS can induce either N-methyl-d aspartate receptors (NMDARs)-mediated long-term potentiation (LTP) or long-term depression (LTD), depending on temporal organization of repetitive bursts. In particular, the IBI plays a relevant role in guiding the shift from LTP to LTD since by using both LBS and SBS LTP is induced by shorter IBI than LTD. By contrast, the sign of long-term effect does not depend on the mean impulse frequency evaluated within the entire stimulation period. Therefore, the patterns of repetitive vestibular activation with different ratios between periods of increased activity and periods of basal activity may lead to LTP or LTD probably causing different levels of postsynaptic Ca(2+). On the whole, this study demonstrates that glutamatergic vestibular synapse in the MVN can undergo NMDAR-dependent bidirectional plasticity and puts forward a new aspect for understanding the adaptive and compensatory plasticity of the oculomotor responses. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Cross-organ sensitization of thoracic spinal neurons receiving noxious cardiac input in rats with gastroesophageal reflux.

    Science.gov (United States)

    Qin, Chao; Malykhina, Anna P; Thompson, Ann M; Farber, Jay P; Foreman, Robert D

    2010-06-01

    Gastroesophageal reflux (GER) frequently triggers or worsens cardiac pain or symptoms in patients with coronary heart disease. This study aimed to determine whether GER enhances the activity of upper thoracic spinal neurons receiving noxious cardiac input. Gastric fundus and pyloric ligations as well as a longitudinal myelotomy at the gastroesophageal junction induced acute GER in pentobarbital-anesthetized, paralyzed, and ventilated male Sprague-Dawley rats. Manual manipulations of the stomach and lower esophagus were used as surgical controls in another group. At 4-9 h after GER surgery, extracellular potentials of single neurons were recorded from the T3 spinal segment. Intrapericardial bradykinin (IB) (10 microg/ml, 0.2 ml, 1 min) injections were used to activate cardiac nociceptors, and esophageal distensions were used to activate esophageal afferent fibers. Significantly more spinal neurons in the GER group responded to IB compared with the control group (69.1 vs. 38%, P neurons in the superficial laminae of GER animals was significantly different from those in deeper layers (1/8 vs. 46/60, P 0.05). Excitatory responses of spinal neurons to IB in the GER group were greater than in the control group [32.4 +/- 3.5 impulses (imp)/s vs. 13.3 +/- 2.3 imp/s, P neurons responded to cardiac input and ED, which was higher than the control group (61.5%, P neurons in deeper laminae of the dorsal horn to noxious cardiac stimulus.

  11. PKA-induced internalization of slack KNa channels produces dorsal root ganglion neuron hyperexcitability.

    Science.gov (United States)

    Nuwer, Megan O; Picchione, Kelly E; Bhattacharjee, Arin

    2010-10-20

    Inflammatory mediators through the activation of the protein kinase A (PKA) pathway sensitize primary afferent nociceptors to mechanical, thermal, and osmotic stimuli. However, it is unclear which ion conductances are responsible for PKA-induced nociceptor hyperexcitability. We have previously shown the abundant expression of Slack sodium-activated potassium (K(Na)) channels in nociceptive dorsal root ganglion (DRG) neurons. Here we show using cultured DRG neurons, that of the total potassium current, I(K), the K(Na) current is predominantly inhibited by PKA. We demonstrate that PKA modulation of K(Na) channels does not happen at the level of channel gating but arises from the internal trafficking of Slack channels from DRG membranes. Furthermore, we found that knocking down the Slack subunit by RNA interference causes a loss of firing accommodation analogous to that observed during PKA activation. Our data suggest that the change in nociceptive firing occurring during inflammation is the result of PKA-induced Slack channel trafficking.

  12. Interactions between visceral afferent signaling and stimulus processing

    Directory of Open Access Journals (Sweden)

    Hugo D Critchley

    2015-08-01

    Full Text Available Visceral afferent signals to the brain influence thoughts, feelings and behaviour. Here we highlight the findings of a set of empirical investigations in humans concerning body-mind interaction that focus on how feedback from states of autonomic arousal shapes cognition and emotion. There is a longstanding debate regarding the contribution of the body, to mental processes. Recent theoretical models broadly acknowledge the role of (autonomically-mediated physiological arousal to emotional, social and motivational behaviours, yet the underlying mechanisms are only partially characterized. Neuroimaging is overcoming this shortfall; first, by demonstrating correlations between autonomic change and discrete patterns of evoked, and task-independent, neural activity; second, by mapping the central consequences of clinical perturbations in autonomic response and; third, by probing how dynamic fluctuations in peripheral autonomic state are integrated with perceptual, cognitive and emotional processes. Building on the notion that an important source of the brain’s representation of physiological arousal is derived from afferent information from arterial baroreceptors, we have exploited the phasic nature of these signals to show their differential contribution to the processing of emotionally-salient stimuli. This recent work highlights the facilitation at neural and behavioral levels of fear and threat processing that contrasts with the more established observations of the inhibition of central pain processing during baroreceptors activation. The implications of this body-brain-mind axis are discussed.

  13. A network of spiking neurons that can represent interval timing: mean field analysis.

    Science.gov (United States)

    Gavornik, Jeffrey P; Shouval, Harel Z

    2011-04-01

    Despite the vital importance of our ability to accurately process and encode temporal information, the underlying neural mechanisms are largely unknown. We have previously described a theoretical framework that explains how temporal representations, similar to those reported in the visual cortex, can form in locally recurrent cortical networks as a function of reward modulated synaptic plasticity. This framework allows networks of both linear and spiking neurons to learn the temporal interval between a stimulus and paired reward signal presented during training. Here we use a mean field approach to analyze the dynamics of non-linear stochastic spiking neurons in a network trained to encode specific time intervals. This analysis explains how recurrent excitatory feedback allows a network structure to encode temporal representations.

  14. [Vestibular compensation studies]. [Vestibular Compensation and Morphological Studies

    Science.gov (United States)

    Perachio, Adrian A. (Principal Investigator)

    1996-01-01

    The following topics are reported: neurophysiological studies on MVN neurons during vestibular compensation; effects of spinal cord lesions on VNC neurons during compensation; a closed-loop vestibular compensation model for horizontally canal-related MVN neurons; spatiotemporal convergence in VNC neurons; contributions of irregularly firing vestibular afferents to linear and angular VOR's; application to flight studies; metabolic measures in vestibular neurons; immediate early gene expression following vestibular stimulation; morphological studies on primary afferents, central vestibular pathways, vestibular efferent projection to the vestibular end organs, and three-dimensional morphometry and imaging.

  15. Effects of uniform extracellular DC electric fields on excitability in rat hippocampal slices in vitro.

    Science.gov (United States)

    Bikson, Marom; Inoue, Masashi; Akiyama, Hiroki; Deans, Jackie K; Fox, John E; Miyakawa, Hiroyoshi; Jefferys, John G R

    2004-05-15

    The effects of uniform steady state (DC) extracellular electric fields on neuronal excitability were characterized in rat hippocampal slices using field, intracellular and voltage-sensitive dye recordings. Small electric fields (tips of basal and apical dendrites. The polarization was biphasic in the mid-apical dendrites; there was a time-dependent shift in the polarity reversal site. DC fields altered the thresholds of action potentials evoked by orthodromic stimulation, and shifted their initiation site along the apical dendrites. Large electric fields could trigger neuronal firing and epileptiform activity, and induce long-term (>1 s) changes in neuronal excitability. Electric fields perpendicular to the apical-dendritic axis did not induce somatic polarization, but did modulate orthodromic responses, indicating an effect on afferents. These results demonstrate that DC fields can modulate neuronal excitability in a time-dependent manner, with no clear threshold, as a result of interactions between neuronal compartments, the non-linear properties of the cell membrane, and effects on afferents.

  16. Decreased contribution from afferent feedback to the soleus muscle during walking in patients with spastic stroke

    DEFF Research Database (Denmark)

    Mazzaro, Nazarena; Nielsen, Jørgen Feldbæk; Grey, Michael James

    2007-01-01

    We investigated the contribution of afferent feedback to the soleus (SOL) muscle activity during the stance phase of walking in patients with spastic stroke. A total of 24 patients with hemiparetic spastic stroke and age-matched healthy volunteers participated in the study. A robotic actuator...... by the Ashworth score. These results indicate that although the stretch reflex response is facilitated during spastic gait, the contribution of afferent feedback to the ongoing locomotor SOL activity is depressed in patients with spastic stroke....

  17. Peripheral axotomy of the rat mandibular trigeminal nerve leads to an increase in VIP and decrease of other primary afferent neuropeptides in the spinal trigeminal nucleus.

    Science.gov (United States)

    Atkinson, M E; Shehab, S A

    1986-12-01

    In the vasoactive intestinal polypeptide (VIP)-rich lumbosacral spinal cord, VIP increases at the expense of other neuropeptides after primary sensory nerve axotomy. This study was undertaken to ascertain whether similar changes occur in peripherally axotomised cranial sensory nerves. VIP immunoreactivity increased in the terminal region of the mandibular nerve in the trigeminal nucleus caudalis following unilateral section of the sensory root of the mandibular trigeminal nerve at the foramen orale. Other primary afferent neuropeptides (substance P, cholecystokinin and somatostatin) were depleted and fluoride-resistant acid phosphatase activity was abolished in the same circumscribed areas of the nucleus caudalis. The rise in VIP and depletion of other markers began 4 days postoperatively and was maximal by 10 days, these levels remaining unchanged up to 1 year postoperatively. VIP-immunoreactive cell bodies were absent from trigeminal ganglia from the unoperated side but small and medium cells stained intensely in the ganglia of the operated side after axotomy. These observations indicate that increase of VIP in sensory nerve terminals is a general phenomenon occurring in both cranial and spinal sensory terminal areas. The intense VIP immunoreactivity in axotomised trigeminal ganglia suggests that the increased levels of VIP in the nucleus caudalis are of peripheral origin, indicating a change in expression of neuropeptides within primary afferent neurons following peripheral axotomy.

  18. Decoding tactile afferent activity to obtain an estimate of instantaneous force and torque applied to the fingerpad

    Science.gov (United States)

    Birznieks, Ingvars; Redmond, Stephen J.

    2015-01-01

    Dexterous manipulation is not possible without sensory information about object properties and manipulative forces. Fundamental neuroscience has been unable to demonstrate how information about multiple stimulus parameters may be continuously extracted, concurrently, from a population of tactile afferents. This is the first study to demonstrate this, using spike trains recorded from tactile afferents innervating the monkey fingerpad. A multiple-regression model, requiring no a priori knowledge of stimulus-onset times or stimulus combination, was developed to obtain continuous estimates of instantaneous force and torque. The stimuli consisted of a normal-force ramp (to a plateau of 1.8, 2.2, or 2.5 N), on top of which −3.5, −2.0, 0, +2.0, or +3.5 mNm torque was applied about the normal to the skin surface. The model inputs were sliding windows of binned spike counts recorded from each afferent. Models were trained and tested by 15-fold cross-validation to estimate instantaneous normal force and torque over the entire stimulation period. With the use of the spike trains from 58 slow-adapting type I and 25 fast-adapting type I afferents, the instantaneous normal force and torque could be estimated with small error. This study demonstrated that instantaneous force and torque parameters could be reliably extracted from a small number of tactile afferent responses in a real-time fashion with stimulus combinations that the model had not been exposed to during training. Analysis of the model weights may reveal how interactions between stimulus parameters could be disentangled for complex population responses and could be used to test neurophysiologically relevant hypotheses about encoding mechanisms. PMID:25948866

  19. Properties of Neurons in External Globus Pallidus Can Support Optimal Action Selection

    Science.gov (United States)

    Bogacz, Rafal; Martin Moraud, Eduardo; Abdi, Azzedine; Magill, Peter J.; Baufreton, Jérôme

    2016-01-01

    The external globus pallidus (GPe) is a key nucleus within basal ganglia circuits that are thought to be involved in action selection. A class of computational models assumes that, during action selection, the basal ganglia compute for all actions available in a given context the probabilities that they should be selected. These models suggest that a network of GPe and subthalamic nucleus (STN) neurons computes the normalization term in Bayes’ equation. In order to perform such computation, the GPe needs to send feedback to the STN equal to a particular function of the activity of STN neurons. However, the complex form of this function makes it unlikely that individual GPe neurons, or even a single GPe cell type, could compute it. Here, we demonstrate how this function could be computed within a network containing two types of GABAergic GPe projection neuron, so-called ‘prototypic’ and ‘arkypallidal’ neurons, that have different response properties in vivo and distinct connections. We compare our model predictions with the experimentally-reported connectivity and input-output functions (f-I curves) of the two populations of GPe neurons. We show that, together, these dichotomous cell types fulfil the requirements necessary to compute the function needed for optimal action selection. We conclude that, by virtue of their distinct response properties and connectivities, a network of arkypallidal and prototypic GPe neurons comprises a neural substrate capable of supporting the computation of the posterior probabilities of actions. PMID:27389780

  20. Characterization of thoracic spinal neurons with noxious convergent inputs from heart and lower airways in rats.

    Science.gov (United States)

    Qin, Chao; Foreman, Robert D; Farber, Jay P

    2007-04-13

    Respiratory symptoms experienced in some patients with cardiac diseases may be due to convergence of noxious cardiac and pulmonary inputs onto neurons of the central nervous system. For example, convergence of cardiac and respiratory inputs onto single solitary tract neurons may be in part responsible for integration of regulatory and defensive reflex control. However, it is unknown whether inputs from the lungs and heart converge onto single neurons of the spinal cord. The present aim was to characterize upper thoracic spinal neurons responding to both noxious stimuli of the heart and lungs in rats. Extracellular potentials of single thoracic (T3) spinal neurons were recorded in pentobarbital anesthetized, paralyzed, and ventilated male rats. A catheter was placed in the pericardial sac to administer bradykinin (BK, 10 microg/ml, 0.2 ml, 1 min) as a noxious cardiac stimulus. The lung irritant, ammonia, obtained as vapor over a 30% solution of NH(4)OH was injected into the inspiratory line of the ventilator (0.5-1.0 ml over 20 s). Intrapericardial bradykinin (IB) altered activity of 58/65 (89%) spinal neurons that responded to inhaled ammonia (IA). Among those cardiopulmonary convergent neurons, 81% (47/58) were excited by both IA and IB, and the remainder had complex response patterns. Bilateral cervical vagotomy revealed that vagal afferents modulated but did not eliminate responses of individual spinal neurons to IB and IA. The convergence of pulmonary and cardiac nociceptive signaling in the spinal cord may be relevant to situations where a disease process in one organ influences the behavior of the other.

  1. Substance P Differentially Modulates Firing Rate of Solitary Complex (SC) Neurons from Control and Chronic Hypoxia-Adapted Adult Rats

    Science.gov (United States)

    Nichols, Nicole L.; Powell, Frank L.; Dean, Jay B.; Putnam, Robert W.

    2014-01-01

    NK1 receptors, which bind substance P, are present in the majority of brainstem regions that contain CO2/H+-sensitive neurons that play a role in central chemosensitivity. However, the effect of substance P on the chemosensitive response of neurons from these regions has not been studied. Hypoxia increases substance P release from peripheral afferents that terminate in the caudal nucleus tractus solitarius (NTS). Here we studied the effect of substance P on the chemosensitive responses of solitary complex (SC: NTS and dorsal motor nucleus) neurons from control and chronic hypoxia-adapted (CHx) adult rats. We simultaneously measured intracellular pH and electrical responses to hypercapnic acidosis in SC neurons from control and CHx adult rats using the blind whole cell patch clamp technique and fluorescence imaging microscopy. Substance P significantly increased the basal firing rate in SC neurons from control and CHx rats, although the increase was smaller in CHx rats. However, substance P did not affect the chemosensitive response of SC neurons from either group of rats. In conclusion, we found that substance P plays a role in modulating the basal firing rate of SC neurons but the magnitude of the effect is smaller for SC neurons from CHx adult rats, implying that NK1 receptors may be down regulated in CHx adult rats. Substance P does not appear to play a role in modulating the firing rate response to hypercapnic acidosis of SC neurons from either control or CHx adult rats. PMID:24516602

  2. Mirror neurons, procedural learning, and the positive new experience: a developmental systems self psychology approach.

    Science.gov (United States)

    Wolf, N S; Gales, M; Shane, E; Shane, M

    2000-01-01

    In summary, we are impressed with the existence of a mirror neuron system in the prefrontal cortex that serves as part of a complex neural network, including afferent and efferent connections to the limbic system, in particular the amygdala, in addition to the premotor and motor cortex. We think it is possible to arrive at an integration that postulates the mirror neuron system and its many types of associated multimodal neurons as contributing significantly to implicit procedural learning, a process that underlies a range of complex nonconscious, unconscious, preconscious and conscious cognitive activities, from playing musical instruments to character formation and traumatic configurations. This type of brain circuitry may establish an external coherence with developmental systems self psychology which implies that positive new experience is meliorative and that the intentional revival of old-old traumatic relational configurations might enhance maladaptive procedural patterns that would lead to the opposite of the intended beneficial change. When analysts revive traumatic transference patterns for the purpose of clarification and interpretation, they may fail to appreciate that such traumatic transference patterns make interpretation ineffective because, as we have stated above, the patient lacks self-reflection under such traumatic conditions. The continued plasticity and immediacy of the mirror neuron system can contribute to positive new experiences that promote the formation of new, adaptive, implicit-procedural patterns. Perhaps this broadened repertoire in the patient of ways of understanding interrelational events through the psychoanalytic process allows the less adaptive patterns ultimately to become vestigial and the newer, more adaptive patterns to emerge as dominant. Finally, as we have stated, we believe that the intentional transferential revival of trauma (i.e., the old-old relational configuration) may not contribute to therapeutic benefit. In

  3. Layer- and Cell Type-Specific Modulation of Excitatory Neuronal Activity in the Neocortex

    Directory of Open Access Journals (Sweden)

    Gabriele Radnikow

    2018-01-01

    Full Text Available From an anatomical point of view the neocortex is subdivided into up to six layers depending on the cortical area. This subdivision has been described already by Meynert and Brodmann in the late 19/early 20. century and is mainly based on cytoarchitectonic features such as the size and location of the pyramidal cell bodies. Hence, cortical lamination is originally an anatomical concept based on the distribution of excitatory neuron. However, it has become apparent in recent years that apart from the layer-specific differences in morphological features, many functional properties of neurons are also dependent on cortical layer or cell type. Such functional differences include changes in neuronal excitability and synaptic activity by neuromodulatory transmitters. Many of these neuromodulators are released from axonal afferents from subcortical brain regions while others are released intrinsically. In this review we aim to describe layer- and cell-type specific differences in the effects of neuromodulator receptors in excitatory neurons in layers 2–6 of different cortical areas. We will focus on the neuromodulator systems using adenosine, acetylcholine, dopamine, and orexin/hypocretin as examples because these neuromodulator systems show important differences in receptor type and distribution, mode of release and functional mechanisms and effects. We try to summarize how layer- and cell type-specific neuromodulation may affect synaptic signaling in cortical microcircuits.

  4. VTA GABA neurons modulate specific learning behaviours through the control of dopamine and cholinergic systems

    Directory of Open Access Journals (Sweden)

    Meaghan C Creed

    2014-01-01

    Full Text Available The mesolimbic reward system is primarily comprised of the ventral tegmental area (VTA and the nucleus accumbens (NAc as well as their afferent and efferent connections. This circuitry is essential for learning about stimuli associated with motivationally-relevant outcomes. Moreover, addictive drugs affect and remodel this system, which may underlie their addictive properties. In addition to DA neurons, the VTA also contains approximately 30% ɣ-aminobutyric acid (GABA neurons. The task of signalling both rewarding and aversive events from the VTA to the NAc has mostly been ascribed to DA neurons and the role of GABA neurons has been largely neglected until recently. GABA neurons provide local inhibition of DA neurons and also long-range inhibition of projection regions, including the NAc. Here we review studies using a combination of in vivo and ex vivo electrophysiology, pharmacogenetic and optogenetic manipulations that have characterized the functional neuroanatomy of inhibitory circuits in the mesolimbic system, and describe how GABA neurons of the VTA regulate reward and aversion-related learning. We also discuss pharmacogenetic manipulation of this system with benzodiazepines (BDZs, a class of addictive drugs, which act directly on GABAA receptors located on GABA neurons of the VTA. The results gathered with each of these approaches suggest that VTA GABA neurons bi-directionally modulate activity of local DA neurons, underlying reward or aversion at the behavioural level. Conversely, long-range GABA projections from the VTA to the NAc selectively target cholinergic interneurons (CINs to pause their firing and temporarily reduce cholinergic tone in the NAc, which modulates associative learning. Further characterization of inhibitory circuit function within and beyond the VTA is needed in order to fully understand the function of the mesolimbic system under normal and pathological conditions.

  5. Selective alterations of neurons and circuits related to early memory loss in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    María eLlorens-Martín

    2014-05-01

    Full Text Available A progressive loss of episodic memory is a well-known clinical symptom that characterizes Alzheimer’s disease (AD. The beginning of this loss of memory has been associated with the very early, pathological accumulation of tau and neuronal degeneration observed in the entorhinal cortex (EC. Tau-related pathology is thought to then spread progressively to the hippocampal formation and other brain areas as the disease progresses. The major cortical afferent source of the hippocampus and dentate gyrus is the EC through the perforant pathway. At least two main circuits participate in the connection between EC and the hippocampus; one originating in layer II and the other in layer III of the EC giving rise to the classical trisynaptic (ECII→dentate gyrus→CA3→CA1 and monosynaptic (ECIII→CA1 circuits. Thus, the study of the early pathological changes in these circuits is of great interest. In this review, we will discuss mainly the alterations of the granule cell neurons of the dentate gyrus and the atrophy of CA1 pyramidal neurons that occur in AD in relation to the possible differential alterations of these two main circuits.

  6. Afferent Neural Feedback Overrides the Modulating Effects of Arousal, Hypercapnia and Hypoxemia on Neonatal Cardio-respiratory Control.

    Science.gov (United States)

    Lumb, Kathleen J; Schneider, Jennifer M; Ibrahim, Thowfique; Rigaux, Anita; Hasan, Shabih U

    2018-04-20

    Evidence at whole animal, organ-system, and cellular and molecular levels suggests that afferent volume feedback is critical for establishment of adequate ventilation at birth. Due to the irreversible nature of vagal ablation studies to date, it was difficult to quantify the roles of afferent volume input, arousal and changes in blood gas tensions on neonatal respiratory control. During reversible perineural vagal block, profound apneas, and hypoxemia and hypercarbia were observed necessitating termination of perineural blockade. Respiratory depression and apneas were independent of the sleep states. We demonstrate that profound apneas and life-threatening respiratory failure in vagally denervated animals do not result from lack of arousal or hypoxemia. Change in sleep state and concomitant respiratory depression result from lack of afferent volume feedback, which appears to be critical for the maintenance of normal breathing patterns and adequate gas exchange during the early postnatal period. Afferent volume feedback plays a vital role in neonatal respiratory control. Mechanisms for the profound respiratory depression and life-threatening apneas observed in vagally denervated neonatal animals remain unclear. We investigated the roles of sleep states, hypoxic-hypercapnia and afferent volume feedback on respiratory depression using reversible perineural vagal block during early postnatal period. Seven lambs were instrumented during the first 48h of life to record/analyze sleep states, diaphragmatic electromyograph, arterial blood gas tensions, systemic arterial blood pressure and rectal temperature. Perineural cuffs were placed around the vagi to attain reversible blockade. Post-operatively, during the awake state, both vagi were blocked using 2% xylocaine for up to 30 minutes. Compared with baseline values, pHa, PaO 2 and SaO 2 decreased and PaCO 2 increased during perineural blockade (P Respiratory depression and apneas were independent of sleep states. This

  7. Maternal Dexamethasone Exposure Alters Synaptic Inputs to Gonadotropin-Releasing Hormone Neurons in the Early Postnatal Rat

    Directory of Open Access Journals (Sweden)

    Wei Ling Lim

    2016-08-01

    Full Text Available Maternal dexamethasone (DEX; a glucocorticoid receptor agonist exposure delays pubertal onset and alters reproductive behaviour in the adult offspring. However, little is known whether maternal DEX exposure affects the offspring’s reproductive function by disrupting the gonadotropin-releasing hormone (GnRH neuronal function in the brain. Therefore, this study determined the exposure of maternal DEX on the GnRH neuronal spine development and synaptic cluster inputs to GnRH neurons using transgenic rats expressing enhanced green fluorescent protein (EGFP under the control of GnRH promoter. Pregnant females were administered with DEX (0.1mg/kg or vehicle (VEH, water daily during gestation day 13-20. Confocal imaging was used to examine the spine density of EGFP-GnRH neurons by three-dimensional rendering and synaptic cluster inputs to EGFP-GnRH neurons by synapsin I immunohistochemistry on postnatal day 0 (P0 males. The spine morphology and number on GnRH neurons did not change between the P0 males following maternal DEX and VEH treatment. The number of synaptic clusters within the organum vasculosum of the lamina terminalis (OVLT was decreased by maternal DEX exposure in P0 males. Furthermore, the number and levels of synaptic cluster inputs in close apposition with GnRH neurons was decreased following maternal DEX exposure in the OVLT region of P0 males. In addition, the post synaptic marker molecule, post-synaptic density 95 was observed in GnRH neurons following both DEX and VEH treatment. These results suggest that maternal DEX exposure alters neural afferent inputs to GnRH neurons during early postnatal stage, which could lead to reproductive dysfunction during adulthood.

  8. Failure of action potential propagation in sensory neurons: mechanisms and loss of afferent filtering in C-type units after painful nerve injury

    NARCIS (Netherlands)

    Gemes, Geza; Koopmeiners, Andrew; Rigaud, Marcel; Lirk, Philipp; Sapunar, Damir; Bangaru, Madhavi Latha; Vilceanu, Daniel; Garrison, Sheldon R.; Ljubkovic, Marko; Mueller, Samantha J.; Stucky, Cheryl L.; Hogan, Quinn H.

    2013-01-01

    The T-junction of sensory neurons in the dorsal root ganglion (DRG) is a potential impediment to action potential (AP) propagation towards the CNS. Using intracellular recordings from rat DRG neuronal somata during stimulation of the dorsal root, we determined that the maximal rate at which all of

  9. Orientation selectivity of synaptic input to neurons in mouse and cat primary visual cortex.

    Science.gov (United States)

    Tan, Andrew Y Y; Brown, Brandon D; Scholl, Benjamin; Mohanty, Deepankar; Priebe, Nicholas J

    2011-08-24

    Primary visual cortex (V1) is the site at which orientation selectivity emerges in mammals: visual thalamus afferents to V1 respond equally to all stimulus orientations, whereas their target V1 neurons respond selectively to stimulus orientation. The emergence of orientation selectivity in V1 has long served as a model for investigating cortical computation. Recent evidence for orientation selectivity in mouse V1 opens cortical computation to dissection by genetic and imaging tools, but also raises two essential questions: (1) How does orientation selectivity in mouse V1 neurons compare with that in previously described species? (2) What is the synaptic basis for orientation selectivity in mouse V1? A comparison of orientation selectivity in mouse and in cat, where such measures have traditionally been made, reveals that orientation selectivity in mouse V1 is weaker than in cat V1, but that spike threshold plays a similar role in narrowing selectivity between membrane potential and spike rate. To uncover the synaptic basis for orientation selectivity, we made whole-cell recordings in vivo from mouse V1 neurons, comparing neuronal input selectivity-based on membrane potential, synaptic excitation, and synaptic inhibition-to output selectivity based on spiking. We found that a neuron's excitatory and inhibitory inputs are selective for the same stimulus orientations as is its membrane potential response, and that inhibitory selectivity is not broader than excitatory selectivity. Inhibition has different dynamics than excitation, adapting more rapidly. In neurons with temporally modulated responses, the timing of excitation and inhibition was different in mice and cats.

  10. Premature Ventricular Contraction Coupling Interval Variability Destabilizes Cardiac Neuronal and Electrophysiological Control: Insights From Simultaneous Cardioneural Mapping.

    Science.gov (United States)

    Hamon, David; Rajendran, Pradeep S; Chui, Ray W; Ajijola, Olujimi A; Irie, Tadanobu; Talebi, Ramin; Salavatian, Siamak; Vaseghi, Marmar; Bradfield, Jason S; Armour, J Andrew; Ardell, Jeffrey L; Shivkumar, Kalyanam

    2017-04-01

    Variability in premature ventricular contraction (PVC) coupling interval (CI) increases the risk of cardiomyopathy and sudden death. The autonomic nervous system regulates cardiac electrical and mechanical indices, and its dysregulation plays an important role in cardiac disease pathogenesis. The impact of PVCs on the intrinsic cardiac nervous system, a neural network on the heart, remains unknown. The objective was to determine the effect of PVCs and CI on intrinsic cardiac nervous system function in generating cardiac neuronal and electric instability using a novel cardioneural mapping approach. In a porcine model (n=8), neuronal activity was recorded from a ventricular ganglion using a microelectrode array, and cardiac electrophysiological mapping was performed. Neurons were functionally classified based on their response to afferent and efferent cardiovascular stimuli, with neurons that responded to both defined as convergent (local reflex processors). Dynamic changes in neuronal activity were then evaluated in response to right ventricular outflow tract PVCs with fixed short, fixed long, and variable CI. PVC delivery elicited a greater neuronal response than all other stimuli ( P <0.001). Compared with fixed short and long CI, PVCs with variable CI had a greater impact on neuronal response ( P <0.05 versus short CI), particularly on convergent neurons ( P <0.05), as well as neurons receiving sympathetic ( P <0.05) and parasympathetic input ( P <0.05). The greatest cardiac electric instability was also observed after variable (short) CI PVCs. Variable CI PVCs affect critical populations of intrinsic cardiac nervous system neurons and alter cardiac repolarization. These changes may be critical for arrhythmogenesis and remodeling, leading to cardiomyopathy. © 2017 American Heart Association, Inc.

  11. Presynaptic inhibition of GABAergic synaptic transmission by adenosine in mouse hypothalamic hypocretin neurons.

    Science.gov (United States)

    Xia, J X; Xiong, J X; Wang, H K; Duan, S M; Ye, J N; Hu, Z A

    2012-01-10

    Hypocretin neurons in the lateral hypothalamus, a new wakefulness-promoting center, have been recently regarded as an important target involved in endogenous adenosine-regulating sleep homeostasis. The GABAergic synaptic transmissions are the main inhibitory afferents to hypocretin neurons, which play an important role in the regulation of excitability of these neurons. The inhibitory effect of adenosine, a homeostatic sleep-promoting factor, on the excitatory glutamatergic synaptic transmissions in hypocretin neurons has been well documented, whether adenosine also modulates these inhibitory GABAergic synaptic transmissions in these neurons has not been investigated. In this study, the effect of adenosine on inhibitory postsynaptic currents (IPSCs) in hypocretin neurons was examined by using perforated patch-clamp recordings in the acute hypothalamic slices. The findings demonstrated that adenosine suppressed the amplitude of evoked IPSCs in a dose-dependent manner, which was completely abolished by 8-cyclopentyltheophylline (CPT), a selective antagonist of adenosine A1 receptor but not adenosine A2 receptor antagonist 3,7-dimethyl-1-(2-propynyl) xanthine. A presynaptic origin was suggested as following: adenosine increased paired-pulse ratio as well as reduced GABAergic miniature IPSC frequency without affecting the miniature IPSC amplitude. Further findings demonstrated that when the frequency of electrical stimulation was raised to 10 Hz, but not 1 Hz, a time-dependent depression of evoked IPSC amplitude was detected in hypocretin neurons, which could be partially blocked by CPT. However, under a higher frequency at 100 Hz stimulation, CPT had no action on the depressed GABAergic synaptic transmission induced by such tetanic stimulation in these hypocretin neurons. These results suggest that endogenous adenosine generated under certain stronger activities of synaptic transmissions exerts an inhibitory effect on GABAergic synaptic transmission in hypocretin

  12. Receptors for sensory neuropeptides in human inflammatory diseases: Implications for the effector role of sensory neurons

    International Nuclear Information System (INIS)

    Mantyh, P.W.; Catton, M.D.; Boehmer, C.G.; Welton, M.L.; Passaro, E.P. Jr.; Maggio, J.E.; Vigna, S.R.

    1989-01-01

    Glutamate and several neuropeptides are synthesized and released by subpopulations of primary afferent neurons. These sensory neurons play a role in regulating the inflammatory and immune responses in peripheral tissues. Using quantitative receptor autoradiography we have explored what changes occur in the location and concentration of receptor binding sites for sensory neurotransmitters in the colon in two human inflammatory diseases, ulcerative colitis and Crohn's disease. The sensory neurotransmitter receptors examined included bombesin, calcitonin gene related peptide-alpha, cholecystokinin, galanin, glutamate, somatostatin, neurokinin A (substance K), substance P, and vasoactive intestinal polypeptide. Of the nine receptor binding sites examined only substance P binding sites associated with arterioles, venules and lymph nodules were dramatically up-regulated in the inflamed tissue. These data suggest that substance P is involved in regulating the inflammatory and immune responses in human inflammatory diseases and indicate a specificity of efferent action for each sensory neurotransmitter in peripheral tissues

  13. The role of capsaicin-sensitive muscle afferents in fatigue-induced modulation of the monosynaptic reflex in the rat.

    Science.gov (United States)

    Pettorossi, V E; Della Torre, G; Bortolami, R; Brunetti, O

    1999-03-01

    1. The role of group III and IV afferent fibres of the lateral gastrocnemious muscle (LG) in modulating the homonymous monosynaptic reflex was investigated during muscle fatigue in spinalized rats. 2. Muscle fatigue was induced by a series of increasing tetanic electrical stimuli (85 Hz, 600 ms) delivered to the LG muscle nerve. Series consisted of increasing train numbers from 1 to 60. 3. Potentials from the spinal cord LG motor pool and from the ventral root were recorded in response to proprioceptive afferent stimulation and analysed before and during tetanic muscle activations. Both the pre- and postsynaptic waves showed an initial enhancement and, after a '12-train' series, an increasing inhibition. 4. The enhancement of the responses to muscle fatiguing stimulation disappeared after L3-L6 dorsal root section, while a partial reflex inhibition was still present. Conversely, after section of the corresponding ventral root, there was only a reduction in the inhibitory effect. 5. The monosynaptic reflex was also studied in animals in which a large number of group III and IV muscle afferents were eliminated by injecting capsaicin (10 mM) into the LG muscle. As a result of capsaicin treatment, the fatigue-induced inhibition of the pre- and postsynaptic waves disappeared, while the response enhancement remained. 6. We concluded that the monosynaptic reflex inhibition, but not the enhancement, was mediated by those group III and IV muscle afferents that are sensitive to the toxic action of capsaicin. The afferents that are responsible for the response enhancement enter the spinal cord through the dorsal root, while those responsible for the inhibition enter the spinal cord through both the ventral and dorsal roots.

  14. Afferent projections to the different medial amygdala subdivisions: a retrograde tracing study in the mouse.

    Science.gov (United States)

    Cádiz-Moretti, Bernardita; Otero-García, Marcos; Martínez-García, Fernando; Lanuza, Enrique

    2016-03-01

    The medial amygdaloid nucleus (Me) is a key node in the socio-sexual brain, composed of anterior (MeA), posteroventral (MePV) and posterodorsal (MePD) subdivisions. These subdivisions have been suggested to play a different role in reproductive and defensive behaviours. In the present work we analyse the afferents of the three Me subdivisions using restricted injections of fluorogold in female outbred CD1 mice. The results reveal that the MeA, MePV and MePD share a common pattern of afferents, with some differences in the density of retrograde labelling in several nuclei. Common afferents to Me subdivisions include: the accessory olfactory bulbs, piriform cortex and endopiriform nucleus, chemosensory amygdala (receiving direct inputs from the olfactory bulbs), posterior part of the medial bed nucleus of the stria terminalis (BSTM), CA1 in the ventral hippocampus and posterior intralaminar thalamus. Minor projections originate from the basolateral amygdala and amygdalo-hippocampal area, septum, ventral striatum, several allocortical and periallocortical areas, claustrum, several hypothalamic structures, raphe and parabrachial complex. MeA and MePV share minor inputs from the frontal cortex (medial orbital, prelimbic, infralimbic and dorsal peduncular cortices), but differ in the lack of main olfactory projections to the MePV. By contrast, the MePD receives preferential projections from the rostral accessory olfactory bulb, the posteromedial BSTM and the ventral premammillary nucleus. In summary, the common pattern of afferents to the Me subdivisions and their interconnections suggest that they play cooperative instead of differential roles in the various behaviours (e.g., sociosexual, defensive) in which the Me has been shown to be involved.

