WorldWideScience

Sample records for sensory neuron corpses

  1. Kappe neurons, a novel population of olfactory sensory neurons

    OpenAIRE

    Ahuja, Gaurav; Nia, Shahrzad Bozorg; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I.

    2014-01-01

    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 ar...

  2. 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.

  3. Complete functional characterization of sensory neurons by system identification.

    Science.gov (United States)

    Wu, Michael C-K; David, Stephen V; Gallant, Jack L

    2006-01-01

    System identification is a growing approach to sensory neurophysiology that facilitates the development of quantitative functional models of sensory processing. This approach provides a clear set of guidelines for combining experimental data with other knowledge about sensory function to obtain a description that optimally predicts the way that neurons process sensory information. This prediction paradigm provides an objective method for evaluating and comparing computational models. In this chapter we review many of the system identification algorithms that have been used in sensory neurophysiology, and we show how they can be viewed as variants of a single statistical inference problem. We then review many of the practical issues that arise when applying these methods to neurophysiological experiments: stimulus selection, behavioral control, model visualization, and validation. Finally we discuss several problems to which system identification has been applied recently, including one important long-term goal of sensory neuroscience: developing models of sensory systems that accurately predict neuronal responses under completely natural conditions.

  4. Expressing exogenous functional odorant receptors in cultured olfactory sensory neurons

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    Fomina Alla F

    2008-09-01

    Full Text Available Abstract Background Olfactory discrimination depends on the large numbers of odorant receptor genes and differential ligand-receptor signaling among neurons expressing different receptors. In this study, we describe an in vitro system that enables the expression of exogenous odorant receptors in cultured olfactory sensory neurons. Olfactory sensory neurons in the culture express characteristic signaling molecules and, therefore, provide a system to study receptor function within its intrinsic cellular environment. Results We demonstrate that cultured olfactory sensory neurons express endogenous odorant receptors. Lentiviral vector-mediated gene transfer enables successful ectopic expression of odorant receptors. We show that the ectopically expressed mouse I7 is functional in the cultured olfactory sensory neurons. When two different odorant receptors are ectopically expressed simultaneously, both receptor proteins co-localized in the same olfactory sensory neurons up to 10 days in vitro. Conclusion This culture technique provided an efficient method to culture olfactory sensory neurons whose morphology, molecular characteristics and maturation progression resembled those observed in vivo. Using this system, regulation of odorant receptor expression and its ligand specificity can be studied in its intrinsic cellular environment.

  5. P2X receptors, sensory neurons and pain.

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    Bele, Tanja; Fabbretti, Elsa

    2015-01-01

    Pain represents a very large social and clinical problem since the current treatment provides insufficient pain relief. Plasticity of pain receptors together with sensitisation of sensory neurons, and the role of soluble mediators released from non-neuronal cells render difficult to understand the spatial and temporal scale of pain development, neuronal responses and disease progression. In pathological conditions, ATP is one of the most powerful mediators that activates P2X receptors that behave as sensitive ATP-detectors, such as neuronal P2X3 receptor subtypes and P2X4 and P2X7 receptors expressed on non-neuronal cells. Dissecting the molecular mechanisms occurring in sensory neurons and in accessory cells allows to design appropriate tissue- and cell- targeted approaches to treat chronic pain.

  6. Dicer maintains the identity and function of proprioceptive sensory neurons.

    Science.gov (United States)

    O'Toole, Sean M; Ferrer, Monica M; Mekonnen, Jennifer; Zhang, Haihan; Shima, Yasuyuki; Ladle, David R; Nelson, Sacha B

    2017-03-01

    Neuronal cell identity is established during development and must be maintained throughout an animal's life (Fishell G, Heintz N. Neuron 80: 602-612, 2013). Transcription factors critical for establishing neuronal identity can be required for maintaining it (Deneris ES, Hobert O. Nat Neurosci 17: 899-907, 2014). Posttranscriptional regulation also plays an important role in neuronal differentiation (Bian S, Sun T. Mol Neurobiol 44: 359-373, 2011), but its role in maintaining cell identity is less established. To better understand how posttranscriptional regulation might contribute to cell identity, we examined the proprioceptive neurons in the dorsal root ganglion (DRG), a highly specialized sensory neuron class, with well-established properties that distinguish them from other neurons in the ganglion. By conditionally ablating Dicer in mice, using parvalbumin (Pvalb)-driven Cre recombinase, we impaired posttranscriptional regulation in the proprioceptive sensory neuron population. Knockout (KO) animals display a progressive form of ataxia at the beginning of the fourth postnatal week that is accompanied by a cell death within the DRG. Before cell loss, expression profiling shows a reduction of proprioceptor specific genes and an increased expression of nonproprioceptive genes normally enriched in other ganglion neurons. Furthermore, although central connections of these neurons are intact, the peripheral connections to the muscle are functionally impaired. Posttranscriptional regulation is therefore necessary to retain the transcriptional identity and support functional specialization of the proprioceptive sensory neurons. NEW & NOTEWORTHY We have demonstrated that selectively impairing Dicer in parvalbumin-positive neurons, which include the proprioceptors, triggers behavioral changes, a lack of muscle connectivity, and a loss of transcriptional identity as observed through RNA sequencing. These results suggest that Dicer and, most likely by extension, micro

  7. Localization of SSeCKS in unmyelinated primary sensory neurons

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    Siegel Sandra M

    2008-03-01

    Full Text Available Abstract Background SSeCKS (Src SupprEssed C Kinase Substrate is a proposed protein kinase C substrate/A kinase anchoring protein (AKAP that has recently been characterized in the rat peripheral nervous system. It has been shown that approximately 40% of small primary sensory neurons contain SSeCKS-immunoreactivity in a population largely separate from substance P (95.2%, calcitonin gene related