  15. Na+-independent, nifedipine-resistant rat afferent arteriolar Ca2+ responses to noradrenaline

    DEFF Research Database (Denmark)

    Salomonsson, Max; Braunstein, Thomas Hartig; von Holstein-Rathlou, Niels-Henrik

    2010-01-01

    Abstract Aim: In rat afferent arterioles we investigated the role of Na(+) entry in noradrenaline (NA)-induced depolarization and voltage-dependent Ca(2+) entry together with the importance of the transient receptor potential channel (TRPC) subfamily for non-voltage-dependent Ca(2+) entry. Methods...

  16. Acid-sensing ion channels (ASICs) in mouse skeletal muscle afferents are heteromers composed of ASIC1a, ASIC2, and ASIC3 subunits

    Science.gov (United States)

    Gautam, Mamta; Benson, Christopher J.

    2013-01-01

    Acid-sensing ion channels (ASICs) are expressed in skeletal muscle afferents, in which they sense extracellular acidosis and other metabolites released during ischemia and exercise. ASICs are formed as homotrimers or heterotrimers of several isoforms (ASIC1a, ASIC1b, ASIC2a, ASIC2b, and ASIC3), with each channel displaying distinct properties. To dissect the ASIC composition in muscle afferents, we used whole-cell patch-clamp recordings to study the properties of acid-evoked currents (amplitude, pH sensitivity, the kinetics of desensitization and recovery from desensitization, and pharmacological modulation) in isolated, labeled mouse muscle afferents from wild-type (C57BL/6J) and specific ASIC−/− mice. We found that ASIC-like currents in wild-type muscle afferents displayed fast desensitization, indicating that they are carried by heteromeric channels. Currents from ASIC1a−/− muscle afferents were less pH-sensitive and displayed faster recovery, currents from ASIC2−/− mice showed diminished potentiation by zinc, and currents from ASIC3−/− mice displayed slower desensitization than those from wild-type mice. Finally, ASIC-like currents were absent from triple-null mice lacking ASIC1a, ASIC2a, and ASIC3. We conclude that ASIC1a, ASIC2a, and ASIC3 heteromers are the principle channels in skeletal muscle afferents. These results will help us understand the role of ASICs in exercise physiology and provide a molecular target for potential drug therapies to treat muscle pain.—Gautam, M., Benson, C. J. Acid-sensing ion channels (ASICs) in mouse skeletal muscle afferents are heteromers composed of ASIC1a, ASIC2, and ASIC3 subunits. PMID:23109675

  17. Projection neuron circuits resolved using correlative array tomography

    Directory of Open Access Journals (Sweden)

    Daniele eOberti

    2011-04-01

    Full Text Available Assessment of three-dimensional morphological structure and synaptic connectivity is essential for a comprehensive understanding of neural processes controlling behavior. Different microscopy approaches have been proposed based on light microcopy (LM, electron microscopy (EM, or a combination of both. Correlative array tomography (CAT is a technique in which arrays of ultrathin serial sections are repeatedly stained with fluorescent antibodies against synaptic molecules and neurotransmitters and imaged with LM and EM (Micheva and Smith, 2007. The utility of this correlative approach is limited by the ability to preserve fluorescence and antigenicity on the one hand, and EM tissue ultrastructure on the other. We demonstrate tissue staining and fixation protocols and a workflow that yield an excellent compromise between these multimodal imaging constraints. We adapt CAT for the study of projection neurons between different vocal brain regions in the songbird. We inject fluorescent tracers of different colors into afferent and efferent areas of HVC in zebra finches. Fluorescence of some tracers is lost during tissue preparation but recovered using anti-dye antibodies. Synapses are identified in EM imagery based on their morphology and ultrastructure and classified into projection neuron type based on fluorescence signal. Our adaptation of array tomography, involving the use of fluorescent tracers and heavy-metal rich staining and embedding protocols for high membrane contrast in EM will be useful for research aimed at statistically describing connectivity between different projection neuron types and for elucidating how sensory signals are routed in the brain and transformed into a meaningful motor output.

  18. Acid-sensing ion channels expression, identity and role in the excitability of the cochlear afferent neurons

    Directory of Open Access Journals (Sweden)

    Antonia eGonzález-Garrido

    2015-12-01

    Full Text Available Acid-sensing ion channels (ASICs are activated by an increase in the extracellular proton concentration. There are four genes (ASIC1-4 that encode six subunits, and they are involved in diverse neuronal functions, such as mechanosensation, learning and memory, nociception, and modulation of retinal function. In this study, we characterize the ASIC currents of spiral ganglion neurons (SGNs. These ASIC currents are primarily carried by Na+, exhibit fast activation and desensitization, display a pH50 of 6.2 and are blocked by amiloride, indicating that these are ASIC currents. The ASIC currents were further characterized using several pharmacological tools. Gadolinium and acetylsalicylic acid reduced these currents, and FMRFamide, zinc (at high concentrations and N,N,N’,N’–tetrakis-(2-piridilmetil-etilendiamina (TPEN increased them, indicating that functional ASICs are composed of the subunits ASIC1, ASIC2 and ASIC3. Neomycin and streptomycin reduced the desensitization rate of the ASIC current in SGNs, indicating that ASICs may contribute to the ototoxic action of aminoglycosides. RT-PCR of the spiral ganglion revealed significant expression of all ASIC subunits. By immunohistochemistry the expression of the ASIC1a, ASIC2a, ASIC2b and ASIC3 subunits was detected in SGNs. Although only a few SGNs exhibited action potential firing in response to an acidic stimulus, protons in the extracellular solution modulated SGN activity during sinusoidal stimulation. Our results show that protons modulate the excitability of SGNs via ASICs.

  19. Acid-Sensing Ion Channels Expression, Identity and Role in the Excitability of the Cochlear Afferent Neurons

    Science.gov (United States)

    González-Garrido, Antonia; Vega, Rosario; Mercado, Francisco; López, Iván A.; Soto, Enrique

    2015-01-01

    Acid-sensing ion channels (ASICs) are activated by an increase in the extracellular proton concentration. There are four genes (ASIC1-4) that encode six subunits, and they are involved in diverse neuronal functions, such as mechanosensation, learning and memory, nociception, and modulation of retinal function. In this study, we characterize the ASIC currents of spiral ganglion neurons (SGNs). These ASIC currents are primarily carried by Na+, exhibit fast activation and desensitization, display a pH50 of 6.2 and are blocked by amiloride, indicating that these are ASIC currents. The ASIC currents were further characterized using several pharmacological tools. Gadolinium and acetylsalicylic acid reduced these currents, and FMRFamide, zinc (at high concentrations) and N,N,N’,N’–tetrakis-(2-piridilmetil)-ethylenediamine increased them, indicating that functional ASICs are composed of the subunits ASIC1, ASIC2, and ASIC3. Neomycin and streptomycin reduced the desensitization rate of the ASIC current in SGNs, indicating that ASICs may contribute to the ototoxic action of aminoglycosides. RT-PCR of the spiral ganglion revealed significant expression of all ASIC subunits. By immunohistochemistry the expression of the ASIC1a, ASIC2a, ASIC2b, and ASIC3 subunits was detected in SGNs. Although only a few SGNs exhibited action potential firing in response to an acidic stimulus, protons in the extracellular solution modulated SGN activity during sinusoidal stimulation. Our results show that protons modulate the excitability of SGNs via ASICs. PMID:26733809

  20. Validation and characterization of a novel method for selective vagal deafferentation of the gut.

    Science.gov (United States)

    Diepenbroek, Charlene; Quinn, Danielle; Stephens, Ricky; Zollinger, Benjamin; Anderson, Seth; Pan, Annabelle; de Lartigue, Guillaume

    2017-10-01

    There is a lack of tools that selectively target vagal afferent neurons (VAN) innervating the gut. We use saporin (SAP), a potent neurotoxin, conjugated to the gastronintestinal (GI) hormone cholecystokinin (CCK-SAP) injected into the nodose ganglia (NG) of male Wistar rats to specifically ablate GI-VAN. We report that CCK-SAP ablates a subpopulation of VAN in culture. In vivo, CCK-SAP injection into the NG reduces VAN innervating the mucosal and muscular layers of the stomach and small intestine but not the colon, while leaving vagal efferent neurons intact. CCK-SAP abolishes feeding-induced c-Fos in the NTS, as well as satiation by CCK or glucagon like peptide-1 (GLP-1). CCK-SAP in the NG of mice also abolishes CCK-induced satiation. Therefore, we provide multiple lines of evidence that injection of CCK-SAP in NG is a novel selective vagal deafferentation technique of the upper GI tract that works in multiple vertebrate models. This method provides improved tissue specificity and superior separation of afferent and efferent signaling compared with vagotomy, capsaicin, and subdiaphragmatic deafferentation. NEW & NOTEWORTHY We develop a new method that allows targeted lesioning of vagal afferent neurons that innervate the upper GI tract while sparing vagal efferent neurons. This reliable approach provides superior tissue specificity and selectivity for vagal afferent over efferent targeting than traditional approaches. It can be used to address questions about the role of gut to brain signaling in physiological and pathophysiological conditions. Copyright © 2017 the American Physiological Society.

  1. Premature Ventricular Contraction Coupling Interval Variability Destabilizes Cardiac Neuronal and Electrophysiological Control: Insights from Simultaneous Cardio-Neural Mapping

    Science.gov (United States)

    Hamon, David; Rajendran, Pradeep S.; Chui, Ray W.; Ajijola, Olujimi A.; Irie, Tadanobu; Talebi, Ramin; Salavatian, Siamak; Vaseghi, Marmar; Bradfield, Jason S.; Armour, J. Andrew; Ardell, Jeffrey L.; Shivkumar, Kalyanam

    2017-01-01

    Background Variability in premature ventricular contraction (PVC) coupling interval (CI) increases the risk of cardiomyopathy and sudden death. The autonomic nervous system regulates cardiac electrical and mechanical indices, and its dysregulation plays an important role in cardiac disease pathogenesis. The impact of PVCs on the intrinsic cardiac nervous system (ICNS), a neural network on the heart, remains unknown. The objective was to determine the effect of PVCs and CI on ICNS function in generating cardiac neuronal and electrical instability using a novel cardio-neural mapping approach. Methods and Results In a porcine model (n=8) neuronal activity was recorded from a ventricular ganglion using a microelectrode array, and cardiac electrophysiological mapping was performed. Neurons were functionally classified based on their response to afferent and efferent cardiovascular stimuli, with neurons that responded to both defined as convergent (local reflex processors). Dynamic changes in neuronal activity were then evaluated in response to right ventricular outflow tract PVCs with fixed short, fixed long, and variable CI. PVC delivery elicited a greater neuronal response than all other stimuli (P<0.001). Compared to fixed short and long CI, PVCs with variable CI had a greater impact on neuronal response (P<0.05 versus short CI), particularly on convergent neurons (P<0.05), as well as neurons receiving sympathetic (P<0.05) and parasympathetic input (P<0.05). The greatest cardiac electrical instability was also observed following variable (short) CI PVCs. Conclusions Variable CI PVCs affect critical populations of ICNS neurons and alter cardiac repolarization. These changes may be critical for arrhythmogenesis and remodeling leading to cardiomyopathy. PMID:28408652

  2. A hepatic amino acid/mTOR/S6K-dependent signalling pathway modulates systemic lipid metabolism via neuronal signals.

    Science.gov (United States)

    Uno, Kenji; Yamada, Tetsuya; Ishigaki, Yasushi; Imai, Junta; Hasegawa, Yutaka; Sawada, Shojiro; Kaneko, Keizo; Ono, Hiraku; Asano, Tomoichiro; Oka, Yoshitomo; Katagiri, Hideki

    2015-08-13

    Metabolism is coordinated among tissues and organs via neuronal signals. Levels of circulating amino acids (AAs), which are elevated in obesity, activate the intracellular target of rapamycin complex-1 (mTORC1)/S6kinase (S6K) pathway in the liver. Here we demonstrate that hepatic AA/mTORC1/S6K signalling modulates systemic lipid metabolism via a mechanism involving neuronal inter-tissue communication. Hepatic expression of an AA transporter, SNAT2, activates the mTORC1/S6K pathway, and markedly elevates serum triglycerides (TGs), while downregulating adipose lipoprotein lipase (LPL). Hepatic Rheb or active-S6K expression have similar metabolic effects, whereas hepatic expression of dominant-negative-S6K inhibits TG elevation in SNAT2 mice. Denervation, pharmacological deafferentation and β-blocker administration suppress obesity-related hypertriglyceridemia with adipose LPL upregulation, suggesting that signals are transduced between liver and adipose tissue via a neuronal pathway consisting of afferent vagal and efferent sympathetic nerves. Thus, the neuronal mechanism uncovered here serves to coordinate amino acid and lipid levels and contributes to the development of obesity-related hypertriglyceridemia.

  3. Facial injections of pruritogens and algogens excite partly overlapping populations of primary and second-order trigeminal neurons in mice.

    Science.gov (United States)

    Akiyama, T; Carstens, M Iodi; Carstens, E

    2010-11-01

    Intradermal cheek injection of pruitogens or algogens differentially elicits hindlimb scratching or forelimb wiping, suggesting that these behaviors distinguish between itch and pain. We studied whether pruritogens and algogens excite separate or overlapping populations of primary afferent and second-order trigeminal neurons in mice. Calcium imaging of primary sensory trigeminal ganglion (TG) cells showed that 15.4% responded to histamine, 5.8% to the protease-activated receptor (PAR)-2 agonist, 13.4% to allyl isothiocyanate (AITC), and 36.7% to capsaicin. AITC and/or capsaicin activated the vast majority of histamine- and PAR-2 agonist-sensitive TG cells. A chemical search strategy identified second-order neurons in trigeminal subnucleus caudalis (Vc) responsive to histamine, the PAR-2 agonist, or AITC. A minority of histamine or PAR-2 agonist-responsive Vc neurons responded to the other pruritogen, whereas a large majority of puritogen-responsive Vc neurons responded to capsaicin and/or AITC. A minority of AITC-responsive Vc neurons responded to pruritogens, whereas most responded to capsaicin. These data indicate that most primary and higher-order trigeminal sensory neurons are activated by both pruritic and algesic stimuli, although a minority exhibit selectivity. The results are discussed in terms of population codes for itch and pain that result in distinct behavioral responses of hindlimb scratching and forelimb wiping that are mediated at lumbar and cervical segmental levels, respectively.

  4. Substance P differentially modulates firing rate of solitary complex (SC neurons from control and chronic hypoxia-adapted adult rats.

    Directory of Open Access Journals (Sweden)

    Nicole L Nichols

    Full Text Available NK1 receptors, which bind substance P, are present in the majority of brainstem regions that contain CO2/H(+-sensitive neurons that play a role in central chemosensitivity. However, the effect of substance P on the chemosensitive response of neurons from these regions has not been studied. Hypoxia increases substance P release from peripheral afferents that terminate in the caudal nucleus tractus solitarius (NTS. Here we studied the effect of substance P on the chemosensitive responses of solitary complex (SC: NTS and dorsal motor nucleus neurons from control and chronic hypoxia-adapted (CHx adult rats. We simultaneously measured intracellular pH and electrical responses to hypercapnic acidosis in SC neurons from control and CHx adult rats using the blind whole cell patch clamp technique and fluorescence imaging microscopy. Substance P significantly increased the basal firing rate in SC neurons from control and CHx rats, although the increase was smaller in CHx rats. However, substance P did not affect the chemosensitive response of SC neurons from either group of rats. In conclusion, we found that substance P plays a role in modulating the basal firing rate of SC neurons but the magnitude of the effect is smaller for SC neurons from CHx adult rats, implying that NK1 receptors may be down regulated in CHx adult rats. Substance P does not appear to play a role in modulating the firing rate response to hypercapnic acidosis of SC neurons from either control or CHx adult rats.

  5. Rimonabant induced anorexia in rodents is not mediated by vagal or sympathetic gut afferents

    DEFF Research Database (Denmark)

    Madsen, Andreas Nygaard; Jelsing, Jacob; van de Wall, Esther H E M

    2009-01-01

    The selective CB1 receptor antagonist rimonabant is a novel weight control agent. Although CB1 receptors and binding sites are present in both the rodent central and peripheral nervous systems, including the afferent vagus nerve, the role of gut afferents in mediating anorexia following CB1R...... blockade is still debated. In the present study we examined rimonabant-induced anorexia in male C57BL/6J mice with subdiaphragmatic vagotomy (VGX) as well as in male Sprague-Dawley rats subjected to either subdiaphragmatic vagal deafferentation (SDA) alone or in combination with a complete celiac...... system, are required for rimonabant to inhibit food intake leading to the hypothesis that centrally located CB1 receptors are the prime mediators of rimonabant-induced anorexia....

  6. Frontal lobe atrophy in motor neuron diseases.

    Science.gov (United States)

    Kiernan, J A; Hudson, A J

    1994-08-01

    Neuronal degeneration in the precentral gyrus alone cannot account for the occurrence of spastic paresis in motor neuron diseases. To look for more extensive cortical atrophy we measured MRIs of the upper parts of the frontal and parietal lobes in 11 sporadic cases of classical amyotrophic lateral sclerosis (ALS), eight patients with primary lateral sclerosis (PLS) and an age- and sex-matched group of 49 neurologically normal people. None of the patients had overt dementia or other mental diseases. In PLS there is progressive spastic paresis but in contrast to ALS there is no lower motor neuron degeneration. The surface area of the precentral gyri and the amount of underlying white matter in PLS were consistently approximately 75% of the normal size. By contrast, there was some shrinkage of the precentral gyri in some of the ALS patients but the mean measurements for the group did not differ significantly from the controls. Anterior to the precentral sulci, the cortical surface area in PLS was approximately 85% of that of the controls, with correspondingly reduced white matter. In ALS the cortical surface areas of the anterior frontal lobes did not differ from those of the controls, but the amount of underlying white matter was reduced almost as much in ALS as it was in PLS. The measured changes in the frontal lobes suggest that in PLS there is simultaneous atrophy of the primary, premotor and supplementary motor areas of the cortex, with consequent degeneration of corticospinal and corticoreticular axons descending through the underlying white matter. These changes could account for the progressive upper motor neuron syndrome. In ALS, with no significant frontal cortical atrophy, the shrinkage of the white matter may be due to degeneration of axons projecting to the frontal cortex from elsewhere. Deprivation of afferents could explain the diminution of motor functions of the frontal lobes in ALS and also the changes in word fluency, judgement and attention that

  7. Immobilization induces changes in presynaptic control of group Ia afferents in healthy humans

    DEFF Research Database (Denmark)

    Jensen, Jesper Lundbye; Nielsen, Jens Bo

    2008-01-01

    immobilized the left foot and ankle joint for 2 weeks in 12 able-bodied subjects. Disynaptic reciprocal inhibition of soleus (SOL) motoneurones and presynaptic control of SOL group Ia afferents was measured before and after the immobilization as well as following 2 weeks of recovery. Following immobilization...... maximal voluntary plantar- and dorsiflexion torque (MVC) was significantly reduced and the maximal SOL H-reflex amplitude increased with no changes in Mmax. Decreased presynaptic inhibition of the Ia afferents likely contributed to the increase of the H-reflex size, since we observed a significant...... decrease in the long-latency depression of the SOL H-reflex evoked by peroneal nerve stimulation (D2 inhibition) and an increase in the size of the monosynaptic Ia facilitation of the SOL H-reflex evoked by femoral nerve stimulation. These two measures provide independent evidence of changes in presynaptic...

  8. Connexin43 Hemichannels in Satellite Glial Cells, Can They Influence Sensory Neuron Activity?

    Directory of Open Access Journals (Sweden)

    Mauricio A. Retamal

    2017-11-01

    Full Text Available In this review article, we summarize the current insight on the role of Connexin- and Pannexin-based channels as modulators of sensory neurons. The somas of sensory neurons are located in sensory ganglia (i.e., trigeminal and nodose ganglia. It is well known that within sensory ganglia, sensory neurons do not form neither electrical nor chemical synapses. One of the reasons for this is that each soma is surrounded by glial cells, known as satellite glial cells (SGCs. Recent evidence shows that connexin43 (Cx43 hemichannels and probably pannexons located at SGCs have an important role in paracrine communication between glial cells and sensory neurons. This communication may be exerted via the release of bioactive molecules from SGCs and their subsequent action on receptors located at the soma of sensory neurons. The glio-neuronal communication seems to be relevant for the establishment of chronic pain, hyperalgesia and pathologies associated with tissue inflammation. Based on the current literature, it is possible to propose that Cx43 hemichannels expressed in SGCs could be a novel pharmacological target for treating chronic pain, which need to be directly evaluated in future studies.

  9. Anatomical evidence for direct fiber projections from the cerebellar nucleus interpositus to rubrospinal neurons. A quantitative EM study in the rat combining anterograde and retrograde intra-axonal tracing methods

    International Nuclear Information System (INIS)

    Dekker, J.J.

    1981-01-01

    A quantitative electron microscopic (EM) study combining the anterograde intra-axonal transport of radioactive amino acids and the retrograde intra-axonal transport of the enzyme horseradish peroxidase (HRP) was performed in the magnocellular red nucleus of the rat to obtain anatomical evidence as to whether there is a direct projection from the cerebellar nucleus interpositus to the cells in the red nucleus that give rise to the rubrospinal tract. Large asymmetrical synaptic terminals were radioactively labeled in the magnocellular red nucleus following injections of [ 3 H]leucine into the cerebellar nucleus interpositus. In these same animals, the postsynaptic target neurons were labeled with HRP granules after injection of this substance in the rubrospinal tract. A quantitative analysis showed that more than 85% of the large and giant neurons in the magnocellular red nucleus were labeled with HRP granules and also received synaptic contacts from radioactively-labeled terminals. Thus, it can be concluded that in the rat, afferents from the cerebellar nucleus interpositus establish asymmetrical synaptic contacts with large and giant rubrospinal neurons, thus confirming and extending the previous physiological evidence of such direct monosynaptic connections. (Auth.)

  10. Inhibition of Parkinsonian tremor with cutaneous afferent evoked by transcutaneous electrical nerve stimulation.

    Science.gov (United States)

    Hao, Man-Zhao; Xu, Shao-Qin; Hu, Zi-Xiang; Xu, Fu-Liang; Niu, Chuan-Xin M; Xiao, Qin; Lan, Ning

    2017-07-14

    Recent study suggests that tremor signals are transmitted by way of multi-synaptic corticospinal pathway. Neurophysiological studies have also demonstrated that cutaneous afferents exert potent inhibition to descending motor commands by way of spinal interneurons. We hypothesize in this study that cutaneous afferents could also affect the transmission of tremor signals, thus, inhibit tremor in patients with PD. We tested this hypothesis by activating cutaneous afferents in the dorsal hand skin innervated by superficial radial nerve using transcutaneous electrical nerve stimulation (TENS). Eight patients with PD having tremor dominant symptom were recruited to participate in this study using a consistent experimental protocol for tremor inhibition. Resting tremor and electromyogram (EMG) of muscles in the upper extremity of these subjects with PD were recorded, while surface stimulation was applied to the dorsal skin of the hand. Fifteen seconds of data were recorded for 5 s prior to, during and post stimulation. Power spectrum densities (PSDs) of tremor and EMG signals were computed for each data segment. The peak values of PSDs in three data segments were compared to detect evidence of tremor inhibition. At stimulation intensity from 1.5 to 1.75 times of radiating sensation threshold, apparent suppressions of tremor at wrist, forearm and upper arm and in the EMGs were observed immediately at the onset of stimulation. After termination of stimulation, tremor and rhythmic EMG bursts reemerged gradually. Statistical analysis of peak spectral amplitudes showed a significant difference in joint tremors and EMGs during and prior to stimulation in all 8 subjects with PD. The average percentage of suppression was 61.56% in tremor across all joints of all subjects, and 47.97% in EMG of all muscles. The suppression appeared to occur mainly in distal joints and muscles. There was a slight, but inconsistent effect on tremor frequency in the 8 patients with PD tested. Our

  11. Neuronal Health – Can Culinary and Medicinal Mushrooms Help?

    Science.gov (United States)

    Sabaratnam, Vikineswary; Kah-Hui, Wong; Naidu, Murali; Rosie David, Pamela

    2013-01-01

    Hericium erinaceus a culinary and medicinal mushroom is a well established candidate for brain and nerve health. Ganoderma lucidum, Grifola frondosa and Sarcodon scabrosus have been reported to have neurite outgrowth and neuronal health benefits. The number of mushrooms, however, studied for neurohealth activity are few compared to the more than 2 000 species of edible and / or medicinal mushrooms identified. In the on-going search for other potent culinary and / or medicinal mushrooms, indigenous mushrooms used in traditional medicines such as Lignosus rhinocerotis and Ganoderma neo-japonicum are also being investigated. Further, the edible mushroom, Pleurotus giganteus can be a potential candidate, too. Can these edible and medicinal mushrooms be tapped to tackle the health concerns of the aging population which is projected to be more than 80-90 million of people age 65 and above in 2050 who may be affected by age-related neurodegenerative disorders. Scientific validation is needed if these mushrooms are to be considered and this can be achieved by understanding the molecular and biochemical mechanisms involved in the stimulation of neurite outgrowth. Though it is difficult to extrapolate the in vitro studies to what may happen in the human brain, studies have shown that there can be improvement in cognitive abilities of the aged if the mushroom is incorporated in their daily diets. PMID:24716157

  12. Neuronal Health – Can Culinary and Medicinal Mushrooms Help?

    Directory of Open Access Journals (Sweden)

    Vikineswary Sabaratnam

    2013-01-01

    Full Text Available Hericium erinaceus a culinary and medicinal mushroom is a well established candidate for brain and nerve health. Ganoderma lucidum, Grifola frondosa and Sarcodon scabrosus have been reported to have neurite outgrowth and neuronal health benefits. The number of mushrooms, however, studied for neurohealth activity are few compared to the more than 2 000 species of edible and / or medicinal mushrooms identified. In the on-going search for other potent culinary and / or medicinal mushrooms, indigenous mushrooms used in traditional medicines such as Lignosus rhinocerotis and Ganoderma neo-japonicum are also being investigated. Further, the edible mushroom, Pleurotus giganteus can be a potential candidate, too. Can these edible and medicinal mushrooms be tapped to tackle the health concerns of the aging population which is projected to be more than 80-90 million of people age 65 and above in 2050 who may be affected by age-related neurodegenerative disorders. Scientific validation is needed if these mushrooms are to be considered and this can be achieved by understanding the molecular and biochemical mechanisms involved in the stimulation of neurite outgrowth. Though it is difficult to extrapolate the in vitro studies to what may happen in the human brain, studies have shown that there can be improvement in cognitive abilities of the aged if the mushroom is incorporated in their daily diets.

  13. Innervation of the mammalian esophagus.

    Science.gov (United States)

    Neuhuber, Winfried L; Raab, Marion; Berthoud, Hans-Rudolf; Wörl, Jürgen

    2006-01-01

    Understanding the innervation of the esophagus is a prerequisite for successful treatment of a variety of disorders, e.g., dysphagia, achalasia, gastroesophageal reflux disease (GERD) and non-cardiac chest pain. Although, at first glance, functions of the esophagus are relatively simple, their neuronal control is considerably complex. Vagal motor neurons of the nucleus ambiguus and preganglionic neurons of the dorsal motor nucleus innervate striated and smooth muscle, respectively. Myenteric neurons represent the interface between the dorsal motor nucleus and smooth muscle but they are also involved in striated muscle innervation. Intraganglionic laminar endings (IGLEs) represent mechanosensory vagal afferent terminals. They also establish intricate connections with enteric neurons. Afferent information is implemented by the swallowing central pattern generator in the brainstem, which generates and coordinates deglutitive activity in both striated and smooth esophageal muscle and orchestrates esophageal sphincters as well as gastric adaptive relaxation. Disturbed excitation/inhibition balance in the lower esophageal sphincter results in motility disorders, e.g., achalasia and GERD. Loss of mechanosensory afferents disrupts adaptation of deglutitive motor programs to bolus variables, eventually leading to megaesophagus. Both spinal and vagal afferents appear to contribute to painful sensations, e.g., non-cardiac chest pain. Extrinsic and intrinsic neurons may be involved in intramural reflexes using acetylcholine, nitric oxide, substance P, CGRP and glutamate as main transmitters. In addition, other molecules, e.g., ATP, GABA and probably also inflammatory cytokines, may modulate these neuronal functions.

  14. Meningeal norepinephrine produces headache behaviors in rats via actions both on dural afferents and fibroblasts.

    Science.gov (United States)

    Wei, Xiaomei; Yan, Jin; Tillu, Dipti; Asiedu, Marina; Weinstein, Nicole; Melemedjian, Ohannes; Price, Theodore; Dussor, Gregory

    2015-10-01

    Stress is commonly reported to contribute to migraine although mechanisms by which this may occur are not fully known. The purpose of these studies was to examine whether norepinephrine (NE), the primary sympathetic efferent transmitter, acts on processes in the meninges that may contribute to the pain of migraine. NE was applied to rat dura using a behavioral model of headache. Primary cultures of rat trigeminal ganglia retrogradely labeled from the dura mater and of rat dural fibroblasts were prepared. Patch-clamp electrophysiology, Western blot, and ELISA were performed to examine the effects of NE. Conditioned media from NE-treated fibroblast cultures was applied to the dura using the behavioral headache model. Dural injection both of NE and media from NE-stimulated fibroblasts caused cutaneous facial and hindpaw allodynia in awake rats. NE application to cultured dural afferents increased action potential firing in response to current injections. Application of NE to dural fibroblasts increased phosphorylation of ERK and caused the release of interleukin-6 (IL-6). These data demonstrate that NE can contribute to pro-nociceptive signaling from the meninges via actions on dural afferents and dural fibroblasts. Together, these actions of NE may contribute to the headache phase of migraine. © International Headache Society 2015.

  15. The median preoptic nucleus reciprocally modulates activity of arousal-related and sleep-related neurons in the perifornical lateral hypothalamus.

    Science.gov (United States)

    Suntsova, Natalia; Guzman-Marin, Ruben; Kumar, Sunil; Alam, Md Noor; Szymusiak, Ronald; McGinty, Dennis

    2007-02-14

    The perifornical-lateral hypothalamic area (PF/LH) contains neuronal groups playing an important role in control of waking and sleep. Among the brain regions that regulate behavioral states, one of the strongest sources of projections to the PF/LH is the median preoptic nucleus (MnPN) containing a sleep-active neuronal population. To evaluate the role of MnPN afferents in the control of PF/LH neuronal activity, we studied the responses of PF/LH cells to electrical stimulation or local chemical manipulation of the MnPN in freely moving rats. Single-pulse electrical stimulation evoked responses in 79% of recorded PF/LH neurons. No cells were activated antidromically. Direct and indirect transsynaptic effects depended on sleep-wake discharge pattern of PF/LH cells. The majority of arousal-related neurons, that is, cells discharging at maximal rates during active waking (AW) or during AW and rapid eye movement (REM) sleep, exhibited exclusively or initially inhibitory responses to stimulation. Sleep-related neurons, the cells with elevated discharge during non-REM and REM sleep or selectively active in REM sleep, exhibited exclusively or initially excitatory responses. Activation of the MnPN via microdialytic application of L-glutamate or bicuculline resulted in reduced discharge of arousal-related and in excitation of sleep-related PF/LH neurons. Deactivation of the MnPN with muscimol caused opposite effects. The results indicate that the MnPN contains subset(s) of neurons, which exert inhibitory control over arousal-related and excitatory control over sleep-related PF/LH neurons. We hypothesize that MnPN sleep-active neuronal group has both inhibitory and excitatory outputs that participate in the inhibitory control of arousal-promoting PF/LH mechanisms.

  16. Central connectivity of transient receptor potential melastatin 8-expressing axons in the brain stem and spinal dorsal horn.

    Directory of Open Access Journals (Sweden)

    Yun Sook Kim

    Full Text Available Transient receptor potential melastatin 8 (TRPM8 ion channels mediate the detection of noxious and innocuous cold and are expressed by primary sensory neurons, but little is known about the processing of the TRPM8-mediated cold information within the trigeminal sensory nuclei (TSN and the spinal dorsal horn (DH. To address this issue, we characterized TRPM8-positive (+ neurons in the trigeminal ganglion and investigated the distribution of TRPM8+ axons and terminals, and their synaptic organization in the TSN and in the DH using light and electron microscopic immunohistochemistry in transgenic mice expressing a genetically encoded axonal tracer in TRPM8+ neurons. TRPM8 was expressed in a fraction of small myelinated primary afferent fibers (23.7% and unmyelinated fibers (76.3%, suggesting that TRPM8-mediated cold is conveyed via C and Aδ afferents. TRPM8+ axons were observed in all TSN, but at different densities in the dorsal and ventral areas of the rostral TSN, which dominantly receive sensory afferents from intra- and peri-oral structures and from the face, respectively. While synaptic boutons arising from Aδ and non-peptidergic C afferents usually receive many axoaxonic contacts and form complex synaptic arrangements, TRPM8+ boutons arising from afferents of the same classes of fibers showed a unique synaptic connectivity; simple synapses with one or two dendrites and sparse axoaxonic contacts. These findings suggest that TRPM8-mediated cold is conveyed via a specific subset of C and Aδ afferent neurons and is processed in a unique manner and differently in the TSN and DH.

  17. Cholera Toxin Induces Sustained Hyperexcitability in Myenteric, but Not Submucosal, AH Neurons in Guinea Pig Jejunum

    Directory of Open Access Journals (Sweden)

    Joel C. Bornstein

    2017-04-01

    Full Text Available Background and Aims: Cholera toxin (CT-induced hypersecretion requires activation of secretomotor pathways in the enteric nervous system (ENS. AH neurons, which have been identified as a population of intrinsic sensory neurons (ISNs, are a source of excitatory input to the secretomotor pathways. We therefore examined effects of CT in the intestinal lumen on myenteric and submucosal AH neurons.Methods: Isolated segments of guinea pig jejunum were incubated for 90 min with saline plus CT (12.5 μg/ml or CT + neurotransmitter antagonist, or CT + tetrodotoxin (TTX in their lumen. After washing CT away, submucosal or myenteric plexus preparations were dissected keeping circumferentially adjacent mucosa intact. Submucosal AH neurons were impaled adjacent to intact mucosa and myenteric AH neurons were impaled adjacent to, more than 5 mm from, and in the absence of intact mucosa. Neuronal excitability was monitored by injecting 500 ms current pulses through the recording electrode.Results: After CT pre-treatment, excitability of myenteric AH neurons adjacent to intact mucosa (n = 29 was greater than that of control neurons (n = 24, but submucosal AH neurons (n = 33, control n = 27 were unaffected. CT also induced excitability increases in myenteric AH neurons impaled distant from the mucosa (n = 6 or in its absence (n = 5. Coincubation with tetrodotoxin or SR142801 (NK3 receptor antagonist, but not SR140333 (NK1 antagonist or granisetron (5-HT3 receptor antagonist prevented the increased excitability induced by CT. Increased excitability was associated with a reduction in the characteristic AHP and an increase in the ADP of these neurons, but not a change in the hyperpolarization-activated inward current, Ih.Conclusions: CT increases excitability of myenteric, but not submucosal, AH neurons. This is neurally mediated and depends on NK3, but not 5-HT3 receptors. Therefore, CT may act to amplify the secretomotor response to CT via an increase in the

  18. CX3CL1-mediated macrophage activation contributed to paclitaxel-induced DRG neuronal apoptosis and painful peripheral neuropathy.

    Science.gov (United States)

    Huang, Zhen-Zhen; Li, Dai; Liu, Cui-Cui; Cui, Yu; Zhu, He-Quan; Zhang, Wen-Wen; Li, Yong-Yong; Xin, Wen-Jun

    2014-08-01

    Painful peripheral neuropathy is a dose-limiting side effect of paclitaxel therapy, which hampers the optimal clinical management of chemotherapy in cancer patients. Currently the underlying mechanisms remain largely unknown. Here we showed that the clinically relevant dose of paclitaxel (3×8mg/kg, cumulative dose 24mg/kg) induced significant upregulation of the chemokine CX3CL1 in the A-fiber primary sensory neurons in vivo and in vitro and infiltration of macrophages into the dorsal root ganglion (DRG) in rats. Paclitaxel treatment also increased cleaved caspase-3 expression, induced the loss of primary afferent terminal fibers and decreased sciatic-evoked A-fiber responses in the spinal dorsal horn, indicating DRG neuronal apoptosis induced by paclitaxel. In addition, the paclitaxel-induced DRG neuronal apoptosis occurred exclusively in the presence of macrophage in vitro study. Intrathecal or systemic injection of CX3CL1 neutralizing antibody blocked paclitaxel-induced macrophage recruitment and neuronal apoptosis in the DRG, and also attenuated paclitaxel-induced allodynia. Furthermore, depletion of macrophage by systemic administration of clodronate inhibited paclitaxel-induced allodynia. Blocking CX3CL1 decreased activation of p38 MAPK in the macrophage, and inhibition of p38 MAPK activity blocked the neuronal apoptosis and development of mechanical allodynia induced by paclitaxel. These findings provide novel evidence that CX3CL1-recruited macrophage contributed to paclitaxel-induced DRG neuronal apoptosis and painful peripheral neuropathy. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Corticospinal inhibition of transmission in propriospinal-like neurones during human walking

    DEFF Research Database (Denmark)

    Iglesias, Caroline; Nielsen, Jens Bo; Marchand-Pauvert, Véronique

    2008-01-01

    It is crucial for human walking that muscles acting at different joints are optimally coordinated in relation to each other. This is ensured by interaction between spinal neuronal networks, sensory feedback and supraspinal control. Here we investigated the cortical control of spinal excitation from...... ankle dorsiflexor afferents to quadriceps motoneurones mediated by propriospinal-like interneurones. During walking and tonic contraction of ankle dorsiflexors and knee extensors while standing [at matched electromyography (EMG) levels], the effect of common peroneal nerve (CPN) stimulation...... was enhanced during walking, and when CPN stimulation was combined with FN or TMS, the resulting H-reflexes and MEPs were inhibited. The CPQ-reflex was also depressed when CPN stimulation was combined with subthreshold TMS. The peripheral (in CPN and FN) and corticospinal volleys may activate inhibitory non...

  20. Effects of intra-articular hyaluronic acid injection on immunohistochemical characterization of joint afferents in a rat model of knee osteoarthritis.

    Science.gov (United States)

    Ikeuchi, M; Izumi, M; Aso, K; Sugimura, N; Kato, T; Tani, T

    2015-03-01

    Intra-articular hyaluronic acid (HA) injection, known as viscosupplementation, is a widely used therapy for pain relief in knee osteoarthritis (OA). Long-term clinical efficacy of HA has been reported in spite of a relatively short residence time. Herein, we evaluated our hypothesis that intra-articular HA injection could reduce the OA-associated changes in joint afferents. OA was induced by intra-articular injection of mono-iodoacetate in rats. Animals in the OA + HA group were given three weekly intra-articular HA injections. Pain-related behaviours, including weight-bearing asymmetry and mechanical hyperalgesia of the paw, knee joint histology and immunohistochemistry of joint afferents identified by retrograde labelling, were compared between groups (naïve, OA and OA + HA). OA rats showed pain-related behaviours and up-regulation of pain-related neurochemical markers [calcitonin gene-related peptide (CGRP), tyrosine receptor kinase A (TrkA) and acid-sensing ion channel 3 (ASIC3)] in joint afferents. HA injections reduced not only the severity of OA and pain behaviours but also OA-associated neurochemical changes in joint afferents. The differences between OA and OA + HA were statistically significant in CGRP (61 ± 10% vs. 51 ± 10%; p = 0.0406) but not significant in TrkA (62 ± 10% vs. 54 ± 9%; p = 0.0878) and ASIC3 (38 ± 9% vs. 32 ± 8%; p = 0.3681). Intra-articular HA injections reduced the severity of OA, decreased mechanical hyperalgesia of the paw, but not weight-bearing asymmetry, and attenuated OA-associated up-regulation of CGRP, but not TrkA and ASIC3, in joint afferents. The modulatory effects of HA on joint afferents is one of the underlying mechanisms of the gap between HA residence time and duration of clinical efficacy. © 2014 European Pain Federation - EFIC®

  1. Populations of auditory cortical neurons can accurately encode acoustic space across stimulus intensity.

    Science.gov (United States)

    Miller, Lee M; Recanzone, Gregg H

    2009-04-07

    The auditory cortex is critical for perceiving a sound's location. However, there is no topographic representation of acoustic space, and individual auditory cortical neurons are often broadly tuned to stimulus location. It thus remains unclear how acoustic space is represented in the mammalian cerebral cortex and how it could contribute to sound localization. This report tests whether the firing rates of populations of neurons in different auditory cortical fields in the macaque monkey carry sufficient information to account for horizontal sound localization ability. We applied an optimal neural decoding technique, based on maximum likelihood estimation, to populations of neurons from 6 different cortical fields encompassing core and belt areas. We found that the firing rate of neurons in the caudolateral area contain enough information to account for sound localization ability, but neurons in other tested core and belt cortical areas do not. These results provide a detailed and plausible population model of how acoustic space could be represented in the primate cerebral cortex and support a dual stream processing model of auditory cortical processing.

  2. Afferent thermosensory function in relapsing-remitting multiple sclerosis following exercise-induced increases in body temperature.

    Science.gov (United States)

    Filingeri, Davide; Chaseling, Georgia; Hoang, Phu; Barnett, Michael; Davis, Scott L; Jay, Ollie

    2017-08-01

    What is the central question of this study? Between 60 and 80% of multiple sclerosis (MS) patients experience transient worsening of symptoms with increased body temperature (heat sensitivity). As sensory abnormalities are common in MS, we asked whether afferent thermosensory function is altered in MS following exercise-induced increases in body temperature. What is the main finding and its importance? Increases in body temperature of as little as ∼0.4°C were sufficient to decrease cold, but not warm, skin thermosensitivity (∼10%) in MS, across a wider temperature range than in age-matched healthy individuals. These findings provide new evidence on the impact of heat sensitivity on afferent function in MS, which could be useful for clinical evaluation of this neurological disease. In multiple sclerosis (MS), increases in body temperature result in transient worsening of clinical symptoms (heat sensitivity or Uhthoff's phenomenon). Although the impact of heat sensitivity on efferent physiological function has been investigated, the effects of heat stress on afferent sensory function in MS are unknown. Hence, we quantified afferent thermosensory function in MS following exercise-induced increases in body temperature with a new quantitative sensory test. Eight relapsing-remitting MS patients (three men and five women; 51.4 ± 9.1 years of age; Expanded Disability Status Scale score 2.8 ± 1.1) and eight age-matched control (CTR) subjects (five men and three women; 47.4 ± 9.1 years of age) rated the perceived magnitude of two cold (26 and 22°C) and two warm stimuli (34 and 38°C) applied to the dorsum of the hand before and after 30 min cycling in the heat (30°C air; 30% relative humidity). Exercise produced similar increases in mean body temperature in MS [+0.39°C (95% CI: +0.21, +0.53) P = 0.001] and CTR subjects [+0.41°C (95% CI: +0.25, +0.58) P = 0.001]. These changes were sufficient to decrease thermosensitivity significantly to all cold [26

  3. Excitatory and inhibitory synaptic mechanisms at the first stage of integration in the electroreception system of the shark

    DEFF Research Database (Denmark)

    Rotem, Naama; Sestieri, Emanuel; Hounsgaard, Jørn Dybkjær

    2014-01-01

    High impulse rate in afferent nerves is a common feature in many sensory systems that serve to accommodate a wide dynamic range. However, the first stage of integration should be endowed with specific properties that enable efficient handling of the incoming information. In elasmobranches...... of this afferent pathway. We found that stimulating the afferent nerve activates a mixture of excitatory and inhibitory synapses mediated by AMPA-like and GABAA receptors, respectively. The excitatory synapses that are extremely efficient in activating the postsynaptic neurons display unusual voltage dependence......, enabling them to operate as a current source. The inhibitory input is powerful enough to completely eliminate the excitatory action of the afferent nerve but is ineffective regarding other excitatory inputs. These observations can be explained by the location and efficiency of the synapses. We conclude...

  4. Noninvasive focused ultrasound stimulation can modulate phase-amplitude coupling between neuronal oscillations in the rat hippocampus

    Directory of Open Access Journals (Sweden)

    Yi Yuan

    2016-07-01

    Full Text Available Noninvasive focused ultrasound stimulation (FUS can be used to modulate neural activity with high spatial resolution. Phase-amplitude coupling (PAC between neuronal oscillations is tightly associated with cognitive processes, including learning, attention and memory. In this study, we investigated the effect of FUS on PAC between neuronal oscillations and established the relationship between the PAC index and ultrasonic intensity. The rat hippocampus was stimulated using focused ultrasound at different spatial-average pulse-average ultrasonic intensities (3.9 W/cm2, 9.6 W/cm2, and 19.2 W/cm2. The local field potentials (LFPs in the rat hippocampus were recorded before and after FUS. Then, we analyzed PAC between neuronal oscillations using a PAC calculation algorithm. Our results showed that FUS significantly modulated PAC between the theta (4-8 Hz and gamma (30-80 Hz bands and between the alpha (9-13 Hz and ripple (81-200 Hz bands in the rat hippocampus, and PAC increased with incremental increases in ultrasonic intensity.

  5. Group II muscle afferents probably contribute to the medium latency soleus stretch reflex during walking in humans

    DEFF Research Database (Denmark)

    Grey, Michael James; Ladouceur, Michel; Andersen, Jacob B.

    2001-01-01

    1. The objective of this study was to determine which afferents contribute to the medium latency response of the soleus stretch reflex resulting from an unexpected perturbation during human walking. 2. Fourteen healthy subjects walked on a treadmill at approximately 3.5 km h(-1) with the left ankle...... = 0.007), whereas the short latency component was unchanged (P = 0.653). 7. An ankle block with lidocaine hydrochloride was performed to suppress the cutaneous afferents of the foot and ankle. Neither the short (P = 0.453) nor medium (P = 0.310) latency reflexes were changed. 8. Our results support...

  6. Modulation of local field potentials by high-frequency stimulation of afferent axons in the hippocampal CA1 region.

    Science.gov (United States)

    Yu, Ying; Feng, Zhouyan; Cao, Jiayue; Guo, Zheshan; Wang, Zhaoxiang; Hu, Na; Wei, Xuefeng

    2016-03-01

    Modulation of the rhythmic activity of local field potentials (LFP) in neuronal networks could be a mechanism of deep brain stimulation (DBS). However, exact changes of LFP during the periods of high-frequency stimulation (HFS) of DBS are unclear because of the interference of dense stimulation artifacts with high amplitudes. In the present study, we investigated LFP changes induced by HFS of afferent axons in the hippocampal CA1 region of urethane-anesthetized rats by using a proper algorithm of artifact removal. Afterward, the LFP changes in the frequency bands of [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] rhythms were studied by power spectrum analysis and coherence analysis for the recorded signals collected in the pyramidal layer and in the stratum radiatum of CA1 region before, during and after 1-min long 100 and 200[Formula: see text]Hz HFS. Results showed that the power of LFP rhythms in higher-frequency band ([Formula: see text] rhythm) increased in the pyramidal layer and the power of LFP rhythms in lower-frequency bands ([Formula: see text], [Formula: see text] and [Formula: see text] rhythms) decreased in the stratum radiatum during HFS. The synchronization of [Formula: see text] rhythm decreased and the synchronization of [Formula: see text] rhythm increased during HFS in the stratum radiatum. These results suggest that axonal HFS could modulate LFP rhythms in the downstream brain areas with a plausible underlying mechanism of partial axonal blockage induced by HFS. The study provides new evidence to support the mechanism of DBS modulating rhythmic activity of neuronal populations.

  7. Effects of 17beta-estradiol on glutamate synaptic transmission and neuronal excitability in the rat medial vestibular nuclei.

    Science.gov (United States)

    Grassi, S; Frondaroli, A; Scarduzio, M; Dutia, M B; Dieni, C; Pettorossi, V E

    2010-02-17

    We investigated the effects of the neurosteroid 17beta-estradiol (E(2)) on the evoked and spontaneous activity of rat medial vestibular nucleus (MVN) neurons in brainstem slices. E(2) enhances the synaptic response to vestibular nerve stimulation in type B neurons and depresses the spontaneous discharge in both type A and B neurons. The amplitude of the field potential, as well as the excitatory post-synaptic potential (EPSP) and current (EPSC), in type B neurons, are enhanced by E(2). Both effects are long-term phenomena since they outlast the drug washout. The enhancement of synaptic response is mainly due to facilitation of glutamate release mediated by pre-synaptic N-methyl-D-aspartate receptors (NMDARs), since the reduction of paired pulse ratio (PPR) and the increase of miniature EPSC frequency after E(2) are abolished under D-(-)-2-amino-5-phosphonopentanoic acid (AP-5). E(2) also facilitates post-synaptic NMDARs, but it does not affect directly alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and group I-metabotropic glutamate receptors (mGluRs-I). In contrast, the depression of the spontaneous discharge of type A and type B neurons appears to depend on E(2) modulation of intrinsic ion conductances, as the effect remains after blockade of glutamate, GABA and glycine receptors (GlyRs). The net effect of E(2) is to enhance the signal-to-noise ratio of the synaptic response in type B neurons, relative to resting activity of all MVN neurons. These findings provide evidence for a novel potential mechanism to modulate the responsiveness of vestibular neurons to afferent inputs, and so regulate vestibular function in vivo.

  8. Chewing-induced hypertension in afferent baroreflex failure: a sympathetic response?

    Science.gov (United States)

    Fuente Mora, Cristina; Norcliffe-Kaufmann, Lucy; Palma, Jose-Alberto; Kaufmann, Horacio

    2015-11-01

    What is the central question of this study? Our goal was to understand the autonomic responses to eating in patients with congenital afferent baroreflex failure, by documenting changes in blood pressure and heart rate with chewing, swallowing and stomach distension. What is the main finding and its importance? Patients born with lesions in the afferent baroreceptor pathways have an exaggerated pressor response to food intake. This appears to be a sympathetically mediated response, triggered by chewing, that occurs independently of swallowing or distension of the stomach. The chewing-induced pressor response may be useful as a counter-manoeuvre to prevent orthostatic hypotension in these patients. Familial dysautonomia (FD) is a rare genetic disease with extremely labile blood pressure resulting from baroreflex deafferentation. Patients have marked surges in sympathetic activity, frequently surrounding meals. We conducted an observational study to document the autonomic responses to eating in patients with FD and to determine whether sympathetic activation was caused by chewing, swallowing or stomach distension. Blood pressure and R-R intervals were measured continuously while chewing gum (n = 15), eating (n = 20) and distending the stomach by percutaneous endoscopic gastrostomy tube feeding (n = 9). Responses were compared with those of normal control subjects (n = 10) and of patients with efferent autonomic failure (n = 10) who have chronically impaired sympathetic outflow. In patients with FD, eating was associated with a marked but transient pressor response (P Chewing gum evoked a similar increase in blood pressure that was higher in patients with FD than in control subjects (P = 0.0001), but was absent in patients with autonomic failure. In patients with FD, distending the stomach by percutaneous endoscopic gastrostomy tube feeding failed to elicit a pressor response. The results provide indirect evidence that chewing triggers sympathetic

  9. Organization of diencephalic and brainstem afferent projections to the lateral septum in the rat

    NARCIS (Netherlands)

    Luiten, Paul G.M.; Kuipers, Folkert; Schuitmaker, Hans

    1982-01-01

    Ascending diencephalic and brainstem afferents to the lateral septal column were studied by retrograde transport of horseradish peroxidase following microiontophoretic injections in the various subdivisions of the lateral septal area. Predominantly ispilateral cells, of which several coincide with

  10. Labeling of neuronal differentiation and neuron cells with biocompatible fluorescent nanodiamonds.

    Science.gov (United States)

    Hsu, Tzu-Chia; Liu, Kuang-Kai; Chang, Huan-Cheng; Hwang, Eric; Chao, Jui-I

    2014-05-16

    Nanodiamond is a promising carbon nanomaterial developed for biomedical applications. Here, we show fluorescent nanodiamond (FND) with the biocompatible properties that can be used for the labeling and tracking of neuronal differentiation and neuron cells derived from embryonal carcinoma stem (ECS) cells. The fluorescence intensities of FNDs were increased by treatment with FNDs in both the mouse P19 and human NT2/D1 ECS cells. FNDs were taken into ECS cells; however, FNDs did not alter the cellular morphology and growth ability. Moreover, FNDs did not change the protein expression of stem cell marker SSEA-1 of ECS cells. The neuronal differentiation of ECS cells could be induced by retinoic acid (RA). Interestingly, FNDs did not affect on the morphological alteration, cytotoxicity and apoptosis during the neuronal differentiation. Besides, FNDs did not alter the cell viability and the expression of neuron-specific marker β-III-tubulin in these differentiated neuron cells. The existence of FNDs in the neuron cells can be identified by confocal microscopy and flow cytometry. Together, FND is a biocompatible and readily detectable nanomaterial for the labeling and tracking of neuronal differentiation process and neuron cells from stem cells.

  11. Severe hypoxia affects exercise performance independently of afferent feedback and peripheral fatigue.

    Science.gov (United States)

    Millet, Guillaume Y; Muthalib, Makii; Jubeau, Marc; Laursen, Paul B; Nosaka, Kazunori

    2012-04-01

    To test the hypothesis that hypoxia centrally affects performance independently of afferent feedback and peripheral fatigue, we conducted two experiments under complete vascular occlusion of the exercising muscle under different systemic O(2) environmental conditions. In experiment 1, 12 subjects performed repeated submaximal isometric contractions of the elbow flexor to exhaustion (RCTE) with inspired O(2) fraction fixed at 9% (severe hypoxia, SevHyp), 14% (moderate hypoxia, ModHyp), 21% (normoxia, Norm), or 30% (hyperoxia, Hyper). The number of contractions (performance), muscle (biceps brachii), and prefrontal near-infrared spectroscopy (NIRS) parameters and high-frequency paired-pulse (PS100) evoked responses to electrical muscle stimulation were monitored. In experiment 2, 10 subjects performed another RCTE in SevHyp and Norm conditions in which the number of contractions, biceps brachii electromyography responses to electrical nerve stimulation (M wave), and transcranial magnetic stimulation responses (motor-evoked potentials, MEP, and cortical silent period, CSP) were recorded. Performance during RCTE was significantly reduced by 10-15% in SevHyp (arterial O(2) saturation, SpO(2) = ∼75%) compared with ModHyp (SpO(2) = ∼90%) or Norm/Hyper (SpO(2) > 97%). Performance reduction in SevHyp occurred despite similar 1) metabolic (muscle NIRS parameters) and functional (changes in PS100 and M wave) muscle states and 2) MEP and CSP responses, suggesting comparable corticospinal excitability and spinal and cortical inhibition between SevHyp and Norm. It is concluded that, in SevHyp, performance and central drive can be altered independently of afferent feedback and peripheral fatigue. It is concluded that submaximal performance in SevHyp is partly reduced by a mechanism related directly to brain oxygenation.

  12. Neural Control of Startle-Induced Locomotion by the Mushroom Bodies and Associated Neurons in Drosophila

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    Jun Sun

    2018-03-01

    Full Text Available Startle-induced locomotion is commonly used in Drosophila research to monitor locomotor reactivity and its progressive decline with age or under various neuropathological conditions. A widely used paradigm is startle-induced negative geotaxis (SING, in which flies entrapped in a narrow column react to a gentle mechanical shock by climbing rapidly upwards. Here we combined in vivo manipulation of neuronal activity and splitGFP reconstitution across cells to search for brain neurons and putative circuits that regulate this behavior. We show that the activity of specific clusters of dopaminergic neurons (DANs afferent to the mushroom bodies (MBs modulates SING, and that DAN-mediated SING regulation requires expression of the DA receptor Dop1R1/Dumb, but not Dop1R2/Damb, in intrinsic MB Kenyon cells (KCs. We confirmed our previous observation that activating the MB α'β', but not αβ, KCs decreased the SING response, and we identified further MB neurons implicated in SING control, including KCs of the γ lobe and two subtypes of MB output neurons (MBONs. We also observed that co-activating the αβ KCs antagonizes α'β' and γ KC-mediated SING modulation, suggesting the existence of subtle regulation mechanisms between the different MB lobes in locomotion control. Overall, this study contributes to an emerging picture of the brain circuits modulating locomotor reactivity in Drosophila that appear both to overlap and differ from those underlying associative learning and memory, sleep/wake state and stress-induced hyperactivity.

  13. Craniofacial Pain: Brainstem Mechanisms

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    Barry J Sessle

    1996-01-01

    Full Text Available This article reviews recent research advances in animals that have identified critical neural elements in the brainstem receiving and transmitting craniofacial nociceptive inputs, as well as some of the mechanisms involved in the modulation and plasticity of nociceptive transmission. Nociceptive neurones in the trigeminal (V brainstem sensory nuclear complex can be classified as nociceptive-specific (NS or wide dynamic range (WDR. Some of these neurones respond exclusively to sensory inputs evoked by stimulation of facial skin or oral mucosa and have features suggesting that they are critical neural elements involved in the ability to localize an acute superficial pain and sense its intensity and duration. Many of the V brainstem nociceptive neurones, however, receive convergent inputs from afferents supplying deep craniofacial tissues (eg, dural vessel, muscle and skin or mucosa. These neurones are likely involved in deep pain, including headache, because few nociceptive neurones receive inputs exclusively from afferents supplying these tissues. These extensive convergent input patterns also appear to be important factors in pain spread and referral, and in central mechanisms underlying neuroplastic changes in V neuronal properties that may occur with injury and inflammation. For example, application of the small fibre excitant and inflammatory irritant mustard oil into the temporomandibular joint, masseter or tongue musculature induces a prolonged but reversible enhancement of responses to cutaneous and deep afferent inputs of most WDR and NS neurones. These effects may be accompanied by increased electromyographic activity reflexly induced in the masticatory muscles by mustard oil, and involve endogenous N-methyl-D-aspartate and opioid neurochemical mechanisms. Such peripherally induced modulation of brainstem nociceptive neuronal properties reflects the functional plasticity of the central V system, and may be involved in the development of

  14. C-tactile afferent stimulating touch carries a positive affective value.

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    Pawling, Ralph; Cannon, Peter R; McGlone, Francis P; Walker, Susannah C

    2017-01-01

    The rewarding sensation of touch in affiliative interactions is hypothesized to be underpinned by a specialized system of nerve fibers called C-Tactile afferents (CTs), which respond optimally to slowly moving, gentle touch, typical of a caress. However, empirical evidence to support the theory that CTs encode socially relevant, rewarding tactile information in humans is currently limited. While in healthy participants, touch applied at CT optimal velocities (1-10cm/sec) is reliably rated as subjectively pleasant, neuronopathy patients lacking large myelinated afferents, but with intact C-fibres, report that the conscious sensation elicited by stimulation of CTs is rather vague. Given this weak perceptual impact the value of self-report measures for assessing the specific affective value of CT activating touch appears limited. Therefore, we combined subjective ratings of touch pleasantness with implicit measures of affective state (facial electromyography) and autonomic arousal (heart rate) to determine whether CT activation carries a positive affective value. We recorded the activity of two key emotion-relevant facial muscle sites (zygomaticus major-smile muscle, positive affect & corrugator supercilii-frown muscle, negative affect) while participants evaluated the pleasantness of experimenter administered stroking touch, delivered using a soft brush, at two velocities (CT optimal 3cm/sec & CT non-optimal 30cm/sec), on two skin sites (CT innervated forearm & non-CT innervated palm). On both sites, 3cm/sec stroking touch was rated as more pleasant and produced greater heart rate deceleration than 30cm/sec stimulation. However, neither self-report ratings nor heart rate responses discriminated stimulation on the CT innervated arm from stroking of the non-CT innervated palm. In contrast, significantly greater activation of the zygomaticus major (smiling muscle) was seen specifically to CT optimal, 3cm/sec, stroking on the forearm in comparison to all other stimuli

  15. C-tactile afferent stimulating touch carries a positive affective value.

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    Ralph Pawling

    Full Text Available The rewarding sensation of touch in affiliative interactions is hypothesized to be underpinned by a specialized system of nerve fibers called C-Tactile afferents (CTs, which respond optimally to slowly moving, gentle touch, typical of a caress. However, empirical evidence to support the theory that CTs encode socially relevant, rewarding tactile information in humans is currently limited. While in healthy participants, touch applied at CT optimal velocities (1-10cm/sec is reliably rated as subjectively pleasant, neuronopathy patients lacking large myelinated afferents, but with intact C-fibres, report that the conscious sensation elicited by stimulation of CTs is rather vague. Given this weak perceptual impact the value of self-report measures for assessing the specific affective value of CT activating touch appears limited. Therefore, we combined subjective ratings of touch pleasantness with implicit measures of affective state (facial electromyography and autonomic arousal (heart rate to determine whether CT activation carries a positive affective value. We recorded the activity of two key emotion-relevant facial muscle sites (zygomaticus major-smile muscle, positive affect & corrugator supercilii-frown muscle, negative affect while participants evaluated the pleasantness of experimenter administered stroking touch, delivered using a soft brush, at two velocities (CT optimal 3cm/sec & CT non-optimal 30cm/sec, on two skin sites (CT innervated forearm & non-CT innervated palm. On both sites, 3cm/sec stroking touch was rated as more pleasant and produced greater heart rate deceleration than 30cm/sec stimulation. However, neither self-report ratings nor heart rate responses discriminated stimulation on the CT innervated arm from stroking of the non-CT innervated palm. In contrast, significantly greater activation of the zygomaticus major (smiling muscle was seen specifically to CT optimal, 3cm/sec, stroking on the forearm in comparison to all

  16. Lectin Ulex europaeus agglutinin I specifically labels a subset of primary afferent fibers which project selectively to the superficial dorsal horn of the spinal cord.

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    Mori, K

    1986-02-19

    To examine differential carbohydrate expression among different subsets of primary afferent fibers, several fluorescein-isothiocyanate conjugated lectins were used in a histochemical study of the dorsal root ganglion (DRG) and spinal cord of the rabbit. The lectin Ulex europaeus agglutinin I specifically labeled a subset of DRG cells and primary afferent fibers which projected to the superficial laminae of the dorsal horn. These results suggest that specific carbohydrates containing L-fucosyl residue is expressed selectively in small diameter primary afferent fibers which subserve nociception or thermoception.

  17. Endomorphin-2 Inhibits the Activity of the Spinoparabrachial Projection Neuron through Presynaptic Mechanisms in the Spinal Dorsal Horn in Rats

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    Jun-Bin Yin

    2018-03-01

    Full Text Available Background/Aims: Spinal dorsal horn (SDH is one of the most important regions for analgesia produced by endomorphin-2 (EM2, which has a higher affinity and specificity for the µ-opioid receptor (MOR than morphine. Many studies have focused on substantia gelatinosa (SG, lamina II neurons to elucidate the cellular basis for its antinociceptive effects. However, the complicated types and local circuits of interneurons in the SG make it difficult to understand the real effects of EM2. Therefore, in the present study, we examined the effects of EM2 on projection neurons (PNs in lamina I. Methods: Tracing, immunofluoresence, and immunoelectron methods were used to examine the morphological connections between EM2-immunoreactive (-ir terminals and PNs. By using in vitro whole cell patch clamp recording technique, we investigated the functional effects of EM2 on PNs. Results: EM2-ir afferent terminals directly contacted PNs projecting to the parabrachial nucleus in lamina I. Their synaptic connections were further confirmed by immunoelectron microscopy, most of which were asymmetric synapses. It was found that EM2 had a strong inhibitory effect on the frequency, but not amplitude, of the spontaneous excitatory postsynaptic current (sEPSC of the spinoparabrachial PNs in lamina I, which could be reversed by MOR antagonist CTOP. However, their spontaneous inhibitory postsynaptic current (sIPSC and intrinsic properties were not changed after EM2 application. Conclusion: Applying EM2 to the SDH could produce analgesia through inhibiting the activities of the spinoparabrachial PNs in lamina I by reducing presynaptic neurotransmitters release from the primary afferent terminals.

  18. Competition model for aperiodic stochastic resonance in a Fitzhugh-Nagumo model of cardiac sensory neurons.

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    Kember, G C; Fenton, G A; Armour, J A; Kalyaniwalla, N

    2001-04-01

    Regional cardiac control depends upon feedback of the status of the heart from afferent neurons responding to chemical and mechanical stimuli as transduced by an array of sensory neurites. Emerging experimental evidence shows that neural control in the heart may be partially exerted using subthreshold inputs that are amplified by noisy mechanical fluctuations. This amplification is known as aperiodic stochastic resonance (ASR). Neural control in the noisy, subthreshold regime is difficult to see since there is a near absence of any correlation between input and the output, the latter being the average firing (spiking) rate of the neuron. This lack of correlation is unresolved by traditional energy models of ASR since these models are unsuitable for identifying "cause and effect" between such inputs and outputs. In this paper, the "competition between averages" model is used to determine what portion of a noisy, subthreshold input is responsible, on average, for the output of sensory neurons as represented by the Fitzhugh-Nagumo equations. A physiologically relevant conclusion of this analysis is that a nearly constant amount of input is responsible for a spike, on average, and this amount is approximately independent of the firing rate. Hence, correlation measures are generally reduced as the firing rate is lowered even though neural control under this model is actually unaffected.

  19. Endocannabinoids and the processing of value-related signals

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    Miriam eMelis

    2012-02-01

    Full Text Available Endocannabinoids serve as retrograde signaling molecules at many synapses within the CNS, particularly GABAergic and glutamatergic synapses. Synapses onto midbrain dopamine (DA neurons in the ventral tegmental area (VTA make no exception to this rule. In fact, the effects of cannabinoids on dopamine transmission as well as DA-related behaviors are generally exerted through the modulation of inhibitory and excitatory afferents impinging onto DA neurons. Endocannabinoids, by regulating different forms of synaptic plasticity in the VTA, provide a critical modulation of the DA neuron output and, ultimately, of the systems driving and regulating motivated behaviors. Because DA cells exhibit diverse states of activity, which crucially depend on their intrinsic properties and afferent drive, the understanding of the role played by endocannabinoids in synaptic modulations is critical for their overall functions. Particularly, endocannabinoids by selectively inhibiting afferent activity may alter the functional states of DA neurons and potentiate the responsiveness of the reward system to phasic DA.

  20. Contribution of synchronized GABAergic neurons to dopaminergic neuron firing and bursting.

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    Morozova, Ekaterina O; Myroshnychenko, Maxym; Zakharov, Denis; di Volo, Matteo; Gutkin, Boris; Lapish, Christopher C; Kuznetsov, Alexey

    2016-10-01

    In the ventral tegmental area (VTA), interactions between dopamine (DA) and γ-aminobutyric acid (GABA) neurons are critical for regulating DA neuron activity and thus DA efflux. To provide a mechanistic explanation of how GABA neurons influence DA neuron firing, we developed a circuit model of the VTA. The model is based on feed-forward inhibition and recreates canonical features of the VTA neurons. Simulations revealed that γ-aminobutyric acid (GABA) receptor (GABAR) stimulation can differentially influence the firing pattern of the DA neuron, depending on the level of synchronization among GABA neurons. Asynchronous activity of GABA neurons provides a constant level of inhibition to the DA neuron and, when removed, produces a classical disinhibition burst. In contrast, when GABA neurons are synchronized by common synaptic input, their influence evokes additional spikes in the DA neuron, resulting in increased measures of firing and bursting. Distinct from previous mechanisms, the increases were not based on lowered firing rate of the GABA neurons or weaker hyperpolarization by the GABAR synaptic current. This phenomenon was induced by GABA-mediated hyperpolarization of the DA neuron that leads to decreases in intracellular calcium (Ca 2+ ) concentration, thus reducing the Ca 2+ -dependent potassium (K + ) current. In this way, the GABA-mediated hyperpolarization replaces Ca 2+ -dependent K + current; however, this inhibition is pulsatile, which allows the DA neuron to fire during the rhythmic pauses in inhibition. Our results emphasize the importance of inhibition in the VTA, which has been discussed in many studies, and suggest a novel mechanism whereby computations can occur locally. Copyright © 2016 the American Physiological Society.

  1. Spinal cord stimulation paresthesia and activity of primary afferents.

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    North, Richard B; Streelman, Karen; Rowland, Lance; Foreman, P Jay

    2012-10-01

    A patient with failed back surgery syndrome reported paresthesia in his hands and arms during a spinal cord stimulation (SCS) screening trial with a low thoracic electrode. The patient's severe thoracic stenosis necessitated general anesthesia for simultaneous decompressive laminectomy and SCS implantation for chronic use. Use of general anesthesia gave the authors the opportunity to characterize the patient's unusual distribution of paresthesia. During SCS implantation, they recorded SCS-evoked antidromic potentials at physiologically relevant amplitudes in the legs to guide electrode placement and in the arms as controls. Stimulation of the dorsal columns at T-8 evoked potentials in the legs (common peroneal nerves) and at similar thresholds, consistent with the sensation of paresthesia in the arms, in the right ulnar nerve. The authors' electrophysiological observations support observations by neuroanatomical specialists that primary afferents can descend several (in this case, at least 8) vertebral segments in the spinal cord before synapsing or ascending. This report thus confirms a physiological basis for unusual paresthesia distribution associated with thoracic SCS.

  2. Kinesthetic perception based on integration of motor imagery and afferent inputs from antagonistic muscles with tendon vibration.

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    Shibata, E; Kaneko, F

    2013-04-29

    The perceptual integration of afferent inputs from two antagonistic muscles, or the perceptual integration of afferent input and motor imagery are related to the generation of a kinesthetic sensation. However, it has not been clarified how, or indeed whether, a kinesthetic perception would be generated by motor imagery if afferent inputs from two antagonistic muscles were simultaneously induced by tendon vibration. The purpose of this study was to investigate how a kinesthetic perception would be generated by motor imagery during co-vibration of the two antagonistic muscles at the same frequency. Healthy subjects participated in this experiment. Illusory movement was evoked by tendon vibration. Next, the subjects imaged wrist flexion movement simultaneously with tendon vibration. Wrist flexor and extensor muscles were vibrated according to 4 patterns such that the difference between the two vibration frequencies was zero. After each trial, the perceived movement sensations were quantified on the basis of the velocity and direction of the ipsilateral hand-tracking movements. When the difference in frequency applied to the wrist flexor and the extensor was 0Hz, no subjects perceived movements without motor imagery. However, during motor imagery, the flexion velocity of the perceived movement was higher than the flexion velocity without motor imagery. This study clarified that the afferent inputs from the muscle spindle interact with motor imagery, to evoke a kinesthetic perception, even when the difference in frequency applied to the wrist flexor and extensor was 0Hz. Furthermore, the kinesthetic perception resulting from integrations of vibration and motor imagery increased depending on the vibration frequency to the two antagonistic muscles. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  3. MR features of a case of afferent loop syndrome presenting as obstructive jaundice; IRM d'un syndrome de l'anse afferente revele par un ictere obstructif

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    Chevallier, P.; Souci, J.; Oddo, F.; Diaine, B.; Padovani, B. [Centre Hospitalier Regional et Universitaire de Nice, Hopital Archet 2., Service d' Imagerie Medicale, 06 - Nice (France); Gueyffier, C. [Centre Hospitalier Regional de Cannes, Service d' Hepato-Gastro-enterologie, 06 - Cannes (France)

    2001-02-01

    The afferent loop syndrome corresponds to an acute or chronic obstruction of the afferent loop following a partial gastrectomy with Billroth II gastro-jejunal anastomosis. We describe the case of a 77-year-old man with history of partial gastrectomy for peptic ulcer disease performed 31 years ago and currently admitted for jaundice and poor general status. MR imaging showed dilatation of biliary and pancreatic ducts and showed a soft tissue mass between the afferent loop and the residual stomach. Endoscopy showed complete obstruction of the afferent loop by a biopsy-proven adenocarcinoma. The patient died of sepsis shortly after endoscopy of septicemia. (authors)

  4. Ulex europaeus agglutinin-I binding to dental primary afferent projections in the spinal trigeminal complex combined with double immunolabeling of substance P and GABA elements using peroxidase and colloidal gold.

    Science.gov (United States)

    Matthews, M A; Hoffmann, K D; Hernandez, T V

    1989-01-01

    Ulex europaeus agglutinin I (UEA-I) is a plant lectin with an affinity for L-fucosyl residues in the chains of lactoseries oligosaccharides associated with medium- and smaller-diameter dorsal root ganglion neurons and their axonal processes. These enter Lissauer's tract and terminate within the superficial laminae of the spinal cord overlapping projections known to have a nociceptive function. This implies that the surface coatings of neuronal membranes may have a relationship with functional modalities. The present investigation further examined this concept by studying a neuronal projection with a nociceptive function to determine whether fucosyl-lactoseries residues were incorporated in its primary afferent terminals. Transganglionic transport of horseradish peroxidase (HRP) following injection into tooth pulp chambers was employed to demonstrate dental pulp terminals in the trigeminal spinal complex, while peroxidase and fluorescent tags were used concomitantly to stain for UEA-I. Double immunolabeling for substance P (SP) and gamma-aminobutyric acid (GABA) using peroxidase and colloidal gold allowed a comparison of the distribution of a known excitatory nociceptive transmitter with that of UEA-I binding in specific subnuclei. Synaptic interrelationships between UEA-I positive dental pulp primary afferent inputs and specific inhibitory terminals were also examined. SP immunoreactivity occurred in laminae I and outer lamina II (IIo) of subnucleus caudalis (Vc) and in the ventrolateral and lateral marginal region of the caudal half of subnucleus interpolaris (Vi), including the periobex area in which Vi is slightly overlapped on its lateral aspect by cellular elements of Vc. The adjacent interstitial nucleus (IN) also showed an intense immunoreactivity for this peptide antibody. UEA-I binding displayed a similar distribution pattern in both Vc and Vi, but extended into lamina IIi and the superficial part of Lamina III in Vc. Dental pulp terminals were found to

  5. Feedback and feedforward control of frequency tuning to naturalistic stimuli.

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    Chacron, Maurice J; Maler, Leonard; Bastian, Joseph

    2005-06-08

    Sensory neurons must respond to a wide variety of natural stimuli that can have very different spatiotemporal characteristics. Optimal responsiveness to subsets of these stimuli can be achieved by devoting specialized neural circuitry to different stimulus categories, or, alternatively, this circuitry can be modulated or tuned to optimize responsiveness to current stimulus conditions. This study explores the mechanisms that enable neurons within the initial processing station of the electrosensory system of weakly electric fish to shift their tuning properties based on the spatial extent of the stimulus. These neurons are tuned to low frequencies when the stimulus is restricted to a small region within the receptive field center but are tuned to higher frequencies when the stimulus impinges on large regions of the sensory epithelium. Through a combination of modeling and in vivo electrophysiology, we reveal the respective contributions of the filtering characteristics of extended dendritic structures and feedback circuitry to this shift in tuning. Our results show that low-frequency tuning can result from the cable properties of an extended dendrite that conveys receptor-afferent information to the cell body. The shift from low- to high-frequency tuning, seen in response to spatially extensive stimuli, results from increased wide-band input attributable to activation of larger populations of receptor afferents, as well as the activation of parallel fiber feedback from the cerebellum. This feedback provides a cancellation signal with low-pass characteristics that selectively attenuates low-frequency responsiveness. Thus, with spatially extensive stimuli, these cells preferentially respond to the higher-frequency components of the receptor-afferent input.

  6. Afferent and Efferent Connections of the Optic Tectum in the Carp (Cyprinus carpio L.)

    NARCIS (Netherlands)

    Luiten, P.G.M.

    1981-01-01

    The afferent and efferent connections of the tectum opticum in the carp (Cyprinus carpio L.) were studied with the HRP method. Following iontophoretic peroxidase injections in several parts of the rectum anterograde transport of the enzyme revealed tectal projections to the lateral geniculate

  7. Cross-Modal Calibration of Vestibular Afference for Human Balance.

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    Martin E Héroux

    Full Text Available To determine how the vestibular sense controls balance, we used instantaneous head angular velocity to drive a galvanic vestibular stimulus so that afference would signal that head movement was faster or slower than actual. In effect, this changed vestibular afferent gain. This increased sway 4-fold when subjects (N = 8 stood without vision. However, after a 240 s conditioning period with stable balance achieved through reliable visual or somatosensory cues, sway returned to normal. An equivalent galvanic stimulus unrelated to sway (not driven by head motion was equally destabilising but in this situation the conditioning period of stable balance did not reduce sway. Reflex muscle responses evoked by an independent, higher bandwidth vestibular stimulus were initially reduced in amplitude by the galvanic stimulus but returned to normal levels after the conditioning period, contrary to predictions that they would decrease after adaptation to increased sensory gain and increase after adaptation to decreased sensory gain. We conclude that an erroneous vestibular signal of head motion during standing has profound effects on balance control. If it is unrelated to current head motion, the CNS has no immediate mechanism of ignoring the vestibular signal to reduce its influence on destabilising balance. This result is inconsistent with sensory reweighting based on disturbances. The increase in sway with increased sensory gain is also inconsistent with a simple feedback model of vestibular reflex action. Thus, we propose that recalibration of a forward sensory model best explains the reinterpretation of an altered reafferent signal of head motion during stable balance.

  8. Distinct subclassification of DRG neurons innervating the distal colon and glans penis/distal urethra based on the electrophysiological current signature.

    Science.gov (United States)

    Rau, Kristofer K; Petruska, Jeffrey C; Cooper, Brian Y; Johnson, Richard D

    2014-09-15

    Spinal sensory neurons innervating visceral and mucocutaneous tissues have unique microanatomic distribution, peripheral modality, and physiological, pharmacological, and biophysical characteristics compared with those neurons that innervate muscle and cutaneous tissues. In previous patch-clamp electrophysiological studies, we have demonstrated that small- and medium-diameter dorsal root ganglion (DRG) neurons can be subclassified on the basis of their patterns of voltage-activated currents (VAC). These VAC-based subclasses were highly consistent in their action potential characteristics, responses to algesic compounds, immunocytochemical expression patterns, and responses to thermal stimuli. For this study, we examined the VAC of neurons retrogradely traced from the distal colon and the glans penis/distal urethra in the adult male rat. The afferent population from the distal colon contained at least two previously characterized cell types observed in somatic tissues (types 5 and 8), as well as four novel cell types (types 15, 16, 17, and 18). In the glans penis/distal urethra, two previously described cell types (types 6 and 8) and three novel cell types (types 7, 14, and 15) were identified. Other characteristics, including action potential profiles, responses to algesic compounds (acetylcholine, capsaicin, ATP, and pH 5.0 solution), and neurochemistry (expression of substance P, CGRP, neurofilament, TRPV1, TRPV2, and isolectin B4 binding) were consistent for each VAC-defined subgroup. With identification of distinct DRG cell types that innervate the distal colon and glans penis/distal urethra, future in vitro studies related to the gastrointestinal and urogenital sensory function in normal as well as abnormal/pathological conditions may be benefitted. Copyright © 2014 the American Physiological Society.

  9. Oxytocin-induced antinociception in the spinal cord is mediated by a subpopulation of glutamatergic neurons in lamina I-II which amplify GABAergic inhibition

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    Schlichter Rémy

    2008-05-01

    Full Text Available Abstract Background Recent evidence suggests that oxytocin (OT, secreted in the superficial spinal cord dorsal horn by descending axons of paraventricular hypothalamic nucleus (PVN neurons, produces antinociception and analgesia. The spinal mechanism of OT is, however, still unclear and requires further investigation. We have used patch clamp recording of lamina II neurons in spinal cord slices and immunocytochemistry in order to identify PVN-activated neurons in the superficial layers of the spinal cord and attempted to determine how this neuronal population may lead to OT-mediated antinociception. Results We show that OT released during PVN stimulation specifically activates a subpopulation of lamina II glutamatergic interneurons which are localized in the most superficial layers of the dorsal horn of the spinal cord (lamina I-II. This OT-specific stimulation of glutamatergic neurons allows the recruitment of all GABAergic interneurons in lamina II which produces a generalized elevation of local inhibition, a phenomenon which might explain the reduction of incoming Aδ and C primary afferent-mediated sensory messages. Conclusion Our results obtained in lamina II of the spinal cord provide the first clear evidence of a specific local neuronal network that is activated by OT release to induce antinociception. This OT-specific pathway might represent a novel and interesting therapeutic target for the management of neuropathic and inflammatory pain.

  10. Acid-sensing ion channels contribute to chemosensitivity of breathing-related neurons of the nucleus of the solitary tract.

    Science.gov (United States)

    Huda, Rafiq; Pollema-Mays, Sarah L; Chang, Zheng; Alheid, George F; McCrimmon, Donald R; Martina, Marco

    2012-10-01

    Cellular mechanisms of central pH chemosensitivity remain largely unknown. The nucleus of the solitary tract (NTS) integrates peripheral afferents with central pathways controlling breathing; NTS neurons function as central chemosensors, but only limited information exists concerning the ionic mechanisms involved. Acid-sensing ion channels (ASICs) mediate chemosensitivity in nociceptive terminals, where pH values ∼6.5 are not uncommon in inflammation, but are also abundantly expressed throughout the brain where pHi s tightly regulated and their role is less clear. Here we test the hypothesis that ASICs are expressed in NTS neurons and contribute to intrinsic chemosensitivity and control of breathing. In electrophysiological recordings from acute rat NTS slices, ∼40% of NTS neurons responded to physiological acidification (pH 7.0) with a transient depolarization. This response was also present in dissociated neurons suggesting an intrinsic mechanism. In voltage clamp recordings in slices, a pH drop from 7.4 to 7.0 induced ASIC-like inward currents (blocked by 100 μM amiloride) in ∼40% of NTS neurons, while at pH ≤ 6.5 these currents were detected in all neurons tested; RT-PCR revealed expression of ASIC1 and, less abundantly, ASIC2 in the NTS. Anatomical analysis of dye-filled neurons showed that ASIC-dependent chemosensitive cells (cells responding to pH 7.0) cluster dorsally in the NTS. Using in vivo retrograde labelling from the ventral respiratory column, 90% (9/10) of the labelled neurons showed an ASIC-like response to pH 7.0, suggesting that ASIC currents contribute to control of breathing. Accordingly, amiloride injection into the NTS reduced phrenic nerve activity of anaesthetized rats with an elevated arterial P(CO(2)) .

  11. Transient receptor potential channels encode volatile chemicals sensed by rat trigeminal ganglion neurons.

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    Matthias Lübbert

    Full Text Available Primary sensory afferents of the dorsal root and trigeminal ganglia constantly transmit sensory information depicting the individual's physical and chemical environment to higher brain regions. Beyond the typical trigeminal stimuli (e.g. irritants, environmental stimuli comprise a plethora of volatile chemicals with olfactory components (odorants. In spite of a complete loss of their sense of smell, anosmic patients may retain the ability to roughly discriminate between different volatile compounds. While the detailed mechanisms remain elusive, sensory structures belonging to the trigeminal system seem to be responsible for this phenomenon. In order to gain a better understanding of the mechanisms underlying the activation of the trigeminal system by volatile chemicals, we investigated odorant-induced membrane potential changes in cultured rat trigeminal neurons induced by the odorants vanillin, heliotropyl acetone, helional, and geraniol. We observed the dose-dependent depolarization of trigeminal neurons upon application of these substances occurring in a stimulus-specific manner and could show that distinct neuronal populations respond to different odorants. Using specific antagonists, we found evidence that TRPA1, TRPM8, and/or TRPV1 contribute to the activation. In order to further test this hypothesis, we used recombinantly expressed rat and human variants of these channels to investigate whether they are indeed activated by the odorants tested. We additionally found that the odorants dose-dependently inhibit two-pore potassium channels TASK1 and TASK3 heterologously expressed In Xenopus laevis oocytes. We suggest that the capability of various odorants to activate different TRP channels and to inhibit potassium channels causes neuronal depolarization and activation of distinct subpopulations of trigeminal sensory neurons, forming the basis for a specific representation of volatile chemicals in the trigeminal ganglia.

  12. Peripheral afferent mechanisms underlying acupuncture inhibition of cocaine behavioral effects in rats.

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    Seol Ah Kim

    Full Text Available Administration of cocaine increases locomotor activity by enhancing dopamine transmission. To explore the peripheral mechanisms underlying acupuncture treatment for drug addiction, we developed a novel mechanical acupuncture instrument (MAI for objective mechanical stimulation. The aim of this study was to evaluate whether acupuncture inhibition of cocaine-induced locomotor activity is mediated through specific peripheral nerves, the afferents from superficial or deep tissues, or specific groups of nerve fibers. Mechanical stimulation of acupuncture point HT7 with MAI suppressed cocaine-induced locomotor activity in a stimulus time-dependent manner, which was blocked by severing the ulnar nerve or by local anesthesia. Suppression of cocaine-induced locomotor activity was elicited after HT7 stimulation at frequencies of either 50 (for Meissner corpuscles or 200 (for Pacinian corpuscles Hz and was not affected by block of C/Aδ-fibers in the ulnar nerve with resiniferatoxin, nor generated by direct stimulation of C/Aδ-fiber afferents with capsaicin. These findings suggest that HT7 inhibition of cocaine-induced locomotor activity is mediated by A-fiber activation of ulnar nerve that originates in superficial and deep tissue.

  13. Co-cultures provide a new tool to probe communication between adult sensory neurons and urothelium.

    Science.gov (United States)

    O'Mullane, Lauren M; Keast, Janet R; Osborne, Peregrine B

    2013-08-01

    Recent evidence suggests that the urothelium functions as a sensory transducer of chemical, mechanical or thermal stimuli and signals to nerve terminals and other cells in the bladder wall. The cellular and molecular basis of neuro-urothelial communication is not easily studied in the intact bladder. This led us to establish a method of co-culturing dorsal root ganglion sensory neurons and bladder urothelial cells. Sensory neurons and urothelial cells obtained from dorsal root ganglia and bladders dissected from adult female Sprague-Dawley® rats were isolated by enzyme treatment and mechanical dissociation. They were plated together or separately on collagen coated substrate and cultured in keratinocyte medium for 48 to 72 hours. Retrograde tracer labeling was performed to identify bladder afferents used for functional testing. Neurite growth and complexity in neurons co-cultured with urothelial cells was increased relative to that in neuronal monocultures. The growth promoting effect of urothelial cells was reduced by the tyrosine kinase inhibitor K252a but upstream inhibition of nerve growth factor signaling with TrkA-Fc had no effect. Fura-2 calcium imaging of urothelial cells showed responses to adenosine triphosphate (100 μM) and activation of TRPV4 (4α-PDD, 10 μM) but not TRPV1 (capsaicin, 1 μM), TRPV3 (farnesyl pyrophosphate, 1 μM) or TRPA1 (mustard oil, 100 μM). In contrast, co-cultured neurons were activated by all agonists except farnesyl pyrophosphate. Co-culturing provides a new methodology for investigating neuro-urothelial interactions in animal models of urological conditions. Results suggest that neuronal properties are maintained in the presence of urothelium and neurite growth is potentiated by a nerve growth factor independent mechanism. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  14. Bioenergetics and ATP Synthesis during Exercise: Role of Group III/IV Muscle Afferents.

    Science.gov (United States)

    Broxterman, Ryan M; Layec, Gwenael; Hureau, Thomas J; Morgan, David E; Bledsoe, Amber D; Jessop, Jacob E; Amann, Markus; Richardson, Russell S

    2017-12-01

    The purpose of this study was to investigate the role of the group III/IV muscle afferents in the bioenergetics of exercising skeletal muscle beyond constraining the magnitude of metabolic perturbation. Eight healthy men performed intermittent isometric knee-extensor exercise to task failure at ~58% maximal voluntary contraction under control conditions (CTRL) and with lumbar intrathecal fentanyl to attenuate group III/IV leg muscle afferents (FENT). Intramuscular concentrations of phosphocreatine (PCr), inorganic phosphate (Pi), diprotonated phosphate (H2PO4), adenosine triphosphate (ATP), and pH were determined using phosphorous magnetic resonance spectroscopy (P-MRS). The magnitude of metabolic perturbation was significantly greater in FENT compared with CTRL for [Pi] (37.8 ± 16.8 vs 28.6 ± 8.6 mM), [H2PO4] (24.3 ± 12.2 vs 17.9 ± 7.1 mM), and [ATP] (75.8% ± 17.5% vs 81.9% ± 15.8% of baseline), whereas there was no significant difference in [PCr] (4.5 ± 2.4 vs 4.4 ± 2.3 mM) or pH (6.51 ± 0.10 vs 6.54 ± 0.14). The rate of perturbation in [PCr], [Pi], [H2PO4], and pH was significantly faster in FENT compared with CTRL. Oxidative ATP synthesis was not significantly different between conditions. However, anaerobic ATP synthesis, through augmented creatine kinase and glycolysis reactions, was significantly greater in FENT than in CTRL, resulting in a significantly greater ATP cost of contraction (0.049 ± 0.016 vs 0.038 ± 0.010 mM·min·N). Group III/IV muscle afferents not only constrain the magnitude of perturbation in intramuscular Pi, H2PO4, and ATP during small muscle mass exercise but also seem to play a role in maintaining efficient skeletal muscle contractile function in men.

  15. A neuron-astrocyte transistor-like model for neuromorphic dressed neurons.

    Science.gov (United States)

    Valenza, G; Pioggia, G; Armato, A; Ferro, M; Scilingo, E P; De Rossi, D

    2011-09-01

    Experimental evidences on the role of the synaptic glia as an active partner together with the bold synapse in neuronal signaling and dynamics of neural tissue strongly suggest to investigate on a more realistic neuron-glia model for better understanding human brain processing. Among the glial cells, the astrocytes play a crucial role in the tripartite synapsis, i.e. the dressed neuron. A well-known two-way astrocyte-neuron interaction can be found in the literature, completely revising the purely supportive role for the glia. The aim of this study is to provide a computationally efficient model for neuron-glia interaction. The neuron-glia interactions were simulated by implementing the Li-Rinzel model for an astrocyte and the Izhikevich model for a neuron. Assuming the dressed neuron dynamics similar to the nonlinear input-output characteristics of a bipolar junction transistor, we derived our computationally efficient model. This model may represent the fundamental computational unit for the development of real-time artificial neuron-glia networks opening new perspectives in pattern recognition systems and in brain neurophysiology. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Stability of Kinesthetic Perception in Efferent-Afferent Spaces: The Concept of Iso-perceptual Manifold.

    Science.gov (United States)

    Latash, Mark L

    2018-02-21

    The main goal of this paper is to introduce the concept of iso-perceptual manifold for perception of body configuration and related variables (kinesthetic perception) and to discuss its relation to the equilibrium-point hypothesis and the concepts of reference coordinate and uncontrolled manifold. Hierarchical control of action is postulated with abundant transformations between sets of spatial reference coordinates for salient effectors at different levels. Iso-perceptual manifold is defined in the combined space of afferent and efferent variables as the subspace corresponding to a stable percept. Examples of motion along an iso-perceptual manifold (perceptually equivalent motion) are considered during various natural actions. Some combinations of afferent and efferent signals, in particular those implying a violation of body's integrity, give rise to variable percepts by artificial projection onto iso-perceptual manifolds. This framework is used to interpret unusual features of vibration-induced kinesthetic illusions and to predict new illusions not yet reported in the literature. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Sensory feedback for upper limb prostheses.

    Science.gov (United States)

    Hsiao, Steven S; Fettiplace, Michael; Darbandi, Bejan

    2011-01-01

    In this chapter, we discuss the neurophysiological basis of how to provide sensory feedback to users with an upper limb prosthesis and discuss some of the theoretical issues that need to be considered when directly stimulating neurons in the somatosensory system. We focus on technologies that are currently available and discuss approaches that are most likely to succeed in providing natural perception from the artificial hand to the user. First, we discuss the advantages and disadvantages of providing feedback by stimulating directly the remaining afferents that originally innervated the arm and hand. In particular, we pay close attention to the normal functional roles that the peripheral afferents play in perception. What are the consequences and implications of stimulating these afferents? We then discuss whether it is reasonable to stimulate neurons in the ascending pathways that carry the information from the afferents to the cortex or directly in neurons in the primary somatosensory cortex. We show that for some modalities there are advantages for stimulating in the spinal cord, while for others it is advantageous to stimulate directly in the somatosensory cortex. Finally, we discuss results from a current experiment in which we used electrical stimuli in primary somatosensory cortex to restore the percept of the intensity of a mechanical probe indented into the hand. The results suggest that the simple percept of stimulus intensity can be provided to the animal from a single finger using four electrodes. We propose that significantly more electrodes will be needed to reproduce more complex aspects of tactile perception. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. A single hidden layer feedforward network with only one neuron in the hidden layer can approximate any univariate function

    OpenAIRE

    Guliyev , Namig; Ismailov , Vugar

    2016-01-01

    The possibility of approximating a continuous function on a compact subset of the real line by a feedforward single hidden layer neural network with a sigmoidal activation function has been studied in many papers. Such networks can approximate an arbitrary continuous function provided that an unlimited number of neurons in a hidden layer is permitted. In this paper, we consider constructive approximation on any finite interval of $\\mathbb{R}$ by neural networks with only one neuron in the hid...

  19. Intercellular K⁺ accumulation depolarizes Type I vestibular hair cells and their associated afferent nerve calyx.

    Science.gov (United States)

    Contini, D; Zampini, V; Tavazzani, E; Magistretti, J; Russo, G; Prigioni, I; Masetto, S

    2012-12-27

    Mammalian vestibular organs contain two types of sensory receptors, named Type I and Type II hair cells. While Type II hair cells are contacted by several small afferent nerve terminals, the basolateral surface of Type I hair cells is almost entirely enveloped by a single large afferent nerve terminal, called calyx. Moreover Type I, but not Type II hair cells, express a low-voltage-activated outward K(+) current, I(K,L), which is responsible for their much lower input resistance (Rm) at rest as compared to Type II hair cells. The functional meaning of I(K,L) and associated calyx is still enigmatic. By combining the patch-clamp whole-cell technique with the mouse whole crista preparation, we have recorded the current- and voltage responses of in situ hair cells. Outward K(+) current activation resulted in K(+) accumulation around Type I hair cells, since it induced a rightward shift of the K(+) reversal potential the magnitude of which depended on the amplitude and duration of K(+) current flow. Since this phenomenon was never observed for Type II hair cells, we ascribed it to the presence of a residual calyx limiting K(+) efflux from the synaptic cleft. Intercellular K(+) accumulation added a slow (τ>100ms) depolarizing component to the cell voltage response. In a few cases we were able to record from the calyx and found evidence for intercellular K(+) accumulation as well. The resulting depolarization could trigger a discharge of action potentials in the afferent nerve fiber. Present results support a model where pre- and postsynaptic depolarization produced by intercellular K(+) accumulation cooperates with neurotransmitter exocytosis in sustaining afferent transmission arising from Type I hair cells. While vesicular transmission together with the low Rm of Type I hair cells appears best suited for signaling fast head movements, depolarization produced by intercellular K(+) accumulation could enhance signal transmission during slow head movements. Copyright

  20. Neurons other than motor neurons in motor neuron disease.

    Science.gov (United States)

    Ruffoli, Riccardo; Biagioni, Francesca; Busceti, Carla L; Gaglione, Anderson; Ryskalin, Larisa; Gambardella, Stefano; Frati, Alessandro; Fornai, Francesco

    2017-11-01

    Amyotrophic lateral sclerosis (ALS) is typically defined by a loss of motor neurons in the central nervous system. Accordingly, morphological analysis for decades considered motor neurons (in the cortex, brainstem and spinal cord) as the neuronal population selectively involved in ALS. Similarly, this was considered the pathological marker to score disease severity ex vivo both in patients and experimental models. However, the concept of non-autonomous motor neuron death was used recently to indicate the need for additional cell types to produce motor neuron death in ALS. This means that motor neuron loss occurs only when they are connected with other cell types. This concept originally emphasized the need for resident glia as well as non-resident inflammatory cells. Nowadays, the additional role of neurons other than motor neurons emerged in the scenario to induce non-autonomous motor neuron death. In fact, in ALS neurons diverse from motor neurons are involved. These cells play multiple roles in ALS: (i) they participate in the chain of events to produce motor neuron loss; (ii) they may even degenerate more than and before motor neurons. In the present manuscript evidence about multi-neuronal involvement in ALS patients and experimental models is discussed. Specific sub-classes of neurons in the whole spinal cord are reported either to degenerate or to trigger neuronal degeneration, thus portraying ALS as a whole spinal cord disorder rather than a disease affecting motor neurons solely. This is associated with a novel concept in motor neuron disease which recruits abnormal mechanisms of cell to cell communication.

  1. Concurrent gradients of ribbon volume and AMPA-receptor patch volume in cochlear afferent synapses on gerbil inner hair cells.

    Science.gov (United States)

    Zhang, Lichun; Engler, Sina; Koepcke, Lena; Steenken, Friederike; Köppl, Christine

    2018-07-01

    The Mongolian gerbil is a classic animal model for age-related hearing loss. As a prerequisite for studying age-related changes, we characterized cochlear afferent synaptic morphology in young adult gerbils, using immunolabeling and quantitative analysis of confocal microscopic images. Cochlear wholemounts were triple-labeled with a hair-cell marker, a marker of presynaptic ribbons, and a marker of postsynaptic AMPA-type glutamate receptors. Seven cochlear positions covering an equivalent frequency range from 0.5 - 32 kHz were evaluated. The spatial positions of synapses were determined in a coordinate system with reference to their individual inner hair cell. Synapse numbers confirmed previous reports for gerbils (on average, 20-22 afferents per inner hair cell). The volumes of presynaptic ribbons and postsynaptic glutamate receptor patches were positively correlated: larger ribbons associated with larger receptor patches and smaller ribbons with smaller patches. Furthermore, the volumes of both presynaptic ribbons and postsynaptic receptor patches co-varied along the modiolar-pillar and the longitudinal axes of their hair cell. The gradients in ribbon volume are consistent with previous findings in cat, guinea pig, mouse and rat and further support a role in differentiating the physiological properties of type I afferents. However, the positive correlation between the volumes of pre- and postsynaptic elements in the gerbil is different to the opposing gradients found in the mouse, suggesting species-specific differences in the postsynaptic AMPA receptors that are unrelated to the fundamental classes of type I afferents. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Calcium signals can freely cross the nuclear envelope in hippocampal neurons: somatic calcium increases generate nuclear calcium transients

    Directory of Open Access Journals (Sweden)

    Bading Hilmar

    2007-07-01

    Full Text Available Abstract Background In hippocampal neurons, nuclear calcium signaling is important for learning- and neuronal survival-associated gene expression. However, it is unknown whether calcium signals generated by neuronal activity at the cell membrane and propagated to the soma can unrestrictedly cross the nuclear envelope to invade the nucleus. The nuclear envelope, which allows ion transit via the nuclear pore complex, may represent a barrier for calcium and has been suggested to insulate the nucleus from activity-induced cytoplasmic calcium transients in some cell types. Results Using laser-assisted uncaging of caged calcium compounds in defined sub-cellular domains, we show here that the nuclear compartment border does not represent a barrier for calcium signals in hippocampal neurons. Although passive diffusion of molecules between the cytosol and the nucleoplasm may be modulated through changes in conformational state of the nuclear pore complex, we found no evidence for a gating mechanism for calcium movement across the nuclear border. Conclusion Thus, the nuclear envelope does not spatially restrict calcium transients to the somatic cytosol but allows calcium signals to freely enter the cell nucleus to trigger genomic events.

  3. Transmission between type II hair cells and bouton afferents in the turtle posterior crista.

    Science.gov (United States)

    Holt, Joseph C; Xue, Jin-Tang; Brichta, Alan M; Goldberg, Jay M

    2006-01-01

    Synaptic activity was recorded with sharp microelectrodes during rest and during 0.3-Hz sinusoidal stimulation from bouton afferents identified by their efferent-mediated inhibitory responses. A glutamate antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) decreased quantal size (qsize) while lowering external Ca(2+) decreased quantal rate (qrate). Miniature excitatory postsynaptic potentials (mEPSPs) had effective durations (qdur) of 3.5-5 ms. Their timing was consistent with Poisson statistics. Mean qsizes ranged in different units from 0.25 to 0.73 mV and mean qrates from 200 to 1,500/s; there was an inverse relation across the afferent population between qrate and qsize. qsize distributions were consistent with the independent release of variable-sized quanta. Channel noise, measured during AMPA-induced depolarizations, was small compared with quantal noise. Excitatory responses were larger than inhibitory responses. Peak qrates, which could approach 3,000/s, led peak excitatory mechanical stimulation by 40 degrees . Quantal parameters varied with stimulation phase with qdur and qsize being maximal during inhibitory stimulation. Voltage modulation (vmod) was in phase with qrate and had a peak depolarization of 1.5-3 mV. On average, 80% of vmod was accounted for by quantal activity; the remaining 20% was a nonquantal component that persisted in the absence of quantal activity. The extracellular accumulation of glutamate and K(+) are potential sources of nonquantal transmission and may provide a basis for the inverse relation between qrate and qsize. Comparison of the phases of synaptic and spike activity suggests that both presynaptic and postsynaptic mechanisms contribute to variations across afferents in the timing of spikes during sinusoidal stimulation.

  4. Decoding thalamic afferent input using microcircuit spiking activity.

    Science.gov (United States)

    Sederberg, Audrey J; Palmer, Stephanie E; MacLean, Jason N

    2015-04-01

    A behavioral response appropriate to a sensory stimulus depends on the collective activity of thousands of interconnected neurons. The majority of cortical connections arise from neighboring neurons, and thus understanding the cortical code requires characterizing information representation at the scale of the cortical microcircuit. Using two-photon calcium imaging, we densely sampled the thalamically evoked response of hundreds of neurons spanning multiple layers and columns in thalamocortical slices of mouse somatosensory cortex. We then used a biologically plausible decoder to characterize the representation of two distinct thalamic inputs, at the level of the microcircuit, to reveal those aspects of the activity pattern that are likely relevant to downstream neurons. Our data suggest a sparse code, distributed across lamina, in which a small population of cells carries stimulus-relevant information. Furthermore, we find that, within this subset of neurons, decoder performance improves when noise correlations are taken into account. Copyright © 2015 the American Physiological Society.

  5. Inhibitory neurons modulate spontaneous signaling in cultured cortical neurons: density-dependent regulation of excitatory neuronal signaling

    International Nuclear Information System (INIS)

    Serra, Michael; Guaraldi, Mary; Shea, Thomas B

    2010-01-01

    Cortical neuronal activity depends on a balance between excitatory and inhibitory influences. Culturing of neurons on multi-electrode arrays (MEAs) has provided insight into the development and maintenance of neuronal networks. Herein, we seeded MEAs with murine embryonic cortical/hippocampal neurons at different densities ( 1000 cells mm −2 ) and monitored resultant spontaneous signaling. Sparsely seeded cultures displayed a large number of bipolar, rapid, high-amplitude individual signals with no apparent temporal regularity. By contrast, densely seeded cultures instead displayed clusters of signals at regular intervals. These patterns were observed even within thinner and thicker areas of the same culture. GABAergic neurons (25% of total neurons in our cultures) mediated the differential signal patterns observed above, since addition of the inhibitory antagonist bicuculline to dense cultures and hippocampal slice cultures induced the signal pattern characteristic of sparse cultures. Sparsely seeded cultures likely lacked sufficient inhibitory neurons to modulate excitatory activity. Differential seeding of MEAs can provide a unique model for analyses of pertubation in the interaction between excitatory and inhibitory function during aging and neuropathological conditions where dysregulation of GABAergic neurons is a significant component

  6. Neuron-Glia Crosstalk and Neuropathic Pain: Involvement in the Modulation of Motor Activity in the Orofacial Region.

    Science.gov (United States)

    Hossain, Mohammad Zakir; Unno, Shumpei; Ando, Hiroshi; Masuda, Yuji; Kitagawa, Junichi

    2017-09-26

    Neuropathic orofacial pain (NOP) is a debilitating condition. Although the pathophysiology remains unclear, accumulating evidence suggests the involvement of multiple mechanisms in the development of neuropathic pain. Recently, glial cells have been shown to play a key pathogenetic role. Nerve injury leads to an immune response near the site of injury. Satellite glial cells are activated in the peripheral ganglia. Various neural and immune mediators, released at the central terminals of primary afferents, lead to the sensitization of postsynaptic neurons and the activation of glia. The activated glia, in turn, release pro-inflammatory factors, further sensitizing the neurons, and resulting in central sensitization. Recently, we observed the involvement of glia in the alteration of orofacial motor activity in NOP. Microglia and astroglia were activated in the trigeminal sensory and motor nuclei, in parallel with altered motor functions and a decreased pain threshold. A microglial blocker attenuated the reduction in pain threshold, reduced the number of activated microglia, and restored motor activity. We also found an involvement of the astroglial glutamate-glutamine shuttle in the trigeminal motor nucleus in the alteration of the jaw reflex. Neuron-glia crosstalk thus plays an important role in the development of pain and altered motor activity in NOP.

  7. Vasodilatation of afferent arterioles and paradoxical increase of renal vascular resistance by furosemide in mice

    DEFF Research Database (Denmark)

    Oppermann, Mona; Hansen, Pernille B; Castrop, Hayo

    2007-01-01

    Loop diuretics like furosemide have been shown to cause renal vasodilatation in dogs and humans, an effect thought to result from both a direct vascular dilator effect and from inhibition of tubuloglomerular feedback. In isolated perfused afferent arterioles preconstricted with angiotensin II or ...

  8. Differential roles of galanin on mechanical and cooling responses at the primary afferent nociceptor

    Directory of Open Access Journals (Sweden)

    Hulse Richard P

    2012-06-01

    Full Text Available Abstract Background Galanin is expressed in a small percentage of intact small diameter sensory neurons of the dorsal root ganglia and in the afferent terminals of the superficial lamina of the dorsal horn of the spinal cord. The neuropeptide modulates nociception demonstrating dose-dependent pro- and anti-nociceptive actions in the naïve animal. Galanin also plays an important role in chronic pain, with the anti-nociceptive actions enhanced in rodent neuropathic pain models. In this study we compared the role played by galanin and its receptors in mechanical and cold allodynia by identifying individual rat C-fibre nociceptors and characterising their responses to mechanical or acetone stimulation. Results Mechanically evoked responses in C-fibre nociceptors from naive rats were sensitised after close intra-arterial infusion of galanin or Gal2-11 (a galanin receptor-2/3 agonist confirming previous data that galanin modulates nociception via activation of GalR2. In contrast, the same dose and route of administration of galanin, but not Gal2-11, inhibited acetone and menthol cooling evoked responses, demonstrating that this inhibitory mechanism is not mediated by activation of GalR2. We then used the partial saphenous nerve ligation injury model of neuropathic pain (PSNI and the complete Freund’s adjuvant model of inflammation in the rat and demonstrated that close intra-arterial infusion of galanin, but not Gal2-11, reduced cooling evoked nociceptor activity and cooling allodynia in both paradigms, whilst galanin and Gal2-11 both decreased mechanical activation thresholds. A previously described transgenic mouse line which inducibly over-expresses galanin (Gal-OE after nerve injury was then used to investigate whether manipulating the levels of endogenous galanin also modulates cooling evoked nociceptive behaviours after PSNI. Acetone withdrawal behaviours in naive mice showed no differences between Gal-OE and wildtype (WT mice. 7-days after

  9. Origin and characterization of retrograde labeled neurons supplying the rat urethra using fiberoptic confocal fluorescent microscopy in vivo and immunohistochemistry.

    Science.gov (United States)

    Lee, Keon-Cheol; Sharma, Seema; Tuttle, Jeremy B; Steers, William D

    2010-10-01

    Autonomic innervation of urethral smooth muscle may influence urinary continence after prostatectomy. It is unclear whether the cavernous nerves carry fibers that influence continence. Using a retrograde axonal tracer combined with real-time in vivo imaging and ex vivo immunohistochemistry we determined the course and type of neurons supplying urethral smooth muscle distal to the prostate in the rat. We injected the retrograde axonal tracers cholera toxin B fragment-Alexa Fluor 488 and Fast Blue in the distal urethral smooth muscle in 10 rats each. Five days later the cavernous nerves and pelvic ganglion were imaged using fiberoptic confocal fluorescence microscopy (cholera toxin B fragment-Alexa Fluor 488) or harvested for immunohistochemistry (Fast Blue). Dual immunofluorescence of Fast Blue neurons with tyrosine hydroxylase or neuronal nitric oxide synthase was done to characterize neurons as noradrenergic or nitrergic. To ascertain whether the cavernous nerves contain fibers to the urethra that originate in the pelvic ganglia we cut the cavernous nerves with their ancillary branches in 3 rats and imaged them for Fast Blue. Fluorescent neurons and axons were detected in cavernous nerves and the pelvic ganglion. Few neurons were seen in rats with cavernous nerve section. Of urethral neurons 53.1% showed neuronal nitric oxide synthase positivity while 40.6% were immunoreactive for tyrosine hydroxylase. About 6.2% of urethral neurons failed to show tyrosine hydroxylase or neuronal nitric oxide synthase immunoreactivity. Most of the autonomic innervation to the urethra beyond the prostatic apex travels in the cavernous nerves. Many nerves may be parasympathetic based on neuronal nitric oxide synthase immunoreactivity. Nerves supplying the urethra outside the cavernous nerves may course posterior to the prostate. Along with afferent fibers, tyrosine hydroxylase immunoreactivity expressing neuron fibers, ie noradrenergic nerves, traveling in the cavernous nerves may

  10. Chemo-nociceptive signalling from the colon is enhanced by mild colitis and blocked by inhibition of transient receptor potential ankyrin 1 channels

    DEFF Research Database (Denmark)

    Mitrovic, Martina; Shahbazian, Anaid; Bock, Elisabeth

    2010-01-01

    Transient receptor potential ankyrin 1 (TRPA1) channels are expressed by primary afferent neurones and activated by irritant chemicals including allyl isothiocyanate (AITC). Here we investigated whether intracolonic AITC causes afferent input to the spinal cord and whether this response is modifi...

  11. Autapse-induced synchronization in a coupled neuronal network

    International Nuclear Information System (INIS)

    Ma, Jun; Song, Xinlin; Jin, Wuyin; Wang, Chuni

    2015-01-01

    Highlights: • The functional effect of autapse on neuronal activity is detected. • Autapse driving plays active role in regulating electrical activities as pacemaker. • It confirms biological experimental results for rhythm synchronization between heterogeneous cells. - Abstract: The effect of autapse on coupled neuronal network is detected. In our studies, three identical neurons are connected with ring type and autapse connected to one neuron of the network. The autapse connected to neuron can impose time-delayed feedback in close loop on the neuron thus the dynamics of membrane potentials can be changed. Firstly, the effect of autapse driving on single neuron is confirmed that negative feedback can calm down the neuronal activity while positive feedback can excite the neuronal activity. Secondly, the collective electrical behaviors of neurons are regulated by a pacemaker, which associated with the autapse forcing. By using appropriate gain and time delay in the autapse, the neurons can reach synchronization and the membrane potentials of all neurons can oscillate with the same rhythm under mutual coupling. It indicates that autapse forcing plays an important role in changing the collective electric activities of neuronal network, and appropriate electric modes can be selected due to the switch of feedback type(positive or negative) in autapse. And the autapse-induced synchronization in network is also consistent with some biological experiments about synchronization between nonidentical neurons.

  12. Tentonin 3/TMEM150c Confers Distinct Mechanosensitive Currents in Dorsal-Root Ganglion Neurons with Proprioceptive Function.

    Science.gov (United States)

    Hong, Gyu-Sang; Lee, Byeongjun; Wee, Jungwon; Chun, Hyeyeon; Kim, Hyungsup; Jung, Jooyoung; Cha, Joo Young; Riew, Tae-Ryong; Kim, Gyu Hyun; Kim, In-Beom; Oh, Uhtaek

    2016-07-06

    Touch sensation or proprioception requires the transduction of mechanical stimuli into electrical signals by mechanoreceptors in the periphery. These mechanoreceptors are equipped with various transducer channels. Although Piezo1 and 2 are mechanically activated (MA) channels with rapid inactivation, MA molecules with other inactivation kinetics have not been identified. Here we report that heterologously expressed Tentonin3 (TTN3)/TMEM150C is activated by mechanical stimuli with distinctly slow inactivation kinetics. Genetic ablation of Ttn3/Tmem150c markedly reduced slowly adapting neurons in dorsal-root ganglion neurons. The MA TTN3 currents were inhibited by known blockers of mechanosensitive ion channels. Moreover, TTN3 was localized in muscle spindle afferents. Ttn3-deficient mice exhibited the loss of coordinated movements and abnormal gait. Thus, TTN3 appears to be a component of a mechanosensitive channel with a slow inactivation rate and contributes to motor coordination. Identification of this gene advances our understanding of the various types of mechanosensations, including proprioception. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Afferent Pathway-Mediated Effect of α1 Adrenergic Antagonist, Tamsulosin, on the Neurogenic Bladder After Spinal Cord Injury.

    Science.gov (United States)

    Han, Jin-Hee; Kim, Sung-Eun; Ko, Il-Gyu; Kim, Jayoung; Kim, Khae Hawn

    2017-09-01

    The functions of the lower urinary tract (LUT), such as voiding and storing urine, are dependent on complex central neural networks located in the brain, spinal cord, and peripheral ganglia. Thus, the functions of the LUT are susceptible to various neurologic disorders including spinal cord injury (SCI). SCI at the cervical or thoracic levels disrupts voluntary control of voiding and the normal reflex pathways coordinating bladder and sphincter functions. In this context, it is noteworthy that α1-adrenoceptor blockers have been reported to relieve voiding symptoms and storage symptoms in elderly men with benign prostatic hyperplasia (BPH). Tamsulosin, an α1-adrenoceptor blocker, is also considered the most effective regimen for patients with LUT symptoms such as BPH and overactive bladder (OAB). In the present study, the effects of tamsulosin on the expression of c-Fos, nerve growth factor (NGF), and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) in the afferent micturition areas, including the pontine micturition center (PMC), the ventrolateral periaqueductal gray matter (vlPAG), and the spinal cord (L5), of rats with an SCI were investigated. SCI was found to remarkably upregulate the expression of c-Fos, NGF, and NADPH-d in the afferent pathway of micturition, the dorsal horn of L5, the vlPAG, and the PMC, resulting in the symptoms of OAB. In contrast, tamsulosin treatment significantly suppressed these neural activities and the production of nitric oxide in the afferent pathways of micturition, and consequently, attenuated the symptoms of OAB. Based on these results, tamsulosin, an α1-adrenoceptor antagonist, could be used to attenuate bladder dysfunction following SCI. However, further studies are needed to elucidate the exact mechanism and effects of tamsulosin on the afferent pathways of micturition.

  14. Afferent loop syndrome - a case report; Sindrome da alca aferente - relato de um caso

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Ana Karina Nascimento; Pinheiro, Marco Antonio Lopes; Galvao, Cristine Norwig [Fundacao Pio XII - Hospital do Cancer de Barretos, SP (Brazil)

    2000-02-01

    The afferent loop syndrome occurs in patients with previous gastric surgery for tumor, when there is anastomotic edema, use of inappropriate reconstruction technique for gastro jejunostomy or recurrent gastric cancer. Complaints such jaundice, intermittent abdominal distension associated with pain, and vomiting should be investigated in order to rule out this syndrome. (author)

  15. Prenatal androgenization of female mice programs an increase in firing activity of gonadotropin-releasing hormone (GnRH) neurons that is reversed by metformin treatment in adulthood.

    Science.gov (United States)

    Roland, Alison V; Moenter, Suzanne M

    2011-02-01

    Prenatal androgenization (PNA) of female mice with dihydrotestosterone programs reproductive dysfunction in adulthood, characterized by elevated luteinizing hormone levels, irregular estrous cycles, and central abnormalities. Here, we evaluated activity of GnRH neurons from PNA mice and the effects of in vivo treatment with metformin, an activator of AMP-activated protein kinase (AMPK) that is commonly used to treat the fertility disorder polycystic ovary syndrome. Estrous cycles were monitored in PNA and control mice before and after metformin administration. Before metformin, cycles were longer in PNA mice and percent time in estrus lower; metformin normalized cycles in PNA mice. Extracellular recordings were used to monitor GnRH neuron firing activity in brain slices from diestrous mice. Firing rate was higher and quiescence lower in GnRH neurons from PNA mice, demonstrating increased GnRH neuron activity. Metformin treatment of PNA mice restored firing activity and LH to control levels. To assess whether AMPK activation contributed to the metformin-induced reduction in GnRH neuron activity, the AMPK antagonist compound C was acutely applied to cells. Compound C stimulated cells from metformin-treated, but not untreated, mice, suggesting that AMPK was activated in GnRH neurons, or afferent neurons, in the former group. GnRH neurons from metformin-treated mice also showed a reduced inhibitory response to low glucose. These studies indicate that PNA causes enhanced firing activity of GnRH neurons and elevated LH that are reversible by metformin, raising the possibility that central AMPK activation by metformin may play a role in its restoration of reproductive cycles in polycystic ovary syndrome.

  16. Neuron matters: electric activation of neuronal tissue is dependent on the interaction between the neuron and the electric field.

    Science.gov (United States)

    Ye, Hui; Steiger, Amanda

    2015-08-12

    In laboratory research and clinical practice, externally-applied electric fields have been widely used to control neuronal activity. It is generally accepted that neuronal excitability is controlled by electric current that depolarizes or hyperpolarizes the excitable cell membrane. What determines the amount of polarization? Research on the mechanisms of electric stimulation focus on the optimal control of the field properties (frequency, amplitude, and direction of the electric currents) to improve stimulation outcomes. Emerging evidence from modeling and experimental studies support the existence of interactions between the targeted neurons and the externally-applied electric fields. With cell-field interaction, we suggest a two-way process. When a neuron is positioned inside an electric field, the electric field will induce a change in the resting membrane potential by superimposing an electrically-induced transmembrane potential (ITP). At the same time, the electric field can be perturbed and re-distributed by the cell. This cell-field interaction may play a significant role in the overall effects of stimulation. The redistributed field can cause secondary effects to neighboring cells by altering their geometrical pattern and amount of membrane polarization. Neurons excited by the externally-applied electric field can also affect neighboring cells by ephaptic interaction. Both aspects of the cell-field interaction depend on the biophysical properties of the neuronal tissue, including geometric (i.e., size, shape, orientation to the field) and electric (i.e., conductivity and dielectricity) attributes of the cells. The biophysical basis of the cell-field interaction can be explained by the electromagnetism theory. Further experimental and simulation studies on electric stimulation of neuronal tissue should consider the prospect of a cell-field interaction, and a better understanding of tissue inhomogeneity and anisotropy is needed to fully appreciate the neural

  17. Attention-driven auditory cortex short-term plasticity helps segregate relevant sounds from noise

    OpenAIRE

    Ahveninen, Jyrki; Hämäläinen, Matti; Jääskeläinen, Iiro P.; Ahlfors, Seppo P.; Huang, Samantha; Lin, Fa-Hsuan; Raij, Tommi; Sams, Mikko; Vasios, Christos E.; Belliveau, John W.

    2011-01-01

    How can we concentrate on relevant sounds in noisy environments? A “gain model” suggests that auditory attention simply amplifies relevant and suppresses irrelevant afferent inputs. However, it is unclear whether this suffices when attended and ignored features overlap to stimulate the same neuronal receptive fields. A “tuning model” suggests that, in addition to gain, attention modulates feature selectivity of auditory neurons. We recorded magnetoencephalography, EEG, and functional MRI (fMR...

  18. Activation of GLP-1 receptors on vascular smooth muscle cells reduces the autoregulatory response in afferent arterioles and increases renal blood flow.

    Science.gov (United States)

    Jensen, Elisa P; Poulsen, Steen S; Kissow, Hannelouise; Holstein-Rathlou, Niels-Henrik; Deacon, Carolyn F; Jensen, Boye L; Holst, Jens J; Sorensen, Charlotte M

    2015-04-15

    Glucagon-like peptide (GLP)-1 has a range of extrapancreatic effects, including renal effects. The mechanisms are poorly understood, but GLP-1 receptors have been identified in the kidney. However, the exact cellular localization of the renal receptors is poorly described. The aim of the present study was to localize renal GLP-1 receptors and describe GLP-1-mediated effects on the renal vasculature. We hypothesized that renal GLP-1 receptors are located in the renal microcirculation and that activation of these affects renal autoregulation and increases renal blood flow. In vivo autoradiography using (125)I-labeled GLP-1, (125)I-labeled exendin-4 (GLP-1 analog), and (125)I-labeled exendin 9-39 (GLP-1 receptor antagonist) was performed in rodents to localize specific GLP-1 receptor binding. GLP-1-mediated effects on blood pressure, renal blood flow (RBF), heart rate, renin secretion, urinary flow rate, and Na(+) and K(+) excretion were investigated in anesthetized rats. Effects of GLP-1 on afferent arterioles were investigated in isolated mouse kidneys. Specific binding of (125)I-labeled GLP-1, (125)I-labeled exendin-4, and (125)I-labeled exendin 9-39 was observed in the renal vasculature, including afferent arterioles. Infusion of GLP-1 increased blood pressure, RBF, and urinary flow rate significantly in rats. Heart rate and plasma renin concentrations were unchanged. Exendin 9-39 inhibited the increase in RBF. In isolated murine kidneys, GLP-1 and exendin-4 significantly reduced the autoregulatory response of afferent arterioles in response to stepwise increases in pressure. We conclude that GLP-1 receptors are located in the renal vasculature, including afferent arterioles. Activation of these receptors reduces the autoregulatory response of afferent arterioles to acute pressure increases and increases RBF in normotensive rats. Copyright © 2015 the American Physiological Society.

  19. Neuronal-glial trafficking

    International Nuclear Information System (INIS)

    Bachelard, H.S.

    2001-01-01

    Full text: The name 'glia' originates from the Greek word for glue, because astro glia (or astrocytes) were thought only to provide an anatomical framework for the electrically-excitable neurones. However, awareness that astrocytes perform vital roles in protecting the neurones, which they surround, emerged from evidence that they act as neuroprotective K + -sinks, and that they remove potentially toxic extracellular glutamate from the vicinity of the neurones. The astrocytes convert the glutamate to non-toxic glutamine which is returned to the neurones and used to replenish transmitter glutamate. This 'glutamate-glutamine cycle' (established in the 1960s by Berl and his colleagues) also contributes to protecting the neurones against a build-up of toxic ammonia. Glial cells also supply the neurones with components for free-radical scavenging glutathione. Recent studies have revealed that glial cells play a more positive interactive role in furnishing the neurones with fuels. Studies using radioactive 14 C, 13 C-MRS and 15 N-GCMS have revealed that glia produce alanine, lactate and proline for consumption by neurones, with increased formation of neurotransmitter glutamate. On neuronal activation the release of NH 4 + and glutamate from the neurones stimulates glucose uptake and glycolysis in the glia to produce more alanine, which can be regarded as an 'alanine-glutamate cycle' Use of 14 C-labelled precursors provided early evidence that neurotransmitter GABA may be partly derived from glial glutamine, and this has been confirmed recently in vivo by MRS isotopomer analysis of the GABA and glutamine labelled from 13 C-acetate. Relative rates of intermediary metabolism in glia and neurones can be calculated using a combination of [1- 13 C] glucose and [1,2- 13 C] acetate. When glutamate is released by neurones there is a net neuronal loss of TCA intermediates which have to be replenished. Part of this is derived from carboxylation of pyruvate, (pyruvate carboxylase

  20. Effects of periodontal afferent inputs on corticomotor excitability in humans

    DEFF Research Database (Denmark)

    Zhang, Y; Boudreau, S; Wang, M

    2010-01-01

    for the first dorsal interosseous (FDI) as an internal control. Burning pain intensity and mechanical sensitivity ratings to a von Frey filament applied to the application site were recorded on an electronic visual analogue scale (VAS). All subjects reported a decreased mechanical sensitivity (anova: P = 0......-injection for the LA (anovas: P > 0.22) or capsaicin (anovas: P > 0.16) sessions. These findings suggest that a transient loss or perturbation in periodontal afferent input to the brain from a single incisor is insufficient to cause changes in corticomotor excitability of the face MI, as measured by TMS in humans....

  1. [Distribution of neural memory, loading factor, its regulation and optimization].

    Science.gov (United States)

    Radchenko, A N

    1999-01-01

    Recording and retrieving functions of the neural memory are simulated as a control of local conformational processes in neural synaptic fields. The localization of conformational changes is related to the afferent temporal-spatial pulse pattern flow, the microstructure of connections and a plurality of temporal delays in synaptic fields and afferent pathways. The loci of conformations are described by sets of afferent addresses named address domains. Being superimposed on each other, address domains form a multilayer covering of the address space of the neuron or the ensemble. The superposition factor determines the dissemination of the conformational process, and the fuzzing of memory, and its accuracy and reliability. The engram is formed as detects in the packing of the address space and hence can be retrieved in inverse form. The accuracy of the retrieved information depends on the threshold level of conformational transitions, the distribution of conformational changes in synaptic fields of the neuronal population, and the memory loading factor. The latter is represented in the model by a slow potential. It reflects total conformational changes and displaces the membrane potential to monostable conformational regimes, by governing the exit from the recording regime, the potentiation of the neurone, and the readiness to reproduction. A relative amplitude of the slow potential and the coefficient of postconformational modification of ionic conductivity, which provides maximum reliability, accuracy, and capacity of memory, are calculated.

  2. The calcium-binding protein parvalbumin modulates the firing 1 properties of the reticular thalamic nucleus bursting neurons.

    Science.gov (United States)

    Albéri, Lavinia; Lintas, Alessandra; Kretz, Robert; Schwaller, Beat; Villa, Alessandro E P

    2013-06-01

    The reticular thalamic nucleus (RTN) of the mouse is characterized by an overwhelming majority of GABAergic neurons receiving afferences from both the thalamus and the cerebral cortex and sending projections mainly on thalamocortical neurons. The RTN neurons express high levels of the "slow Ca(2+) buffer" parvalbumin (PV) and are characterized by low-threshold Ca(2+) currents, I(T). We performed extracellular recordings in ketamine/xylazine anesthetized mice in the rostromedial portion of the RTN. In the RTN of wild-type and PV knockout (PVKO) mice we distinguished four types of neurons characterized on the basis of their firing pattern: irregular firing (type I), medium bursting (type II), long bursting (type III), and tonically firing (type IV). Compared with wild-type mice, we observed in the PVKOs the medium bursting (type II) more frequently than the long bursting type and longer interspike intervals within the burst without affecting the number of spikes. This suggests that PV may affect the firing properties of RTN neurons via a mechanism associated with the kinetics of burst discharges. Ca(v)3.2 channels, which mediate the I(T) currents, were more localized to the somatic plasma membrane of RTN neurons in PVKO mice, whereas Ca(v)3.3 expression was similar in both genotypes. The immunoelectron microscopy analysis showed that Ca(v)3.2 channels were localized at active axosomatic synapses, thus suggesting that the differential localization of Ca(v)3.2 in the PVKOs may affect bursting dynamics. Cross-correlation analysis of simultaneously recorded neurons from the same electrode tip showed that about one-third of the cell pairs tended to fire synchronously in both genotypes, independent of PV expression. In summary, PV deficiency does not affect the functional connectivity between RTN neurons but affects the distribution of Ca(v)3.2 channels and the dynamics of burst discharges of RTN cells, which in turn regulate the activity in the thalamocortical circuit.

  3. Expression of phosphorylated cAMP response element binding protein (p-CREB) in bladder afferent pathways in VIP-/- mice with cyclophosphamide (CYP)-induced cystitis

    DEFF Research Database (Denmark)

    Jensen, Dorthe G; Studeny, Simon; May, Victor

    2008-01-01

    The expression of phosphorylated cAMP response element binding protein (p-CREB) in dorsal root ganglia (DRG) with and without cyclophosphamide (CYP)-induced cystitis (150 mg/kg, i.p; 48 h) was determined in VIP(-/-) and wild-type (WT) mice. p-CREB immunoreactivity (IR) was determined in bladder...... (Fast blue) afferent cells. Nerve growth factor (NGF) bladder content was determined by enzyme-linked immunosorbent assays. Basal expression of p-CREB-IR in DRG of VIP(-/-) mice was (p DRG compared to WT mice. CYP treatment in WT mice increased (p ...-CREB-IR in L1, L2, L5-S1 DRG. CYP treatment in VIP(-/-) mice (p DRG compared to WT with CYP. In WT mice, bladder afferent cells (20-38%) in DRG expressed p-CREB-IR under basal conditions. With CYP, p-CREB-IR increased in bladder afferent cells (60...

  4. Social Isolation During Postweaning Development Causes Hypoactivity of Neurons in the Medial Nucleus of the Male Rat Amygdala

    Science.gov (United States)

    Adams, Thomas; Rosenkranz, J Amiel

    2016-01-01

    Children exposed to neglect or social deprivation are at heightened risk for psychiatric disorders and abnormal social patterns as adults. There is also evidence that prepubertal neglect in children causes abnormal metabolic activity in several brain regions, including the amygdala area. The medial nucleus of the amygdala (MeA) is a key region for performance of social behaviors and still undergoes maturation during the periadolescent period. As such, the normal development of this region may be disrupted by social deprivation. In rodents, postweaning social isolation causes a range of deficits in sexual and agonistic behaviors that normally rely on the posterior MeA (MeAp). However, little is known about the effects of social isolation on the function of MeA neurons. In this study, we tested whether postweaning social isolation caused abnormal activity of MeA neurons. We found that postweaning social isolation caused a decrease of in vivo firing activity of MeAp neurons, and reduced drive from excitatory afferents. In vitro electrophysiological studies found that postweaning social isolation caused a presynaptic impairment of excitatory input to the dorsal MeAp, but a progressive postsynaptic reduction of membrane excitability in the ventral MeAp. These results demonstrate discrete, subnucleus-specific effects of social deprivation on the physiology of MeAp neurons. This pathophysiology may contribute to the disruption of social behavior after developmental social deprivation, and may be a novel target to facilitate the treatment of social disorders. PMID:26677945

  5. Social Isolation During Postweaning Development Causes Hypoactivity of Neurons in the Medial Nucleus of the Male Rat Amygdala.

    Science.gov (United States)

    Adams, Thomas; Rosenkranz, J Amiel

    2016-06-01

    Children exposed to neglect or social deprivation are at heightened risk for psychiatric disorders and abnormal social patterns as adults. There is also evidence that prepubertal neglect in children causes abnormal metabolic activity in several brain regions, including the amygdala area. The medial nucleus of the amygdala (MeA) is a key region for performance of social behaviors and still undergoes maturation during the periadolescent period. As such, the normal development of this region may be disrupted by social deprivation. In rodents, postweaning social isolation causes a range of deficits in sexual and agonistic behaviors that normally rely on the posterior MeA (MeAp). However, little is known about the effects of social isolation on the function of MeA neurons. In this study, we tested whether postweaning social isolation caused abnormal activity of MeA neurons. We found that postweaning social isolation caused a decrease of in vivo firing activity of MeAp neurons, and reduced drive from excitatory afferents. In vitro electrophysiological studies found that postweaning social isolation caused a presynaptic impairment of excitatory input to the dorsal MeAp, but a progressive postsynaptic reduction of membrane excitability in the ventral MeAp. These results demonstrate discrete, subnucleus-specific effects of social deprivation on the physiology of MeAp neurons. This pathophysiology may contribute to the disruption of social behavior after developmental social deprivation, and may be a novel target to facilitate the treatment of social disorders.

  6. A food-predictive cue attributed with incentive salience engages subcortical afferents and efferents of the paraventricular nucleus of the thalamus.

    Science.gov (United States)

    Haight, Joshua L; Fuller, Zachary L; Fraser, Kurt M; Flagel, Shelly B

    2017-01-06

    The paraventricular nucleus of the thalamus (PVT) has been implicated in behavioral responses to reward-associated cues. However, the precise role of the PVT in these behaviors has been difficult to ascertain since Pavlovian-conditioned cues can act as both predictive and incentive stimuli. The "sign-tracker/goal-tracker" rat model has allowed us to further elucidate the role of the PVT in cue-motivated behaviors, identifying this structure as a critical component of the neural circuitry underlying individual variation in the propensity to attribute incentive salience to reward cues. The current study assessed differences in the engagement of specific PVT afferents and efferents in response to presentation of a food-cue that had been attributed with only predictive value or with both predictive and incentive value. The retrograde tracer fluorogold (FG) was injected into the PVT or the nucleus accumbens (NAc) of rats, and cue-induced c-Fos in FG-labeled cells was quantified. Presentation of a predictive stimulus that had been attributed with incentive value elicited c-Fos in PVT afferents from the lateral hypothalamus, medial amygdala (MeA), and the prelimbic cortex (PrL), as well as posterior PVT efferents to the NAc. PVT afferents from the PrL also showed elevated c-Fos levels following presentation of a predictive stimulus alone. Thus, presentation of an incentive stimulus results in engagement of subcortical brain regions; supporting a role for the hypothalamic-thalamic-striatal axis, as well as the MeA, in mediating responses to incentive stimuli; whereas activity in the PrL to PVT pathway appears to play a role in processing the predictive qualities of reward-paired stimuli. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Short and Long-Term Attentional Firing Rates Can Be Explained by ST-Neuron Dynamics

    Directory of Open Access Journals (Sweden)

    Oscar J. Avella Gonzalez

    2018-03-01

    Full Text Available Attention modulates neural selectivity and optimizes the allocation of cortical resources during visual tasks. A large number of experimental studies in primates and humans provide ample evidence. As an underlying principle of visual attention, some theoretical models suggested the existence of a gain element that enhances contrast of the attended stimuli. In contrast, the Selective Tuning model of attention (ST proposes an attentional mechanism based on suppression of irrelevant signals. In this paper, we present an updated characterization of the ST-neuron proposed by the Selective Tuning model, and suggest that the inclusion of adaptation currents (Ih to ST-neurons may explain the temporal profiles of the firing rates recorded in single V4 cells during attentional tasks. Furthermore, using the model we show that the interaction between stimulus-selectivity of a neuron and attention shapes the profile of the firing rate, and is enough to explain its fast modulation and other discontinuities observed, when the neuron responds to a sudden switch of stimulus, or when one stimulus is added to another during a visual task.

  8. Evaluation of afferent pain pathways in adrenomyeloneuropathic patients.

    Science.gov (United States)

    Yagüe, Sara; Veciana, Misericordia; Casasnovas, Carlos; Ruiz, Montserrat; Pedro, Jordi; Valls-Solé, Josep; Pujol, Aurora

    2018-03-01

    Patients with adrenomyeloneuropathy may have dysfunctions of visual, auditory, motor and somatosensory pathways. We thought on examining the nociceptive pathways by means of laser evoked potentials (LEPs), to obtain additional information on the pathophysiology of this condition. In 13 adrenomyeloneuropathic patients we examined LEPs to leg, arm and face stimulation. Normative data were obtained from 10 healthy subjects examined in the same experimental conditions. We also examined brainstem auditory evoked potentials (BAEPs), pattern reversal full-field visual evoked potentials (VEPs), motor evoked potentials (MEPs) and somatosensory evoked potentials (SEPs). Upper and lower limb MEPs and SEPs, as well as BAEPs, were abnormal in all patients, while VEPs were abnormal in 3 of them (23.1%). LEPs revealed abnormalities to stimulation of the face in 4 patients (30.7%), the forearm in 4 patients (30.7%) and the leg in 10 patients (76.9%). The pathologic process of adrenomyeloneuropathy is characterized by a preferential involvement of auditory, motor and somatosensory tracts and less severely of the visual and nociceptive pathways. This non-inflammatory distal axonopathy preferably damages large myelinated spinal tracts but there is also partial involvement of small myelinated fibres. LEPs studies can provide relevant information about afferent pain pathways involvement in adrenomyeloneuropathic patients. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  9. BlastNeuron for Automated Comparison, Retrieval and Clustering of 3D Neuron Morphologies.

    Science.gov (United States)

    Wan, Yinan; Long, Fuhui; Qu, Lei; Xiao, Hang; Hawrylycz, Michael; Myers, Eugene W; Peng, Hanchuan

    2015-10-01

    Characterizing the identity and types of neurons in the brain, as well as their associated function, requires a means of quantifying and comparing 3D neuron morphology. Presently, neuron comparison methods are based on statistics from neuronal morphology such as size and number of branches, which are not fully suitable for detecting local similarities and differences in the detailed structure. We developed BlastNeuron to compare neurons in terms of their global appearance, detailed arborization patterns, and topological similarity. BlastNeuron first compares and clusters 3D neuron reconstructions based on global morphology features and moment invariants, independent of their orientations, sizes, level of reconstruction and other variations. Subsequently, BlastNeuron performs local alignment between any pair of retrieved neurons via a tree-topology driven dynamic programming method. A 3D correspondence map can thus be generated at the resolution of single reconstruction nodes. We applied BlastNeuron to three datasets: (1) 10,000+ neuron reconstructions from a public morphology database, (2) 681 newly and manually reconstructed neurons, and (3) neurons reconstructions produced using several independent reconstruction methods. Our approach was able to accurately and efficiently retrieve morphologically and functionally similar neuron structures from large morphology database, identify the local common structures, and find clusters of neurons that share similarities in both morphology and molecular profiles.

  10. Firing dynamics of an autaptic neuron

    International Nuclear Information System (INIS)

    Wang Heng-Tong; Chen Yong

    2015-01-01

    Autapses are synapses that connect a neuron to itself in the nervous system. Previously, both experimental and theoretical studies have demonstrated that autaptic connections in the nervous system have a significant physiological function. Autapses in nature provide self-delayed feedback, thus introducing an additional timescale to neuronal activities and causing many dynamic behaviors in neurons. Recently, theoretical studies have revealed that an autapse provides a control option for adjusting the response of a neuron: e.g., an autaptic connection can cause the electrical activities of the Hindmarsh–Rose neuron to switch between quiescent, periodic, and chaotic firing patterns; an autapse can enhance or suppress the mode-locking status of a neuron injected with sinusoidal current; and the firing frequency and interspike interval distributions of the response spike train can also be modified by the autapse. In this paper, we review recent studies that showed how an autapse affects the response of a single neuron. (topical review)

  11. Synchronization of Coupled Neurons Controlled by a Pacemaker

    International Nuclear Information System (INIS)

    Li Mei-Sheng; Zhang Hong-Hui; Zhao Yong; Shi Xia

    2011-01-01

    We investigate synchronization of Hindmarsh—Rose neurons with gap junctions under the control of a pacemaker. In a ring Hindmarsh—Rose neuronal network, the coupled neurons with the pacemaker can occur in synchronization more easily than those without the pacemaker. Furthermore, the pacemaker can induce phase synchronization or nearly-complete synchronization of nonidentical neurons. This synchronization can occur more easily when time delay is considered. Theses results can be helpful to understand the activities of the real neuronal system. (general)

  12. Fractalkine Signaling Regulates Macrophage Recruitment into the Cochlea and Promotes the Survival of Spiral Ganglion Neurons after Selective Hair Cell Lesion.

    Science.gov (United States)

    Kaur, Tejbeer; Zamani, Darius; Tong, Ling; Rubel, Edwin W; Ohlemiller, Kevin K; Hirose, Keiko; Warchol, Mark E

    2015-11-11

    Macrophages are recruited into the cochlea in response to injury caused by acoustic trauma or ototoxicity, but the nature of the interaction between macrophages and the sensory structures of the inner ear remains unclear. The present study examined the role of fractalkine signaling in regulating the injury-evoked behavior of macrophages following the selective ablation of cochlear hair cells. We used a novel transgenic mouse model in which the human diphtheria toxin receptor (huDTR) is selectively expressed under the control of Pou4f3, a hair cell-specific transcription factor. Administration of diphtheria toxin (DT) to these mice resulted in nearly complete ablation of cochlear hair cells, with no evident pathology among supporting cells, spiral ganglion neurons, or cells of the cochlear lateral wall. Hair cell death led to an increase in macrophages associated with the sensory epithelium of the cochlea. Their numbers peaked at 14 days after DT and then declined at later survival times. Increased macrophages were also observed within the spiral ganglion, but their numbers remained elevated for (at least) 56 d after DT. To investigate the role of fractalkine signaling in macrophage recruitment, we crossed huDTR mice to a mouse line that lacks expression of the fractalkine receptor (CX3CR1). Disruption of fractalkine signaling reduced macrophage recruitment into both the sensory epithelium and spiral ganglion and also resulted in diminished survival of spiral ganglion neurons after hair cell death. Our results suggest a fractalkine-mediated interaction between macrophages and the neurons of the cochlea. It is known that damage to the inner ear leads to recruitment of inflammatory cells (macrophages), but the chemical signals that initiate this recruitment and the functions of macrophages in the damaged ear are unclear. Here we show that fractalkine signaling regulates macrophage recruitment into the cochlea and also promotes the survival of cochlear afferents after

  13. Functional and neurochemical characterization of angiotensin type 1A receptor-expressing neurons in the nucleus of the solitary tract of the mouse.

    Science.gov (United States)

    Carter, D A; Choong, Y-T; Connelly, A A; Bassi, J K; Hunter, N O; Thongsepee, N; Llewellyn-Smith, I J; Fong, A Y; McDougall, S J; Allen, A M

    2017-10-01

    Angiotensin II acts via two main receptors within the central nervous system, with the type 1A receptor (AT 1A R) most widely expressed in adult neurons. Activation of the AT 1 R in the nucleus of the solitary tract (NTS), the principal nucleus receiving central synapses of viscerosensory afferents, modulates cardiovascular reflexes. Expression of the AT 1 R occurs in high density within the NTS of most mammals, including humans, but the fundamental electrophysiological and neurochemical characteristics of the AT 1A R-expressing NTS neurons are not known. To address this, we have used a transgenic mouse, in which the AT 1A R promoter drives expression of green fluorescent protein (GFP). Approximately one-third of AT 1A R-expressing neurons express the catecholamine-synthetic enzyme tyrosine hydroxylase (TH), and a subpopulation of these stained for the transcription factor paired-like homeobox 2b (Phox2b). A third group, comprising approximately two-thirds of the AT 1A R-expressing NTS neurons, showed Phox2b immunoreactivity alone. A fourth group in the ventral subnucleus expressed neither TH nor Phox2b. In whole cell recordings from slices in vitro, AT 1A R-GFP neurons exhibited voltage-activated potassium currents, including the transient outward current and the M-type potassium current. In two different mouse strains, both AT 1A R-GFP neurons and TH-GFP neurons showed similar AT 1A R-mediated depolarizing responses to superfusion with angiotensin II. These data provide a comprehensive description of AT 1A R-expressing neurons in the NTS and increase our understanding of the complex actions of this neuropeptide in the modulation of viscerosensory processing. Copyright © 2017 the American Physiological Society.

  14. Glutamate acts as a neurotransmitter for gastrin releasing peptide-sensitive and insensitive itch-related synaptic transmission in mammalian spinal cord

    Directory of Open Access Journals (Sweden)

    Ling Jennifer

    2011-06-01

    Full Text Available Abstract Itch sensation is one of the major sensory experiences of human and animals. Recent studies have proposed that gastrin releasing peptide (GRP is a key neurotransmitter for itch in spinal cord. However, no direct evidence is available to indicate that GRP actually mediate responses between primary afferent fibers and dorsal horn neurons. Here we performed integrative neurobiological experiments to test this question. We found that a small population of rat dorsal horn neurons responded to GRP application with increases in calcium signaling. Whole-cell patch-clamp recordings revealed that a part of superficial dorsal horn neurons responded to GRP application with the increase of action potential firing in adult rats and mice, and these dorsal horn neurons received exclusively primary afferent C-fiber inputs. On the other hands, few Aδ inputs receiving cells were found to be GRP positive. Finally, we found that evoked sensory responses between primary afferent C fibers and GRP positive superficial dorsal horn neurons are mediated by glutamate but not GRP. CNQX, a blocker of AMPA and kainate (KA receptors, completely inhibited evoked EPSCs, including in those Fos-GFP positive dorsal horn cells activated by itching. Our findings provide the direct evidence that glutamate is the principal excitatory transmitter between C fibers and GRP positive dorsal horn neurons. Our results will help to understand the neuronal mechanism of itch and aid future treatment for patients with pruritic disease.

  15. Cell Type–Specific Three-Dimensional Structure of Thalamocortical Circuits in a Column of Rat Vibrissal Cortex

    Science.gov (United States)

    de Kock, Christiaan P. J.; Bruno, Randy M.; Ramirez, Alejandro; Meyer, Hanno S.; Dercksen, Vincent J.; Helmstaedter, Moritz; Sakmann, Bert

    2012-01-01

    Soma location, dendrite morphology, and synaptic innervation may represent key determinants of functional responses of individual neurons, such as sensory-evoked spiking. Here, we reconstruct the 3D circuits formed by thalamocortical afferents from the lemniscal pathway and excitatory neurons of an anatomically defined cortical column in rat vibrissal cortex. We objectively classify 9 cortical cell types and estimate the number and distribution of their somata, dendrites, and thalamocortical synapses. Somata and dendrites of most cell types intermingle, while thalamocortical connectivity depends strongly upon the cell type and the 3D soma location of the postsynaptic neuron. Correlating dendrite morphology and thalamocortical connectivity to functional responses revealed that the lemniscal afferents can account for some of the cell type- and location-specific subthreshold and spiking responses after passive whisker touch (e.g., in layer 4, but not for other cell types, e.g., in layer 5). Our data provides a quantitative 3D prediction of the cell type–specific lemniscal synaptic wiring diagram and elucidates structure–function relationships of this physiologically relevant pathway at single-cell resolution. PMID:22089425

  16. GABAA receptor drugs and neuronal plasticity in reward and aversion: focus on the ventral tegmental area

    Directory of Open Access Journals (Sweden)

    Elena eVashchinkina

    2014-11-01

    Full Text Available GABAA receptors are the main fast inhibitory neurotransmitter receptors in the mammalian brain, and targets for many clinically important drugs widely used in the treatment of anxiety disorders, insomnia and in anesthesia. Nonetheless, there are significant risks associated with the long-term use of these drugs particularly related to development of tolerance and addiction. Addictive mechanisms of GABAA receptor drugs are poorly known, but recent findings suggest that those drugs may induce aberrant neuroadaptations in the brain reward circuitry. Recently, benzodiazepines, acting on synaptic GABAA receptors, and modulators of extrasynaptic GABAA receptors (THIP and neurosteroids have been found to induce plasticity in the ventral tegmental area (VTA dopamine neurons and their main target projections. Furthermore, depending whether synaptic or extrasynaptic GABAA receptor populations are activated, the behavioral outcome of repeated administration seems to correlate with rewarding or aversive behavioral responses, respectively. The VTA dopamine neurons project to forebrain centers such as the nucleus accumbens and medial prefrontal cortex, and receive afferent projections from these brain regions and especially from the extended amygdala and lateral habenula, forming the major part of the reward and aversion circuitry. Both synaptic and extrasynaptic GABAA drugs inhibit the VTA GABAergic interneurons, thus activating the VTA DA neurons by disinhibition and this way inducing glutamatergic synaptic plasticity. However, the GABAA drugs failed to alter synaptic spine numbers as studied from Golgi-Cox-stained VTA dendrites. Since the GABAergic drugs are known to depress the brain metabolism and gene expression, their likely way of inducing neuroplasticity in mature neurons is by disinhibiting the principal neurons, which remains to be rigorously tested for a number of clinically important anxiolytics, sedatives and anesthetics in different parts of

  17. Spike timing precision of neuronal circuits.

    Science.gov (United States)

    Kilinc, Deniz; Demir, Alper

    2018-04-17

    Spike timing is believed to be a key factor in sensory information encoding and computations performed by the neurons and neuronal circuits. However, the considerable noise and variability, arising from the inherently stochastic mechanisms that exist in the neurons and the synapses, degrade spike timing precision. Computational modeling can help decipher the mechanisms utilized by the neuronal circuits in order to regulate timing precision. In this paper, we utilize semi-analytical techniques, which were adapted from previously developed methods for electronic circuits, for the stochastic characterization of neuronal circuits. These techniques, which are orders of magnitude faster than traditional Monte Carlo type simulations, can be used to directly compute the spike timing jitter variance, power spectral densities, correlation functions, and other stochastic characterizations of neuronal circuit operation. We consider three distinct neuronal circuit motifs: Feedback inhibition, synaptic integration, and synaptic coupling. First, we show that both the spike timing precision and the energy efficiency of a spiking neuron are improved with feedback inhibition. We unveil the underlying mechanism through which this is achieved. Then, we demonstrate that a neuron can improve on the timing precision of its synaptic inputs, coming from multiple sources, via synaptic integration: The phase of the output spikes of the integrator neuron has the same variance as that of the sample average of the phases of its inputs. Finally, we reveal that weak synaptic coupling among neurons, in a fully connected network, enables them to behave like a single neuron with a larger membrane area, resulting in an improvement in the timing precision through cooperation.

  18. Neurons from the adult human dentate nucleus: neural networks in the neuron classification.

    Science.gov (United States)

    Grbatinić, Ivan; Marić, Dušica L; Milošević, Nebojša T

    2015-04-07

    Topological (central vs. border neuron type) and morphological classification of adult human dentate nucleus neurons according to their quantified histomorphological properties using neural networks on real and virtual neuron samples. In the real sample 53.1% and 14.1% of central and border neurons, respectively, are classified correctly with total of 32.8% of misclassified neurons. The most important result present 62.2% of misclassified neurons in border neurons group which is even greater than number of correctly classified neurons (37.8%) in that group, showing obvious failure of network to classify neurons correctly based on computational parameters used in our study. On the virtual sample 97.3% of misclassified neurons in border neurons group which is much greater than number of correctly classified neurons (2.7%) in that group, again confirms obvious failure of network to classify neurons correctly. Statistical analysis shows that there is no statistically significant difference in between central and border neurons for each measured parameter (p>0.05). Total of 96.74% neurons are morphologically classified correctly by neural networks and each one belongs to one of the four histomorphological types: (a) neurons with small soma and short dendrites, (b) neurons with small soma and long dendrites, (c) neuron with large soma and short dendrites, (d) neurons with large soma and long dendrites. Statistical analysis supports these results (pneurons can be classified in four neuron types according to their quantitative histomorphological properties. These neuron types consist of two neuron sets, small and large ones with respect to their perykarions with subtypes differing in dendrite length i.e. neurons with short vs. long dendrites. Besides confirmation of neuron classification on small and large ones, already shown in literature, we found two new subtypes i.e. neurons with small soma and long dendrites and with large soma and short dendrites. These neurons are

  19. Alteration of the cell adhesion molecule L1 expression in a specific subset of primary afferent neurons contributes to neuropathic pain.

    Science.gov (United States)

    Yamanaka, Hiroki; Obata, Koichi; Kobayashi, Kimiko; Dai, Yi; Fukuoka, Tetsuo; Noguchi, Koichi

    2007-02-01

    The cell adhesion molecule L1 (L1-CAM) plays important functional roles in the developing and adult nervous systems. Here we show that peripheral nerve injury induced dynamic post-transcriptional alteration of L1-CAM in the rat dorsal root ganglia (DRGs) and spinal cord. Sciatic nerve transection (SCNT) changed the expression of L1-CAM protein but not L1-CAM mRNA. In DRGs, SCNT induced accumulation of the L1-CAM into the surface of somata, which resulted in the formation of immunoreactive ring structures in a number of unmyelinated C-fiber neurons. These neurons with L1-CAM-immunoreactive ring structures were heavily colocalized with phosphorylated p38 MAPK. Western blot analysis revealed the increase of full-length L1-CAM and decrease of fragments of L1-CAM after SCNT in DRGs. Following SCNT, L1-CAM-immunoreactive profiles in the dorsal horn showed an increase mainly in pre-synaptic areas of laminae I-II with a delayed onset and colocalized with growth-associated protein 43. In contrast to DRGs, SCNT increased the proteolytic 80-kDa fragment of L1-CAM and decreased full-length L1-CAM in the spinal cord. The intrathecal injection of L1-CAM antibody for the extracellular domain of L1-CAM inhibited activation of p38 MAPK and emergence of ring structures of L1-CAM immunoreactivity in injured DRG neurons. Moreover, inhibition of extracellular L1-CAM binding by intrathecal administration of antibody suppressed the mechanical allodynia and thermal hyperalgesia induced by partial SCNT. Collectively, these data suggest that the modification of L1-CAM in nociceptive pathways might be an important pathomechanism of neuropathic pain.

  20. Phosphorylation of ERK in neurokinin 1 receptor-expressing neurons in laminae III and IV of the rat spinal dorsal horn following noxious stimulation

    Directory of Open Access Journals (Sweden)

    Watanabe Masahiko

    2007-02-01

    Full Text Available Abstract Background There is a population of large neurons with cell bodies in laminae III and IV of the spinal dorsal horn which express the neurokinin 1 receptor (NK1r and have dendrites that enter the superficial laminae. Although it has been shown that these are all projection neurons and that they are innervated by substance P-containing (nociceptive primary afferents, we know little about their responses to noxious stimuli. In this study we have looked for phosphorylation of extracellular signal-regulated kinases (ERKs in these neurons in response to different types of noxious stimulus applied to one hindlimb of anaesthetised rats. The stimuli were mechanical (repeated pinching, thermal (immersion in water at 52°C or chemical (injection of 2% formaldehyde. Results Five minutes after each type of stimulus we observed numerous cells with phosphorylated ERK (pERK in laminae I and IIo, together with scattered positive cells in deeper laminae. We found that virtually all of the lamina III/IV NK1r-immunoreactive neurons contained pERK after each of these stimuli and that in the great majority of cases there was internalisation of the NK1r on the dorsal dendrites of these cells. In addition, we also saw neurons in lamina III that were pERK-positive but lacked the NK1r, and these were particularly evident in animals that had had the pinch stimulus. Conclusion Our results demonstrate that lamina III/IV NK1r-immunoreactive neurons show receptor internalisation and ERK phosphorylation after mechanical, thermal or chemical noxious stimuli.

  1. Acid-sensing ion channels (ASICs) in mouse skeletal muscle afferents are heteromers composed of ASIC1a, ASIC2, and ASIC3 subunits

    OpenAIRE

    Gautam, Mamta; Benson, Christopher J.

    2013-01-01

    Acid-sensing ion channels (ASICs) are expressed in skeletal muscle afferents, in which they sense extracellular acidosis and other metabolites released during ischemia and exercise. ASICs are formed as homotrimers or heterotrimers of several isoforms (ASIC1a, ASIC1b, ASIC2a, ASIC2b, and ASIC3), with each channel displaying distinct properties. To dissect the ASIC composition in muscle afferents, we used whole-cell patch-clamp recordings to study the properties of acid-evoked currents (amplitu...

  2. Pooling and correlated neural activity

    Directory of Open Access Journals (Sweden)

    Robert Rosenbaum

    2010-04-01

    Full Text Available Correlations between spike trains can strongly modulate neuronal activity and affect the ability of neurons to encode information. Neurons integrate inputs from thousands of afferents. Similarly, a number of experimental techniques are designed to record pooled cell activity. We review and generalize a number of previous results that show how correlations between cells in a population can be amplified and distorted in signals that reflect their collective activity. The structure of the underlying neuronal response can significantly impact correlations between such pooled signals. Therefore care needs to be taken when interpreting pooled recordings, or modeling networks of cells that receive inputs from large presynaptic populations. We also show that the frequently observed runaway synchrony in feedforward chains is primarily due to the pooling of correlated inputs.

  3. The nature of catecholamine-containing neurons in the enteric nervous system in relationship with organogenesis, normal human anatomy and neurodegeneration.

    Science.gov (United States)

    Natale, G; Ryskalin, L; Busceti, C L; Biagioni, F; Fornai, F

    2017-09-01

    The gastrointestinal tract is provided with extrinsic and intrinsic innervation. The extrinsic innervation includes the classic vagal parasympathetic and sympathetic components, with afferent sensitive and efferent secretomotor fibers. The intrinsic innervations is represented by the enteric nervous system (ENS), which is recognized as a complex neural network controlling a variety of cell populations, including smooth muscle cells, mucosal secretory cells, endocrine cells, microvasculature, immune and inflammatory cells. This is finalized to regulate gastrointestinal secretion, absorption and motility. In particular, this network is organized in several plexuses each one providing quite autonomous control of gastrointestinal functions (hence the definition of "second brain"). The similarity between ENS and CNS is further substantiated by the presence of local sensitive pseudo- unipolar ganglionic neurons with both peripheral and central branching which terminate in the enteric wall. A large variety of neurons and neurotransmitters takes part in the ENS. However, the nature of these neurons and their role in the regulation of gastrointestinal functions is debatable. In particular, the available literature reporting the specific nature of catecholamine- containing neurons provides conflicting evidence. This is critical both for understanding the specific role of each catecholamine in the gut and, mostly, to characterize specifically the enteric neuropathology occurring in a variety of diseases. An emphasis is posed on neurodegenerative disorders, such as Parkinson's disease, which is associated with the loss of catecholamine neurons. In this respect, the recognition of the nature of such neurons within the ENS would contribute to elucidate the pathological mechanisms which produce both CNS and ENS degeneration and to achieve more effective therapeutic approaches. Despite a great emphasis is posed on the role of noradrenaline to regulate enteric activities only a few

  4. Orofacial neuropathic pain induced by oxaliplatin: downregulation of KCNQ2 channels in V2 trigeminal ganglion neurons and treatment by the KCNQ2 channel potentiator retigabine.

    Science.gov (United States)

    Ling, Jennifer; Erol, Ferhat; Viatchenko-Karpinski, Viacheslav; Kanda, Hirosato; Gu, Jianguo G

    2017-01-01

    Neuropathic pain induced by chemotherapy drugs such as oxaliplatin is a dose-limiting side effect in cancer treatment. The mechanisms underlying chemotherapy-induced neuropathic pain are not fully understood. KCNQ2 channels are low-threshold voltage-gated K+ channels that play a role in controlling neuronal excitability. Downregulation of KCNQ2 channels has been proposed to be an underlying mechanism of sensory hypersensitivity that leads to neuropathic pain. However, it is currently unknown whether KCNQ channels may be downregulated by chemotherapy drugs in trigeminal ganglion neurons to contribute to the pathogenesis of chemotherapy-induced orofacial neuropathic pain. In the present study, mechanical sensitivity in orofacial regions is measured using the operant behavioral test in rats treated with oxaliplatin. Operant behaviors in these animals show the gradual development of orofacial neuropathic pain that manifests with orofacial mechanical allodynia. Immunostaining shows strong KCNQ2 immunoreactivity in small-sized V2 trigeminal ganglion neurons in controls, and the numbers of KCNQ2 immunoreactivity positive V2 trigeminal ganglion neurons are significantly reduced in oxaliplatin-treated animals. Immunostaining is also performed in brainstem and shows strong KCNQ2 immunoreactivity at the trigeminal afferent central terminals innervating the caudal spinal trigeminal nucleus (Vc) in controls, but the KCNQ2 immunoreactivity intensity is significantly reduced in oxaliplatin-treated animals. We further show with the operant behavioral test that oxaliplatin-induced orofacial mechanical allodynia can be alleviated by the KCNQ2 potentiator retigabine. Taken together, these findings suggest that KCNQ2 downregulation may be a cause of oxaliplatin-induced orofacial neuropathic pain and KCNQ2 potentiators may be useful for alleviating the neuropathic pain.

  5. NBLAST: Rapid, Sensitive Comparison of Neuronal Structure and Construction of Neuron Family Databases.

    Science.gov (United States)

    Costa, Marta; Manton, James D; Ostrovsky, Aaron D; Prohaska, Steffen; Jefferis, Gregory S X E

    2016-07-20

    Neural circuit mapping is generating datasets of tens of thousands of labeled neurons. New computational tools are needed to search and organize these data. We present NBLAST, a sensitive and rapid algorithm, for measuring pairwise neuronal similarity. NBLAST considers both position and local geometry, decomposing neurons into short segments; matched segments are scored using a probabilistic scoring matrix defined by statistics of matches and non-matches. We validated NBLAST on a published dataset of 16,129 single Drosophila neurons. NBLAST can distinguish neuronal types down to the finest level (single identified neurons) without a priori information. Cluster analysis of extensively studied neuronal classes identified new types and unreported topographical features. Fully automated clustering organized the validation dataset into 1,052 clusters, many of which map onto previously described neuronal types. NBLAST supports additional query types, including searching neurons against transgene expression patterns. Finally, we show that NBLAST is effective with data from other invertebrates and zebrafish. VIDEO ABSTRACT. Copyright © 2016 MRC Laboratory of Molecular Biology. Published by Elsevier Inc. All rights reserved.

  6. Extracellular adenosine 5'-triphosphate concentrations changes in rat spinal cord associated with the activation of urinary bladder afferents. A microdialysis study.

    Science.gov (United States)

    Rocha, Jeová Nina

    2016-01-01

    To determine adenosine 5'-triphosphate levels in the interstice of spinal cord L6-S1 segment, under basal conditions or during mechanical and chemical activation of urinary bladder afferents. A microdialysis probe was transversally implanted in the dorsal half of spinal cord L6-S1 segment in female rats. Microdialysate was collected at 15 minutes intervals during 135 minutes, in anesthetized animals. Adenosine 5'-triphosphate concentrations were determined with a bioluminescent assay. In one group of animals (n=7) microdialysate samples were obtained with an empty bladder during a 10-minutes bladder distension to 20 or 40cmH2O with either saline, saline with acetic acid or saline with capsaicin. In another group of animals (n=6) bladder distention was performed and the microdialysis solution contained the ectonucleotidase inhibitor ARL 67156. Basal extracellular adenosine triphosphate levels were 110.9±35.34fmol/15 minutes, (mean±SEM, n=13), and bladder distention was associated with a significant increase in adenosine 5'-triphosphate levels which was not observed after bladder distention with saline solution containing capsaicin (10µM). Microdialysis with solution containing ARL 67156 (1mM) was associated with significantly higher extracellular adenosine 5'-triphosphate levels and no further increase in adenosine 5'-triphosphate was observed during bladder distension. Adenosine 5'-triphosphate was present in the interstice of L6-S1 spinal cord segments, was degraded by ectonucleotidase, and its concentration increased following the activation of bladder mechanosensitive but not of the chemosensitive afferents fibers. Adenosine 5'-triphosphate may originate either from the central endings of bladder mechanosensitive primary afferent neurons, or most likely from intrinsic spinal neurons, or glial cells and its release appears to be modulated by capsaicin activated bladder primary afferent or by adenosine 5'-triphosphate itself. Determinar as concentra

  7. Thrombospondins 1 and 2 are important for afferent synapse formation and function in the inner ear.

    Science.gov (United States)

    Mendus, Diana; Sundaresan, Srividya; Grillet, Nicolas; Wangsawihardja, Felix; Leu, Rose; Müller, Ulrich; Jones, Sherri M; Mustapha, Mirna

    2014-04-01

    Thrombospondins (TSPs) constitute a family of secreted extracellular matrix proteins that have been shown to be involved in the formation of synapses in the central nervous system. In this study, we show that TSP1 and TSP2 are expressed in the cochlea, and offer the first description of their putative roles in afferent synapse development and function in the inner ear. We examined mice with deletions of TSP1, TSP2 and both (TSP1/TSP2) for inner ear development and function. Immunostaining for synaptic markers indicated a significant decrease in the number of formed afferent synapses in the cochleae of TSP2 and TSP1/TSP2 knockout (KO) mice at postnatal day (P)29. In functional studies, TSP2 and TSP1/TSP2 KO mice showed elevated auditory brainstem response (ABR) thresholds as compared with wild-type littermates, starting at P15, with the most severe phenotype being seen for TSP1/TSP2 KO mice. TSP1/TSP2 KO mice also showed reduced wave I amplitudes of ABRs and vestibular evoked potentials, suggesting synaptic dysfunction in both the auditory and vestibular systems. Whereas ABR thresholds in TSP1 KO mice were relatively unaffected at early ages, TSP1/TSP2 KO mice showed the most severe phenotype among all of the genotypes tested, suggesting functional redundancy between the two genes. On the basis of the above results, we propose that TSPs play an important role in afferent synapse development and function of the inner ear. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  8. Different corticostriatal integration in spiny projection neurons from direct and indirect pathways

    Directory of Open Access Journals (Sweden)

    Edén Flores-Barrera

    2010-06-01

    Full Text Available The striatum is the principal input structure of the basal ganglia (BG. Major glutamatergic afferents to the striatum come from the cerebral cortex and make monosynaptic contacts with medium spiny projection neurons (MSNs and interneurons. Despite differences in axonal projections, dopamine receptors expression and differences in excitability between MSNs from “direct” and “indirect” BG pathways, these neuronal classes have been thought as electrophysiologically very similar. Based on work with BAC transgenic mice, here it is shown that corticostriatal responses in D1- and D2-receptor expressing MSNs (D1- and D2-MSNs are radically different so as to establish an electrophysiological footprint that readily differentiates between them. Experiments in BAC mice allowed us to predict, with high probability (P>0.9, in rats or non-BAC mice, whether a recorded neuron, from rat or mouse, was going to be substance P or enkephalin immunoreactive. Responses are more prolonged and evoke more action potentials in D1-MSNs, while they are briefer and exhibit intrinsic autoregenerative responses in D2-MSNs. A main cause for these differences was the interaction of intrinsic properties with the inhibitory contribution in each response Inhibition always depressed corticostriatal depolarization in D2-MSNs, while it helped in sustaining prolonged depolarizations in D1-MSNs, in spite of depressing early discharge. Corticostriatal responses changed dramatically after striatal DA-depletion in 6-hydroxy-dopamine (6-OHDA lesioned animals: a response reduction was seen in SP+ MSNs whereas an enhanced response was seen in ENK+ MSNs. The end result was that differences in the responses were greatly diminished after DA depletion.

  9. NMClab, a model to assess the contributions of muscle visco-elasticity and afferent feedback to joint dynamics

    NARCIS (Netherlands)

    Schouten, Alfred Christiaan; Mugge, Winfred; van der Helm, F.C.T.

    2008-01-01

    The dynamic behavior of a neuromusculoskeletal system results from the complex mechanical interaction between muscle visco-elasticity resulting from (co-)contraction and afferent feedback from muscle spindles and Golgi tendon organs. As a result of the multiple interactions the individual effect of

  10. Bilateral sensory deprivation of trigeminal afferent fibers on corticomotor control of human tongue musculature: A preliminary study

    DEFF Research Database (Denmark)

    Kothari, Mohit; Baad-Hansen, Lene; Svensson, Peter

    2016-01-01

    Background: Transcranial magnetic stimulation (TMS) has demonstrated changes in motor evoked potentials (MEPs) in human limb muscles following modulation of sensory afferent inputs. Objective: The aim of the present study was to determine whether bilateral local anaesthesia (LA) of the lingual ne...

  11. Neurosteroid modulation of neuronal excitability and synaptic transmission in the rat medial vestibular nuclei.

    Science.gov (United States)

    Grassi, Silvarosa; Frondaroli, Adele; Dieni, Cristina; Dutia, Mayank B; Pettorossi, Vito E

    2007-07-01

    In rat brainstem slices, we investigated the influence of the neurosteroids tetrahydrodeoxycorticosterone (THDOC) and allopregnanolone (ALLO) on the synaptically driven and spontaneous activity of vestibular neurons, by analysing their effects on the amplitude of the field potentials evoked in the medial vestibular nuclei (MVN) by vestibular afferent stimulation and on the spontaneous firing rate of MVN neurons. Furthermore, the interaction with gamma-aminobutyric acid (GABA) and glutamate receptors was analysed by using specific antagonists for GABA(A) (bicuculline), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/ kainate [2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo(f)quinoxaline-7-sulphonamide disodium salt (NBQX)], N-methyl-D-aspartate (NMDA) [D-(-)-2-amino-5-phosphonopentanoic acid (AP-5)] and group I metabotropic glutamate receptors (mGlu-I) [(R,S)-1-aminoindan-1,5-dicarboxylic acid (AIDA)] receptors. THDOC and ALLO evoked two opposite long-lasting effects, consisting of either a potentiation or a reduction of field potential and firing rate, which showed early and late components, occurring in conjunction or separately after neurosteroid application. The depressions depended on GABA(A) receptors, as they were abolished by bicuculline, while early potentiation involved glutamate AMPA/kainate receptors, as NBQX markedly reduced the incidence of early firing rate enhancement and, in the case of ALLO, even provoked depression. This suggests that THDOC and ALLO enhance the GABA(A) inhibitory influence on the MVN neurons and facilitate the AMPA/kainate facilitatory one. Conversely, a late potentiation effect, which was still induced after glutamate and GABA(A) receptor blockade, might involve a different mechanism. We conclude that the modulation of neuronal activity in the MVN by THDOC and ALLO, through their actions on GABA(A) and AMPA/kainate receptors, may have a physiological role in regulating the vestibular system function under normal

  12. The effect of type of afferent feedback timed with motor imagery on the induction of cortical plasticity

    DEFF Research Database (Denmark)

    Mrachacz-Kersting, Natalie; Voigt, Michael; Stevenson, Andrew James Thomas

    2017-01-01

    : 8-35 mAmp) or a passive ankle movement (amplitude and velocity matched to a normal gait cycle) was applied such that the first afferent inflow would coincide with the PN of the MRCP. The change in the output of the primary motor cortex (M1) was quantified by applying single transcranial magnetic...... compared these two interventions (BCIFES and BCIpassive) where the afferent input was timed to arrive at the motor cortex during the PN of the MRCP. Twelve healthy participants attended two experimental sessions. They were asked to perform 30 dorsiflexion movements timed to a cue while continuous...... stimuli to the area of M1 controlling the tibialis anterior (TA) muscle and measuring the motor evoked potential (MEP). Spinal changes were assessed pre and post by eliciting the TA stretch reflex. Both BCIFES and BCIpassive led to significant increases in the excitability of the cortical projections...

  13. Activity patterns of cochlear ganglion neurones in the starling.

    Science.gov (United States)

    Manley, G A; Gleich, O; Leppelsack, H J; Oeckinghaus, H

    1985-09-01

    Spontaneous activity and responses to simple tonal stimuli were studied in cochlear ganglion neurones of the starling. Both regular and irregular spontaneous activity were recorded. Non-auditory cells have their origin in the macula lagenae. Mean spontaneous rate for auditory cells (all irregularly spiking) was 45 spikes s-1. In half the units having characteristic frequencies (CFs) less than 1.5 kHz, time-interval histograms (TIHs) of spontaneous activity showed regularly-spaced peaks or 'preferred' intervals. The spacing of the peak intervals was, on average, 15% greater than the CF-period interval of the respective units. In TIH of lower-frequency cells without preferred intervals, the modal interval was also on average about 15% longer than the CF-period interval. Apparently, the resting oscillation frequency of these cells lies below their CF. Tuning curves (TCs) of neurones to short tone bursts show no systematic asymmetry as in mammals. Below CF 1 kHz, the low-frequency flanks of the TCs are, on average, steeper than the high-frequency flanks. Above CF 1 kHz, the reverse is true. The cochlear ganglion and nerve are tonotopically organized. Low-frequency fibres arise apically in the papilla basilaris and are found near non-auditory (lagenar) fibres. Discharge rates to short tones were monotonically related to sound pressure level. Saturation rates often exceeded 300 spikes s-1. 'On-off' responses and primary suppression of spontaneous activity were observed. A direct comparison of spontaneous activity and tuning-curve symmetry revealed that, apart from quantitative differences, fundamental qualitative differences exist between starling and guinea-pig primary afferents.

  14. Cerebellar Nuclear Neurons Use Time and Rate Coding to Transmit Purkinje Neuron Pauses.

    Science.gov (United States)

    Sudhakar, Shyam Kumar; Torben-Nielsen, Benjamin; De Schutter, Erik

    2015-12-01

    Neurons of the cerebellar nuclei convey the final output of the cerebellum to their targets in various parts of the brain. Within the cerebellum their direct upstream connections originate from inhibitory Purkinje neurons. Purkinje neurons have a complex firing pattern of regular spikes interrupted by intermittent pauses of variable length. How can the cerebellar nucleus process this complex input pattern? In this modeling study, we investigate different forms of Purkinje neuron simple spike pause synchrony and its influence on candidate coding strategies in the cerebellar nuclei. That is, we investigate how different alignments of synchronous pauses in synthetic Purkinje neuron spike trains affect either time-locking or rate-changes in the downstream nuclei. We find that Purkinje neuron synchrony is mainly represented by changes in the firing rate of cerebellar nuclei neurons. Pause beginning synchronization produced a unique effect on nuclei neuron firing, while the effect of pause ending and pause overlapping synchronization could not be distinguished from each other. Pause beginning synchronization produced better time-locking of nuclear neurons for short length pauses. We also characterize the effect of pause length and spike jitter on the nuclear neuron firing. Additionally, we find that the rate of rebound responses in nuclear neurons after a synchronous pause is controlled by the firing rate of Purkinje neurons preceding it.

  15. Cerebellar Nuclear Neurons Use Time and Rate Coding to Transmit Purkinje Neuron Pauses

    Science.gov (United States)

    Sudhakar, Shyam Kumar; Torben-Nielsen, Benjamin; De Schutter, Erik

    2015-01-01

    Neurons of the cerebellar nuclei convey the final output of the cerebellum to their targets in various parts of the brain. Within the cerebellum their direct upstream connections originate from inhibitory Purkinje neurons. Purkinje neurons have a complex firing pattern of regular spikes interrupted by intermittent pauses of variable length. How can the cerebellar nucleus process this complex input pattern? In this modeling study, we investigate different forms of Purkinje neuron simple spike pause synchrony and its influence on candidate coding strategies in the cerebellar nuclei. That is, we investigate how different alignments of synchronous pauses in synthetic Purkinje neuron spike trains affect either time-locking or rate-changes in the downstream nuclei. We find that Purkinje neuron synchrony is mainly represented by changes in the firing rate of cerebellar nuclei neurons. Pause beginning synchronization produced a unique effect on nuclei neuron firing, while the effect of pause ending and pause overlapping synchronization could not be distinguished from each other. Pause beginning synchronization produced better time-locking of nuclear neurons for short length pauses. We also characterize the effect of pause length and spike jitter on the nuclear neuron firing. Additionally, we find that the rate of rebound responses in nuclear neurons after a synchronous pause is controlled by the firing rate of Purkinje neurons preceding it. PMID:26630202

  16. Oncostatin M induces heat hypersensitivity by gp130-dependent sensitization of TRPV1 in sensory neurons

    Directory of Open Access Journals (Sweden)

    Langeslag Michiel

    2011-12-01

    Full Text Available Abstract Oncostatin M (OSM is a member of the interleukin-6 cytokine family and regulates eg. gene activation, cell survival, proliferation and differentiation. OSM binds to a receptor complex consisting of the ubiquitously expressed signal transducer gp130 and the ligand binding OSM receptor subunit, which is expressed on a specific subset of primary afferent neurons. In the present study, the effect of OSM on heat nociception was investigated in nociceptor-specific gp130 knock-out (SNS-gp130-/- and gp130 floxed (gp130fl/fl mice. Subcutaneous injection of pathophysiologically relevant concentrations of OSM into the hind-paw of C57BL6J wild type mice significantly reduced paw withdrawal latencies to heat stimulation. In contrast to gp130fl/fl mice, OSM did not induce heat hypersensitivity in vivo in SNS-gp130-/- mice. OSM applied at the receptive fields of sensory neurons in in vitro skin-nerve preparations showed that OSM significantly increased the discharge rate during a standard ramp-shaped heat stimulus. The capsaicin- and heat-sensitive ion channel TRPV1, expressed on a subpopulation of nociceptive neurons, has been shown to play an important role in inflammation-induced heat hypersensitivity. Stimulation of cultured dorsal root ganglion neurons with OSM resulted in potentiation of capsaicin induced ionic currents. In line with these recordings, mice with a null mutation of the TRPV1 gene did not show any signs of OSM-induced heat hypersensitivity in vivo. The present data suggest that OSM induces thermal hypersensitivity by directly sensitizing nociceptors via OSMR-gp130 receptor mediated potentiation of TRPV1.

  17. Spike Timing Matters in Novel Neuronal Code Involved in Vibrotactile Frequency Perception.

    Science.gov (United States)

    Birznieks, Ingvars; Vickery, Richard M

    2017-05-22

    Skin vibrations sensed by tactile receptors contribute significantly to the perception of object properties during tactile exploration [1-4] and to sensorimotor control during object manipulation [5]. Sustained low-frequency skin vibration (perception of frequency is still unknown. Measures based on mean spike rates of neurons in the primary somatosensory cortex are sufficient to explain performance in some frequency discrimination tasks [7-11]; however, there is emerging evidence that stimuli can be distinguished based also on temporal features of neural activity [12, 13]. Our study's advance is to demonstrate that temporal features are fundamental for vibrotactile frequency perception. Pulsatile mechanical stimuli were used to elicit specified temporal spike train patterns in tactile afferents, and subsequently psychophysical methods were employed to characterize human frequency perception. Remarkably, the most salient temporal feature determining vibrotactile frequency was not the underlying periodicity but, rather, the duration of the silent gap between successive bursts of neural activity. This burst gap code for frequency represents a previously unknown form of neural coding in the tactile sensory system, which parallels auditory pitch perception mechanisms based on purely temporal information where longer inter-pulse intervals receive higher perceptual weights than short intervals [14]. Our study also demonstrates that human perception of stimuli can be determined exclusively by temporal features of spike trains independent of the mean spike rate and without contribution from population response factors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. A novel perspective on neuron study: damaging and promoting effects in different neurons induced by mechanical stress.

    Science.gov (United States)

    Wang, Yazhou; Wang, Wei; Li, Zong; Hao, Shilei; Wang, Bochu

    2016-10-01

    A growing volume of experimental evidence demonstrates that mechanical stress plays a significant role in growth, proliferation, apoptosis, gene expression, electrophysiological properties and many other aspects of neurons. In this review, first, the mechanical microenvironment and properties of neurons under in vivo conditions are introduced and analyzed. Second, research works in recent decades on the effects of different mechanical forces, especially compression and tension, on various neurons, including dorsal root ganglion neurons, retinal ganglion cells, cerebral cortex neurons, hippocampus neurons, neural stem cells, and other neurons, are summarized. Previous research results demonstrate that mechanical stress can not only injure neurons by damaging their morphology, impacting their electrophysiological characteristics and gene expression, but also promote neuron self-repair. Finally, some future perspectives in neuron research are discussed.

  19. Capsaicin-sensitive muscle afferents modulate the monosynaptic reflex in response to muscle ischemia and fatigue in the rat.

    Science.gov (United States)

    Della Torre, G; Brunetti, O; Pettorossi, V E

    2002-01-01

    The role of muscle ischemia and fatigue in modulating the monosynaptic reflex was investigated in decerebrate and spinalized rats. Field potentials and fast motoneuron single units in the lateral gastrocnemious (LG) motor pool were evoked by dorsal root stimulation. Muscle ischemia was induced by occluding the LG vascular supply and muscle fatigue by prolonged tetanic electrical stimulation of the LG motor nerve. Under muscle ischemia the monosynaptic reflex was facilitated since the size of the early and late waves of the field potential and the excitability of the motoneuron units increased. This effect was abolished after L3-L6 dorsal rhizotomy, but it was unaffected after L3-L6 ventral rhizotomy. By contrast, the monosynaptic reflex was inhibited by muscle fatiguing stimulation, and this effect did not fully depend on the integrity of the dorsal root. However, when ischemia was combined with repetitive tetanic muscle stimulation the inhibitory effect of fatigue was significantly enhanced. Both the ischemia and fatigue effects were abolished by capsaicin injected into the LG muscle at a dose that blocked a large number of group III and IV muscle afferents. We concluded that muscle ischemia and fatigue activate different groups of muscle afferents that are both sensitive to capsaicin, but enter the spinal cord through different roots. They are responsible for opposite effects, when given separately: facilitation during ischemia and inhibition during fatigue; however, in combination, ischemia enhances the responsiveness of the afferent fibres to fatigue.

  20. Ex vivo dissection of optogenetically activated mPFC and hippocampal inputs to neurons in the basolateral amygdala: implications for fear and emotional memory

    Directory of Open Access Journals (Sweden)

    Cora eHübner

    2014-03-01

    Full Text Available Many lines of evidence suggest that a reciprocally interconnected network comprising the amygdala, ventral hippocampus (vHC, and medial prefrontal cortex (mPFC participates in different aspects of the acquisition and extinction of conditioned fear responses and fear behavior. This could at least in part be mediated by direct connections from mPFC or vHC to amygdala to control amygdala activity and output. However, currently the interactions between mPFC and vHC afferents and their specific targets in the amygdala are still poorly understood. Here, we use an ex-vivo optogenetic approach to dissect synaptic properties of inputs from mPFC and vHC to defined neuronal populations in the basal amygdala (BA, the area that we identify as a major target of these projections. We find that BA principal neurons (PNs and local BA interneurons (INs receive monosynaptic excitatory inputs from mPFC and vHC. In addition, both these inputs also recruit GABAergic feedforward inhibition in a substantial fraction of PNs, in some neurons this also comprises a slow GABAB-component. Amongst the innervated PNs we identify neurons that project back to subregions of the mPFC, indicating a loop between neurons in mPFC and BA, and a pathway from vHC to mPFC via BA. Interestingly, mPFC inputs also recruit feedforward inhibition in a fraction of INs, suggesting that these inputs can activate dis-inhibitory circuits in the BA. A general feature of both mPFC and vHC inputs to local INs is that excitatory inputs display faster rise and decay kinetics than in PNs, which would enable temporally precise signaling. However, mPFC and vHC inputs to both PNs and INs differ in their presynaptic release properties, in that vHC inputs are more depressing. In summary, our data describe novel wiring, and features of synaptic connections from mPFC and vHC to amygdala that could help to interpret functions of these interconnected brain areas at the network level.

  1. Ex vivo dissection of optogenetically activated mPFC and hippocampal inputs to neurons in the basolateral amygdala: implications for fear and emotional memory

    Science.gov (United States)

    Hübner, Cora; Bosch, Daniel; Gall, Andrea; Lüthi, Andreas; Ehrlich, Ingrid

    2014-01-01

    Many lines of evidence suggest that a reciprocally interconnected network comprising the amygdala, ventral hippocampus (vHC), and medial prefrontal cortex (mPFC) participates in different aspects of the acquisition and extinction of conditioned fear responses and fear behavior. This could at least in part be mediated by direct connections from mPFC or vHC to amygdala to control amygdala activity and output. However, currently the interactions between mPFC and vHC afferents and their specific targets in the amygdala are still poorly understood. Here, we use an ex-vivo optogenetic approach to dissect synaptic properties of inputs from mPFC and vHC to defined neuronal populations in the basal amygdala (BA), the area that we identify as a major target of these projections. We find that BA principal neurons (PNs) and local BA interneurons (INs) receive monosynaptic excitatory inputs from mPFC and vHC. In addition, both these inputs also recruit GABAergic feedforward inhibition in a substantial fraction of PNs, in some neurons this also comprises a slow GABAB-component. Amongst the innervated PNs we identify neurons that project back to subregions of the mPFC, indicating a loop between neurons in mPFC and BA, and a pathway from vHC to mPFC via BA. Interestingly, mPFC inputs also recruit feedforward inhibition in a fraction of INs, suggesting that these inputs can activate dis-inhibitory circuits in the BA. A general feature of both mPFC and vHC inputs to local INs is that excitatory inputs display faster rise and decay kinetics than in PNs, which would enable temporally precise signaling. However, mPFC and vHC inputs to both PNs and INs differ in their presynaptic release properties, in that vHC inputs are more depressing. In summary, our data describe novel wiring, and features of synaptic connections from mPFC and vHC to amygdala that could help to interpret functions of these interconnected brain areas at the network level. PMID:24634648

  2. Neuron-to-neuron transmission of α-synuclein fibrils through axonal transport

    Science.gov (United States)

    Freundt, Eric C.; Maynard, Nate; Clancy, Eileen K.; Roy, Shyamali; Bousset, Luc; Sourigues, Yannick; Covert, Markus; Melki, Ronald; Kirkegaard, Karla; Brahic, Michel

    2012-01-01

    Objective The lesions of Parkinson's disease spread through the brain in a characteristic pattern that corresponds to axonal projections. Previous observations suggest that misfolded α-synuclein could behave as a prion, moving from neuron to neuron and causing endogenous α-synuclein to misfold. Here, we characterized and quantified the axonal transport of α-synuclein fibrils and showed that fibrils could be transferred from axons to second-order neurons following anterograde transport. Methods We grew primary cortical mouse neurons in microfluidic devices to separate soma from axonal projections in fluidically isolated microenvironments. We used live-cell imaging and immunofluorescence to characterize the transport of fluorescent α-synuclein fibrils and their transfer to second-order neurons. Results Fibrillar α-synuclein was internalized by primary neurons and transported in axons with kinetics consistent with slow component-b of axonal transport (fast axonal transport with saltatory movement). Fibrillar α-synuclein was readily observed in the cell bodies of second-order neurons following anterograde axonal transport. Axon-to-soma transfer appeared not to require synaptic contacts. Interpretation These results support the hypothesis that the progression of Parkinson's disease can be caused by neuron-to-neuron spread of α-synuclein aggregates and that the anatomical pattern of progression of lesions between axonally connected areas results from the axonal transport of such aggregates. That the transfer did not appear to be transsynaptic gives hope that α-synuclein fibrils could be intercepted by drugs during the extra-cellular phase of their journey. PMID:23109146

  3. Ultrasonography as a tool to study afferent feedback from the muscle-tendon complex during human walking

    DEFF Research Database (Denmark)

    Cronin, Neil J.; Klint, Richard af; Grey, Michael James

    2011-01-01

    In humans, one of the most common tasks in everyday life is walking, and sensory afferent feedback from peripheral receptors, particularly the muscle spindles and Golgi tendon organs (GTO), makes an important contribution to the motor control of this task. One factor that can complicate the ability...... with an examination of muscle activation to give a broader insight to neuromuscular interaction during walking. Despite the advances in understanding that these techniques have brought, there is clearly still a need for more direct methods to study both neural and mechanical parameters during human walking in order...... of these receptors to act as length, velocity and force transducers is the complex pattern of interaction between muscle and tendinous tissues, as tendon length is often considerably greater than muscle fibre length in the human lower limb. In essence, changes in muscle-tendon mechanics can influence the firing...

  4. A simple parameter can switch between different weak-noise-induced phenomena in a simple neuron model

    Science.gov (United States)

    Yamakou, Marius E.; Jost, Jürgen

    2017-10-01

    In recent years, several, apparently quite different, weak-noise-induced resonance phenomena have been discovered. Here, we show that at least two of them, self-induced stochastic resonance (SISR) and inverse stochastic resonance (ISR), can be related by a simple parameter switch in one of the simplest models, the FitzHugh-Nagumo (FHN) neuron model. We consider a FHN model with a unique fixed point perturbed by synaptic noise. Depending on the stability of this fixed point and whether it is located to either the left or right of the fold point of the critical manifold, two distinct weak-noise-induced phenomena, either SISR or ISR, may emerge. SISR is more robust to parametric perturbations than ISR, and the coherent spike train generated by SISR is more robust than that generated deterministically. ISR also depends on the location of initial conditions and on the time-scale separation parameter of the model equation. Our results could also explain why real biological neurons having similar physiological features and synaptic inputs may encode very different information.

  5. Subcortical orientation biases explain orientation selectivity of visual cortical cells.

    Science.gov (United States)

    Vidyasagar, Trichur R; Jayakumar, Jaikishan; Lloyd, Errol; Levichkina, Ekaterina V

    2015-04-01

    The primary visual cortex of carnivores and primates shows an orderly progression of domains of neurons that are selective to a particular orientation of visual stimuli such as bars and gratings. We recorded from single-thalamic afferent fibers that terminate in these domains to address the issue whether the orientation sensitivity of these fibers could form the basis of the remarkable orientation selectivity exhibited by most cortical cells. We first performed optical imaging of intrinsic signals to obtain a map of orientation domains on the dorsal aspect of the anaesthetized cat's area 17. After confirming using electrophysiological recordings the orientation preferences of single neurons within one or two domains in each animal, we pharmacologically silenced the cortex to leave only the afferent terminals active. The inactivation of cortical neurons was achieved by the superfusion of either kainic acid or muscimol. Responses of single geniculate afferents were then recorded by the use of high impedance electrodes. We found that the orientation preferences of the afferents matched closely with those of the cells in the orientation domains that they terminated in (Pearson's r = 0.633, n = 22, P = 0.002). This suggests a possible subcortical origin for cortical orientation selectivity. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  6. Striola magica. A functional explanation of otolith geometry.

    Science.gov (United States)

    Dimiccoli, Mariella; Girard, Benoît; Berthoz, Alain; Bennequin, Daniel

    2013-10-01

    Otolith end organs of vertebrates sense linear accelerations of the head and gravitation. The hair cells on their epithelia are responsible for transduction. In mammals, the striola, parallel to the line where hair cells reverse their polarization, is a narrow region centered on a curve with curvature and torsion. It has been shown that the striolar region is functionally different from the rest, being involved in a phasic vestibular pathway. We propose a mathematical and computational model that explains the necessity of this amazing geometry for the striola to be able to carry out its function. Our hypothesis, related to the biophysics of the hair cells and to the physiology of their afferent neurons, is that striolar afferents collect information from several type I hair cells to detect the jerk in a large domain of acceleration directions. This predicts a mean number of two calyces for afferent neurons, as measured in rodents. The domain of acceleration directions sensed by our striolar model is compatible with the experimental results obtained on monkeys considering all afferents. Therefore, the main result of our study is that phasic and tonic vestibular afferents cover the same geometrical fields, but at different dynamical and frequency domains.

  7. Estimation of the number of angiotensin II AT1 receptors in rat kidney afferent and efferent arterioles

    DEFF Research Database (Denmark)

    Razga, Zsolt; Nyengaard, Jens Randel

    2007-01-01

    of angiotensin II AT1 receptors along the length of the arterioles and per arteriole, we combined immunoelectron microscopy with stereology. RESULTS: The number of AT1 receptor molecules was significantly lower in the renin-positive smooth muscle cells (SMCs) than in the renin-negative SMCs of the afferent...

  8. Learning of time series through neuron-to-neuron instruction

    Energy Technology Data Exchange (ETDEWEB)

    Miyazaki, Y [Department of Physics, Kyoto University, Kyoto 606-8502, (Japan); Kinzel, W [Institut fuer Theoretische Physik, Universitaet Wurzburg, 97074 Wurzburg (Germany); Shinomoto, S [Department of Physics, Kyoto University, Kyoto (Japan)

    2003-02-07

    A model neuron with delayline feedback connections can learn a time series generated by another model neuron. It has been known that some student neurons that have completed such learning under the instruction of a teacher's quasi-periodic sequence mimic the teacher's time series over a long interval, even after instruction has ceased. We found that in addition to such faithful students, there are unfaithful students whose time series eventually diverge exponentially from that of the teacher. In order to understand the circumstances that allow for such a variety of students, the orbit dimension was estimated numerically. The quasi-periodic orbits in question were found to be confined in spaces with dimensions significantly smaller than that of the full phase space.

  9. Learning of time series through neuron-to-neuron instruction

    International Nuclear Information System (INIS)

    Miyazaki, Y; Kinzel, W; Shinomoto, S

    2003-01-01

    A model neuron with delayline feedback connections can learn a time series generated by another model neuron. It has been known that some student neurons that have completed such learning under the instruction of a teacher's quasi-periodic sequence mimic the teacher's time series over a long interval, even after instruction has ceased. We found that in addition to such faithful students, there are unfaithful students whose time series eventually diverge exponentially from that of the teacher. In order to understand the circumstances that allow for such a variety of students, the orbit dimension was estimated numerically. The quasi-periodic orbits in question were found to be confined in spaces with dimensions significantly smaller than that of the full phase space

  10. Presynaptic control of group Ia afferents in relation to acquisition of a visuo-motor skill in healthy humans

    DEFF Research Database (Denmark)

    Perez, Monica A.; Lungholt, Bjarke K.S.; Nielsen, Jens Bo

    2005-01-01

    Sensory information continuously converges on the spinal cord during a variety of motor behaviours. Here, we examined presynaptic control of group Ia afferents in relation to acquisition of a novel motor skill. We tested whether repetition of two motor tasks with different degrees of difficulty......, a novel visuo-motor task involving the ankle muscles, and a control task involving simple voluntary ankle movements, would induce changes in the size of the soleus H-reflex. The slope of the H-reflex recruitment curve and the H-max/M-max ratio were depressed after repetition of the visuo-motor skill task...... of the monosynaptic Ia facilitation of the soleus H-reflex evoked by femoral nerve stimulation. The D1 inhibition was increased and the femoral nerve facilitation was decreased following the visuo-motor skill task, suggesting an increase in presynaptic inhibition of Ia afferents. No changes were observed...

  11. Glycogen metabolism in brain and neurons - astrocytes metabolic cooperation can be altered by pre- and neonatal lead (Pb) exposure.

    Science.gov (United States)

    Baranowska-Bosiacka, Irena; Falkowska, Anna; Gutowska, Izabela; Gąssowska, Magdalena; Kolasa-Wołosiuk, Agnieszka; Tarnowski, Maciej; Chibowska, Karina; Goschorska, Marta; Lubkowska, Anna; Chlubek, Dariusz

    2017-09-01

    Lead (Pb) is an environmental neurotoxin which particularly affects the developing brain but the molecular mechanism of its neurotoxicity still needs clarification. The aim of this paper was to examine whether pre- and neonatal exposure to Pb (concentration of Pb in rat offspring blood below the "threshold level") may affect the brain's energy metabolism in neurons and astrocytes via the amount of available glycogen. We investigated the glycogen concentration in the brain, as well as the expression of the key enzymes involved in glycogen metabolism in brain: glycogen synthase 1 (Gys1), glycogen phosphorylase (PYGM, an isoform active in astrocytes; and PYGB, an isoform active in neurons) and phosphorylase kinase β (PHKB). Moreover, the expression of connexin 43 (Cx43) was evaluated to analyze whether Pb poisoning during the early phase of life may affect the neuron-astrocytes' metabolic cooperation. This work shows for the first time that exposure to Pb in early life can impair brain energy metabolism by reducing the amount of glycogen and decreasing the rate of its metabolism. This reduction in brain glycogen level was accompanied by a decrease in Gys1 expression. We noted a reduction in the immunoreactivity and the gene expression of both PYGB and PYGM isoform, as well as an increase in the expression of PHKB in Pb-treated rats. Moreover, exposure to Pb induced decrease in connexin 43 immunoexpression in all the brain structures analyzed, both in astrocytes as well as in neurons. Our data suggests that exposure to Pb in the pre- and neonatal periods results in a decrease in the level of brain glycogen and a reduction in the rate of its metabolism, thereby reducing glucose availability, which as a further consequence may lead to the impairment of brain energy metabolism and the metabolic cooperation between neurons and astrocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Cooling reduces the cutaneous afferent firing response to vibratory stimuli in glabrous skin of the human foot sole.

    Science.gov (United States)

    Lowrey, Catherine R; Strzalkowski, Nicholas D J; Bent, Leah R

    2013-02-01

    Skin on the foot sole plays an important role in postural control. Cooling the skin of the foot is often used to induce anesthesia to determine the role of skin in motor and balance control. The effect of cooling on the four classes of mechanoreceptor in the skin is largely unknown, and thus the aim of the present study was to characterize the effects of cooling on individual skin receptors in the foot sole. Such insight will better isolate individual receptor contributions to balance control. Using microneurography, we recorded 39 single nerve afferents innervating mechanoreceptors in the skin of the foot sole in humans. Afferents were identified as fast-adapting (FA) or slowly adapting (SA) type I or II (FA I n = 16, FA II n = 7, SA I n = 6, SA II n = 11). Receptor response to vibration was compared before and after cooling of the receptive field (2-20 min). Overall, firing response was abolished in 30% of all receptors, and this was equally distributed across receptor type (P = 0.69). Longer cooling times were more likely to reduce firing response below 50% of baseline; however, some afferent responses were abolished with shorter cooling times (2-5 min). Skin temperature was not a reliable indicator of the level of receptor activation and often became uncoupled from receptor response levels, suggesting caution in the use of this parameter as an indicator of anesthesia. When cooled, receptors preferentially coded lower frequencies in response to vibration. In response to a sustained indentation, SA receptors responded more like FA receptors, primarily coding "on-off" events.

  13. Afferent input selects NMDA receptor subtype to determine the persistency of hippocampal LTP in freely behaving mice

    Directory of Open Access Journals (Sweden)

    Jesús Javier Ballesteros

    2016-10-01

    Full Text Available The glutamatergic N-methyl-D-aspartate receptor (NMDAR is critically involved in many forms of hippocampus-dependent memory that may be enabled by synaptic plasticity. Behavioral studies with NMDAR antagonists and NMDAR subunit (GluN2 mutants revealed distinct contributions from GluN2A- and GluN2B-containing NMDARs to rapidly and slowly acquired memory performance. Furthermore, studies of synaptic plasticity, in genetically modified mice in vitro, suggest that GluN2A and GluN2B may contribute in different ways to the induction and longevity of synaptic plasticity. In contrast to the hippocampal slice preparation, in behaving mice, the afferent frequencies that induce synaptic plasticity are very restricted and specific. In fact, it is the stimulus pattern, and not variations in afferent frequency that determine the longevity of long-term potentiation (LTP. Here, we explored the contribution of GluN2A and GluN2B to LTP of differing magnitudes and persistencies in freely behaving mice. We applied differing high-frequency stimulation (HFS patterns at 100 Hz to the hippocampal CA1 region, to induce NMDAR-dependent LTP in wild-type (WT mice, that endured for 24h (late (L-LTP. In GluN2A-KO mice, E-LTP (HFS, 50 pulses was significantly reduced in magnitude and duration, whereas LTP (HFS, 2 x 50 pulses and L-LTP (HFS, 4 x 50 pulses were unaffected compared to responses in WT animals. By contrast, pharmacological antagonism of GluN2B in WT had no effect on E-LTP but significantly prevented LTP. E- LTP and LTP were significantly impaired by GluN2B antagonism in GluN2A-KO mice. These data indicate that the pattern of afferent stimulation is decisive for the recruitment of distinct GluN2A and GluN2B signaling pathways that in turn determine the persistency of hippocampal LTP. Whereas brief bursts of patterned stimulation preferentially recruit GluN2A and lead to weak and short-lived forms of LTP, prolonged, more intense, afferent activation recruits GluN2B

  14. Effects of adding Braun jejunojejunostomy to standard Whipple procedure on reduction of afferent loop syndrome - a randomized clinical trial.

    Science.gov (United States)

    Kakaei, Farzad; Beheshtirouy, Samad; Nejatollahi, Seyed Moahammad Reza; Rashidi, Iqbal; Asvadi, Touraj; Habibzadeh, Afshin; Oliaei-Motlagh, Mohammad

    2015-12-01

    Whipple surgery (pancreaticodeudenectomy) has a high complication rate. We aimed to evaluate whether adding Braun jejunojejunostomy (side-to-side anastomosis of afferent and efferent loops distal to the gastrojejunostomy site) to a standard Whipple procedure would reduce postoperative complications. We conducted a randomized clinical trial comparing patients who underwent standard Whipple surgery (standard group) and patients who underwent standard Whipple surgery with Braun jejunojejunostomy (Braun group). Patients were followed for 1 month after the procedure and postoperative complications were recorded. Our study included 30 patients: 15 in the Braun and 15 in the standard group. In the Braun group, 4 (26.7%) patients experienced 6 complications, whereas in the standard group, 7 (46.7%) patients experienced 11 complications (p = 0.14). Complications in the Braun group were gastrointestinal bleeding and wound infection (n = 1 each) and delayed gastric emptying and pulmonary infection (n = 2 each). Complications in the standard group were death, pancreatic anastomosis leak and biliary anastomosis leak (n = 1 each); gastrointestinal bleeding (n = 2); and afferent loop syndrome and delayed gastric emptying (n = 3 each). There was no significant difference between groups in the subtypes of complications. Our results showed that adding Braun jejunojejunostomy to standard Whipple procedure was associated with lower rates of afferent loop syndrome and delayed gastric emptying. However, more studies are needed to define the role of Braun jejunojejunostomy in this regard. IRCT2014020316473N1 (www.irct.ir).

  15. Facial expressions : What the mirror neuron system can and cannot tell us

    NARCIS (Netherlands)

    van der Gaag, Christiaan; Minderaa, Ruud B.; Keysers, Christian

    2007-01-01

    Facial expressions contain both motor and emotional components. The inferior frontal gyrus (IFG) and posterior parietal cortex have been considered to compose a mirror neuron system (MNS) for the motor components of facial expressions, while the amygdala and insula may represent an "additional" MNS

  16. The PM1 neurons, movement sensitive centrifugal visual brain neurons in the locust: anatomy, physiology, and modulation by identified octopaminergic neurons.

    Science.gov (United States)

    Stern, Michael

    2009-02-01

    The locust's optic lobe contains a system of wide-field, multimodal, centrifugal neurons. Two of these cells, the protocerebrum-medulla-neurons PM4a and b, are octopaminergic. This paper describes a second pair of large centrifugal neurons (the protocerebrum-medulla-neurons PM1a and PM1b) from the brain of Locusta migratoria based on intracellular cobalt fills, electrophysiology, and immunocytochemistry. They originate and arborise in the central brain and send processes into the medulla of the optic lobe. Double intracellular recording from the same cell suggests input in the central brain and output in the optic lobe. The neurons show immunoreactivity to gamma-amino-butyric acid and its synthesising enzyme, glutamate decarboxylase. The PM1 cells are movement sensitive and show habituation to repeated visual stimulation. Bath application of octopamine causes the response to dishabituate. A very similar effect is produced by electrical stimulation of one of an octopaminergic PM4 neuron. This effect can be blocked by application of the octopamine antagonists, mianserin and phentolamine. This readily accessible system of four wide-field neurons provides a system suitable for the investigation of octopaminergic effects on the visual system at the cellular level.

  17. Optimal compensation for neuron loss

    Science.gov (United States)

    Barrett, David GT; Denève, Sophie; Machens, Christian K

    2016-01-01

    The brain has an impressive ability to withstand neural damage. Diseases that kill neurons can go unnoticed for years, and incomplete brain lesions or silencing of neurons often fail to produce any behavioral effect. How does the brain compensate for such damage, and what are the limits of this compensation? We propose that neural circuits instantly compensate for neuron loss, thereby preserving their function as much as possible. We show that this compensation can explain changes in tuning curves induced by neuron silencing across a variety of systems, including the primary visual cortex. We find that compensatory mechanisms can be implemented through the dynamics of networks with a tight balance of excitation and inhibition, without requiring synaptic plasticity. The limits of this compensatory mechanism are reached when excitation and inhibition become unbalanced, thereby demarcating a recovery boundary, where signal representation fails and where diseases may become symptomatic. DOI: http://dx.doi.org/10.7554/eLife.12454.001 PMID:27935480

  18. Statistics of Visual Responses to Image Object Stimuli from Primate AIT Neurons to DNN Neurons.

    Science.gov (United States)

    Dong, Qiulei; Wang, Hong; Hu, Zhanyi

    2018-02-01

    Under the goal-driven paradigm, Yamins et al. ( 2014 ; Yamins & DiCarlo, 2016 ) have shown that by optimizing only the final eight-way categorization performance of a four-layer hierarchical network, not only can its top output layer quantitatively predict IT neuron responses but its penultimate layer can also automatically predict V4 neuron responses. Currently, deep neural networks (DNNs) in the field of computer vision have reached image object categorization performance comparable to that of human beings on ImageNet, a data set that contains 1.3 million training images of 1000 categories. We explore whether the DNN neurons (units in DNNs) possess image object representational statistics similar to monkey IT neurons, particularly when the network becomes deeper and the number of image categories becomes larger, using VGG19, a typical and widely used deep network of 19 layers in the computer vision field. Following Lehky, Kiani, Esteky, and Tanaka ( 2011 , 2014 ), where the response statistics of 674 IT neurons to 806 image stimuli are analyzed using three measures (kurtosis, Pareto tail index, and intrinsic dimensionality), we investigate the three issues in this letter using the same three measures: (1) the similarities and differences of the neural response statistics between VGG19 and primate IT cortex, (2) the variation trends of the response statistics of VGG19 neurons at different layers from low to high, and (3) the variation trends of the response statistics of VGG19 neurons when the numbers of stimuli and neurons increase. We find that the response statistics on both single-neuron selectivity and population sparseness of VGG19 neurons are fundamentally different from those of IT neurons in most cases; by increasing the number of neurons in different layers and the number of stimuli, the response statistics of neurons at different layers from low to high do not substantially change; and the estimated intrinsic dimensionality values at the low

  19. Context-aware modeling of neuronal morphologies

    Directory of Open Access Journals (Sweden)

    Benjamin eTorben-Nielsen

    2014-09-01

    Full Text Available Neuronal morphologies are pivotal for brain functioning: physical overlap between dendrites and axons constrain the circuit topology, and the precise shape and composition of dendrites determine the integration of inputs to produce an output signal. At the same time, morphologies are highly diverse and variant. The variance, presumably, originates from neurons developing in a densely packed brain substrate where they interact (e.g., repulsion or attraction with other actors in this substrate. However, when studying neurons their context is never part of the analysis and they are treated as if they existed in isolation.Here we argue that to fully understand neuronal morphology and its variance it is important to consider neurons in relation to each other and to other actors in the surrounding brain substrate, i.e., their context. We propose a context-aware computational framework, NeuroMaC, in which large numbers of neurons can be grown simultaneously according to growth rules expressed in terms of interactions between the developing neuron and the surrounding brain substrate.As a proof of principle, we demonstrate that by using NeuroMaC we can generate accurate virtual morphologies of distinct classes both in isolation and as part of neuronal forests. Accuracy is validated against population statistics of experimentally reconstructed morphologies. We show that context-aware generation of neurons can explain characteristics of variation. Indeed, plausible variation is an inherent property of the morphologies generated by context-aware rules. We speculate about the applicability of this framework to investigate morphologies and circuits, to classify healthy and pathological morphologies, and to generate large quantities of morphologies for large-scale modeling.

  20. Gastroesophageal Variceal Filling and Drainage Pathways: An Angiographic Description of Afferent and Efferent Venous Anatomic Patterns

    Directory of Open Access Journals (Sweden)

    Ron C Gaba

    2015-01-01

    Full Text Available Varices commonly occur in liver cirrhosis patients and are classified as esophageal (EV, gastroesophageal (GEV, or isolated gastric (IGV varices. These vessels may be supplied and drained by several different afferent and efferent pathways. A working knowledge of variceal anatomy is imperative for Interventional Radiologists performing transjugular intrahepatic portosystemic shunt and embolization/obliteration procedures. This pictorial essay characterizes the angiographic anatomy of varices in terms of type and frequency of venous filling and drainage, showing that different varices have distinct vascular anatomy. EVs typically show left gastric vein filling and “uphill” drainage, and GEVs and IGVs exhibit additional posterior/short gastric vein contribution and “downhill” outflow. An understanding of these variceal filling and drainage pathways can facilitate successful portal decompression and embolization/obliteration procedures.

  1. Central projections of gustatory receptor neurons in the medial and the lateral sensilla styloconica of Helicoverpa armigera larvae.

    Directory of Open Access Journals (Sweden)

    Qing-Bo Tang

    Full Text Available Food selection behavior of lepidopteran larvae is predominantly governed by the activation of taste neurons present in two sensilla styloconica located on the galea of the maxilla. In this study, we present the ultrastructure of the sensilla styloconica and the central projection pattern of their associated receptor neurons in larvae of the heliothine moth, Helicoverpa armigera. By means of light microscopy and scanning electron microscopy, the previous findings of two morphologically fairly similar sensilla comprising a socketed conic tip inserted into a large peg were confirmed. However, the peg size of the medial sensillum was found to be significantly bigger than that of the lateral sensillum. The sensory neurons derived from each sensillum styloconicum were mapped separately using anterograde staining experiments combined with confocal laser-scanning microscopy. For determining the afferents' target regions relative to each other, we reconstructed the labeled axons and placed them into a common reference framework. The sensory axons from both sensilla projected via the ipsilateral maxillary nerve to the suboesophageal ganglion and further through the ipsilateral circumoesophageal connective to the brain. In the suboesophageal ganglion, the sensory projections targeted two areas of the ipsilateral maxillary neuropil, one located in the ventrolateral neuromere and the other adjacent to the neuromere midline. In the brain, the axon terminals targeted the dorso-anterior area of the ipsilateral tritocerebrum. As confirmed by the three-dimensional reconstructions, the target regions of the neural projections originating from each of the two sensilla styloconica were identical.

  2. Central projections of gustatory receptor neurons in the medial and the lateral sensilla styloconica of Helicoverpa armigera larvae.

    Science.gov (United States)

    Tang, Qing-Bo; Zhan, Huan; Cao, Huan; Berg, Bente G; Yan, Feng-Ming; Zhao, Xin-Cheng

    2014-01-01

    Food selection behavior of lepidopteran larvae is predominantly governed by the activation of taste neurons present in two sensilla styloconica located on the galea of the maxilla. In this study, we present the ultrastructure of the sensilla styloconica and the central projection pattern of their associated receptor neurons in larvae of the heliothine moth, Helicoverpa armigera. By means of light microscopy and scanning electron microscopy, the previous findings of two morphologically fairly similar sensilla comprising a socketed conic tip inserted into a large peg were confirmed. However, the peg size of the medial sensillum was found to be significantly bigger than that of the lateral sensillum. The sensory neurons derived from each sensillum styloconicum were mapped separately using anterograde staining experiments combined with confocal laser-scanning microscopy. For determining the afferents' target regions relative to each other, we reconstructed the labeled axons and placed them into a common reference framework. The sensory axons from both sensilla projected via the ipsilateral maxillary nerve to the suboesophageal ganglion and further through the ipsilateral circumoesophageal connective to the brain. In the suboesophageal ganglion, the sensory projections targeted two areas of the ipsilateral maxillary neuropil, one located in the ventrolateral neuromere and the other adjacent to the neuromere midline. In the brain, the axon terminals targeted the dorso-anterior area of the ipsilateral tritocerebrum. As confirmed by the three-dimensional reconstructions, the target regions of the neural projections originating from each of the two sensilla styloconica were identical.

  3. Serotonergic transmission at Merkel discs: modulation by exogenously applied chemical messengers and involvement of Ih currents.

    Science.gov (United States)

    Chang, Weipang; Kanda, Hirosato; Ikeda, Ryo; Ling, Jennifer; Gu, Jianguo G

    2017-05-01

    The Merkel disc is a main type of tactile end organ consisting of Merkel cells and Aβ-afferent endings that responds to tactile stimulation with slowly adapting type 1 (SA1) afferent impulses. Our recent study has shown that Merkel discs in whisker hair follicles are serotonergic synapses using endogenous serotonin to transmit tactile signals from Merkel cells to Aβ-afferent endings. In this study, we hypothesize that tactile sensitivity of Merkel discs can be modulated by chemical messengers. We tested this hypothesis by determining whether and how SA1 responses of mouse whisker hair follicles may be affected by exogenously applied chemical messengers. We found that SA1 responses were potentiated by serotonin at low concentration (10 μM) but almost completely occluded by serotonin at high concentration (2 mM). In contrast, SA1 responses were not significantly affected by ATP and its metabolically stable analog α,β-methylene-ATP, glutamate, γ-aminobutyric acid (GABA), and histamine. SA1 responses were also not affected by antagonists for P2X receptors, ionotropic glutamate receptors, and ionotropic GABA and glycine receptors. Whole-cell patch-clamp recordings reconfirm the presence of both ionotropic and metabotropic 5-HT receptors on afferent neurons and their terminals innervating whisker hair follicles. All whisker afferent neurons expressed hyperpolarization-activated inward currents (I h ), which are potentiated by serotonin through the activation of metabotropic 5-HT receptors. Taken together, the findings substantiate the serotonergic mechanism of tactile transmission at Merkel discs and identify the involvement of I h currents in postsynaptic excitatory actions of serotonin. In addition, the findings do not favor any significant involvement of ATP, glutamate, histamine, GABA, or glycine in tactile transmission at the Merkel discs of whisker hair follicles. © 2017 International Society for Neurochemistry.

  4. Physiological recruitment of motor units by high-frequency electrical stimulation of afferent pathways.

    Science.gov (United States)

    Dideriksen, Jakob L; Muceli, Silvia; Dosen, Strahinja; Laine, Christopher M; Farina, Dario

    2015-02-01

    Neuromuscular electrical stimulation (NMES) is commonly used in rehabilitation, but electrically evoked muscle activation is in several ways different from voluntary muscle contractions. These differences lead to challenges in the use of NMES for restoring muscle function. We investigated the use of low-current, high-frequency nerve stimulation to activate the muscle via the spinal motoneuron (MN) pool to achieve more natural activation patterns. Using a novel stimulation protocol, the H-reflex responses to individual stimuli in a train of stimulation pulses at 100 Hz were reliably estimated with surface EMG during low-level contractions. Furthermore, single motor unit recruitment by afferent stimulation was analyzed with intramuscular EMG. The results showed that substantially elevated H-reflex responses were obtained during 100-Hz stimulation with respect to a lower stimulation frequency. Furthermore, motor unit recruitment using 100-Hz stimulation was not fully synchronized, as it occurs in classic NMES, and the discharge rates differed among motor units because each unit was activated only after a specific number of stimuli. The most likely mechanism behind these observations is the temporal summation of subthreshold excitatory postsynaptic potentials from Ia fibers to the MNs. These findings and their interpretation were also verified by a realistic simulation model of afferent stimulation of a MN population. These results suggest that the proposed stimulation strategy may allow generation of considerable levels of muscle activation by motor unit recruitment that resembles the physiological conditions. Copyright © 2015 the American Physiological Society.

  5. Ventral tegmental area dopamine revisited: effects of acute and repeated stress

    Science.gov (United States)

    Holly, Elizabeth N.; Miczek, Klaus A.

    2015-01-01

    Aversive events rapidly and potently excite certain dopamine neurons in the ventral tegmental area (VTA), promoting phasic increases in the medial prefrontal cortex and nucleus accumbens. This is in apparent contradiction to a wealth of literature demonstrating that most VTA dopamine neurons are strongly activated by reward and reward-predictive cues while inhibited by aversive stimuli. How can these divergent processes both be mediated by VTA dopamine neurons? The answer may lie within the functional and anatomical heterogeneity of the VTA. We focus on VTA heterogeneity in anatomy, neurochemistry, electrophysiology, and afferent/efferent connectivity. Second, recent evidence for a critical role of VTA dopamine neurons in response to both acute and repeated stress will be discussed. Understanding which dopamine neurons are activated by stress, the neural mechanisms driving the activation, and where these neurons project will provide valuable insight into how stress can promote psychiatric disorders associated with the dopamine system, such as addiction and depression. PMID:26676983

  6. Neural control of left ventricular contractility in the dog heart: synaptic interactions of negative inotropic vagal preganglionic neurons in the nucleus ambiguus with tyrosine hydroxylase immunoreactive terminals.

    Science.gov (United States)

    Massari, V J; Dickerson, L W; Gray, A L; Lauenstein, J M; Blinder, K J; Newsome, J T; Rodak, D J; Fleming, T J; Gatti, P J; Gillis, R A

    1998-08-17

    Recent physiological evidence indicates that vagal postganglionic control of left ventricular contractility is mediated by neurons found in a ventricular epicardial fat pad ganglion. In the dog this region has been referred to as the cranial medial ventricular (CMV) ganglion [J.L. Ardell, Structure and function of mammalian intrinsic cardiac neurons, in: J.A. Armour, J.L. Ardell (Eds.). Neurocardiology, Oxford Univ. Press, New York, 1994, pp. 95-114; B.X. Yuan, J.L. Ardell, D.A. Hopkins, A.M. Losier, J.A. Armour, Gross and microscopic anatomy of the canine intrinsic cardiac nervous system, Anat. Rec., 239 (1994) 75-87]. Since activation of the vagal neuronal input to the CMV ganglion reduces left ventricular contractility without influencing cardiac rate or AV conduction, this ganglion contains a functionally selective pool of negative inotropic parasympathetic postganglionic neurons. In the present report we have defined the light microscopic distribution of preganglionic negative inotropic neurons in the CNS which are retrogradely labeled from the CMV ganglion. Some tissues were also processed for the simultaneous immunocytochemical visualization of tyrosine hydroxylase (TH: a marker for catecholaminergic neurons) and examined with both light microscopic and electron microscopic methods. Histochemically visualized neurons were observed in a long slender column in the ventrolateral nucleus ambiguus (NA-VL). The greatest number of retrogradely labeled neurons were observed just rostral to the level of the area postrema. TH perikarya and dendrites were commonly observed interspersed with vagal motoneurons in the NA-VL. TH nerve terminals formed axo-dendritic synapses upon negative inotropic vagal motoneurons, however the origin of these terminals remains to be determined. We conclude that synaptic interactions exist which would permit the parasympathetic preganglionic vagal control of left ventricular contractility to be modulated monosynaptically by

  7. Intracellular signalling pathways in the vasoconstrictor response of mouse afferent arterioles to adenosine

    DEFF Research Database (Denmark)

    Hansen, Pernille B. Lærkegaard; Friis, Ulla Glenert; Uhrenholt, Torben Rene

    2007-01-01

    of calcium from the sarcoplasmic reticulum (SR), stimulated presumably by IP(3), is involved in the adenosine contraction mechanism of the afferent arteriole. In agreement with this notion is the observation that 2 aminoethoxydiphenyl borate (100 microM) blocked the adenosine-induced constriction whereas...... was abolished by IAA-94. Furthermore, the vasoconstriction caused by adenosine was significantly inhibited by 5 microM nifedipine (control 8.3 +/- 0.2 microM, ado 3.6 +/- 0.6 microM, ado + nifedipine 6.8 +/- 0.2 microM) suggesting involvement of voltage-dependent calcium channels. CONCLUSION: We conclude...

  8. Adenosine induces vasoconstriction through Gi-dependent activation of phospholipase C in isolated perfused afferent arterioles of mice

    DEFF Research Database (Denmark)

    Hansen, Pernille B; Castrop, Hayo; Briggs, Josie

    2003-01-01

    -induced vasoconstriction was stable for up to 30 min and was most pronounced in the most distal part of the afferent arterioles. Adenosine did not cause vasoconstriction in arterioles from A1AR-/- mice. Pretreatment with pertussis toxin (PTX) (400 ng/ml) for 2 h blocked the vasoconstricting action of adenosine or N(6...

  9. Toward functional classification of neuronal types.

    Science.gov (United States)

    Sharpee, Tatyana O

    2014-09-17

    How many types of neurons are there in the brain? This basic neuroscience question remains unsettled despite many decades of research. Classification schemes have been proposed based on anatomical, electrophysiological, or molecular properties. However, different schemes do not always agree with each other. This raises the question of whether one can classify neurons based on their function directly. For example, among sensory neurons, can a classification scheme be devised that is based on their role in encoding sensory stimuli? Here, theoretical arguments are outlined for how this can be achieved using information theory by looking at optimal numbers of cell types and paying attention to two key properties: correlations between inputs and noise in neural responses. This theoretical framework could help to map the hierarchical tree relating different neuronal classes within and across species. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Limb venous distension evokes sympathetic activation via stimulation of the limb afferents in humans

    Science.gov (United States)

    Cui, Jian; McQuillan, Patrick M.; Blaha, Cheryl; Kunselman, Allen R.

    2012-01-01

    We have recently shown that a saline infusion in the veins of an arterially occluded human forearm evokes a systemic response with increases in muscle sympathetic nerve activity (MSNA) and blood pressure. In this report, we examined whether this response was a reflex that was due to venous distension. Blood pressure (Finometer), heart rate, and MSNA (microneurography) were assessed in 14 young healthy subjects. In the saline trial (n = 14), 5% forearm volume normal saline was infused in an arterially occluded arm. To block afferents in the limb, 90 mg of lidocaine were added to the same volume of saline in six subjects during a separate visit. To examine whether interstitial perfusion of normal saline alone induced the responses, the same volume of albumin solution (5% concentration) was infused in 11 subjects in separate studies. Lidocaine abolished the MSNA and blood pressure responses seen with saline infusion. Moreover, compared with the saline infusion, an albumin infusion induced a larger (MSNA: Δ14.3 ± 2.7 vs. Δ8.5 ± 1.3 bursts/min, P blood pressure responses. These data suggest that venous distension activates afferent nerves and evokes a powerful systemic sympathoexcitatory reflex. We posit that the venous distension plays an important role in evoking the autonomic adjustments seen with postural stress in human subjects. PMID:22707559

  11. Glass promotes the differentiation of neuronal and non-neuronal cell types in the Drosophila eye

    Science.gov (United States)

    Morrison, Carolyn A.; Chen, Hao; Cook, Tiffany; Brown, Stuart

    2018-01-01

    Transcriptional regulators can specify different cell types from a pool of equivalent progenitors by activating distinct developmental programs. The Glass transcription factor is expressed in all progenitors in the developing Drosophila eye, and is maintained in both neuronal and non-neuronal cell types. Glass is required for neuronal progenitors to differentiate as photoreceptors, but its role in non-neuronal cone and pigment cells is unknown. To determine whether Glass activity is limited to neuronal lineages, we compared the effects of misexpressing it in neuroblasts of the larval brain and in epithelial cells of the wing disc. Glass activated overlapping but distinct sets of genes in these neuronal and non-neuronal contexts, including markers of photoreceptors, cone cells and pigment cells. Coexpression of other transcription factors such as Pax2, Eyes absent, Lozenge and Escargot enabled Glass to induce additional genes characteristic of the non-neuronal cell types. Cell type-specific glass mutations generated in cone or pigment cells using somatic CRISPR revealed autonomous developmental defects, and expressing Glass specifically in these cells partially rescued glass mutant phenotypes. These results indicate that Glass is a determinant of organ identity that acts in both neuronal and non-neuronal cells to promote their differentiation into functional components of the eye. PMID:29324767

  12. Mirror neurons: from origin to function.

    Science.gov (United States)

    Cook, Richard; Bird, Geoffrey; Catmur, Caroline; Press, Clare; Heyes, Cecilia

    2014-04-01

    This article argues that mirror neurons originate in sensorimotor associative learning and therefore a new approach is needed to investigate their functions. Mirror neurons were discovered about 20 years ago in the monkey brain, and there is now evidence that they are also present in the human brain. The intriguing feature of many mirror neurons is that they fire not only when the animal is performing an action, such as grasping an object using a power grip, but also when the animal passively observes a similar action performed by another agent. It is widely believed that mirror neurons are a genetic adaptation for action understanding; that they were designed by evolution to fulfill a specific socio-cognitive function. In contrast, we argue that mirror neurons are forged by domain-general processes of associative learning in the course of individual development, and, although they may have psychological functions, they do not necessarily have a specific evolutionary purpose or adaptive function. The evidence supporting this view shows that (1) mirror neurons do not consistently encode action "goals"; (2) the contingency- and context-sensitive nature of associative learning explains the full range of mirror neuron properties; (3) human infants receive enough sensorimotor experience to support associative learning of mirror neurons ("wealth of the stimulus"); and (4) mirror neurons can be changed in radical ways by sensorimotor training. The associative account implies that reliable information about the function of mirror neurons can be obtained only by research based on developmental history, system-level theory, and careful experimentation.

  13. Modeling the differentiation of A- and C-type baroreceptor firing patterns

    DEFF Research Database (Denmark)

    Sturdy, Jacob; Ottesen, Johnny T.; Olufsen, Mette

    2017-01-01

    The baroreceptor neurons serve as the primary transducers of blood pressure for the autonomic nervous system and are thus critical in enabling the body to respond effectively to changes in blood pressure. These neurons can be separated into two types (A and C) based on the myelination...... of their axons and their distinct firing patterns elicited in response to specific pressure stimuli. This study has developed a comprehensive model of the afferent baroreceptor discharge built on physiological knowledge of arterial wall mechanics, firing rate responses to controlled pressure stimuli, and ion...

  14. Liver afferents contribute to water drinking-induced sympathetic activation in human subjects: a clinical trial.

    Directory of Open Access Journals (Sweden)

    Marcus May

    Full Text Available Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (p<0.05 between groups after 30-40 minutes of water drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects.ClinicalTrials.gov NCT01237431.

  15. Liver Afferents Contribute to Water Drinking-Induced Sympathetic Activation in Human Subjects: A Clinical Trial

    Science.gov (United States)

    May, Marcus; Gueler, Faikah; Barg-Hock, Hannelore; Heiringhoff, Karl-Heinz; Engeli, Stefan; Heusser, Karsten; Diedrich, André; Brandt, André; Strassburg, Christian P.; Tank, Jens; Sweep, Fred C. G. J.; Jordan, Jens

    2011-01-01

    Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant) as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant) as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (pwater drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects. Trial Registration ClinicalTrials.gov NCT01237431 PMID:22016786

  16. Vagotomy decreases the neuronal activities of medulla oblongata and alleviates neurogenic inflammation of airways induced by repeated intra-esophageal instillation of HCl in guinea pigs.

    Science.gov (United States)

    Chen, Zhe; Chen, Hui; Chen, Fagui; Gu, Dachuan; Sun, Lejia; Zhang, Weitao; Fan, Linfeng; Lin, Yong; Dong, Rong; Lai, Kefang

    2017-12-20

    Neuronal activity in the medulla oblongata and neurogenic inflammation of airways were investigated in a guinea pig model induced by repeated intra-esophageal instillation of hydrochloric acid (HCl) after vagotomy. Unilateral vagotomy was performed in the vagotomy group, while a sham-operation was performed in the sham group. Operation was not conducted in sham control group. Airway inflammation was observed with hematoxylin and eosin (HE) staining. C-fos protein was measured by immunohistochemistry (IHC) and Western blot (WB). Substance P was examined by IHC and enzyme-linked immuno sorbent assay (ELISA). Airway microvascular permeability was detected by evans blue dye (EBD) fluorescence. Inflammation of airway was observed in the trachea and bronchi after chronic HCl perfusion into the lower esophagus, and was alleviated after unilateral vagotomy. C-fos expression in the medulla oblongata was lower in the vagotomy group compared to the sham control and sham groups. Substance P-like immunoreactivity (SP-li), concentration and microvascular leakage in airway were lower in the vagotomy group than that in the other groups. Our results suggest that vagotomy improved neurogenic inflammation of airways and decreased neuronal activities, the afferent nerves and neurons in medulla oblongata may be involved in neurogenic inflammation of airways mediated by esophageal-bronchial reflex.

  17. Biogenic Amines in Insect Antennae

    Directory of Open Access Journals (Sweden)

    Marianna I. Zhukovskaya

    2017-06-01

    Full Text Available Insect antenna is a multisensory organ, each modality of which can be modulated by biogenic amines. Octopamine (OA and its metabolic precursor tyramine (TA affect activity of antennal olfactory receptor neurons. There is some evidence that dopamine (DA modulates gustatory neurons. Serotonin can serve as a neurotransmitter in some afferent mechanosensory neurons and both as a neurotransmitter and neurohormone in efferent fibers targeted at the antennal vessel and mechanosensory organs. As a neurohormone, serotonin affects the generation of the transepithelial potential by sensillar accessory cells. Other possible targets of biogenic amines in insect antennae are hygro- and thermosensory neurons and epithelial cells. We suggest that the insect antenna is partially autonomous in the sense that biologically active substances entering its hemolymph may exert their effects and be cleared from this compartment without affecting other body parts.

  18. Neuronal replacement therapy: previous achievements and challenges ahead

    Science.gov (United States)

    Grade, Sofia; Götz, Magdalena

    2017-10-01

    Lifelong neurogenesis and incorporation of newborn neurons into mature neuronal circuits operates in specialized niches of the mammalian brain and serves as role model for neuronal replacement strategies. However, to which extent can the remaining brain parenchyma, which never incorporates new neurons during the adulthood, be as plastic and readily accommodate neurons in networks that suffered neuronal loss due to injury or neurological disease? Which microenvironment is permissive for neuronal replacement and synaptic integration and which cells perform best? Can lost function be restored and how adequate is the participation in the pre-existing circuitry? Could aberrant connections cause malfunction especially in networks dominated by excitatory neurons, such as the cerebral cortex? These questions show how important connectivity and circuitry aspects are for regenerative medicine, which is the focus of this review. We will discuss the impressive advances in neuronal replacement strategies and success from exogenous as well as endogenous cell sources. Both have seen key novel technologies, like the groundbreaking discovery of induced pluripotent stem cells and direct neuronal reprogramming, offering alternatives to the transplantation of fetal neurons, and both herald great expectations. For these to become reality, neuronal circuitry analysis is key now. As our understanding of neuronal circuits increases, neuronal replacement therapy should fulfill those prerequisites in network structure and function, in brain-wide input and output. Now is the time to incorporate neural circuitry research into regenerative medicine if we ever want to truly repair brain injury.

  19. Spiking neuron devices consisting of single-flux-quantum circuits

    International Nuclear Information System (INIS)

    Hirose, Tetsuya; Asai, Tetsuya; Amemiya, Yoshihito

    2006-01-01

    Single-flux-quantum (SFQ) circuits can be used for making spiking neuron devices, which are useful elements for constructing intelligent, brain-like computers. The device we propose is based on the leaky integrate-and-fire neuron (IFN) model and uses a SFQ pulse as an action signal or a spike of neurons. The operation of the neuron device is confirmed by computer simulator. It can operate with a short delay of 100 ps or less and is the highest-speed neuron device ever reported

  20. Bursting synchronization in clustered neuronal networks

    International Nuclear Information System (INIS)

    Yu Hai-Tao; Wang Jiang; Deng Bin; Wei Xi-Le

    2013-01-01

    Neuronal networks in the brain exhibit the modular (clustered) property, i.e., they are composed of certain subnetworks with differential internal and external connectivity. We investigate bursting synchronization in a clustered neuronal network. A transition to mutual-phase synchronization takes place on the bursting time scale of coupled neurons, while on the spiking time scale, they behave asynchronously. This synchronization transition can be induced by the variations of inter- and intracoupling strengths, as well as the probability of random links between different subnetworks. Considering that some pathological conditions are related with the synchronization of bursting neurons in the brain, we analyze the control of bursting synchronization by using a time-periodic external signal in the clustered neuronal network. Simulation results show a frequency locking tongue in the driving parameter plane, where bursting synchronization is maintained, even in the presence of external driving. Hence, effective synchronization suppression can be realized with the driving parameters outside the frequency locking region. (interdisciplinary physics and related areas of science and technology)

  1. Radiation-induced reduction of the glial population during development disrupts the formation of olfactory glomeruli in an insect

    International Nuclear Information System (INIS)

    Oland, L.A.; Tolbert, L.P.; Mossman, K.L.

    1988-01-01

    Interactions between neurons and between neurons and glial cells have been shown by a number of investigators to be critical for normal development of the nervous system. In the olfactory system of Manduca sexta, sensory axons have been shown to induce the formation of synaptic glomeruli in the antennal lobe of the brain. Oland and Tolbert (1987) found that the growth of sensory axons into the developing antennal lobe causes changes in glial shape and disposition that presage the establishment of glomeruli, each surrounded by a glial envelope. Several lines of evidence lead us to hypothesize that the glial cells of the lobe may be acting as intermediaries in developmental interactions between sensory axons and neurons of the antennal lobe. In the present study, we have tested this hypothesis by using gamma-radiation to reduce the number of glial cells at a time when neurons of the antennal system are postmitotic but glomeruli have not yet developed. When glial numbers are severely reduced, the neuropil of the resulting lobe lacks glomeruli. Despite the presence of afferent axons, the irradiated lobe has many of the features of a lobe that developed in the absence of afferent axons. Our findings indicate that the glial cells must play a necessary role in the inductive influence of the afferent axons

  2. Sensory and motor innervation of the crural diaphragm by the vagus nerves.

    Science.gov (United States)

    Young, Richard L; Page, Amanda J; Cooper, Nicole J; Frisby, Claudine L; Blackshaw, L Ashley

    2010-03-01

    During gastroesophageal reflux, transient lower esophageal sphincter relaxation and crural diaphragm (CD) inhibition occur concomitantly. Modifying vagus nerve control of transient lower esophageal sphincter relaxation is a major focus of development of therapeutics for gastroesophageal reflux disease, but neural mechanisms that coordinate the CD are poorly understood. Nerve tracing and immunolabeling were used to assess innervation of the diaphragm and lower esophageal sphincter in ferrets. Mechanosensory responses of vagal afferents in the CD and electromyography responses of the CD were recorded in novel in vitro preparations and in vivo. Retrograde tracing revealed a unique population of vagal CD sensory neurons in nodose ganglia and CD motor neurons in brainstem vagal nuclei. Anterograde tracing revealed specialized vagal endings in the CD and phrenoesophageal ligament-sites of vagal afferent mechanosensitivity recorded in vitro. Spontaneous electromyography activity persisted in the CD following bilateral phrenicotomy in vivo, while vagus nerve stimulation evoked electromyography responses in the CD in vitro and in vivo. We conclude that vagal sensory and motor neurons functionally innervate the CD and phrenoesophageal ligament. CD vagal afferents show mechanosensitivity to distortion of the gastroesophageal junction, while vagal motor neurons innervate both CD and distal esophagus and may represent a common substrate for motor control of the reflux barrier. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

  3. Neuromorphic Silicon Neuron Circuits

    Science.gov (United States)

    Indiveri, Giacomo; Linares-Barranco, Bernabé; Hamilton, Tara Julia; van Schaik, André; Etienne-Cummings, Ralph; Delbruck, Tobi; Liu, Shih-Chii; Dudek, Piotr; Häfliger, Philipp; Renaud, Sylvie; Schemmel, Johannes; Cauwenberghs, Gert; Arthur, John; Hynna, Kai; Folowosele, Fopefolu; Saighi, Sylvain; Serrano-Gotarredona, Teresa; Wijekoon, Jayawan; Wang, Yingxue; Boahen, Kwabena

    2011-01-01

    Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain–machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance-based Hodgkin–Huxley models to bi-dimensional generalized adaptive integrate and fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips. PMID:21747754

  4. Neuromorphic silicon neuron circuits

    Directory of Open Access Journals (Sweden)

    Giacomo eIndiveri

    2011-05-01

    Full Text Available Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain-machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance based Hodgkin-Huxley models to bi-dimensional generalized adaptive Integrate and Fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips.

  5. Selective neuronal PTEN deletion: can we take the brakes off of growth without losing control?

    Directory of Open Access Journals (Sweden)

    Erin A Gutilla

    2016-01-01

    Full Text Available The limited ability for injured adult axons to regenerate is a major cause for limited functional recovery after injury to the nervous system, motivating numerous efforts to uncover mechanisms capable of enhancing regeneration potential. One promising strategy involves deletion or knockdown of the phosphatase and tensin (PTEN gene. Conditional genetic deletion of PTEN before, immediately following, or several months after spinal cord injury enables neurons of the corticospinal tract (CST to regenerate their axons across the lesion, which is accompanied by enhanced recovery of skilled voluntary motor functions mediated by the CST. Although conditional genetic deletion or knockdown ofPTEN in neurons enables axon regeneration, PTEN is a well-known tumor suppressor and mutations of the PTEN gene disrupt brain development leading to neurological abnormalities including macrocephaly, seizures, and early mortality. The long-term consequences of manipulating PTEN in the adult nervous system, as would be done for therapeutic intervention after injury, are only now being explored. Here, we summarize evidence indicating that long-term deletion of PTEN in mature neurons does not cause evident pathology; indeed, cortical neurons that have lived without PTEN for over 1 year appear robust and healthy. Studies to date provide only a first look at potential negative consequences of PTEN deletion or knockdown, but the absence of any detectable neuropathology supports guarded optimism that interventions to enable axon regeneration after injury are achievable.

  6. Beyond Critical Exponents in Neuronal Avalanches

    Science.gov (United States)

    Friedman, Nir; Butler, Tom; Deville, Robert; Beggs, John; Dahmen, Karin

    2011-03-01

    Neurons form a complex network in the brain, where they interact with one another by firing electrical signals. Neurons firing can trigger other neurons to fire, potentially causing avalanches of activity in the network. In many cases these avalanches have been found to be scale independent, similar to critical phenomena in diverse systems such as magnets and earthquakes. We discuss models for neuronal activity that allow for the extraction of testable, statistical predictions. We compare these models to experimental results, and go beyond critical exponents.

  7. Kappe neurons, a novel population of olfactory sensory neurons.

    Science.gov (United States)

    Ahuja, Gaurav; Bozorg Nia, Shahrzad; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I

    2014-02-10

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons are identified by their Go-like immunoreactivity, and show a distinct spatial distribution within the olfactory epithelium, similar to, but significantly different from that of crypt neurons. Furthermore, kappe neurons project to a single identified target glomerulus within the olfactory bulb, mdg5 of the mediodorsal cluster, whereas crypt neurons are known to project exclusively to the mdg2 glomerulus. Kappe neurons are negative for established markers of ciliated, microvillous and crypt neurons, but appear to have microvilli. Kappe neurons constitute the fourth type of olfactory sensory neurons reported in teleost fishes and their existence suggests that encoding of olfactory stimuli may require a higher complexity than hitherto assumed already in the peripheral olfactory system.

  8. First-spike latency in Hodgkin's three classes of neurons.

    Science.gov (United States)

    Wang, Hengtong; Chen, Yueling; Chen, Yong

    2013-07-07

    We study the first-spike latency (FSL) in Hodgkin's three classes of neurons with the Morris-Lecar neuron model. It is found that all the three classes of neurons can encode an external stimulus into FSLs. With DC inputs, the FSLs of all of the neurons decrease with input intensity. With input current decreased to the threshold, class 1 neurons show an arbitrary long FSL whereas class 2 and 3 neurons exhibit the short-limit FSLs. When the input current is sinusoidal, the amplitude, frequency and initial phase can be encoded by all the three classes of neurons. The FSLs of all of the neurons decrease with the input amplitude and frequency. When the input frequency is too high, all of the neurons respond with infinite FSLs. When the initial phase increases, the FSL decreases and then jumps to a maximal value and finally decreases linearly. With changes in the input parameters, the FSLs of the class 1 and 2 neurons exhibit similar properties. However, the FSL of the class 3 neurons became slightly longer and only produces responses for a narrow range of initial phase if input frequencies are low. Moreover, our results also show that the FSL and firing rate responses are mutually independent processes and that neurons can encode an external stimulus into different FSLs and firing rates simultaneously. This finding is consistent with the current theory of dual or multiple complementary coding mechanisms. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Neurochemistry of neurons in the ventrolateral medulla activated by hypotension: Are the same neurons activated by glucoprivation?

    Science.gov (United States)

    Parker, Lindsay M; Le, Sheng; Wearne, Travis A; Hardwick, Kate; Kumar, Natasha N; Robinson, Katherine J; McMullan, Simon; Goodchild, Ann K

    2017-06-15

    Previous studies have demonstrated that a range of stimuli activate neurons, including catecholaminergic neurons, in the ventrolateral medulla. Not all catecholaminergic neurons are activated and other neurochemical content is largely unknown hence whether stimulus specific populations exist is unclear. Here we determine the neurochemistry (using in situ hybridization) of catecholaminergic and noncatecholaminergic neurons which express c-Fos immunoreactivity throughout the rostrocaudal extent of the ventrolateral medulla, in Sprague Dawley rats treated with hydralazine or saline. Distinct neuronal populations containing PPCART, PPPACAP, and PPNPY mRNAs, which were largely catecholaminergic, were activated by hydralazine but not saline. Both catecholaminergic and noncatecholaminergic neurons containing preprotachykinin and prepro-enkephalin (PPE) mRNAs were also activated, with the noncatecholaminergic population located in the rostral C1 region. Few GlyT2 neurons were activated. A subset of these data was then used to compare the neuronal populations activated by 2-deoxyglucose evoked glucoprivation (Brain Structure and Function (2015) 220:117). Hydralazine activated more neurons than 2-deoxyglucose but similar numbers of catecholaminergic neurons. Commonly activated populations expressing PPNPY and PPE mRNAs were defined. These likely include PPNPY expressing catecholaminergic neurons projecting to vasopressinergic and corticotrophin releasing factor neurons in the paraventricular nucleus, which when activated result in elevated plasma vasopressin and corticosterone. Stimulus specific neurons included noncatecholaminergic neurons and a few PPE positive catecholaminergic neuron but neurochemical codes were largely unidentified. Reasons for the lack of identification of stimulus specific neurons, readily detectable using electrophysiology in anaesthetized preparations and for which neural circuits can be defined, are discussed. © 2017 Wiley Periodicals, Inc.

  10. Influences of reduced masticatory sensory input from soft-diet feeding upon spatial memory/learning ability in mice.

    Science.gov (United States)

    Tsutsui, Keisuke; Kaku, Masato; Motokawa, Masahide; Tohma, Yuiko; Kawata, Toshitsugu; Fujita, Tadashi; Kohno, Shinya; Ohtani, Junji; Tenjoh, Kaoru; Nakano, Mao; Kamada, Hiroko; Tanne, Kazuo

    2007-02-01

    It has been reported that reduction of masticatory afferent stimulation might influence learning and memory function. In order to clarify the influences of reduced masticatory sensory input on spatial memory/learning ability and neuropathological changes, we conducted the Morris water maze experiment and investigated the number of hippocampal neurons in association with the differences in masticatory afferent stimuli from hard- and soft-diet feeding in mice. The water maze experiment showed no significant difference in learning ability between 180-day-old solid- and powderdiet groups. Meanwhile, the ability was significantly reduced in the 360-day-old powder-diet group as compared with the age-matched solid-diet group. The total number of pyramidal cells in the hippocampal CA1 and CA3 regions was significantly smaller in 360-day-old powder-diet group than in the remaining groups. These results demonstrate that reduction of masticatory afferent stimuli due to long-term soft-diet feeding may induce neuron loss in the hippocampus and reduced memory/learning ability.

  11. Interactive Exploration for Continuously Expanding Neuron Databases.

    Science.gov (United States)

    Li, Zhongyu; Metaxas, Dimitris N; Lu, Aidong; Zhang, Shaoting

    2017-02-15

    This paper proposes a novel framework to help biologists explore and analyze neurons based on retrieval of data from neuron morphological databases. In recent years, the continuously expanding neuron databases provide a rich source of information to associate neuronal morphologies with their functional properties. We design a coarse-to-fine framework for efficient and effective data retrieval from large-scale neuron databases. In the coarse-level, for efficiency in large-scale, we employ a binary coding method to compress morphological features into binary codes of tens of bits. Short binary codes allow for real-time similarity searching in Hamming space. Because the neuron databases are continuously expanding, it is inefficient to re-train the binary coding model from scratch when adding new neurons. To solve this problem, we extend binary coding with online updating schemes, which only considers the newly added neurons and update the model on-the-fly, without accessing the whole neuron databases. In the fine-grained level, we introduce domain experts/users in the framework, which can give relevance feedback for the binary coding based retrieval results. This interactive strategy can improve the retrieval performance through re-ranking the above coarse results, where we design a new similarity measure and take the feedback into account. Our framework is validated on more than 17,000 neuron cells, showing promising retrieval accuracy and efficiency. Moreover, we demonstrate its use case in assisting biologists to identify and explore unknown neurons. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. A natural form of learning can increase and decrease the survival of new neurons in the dentate gyrus.

    Science.gov (United States)

    Olariu, Ana; Cleaver, Kathryn M; Shore, Lauren E; Brewer, Michelle D; Cameron, Heather A

    2005-01-01

    Granule cells born in the adult dentate gyrus undergo a 4-week developmental period characterized by high susceptibility to cell death. Two forms of hippocampus-dependent learning have been shown to rescue many of the new neurons during this critical period. Here, we show that a natural form of associative learning, social transmission of food preference (STFP), can either increase or decrease the survival of young granule cells in adult rats. Increased numbers of pyknotic as well as phospho-Akt-expressing BrdU-labeled cells were seen 1 day after STFP training, indicating that training rapidly induces both cell death and active suppression of cell death in different subsets. A single day of training for STFP increased the survival of 8-day-old BrdU-labeled cells when examined 1 week later. In contrast, 2 days of training decreased the survival of BrdU-labeled cells and the density of immature neurons, identified with crmp-4. This change from increased to decreased survival could not be accounted for by the ages of the cells. Instead, we propose that training may initially increase young granule cell survival, then, if continued, cause them to die. This complex regulation of cell death could potentially serve to maintain granule cells that are actively involved in memory consolidation, while rapidly using and discarding young granule cells whose training is complete to make space for new naïve neurons. Published 2005 Wiley-Liss, Inc.

  13. Neuro-fuzzy decoding of sensory information from ensembles of simultaneously recorded dorsal root ganglion neurons for functional electrical stimulation applications

    Science.gov (United States)

    Rigosa, J.; Weber, D. J.; Prochazka, A.; Stein, R. B.; Micera, S.

    2011-08-01

    Functional electrical stimulation (FES) is used to improve motor function after injury to the central nervous system. Some FES systems use artificial sensors to switch between finite control states. To optimize FES control of the complex behavior of the musculo-skeletal system in activities of daily life, it is highly desirable to implement feedback control. In theory, sensory neural signals could provide the required control signals. Recent studies have demonstrated the feasibility of deriving limb-state estimates from the firing rates of primary afferent neurons recorded in dorsal root ganglia (DRG). These studies used multiple linear regression (MLR) methods to generate estimates of limb position and velocity based on a weighted sum of firing rates in an ensemble of simultaneously recorded DRG neurons. The aim of this study was to test whether the use of a neuro-fuzzy (NF) algorithm (the generalized dynamic fuzzy neural networks (GD-FNN)) could improve the performance, robustness and ability to generalize from training to test sets compared to the MLR technique. NF and MLR decoding methods were applied to ensemble DRG recordings obtained during passive and active limb movements in anesthetized and freely moving cats. The GD-FNN model provided more accurate estimates of limb state and generalized better to novel movement patterns. Future efforts will focus on implementing these neural recording and decoding methods in real time to provide closed-loop control of FES using the information extracted from sensory neurons.

  14. Neuro-fuzzy decoding of sensory information from ensembles of simultaneously recorded dorsal root ganglion neurons for functional electrical stimulation applications.

    Science.gov (United States)

    Rigosa, J; Weber, D J; Prochazka, A; Stein, R B; Micera, S

    2011-08-01

    Functional electrical stimulation (FES) is used to improve motor function after injury to the central nervous system. Some FES systems use artificial sensors to switch between finite control states. To optimize FES control of the complex behavior of the musculo-skeletal system in activities of daily life, it is highly desirable to implement feedback control. In theory, sensory neural signals could provide the required control signals. Recent studies have demonstrated the feasibility of deriving limb-state estimates from the firing rates of primary afferent neurons recorded in dorsal root ganglia (DRG). These studies used multiple linear regression (MLR) methods to generate estimates of limb position and velocity based on a weighted sum of firing rates in an ensemble of simultaneously recorded DRG neurons. The aim of this study was to test whether the use of a neuro-fuzzy (NF) algorithm (the generalized dynamic fuzzy neural networks (GD-FNN)) could improve the performance, robustness and ability to generalize from training to test sets compared to the MLR technique. NF and MLR decoding methods were applied to ensemble DRG recordings obtained during passive and active limb movements in anesthetized and freely moving cats. The GD-FNN model provided more accurate estimates of limb state and generalized better to novel movement patterns. Future efforts will focus on implementing these neural recording and decoding methods in real time to provide closed-loop control of FES using the information extracted from sensory neurons.

  15. Direct Reprogramming of Spiral Ganglion Non-neuronal Cells into Neurons: Toward Ameliorating Sensorineural Hearing Loss by Gene Therapy

    Directory of Open Access Journals (Sweden)

    Teppei Noda

    2018-02-01

    Full Text Available Primary auditory neurons (PANs play a critical role in hearing by transmitting sound information from the inner ear to the brain. Their progressive degeneration is associated with excessive noise, disease and aging. The loss of PANs leads to permanent hearing impairment since they are incapable of regenerating. Spiral ganglion non-neuronal cells (SGNNCs, comprised mainly of glia, are resident within the modiolus and continue to survive after PAN loss. These attributes make SGNNCs an excellent target for replacing damaged PANs through cellular reprogramming. We used the neurogenic pioneer transcription factor Ascl1 and the auditory neuron differentiation factor NeuroD1 to reprogram SGNNCs into induced neurons (iNs. The overexpression of both Ascl1 and NeuroD1 in vitro generated iNs at high efficiency. Transcriptome analyses revealed that iNs displayed a transcriptome profile resembling that of endogenous PANs, including expression of several key markers of neuronal identity: Tubb3, Map2, Prph, Snap25, and Prox1. Pathway analyses indicated that essential pathways in neuronal growth and maturation were activated in cells upon neuronal induction. Furthermore, iNs extended projections toward cochlear hair cells and cochlear nucleus neurons when cultured with each respective tissue. Taken together, our study demonstrates that PAN-like neurons can be generated from endogenous SGNNCs. This work suggests that gene therapy can be a viable strategy to treat sensorineural hearing loss caused by degeneration of PANs.

  16. Can inhibitory and facilitatory kinesiotaping techniques affect motor neuron excitability? A randomized cross-over trial.

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    Yoosefinejad, Amin Kordi; Motealleh, Alireza; Abbasalipur, Shekoofeh; Shahroei, Mahan; Sobhani, Sobhan

    2017-04-01

    The aim of this study was to investigate the immediate effects of facilitatory and inhibitory kinesiotaping on motor neuron excitability. Randomized cross-over trial. Twenty healthy people received inhibitory and facilitatory kinesiotaping on two testing days. The H- and M-waves of the lateral gasterocnemius were recorded before and immediately after applying the two modes of taping. The Hmax/Mmax ratio (a measure of motor neuron excitability) was determined and analyzed. The mean Hmax/Mmax ratios were -0.013 (95% CI: -0.033 to 0.007) for inhibitory taping and 0.007 (95% CI: -0.013 to 0.027) for facilitatory taping. The mean difference between groups was -0.020 (95% CI: -0.048 to 0.008). The statistical model revealed no significant differences between the two interventions (P = 0.160). Furthermore, there were no within-group differences in Hmax/Mmax ratio for either group. Our findings did not disclose signs of immediate change in motor neuron excitability in the lateral gasterocnemius. Copyright © 2016. Published by Elsevier Ltd.

  17. The hippocampus of the eastern rock sengi: cytoarchitecture, markers of neuronal function, principal cell numbers and adult neurogenesis

    Directory of Open Access Journals (Sweden)

    Lutz eSlomianka

    2013-10-01

    Full Text Available The brains of sengis (elephant shrews, order Macroscelidae have long been known to contain a hippocampus that in terms of allometric progression indices is larger than that of most primates and equal in size to that of humans. In this report, we provide descriptions of hippocampal cytoarchitecture in the eastern rock sengi (Elephantulus myurus, of the distributions of hippocampal calretinin, calbindin, parvalbumin and somatostatin, of principal neuron numbers and of cell numbers related to proliferation and neuronal differentiation in adult hippocampal neurogenesis. Sengi hippocampal cytoarchitecture is an amalgamation of characters that are found in CA1 of, e.g., guinea pig and rabbits and in CA3 and dentate gyrus of primates. Correspondence analysis of total cell numbers and quantitative relations between principal cell populations relate this sengi to macaque monkeys and domestic pigs, and distinguish the sengi from distinct patterns of relations found in humans, dogs and murine rodents. Calretinin and calbindin are present in some cell populations that also express these proteins in other species, e.g., interneurons at the stratum oriens/alveus border or temporal hilar mossy cells, but neurons expressing these markers are often scarce or absent in other layers. The distributions of parvalbumin and somatostatin resemble those in other species. Normalized numbers of PCNA+ proliferating cells and doublecortin+ differentiating cells of neuronal lineage fall within the overall ranges of murid rodents, but differed from three murid species captured in the same habitat in that fewer doublecortin+ cells relative to PCNA+ were observed . The large and well-differentiated sengi hippocampus is not accompanied by correspondingly sized cortical and subcortical limbic areas that are the main hippocampal sources of afferents and targets of efferents. This points to intrinsic hippocampal information processing as the selective advantage of the large sengi

  18. Signals and Circuits in the Purkinje Neuron

    Directory of Open Access Journals (Sweden)

    Ze'ev R Abrams

    2011-09-01

    Full Text Available Purkinje neurons in the cerebellum have over 100,000 inputs organized in an orthogonal geometry, and a single output channel. As the sole output of the cerebellar cortex layer, their complex firing pattern has been associated with motor control and learning. As such they have been extensively modeled and measured using tools ranging from electrophysiology and neuroanatomy, to dynamic systems and artificial intelligence methods. However, there is an alternative approach to analyze and describe the neuronal output of these cells using concepts from Electrical Engineering, particularly signal processing and digital/analog circuits. By viewing the Purkinje neuron as an unknown circuit to be reverse-engineered, we can use the tools that provide the foundations of today’s integrated circuits and communication systems to analyze the Purkinje system at the circuit level. We use Fourier transforms to analyze and isolate the inherent frequency modes in the Purkinje neuron and define 3 unique frequency ranges associated with the cells’ output. Comparing the Purkinje neuron to a signal generator that can be externally modulated adds an entire level of complexity to the functional role of these neurons both in terms of data analysis and information processing, relying on Fourier analysis methods in place of statistical ones. We also re-describe some of the recent literature in the field, using the nomenclature of signal processing. Furthermore, by comparing the experimental data of the past decade with basic electronic circuitry, we can resolve the outstanding controversy in the field, by recognizing that the Purkinje neuron can act as a multivibrator circuit.

  19. Physiological basis of tingling paresthesia evoked by hydroxy-α-sanshool

    Science.gov (United States)

    Lennertz, Richard C; Tsunozaki, Makoto; Bautista, Diana M; Stucky, Cheryl L

    2010-01-01

    Hydroxy-α-sanshool, the active ingredient in plants of the prickly ash plant family, induces robust tingling paresthesia by activating a subset of somatosensory neurons. However, the subtypes and physiological function of sanshool-sensitive neurons remain unknown. Here we use the ex vivo skin-nerve preparation to examine the pattern and intensity with which the sensory terminals of cutaneous neurons respond to hydroxy-α-sanshool. We found that sanshool excites virtually all D-hair afferents, a distinct subset of ultra-sensitive light touch receptors in the skin, and targets novel populations of Aβ and C-fiber nerve afferents. Thus, sanshool provides a novel pharmacological tool for discriminating functional subtypes of cutaneous mechanoreceptors. The identification of sanshool-sensitive fibers represents an essential first step in identifying the cellular and molecular mechanisms underlying tingling paresthesia that accompanies peripheral neuropathy and injury. PMID:20335471

  20. Physiological basis of tingling paresthesia evoked by hydroxy-alpha-sanshool.

    Science.gov (United States)

    Lennertz, Richard C; Tsunozaki, Makoto; Bautista, Diana M; Stucky, Cheryl L

    2010-03-24

    Hydroxy-alpha-sanshool, the active ingredient in plants of the prickly ash plant family, induces robust tingling paresthesia by activating a subset of somatosensory neurons. However, the subtypes and physiological function of sanshool-sensitive neurons remain unknown. Here we use the ex vivo skin-nerve preparation to examine the pattern and intensity with which the sensory terminals of cutaneous neurons respond to hydroxy-alpha-sanshool. We found that sanshool excites virtually all D-hair afferents, a distinct subset of ultrasensitive light-touch receptors in the skin and targets novel populations of Abeta and C fiber nerve afferents. Thus, sanshool provides a novel pharmacological tool for discriminating functional subtypes of cutaneous mechanoreceptors. The identification of sanshool-sensitive fibers represents an essential first step in identifying the cellular and molecular mechanisms underlying tingling paresthesia that accompanies peripheral neuropathy and injury.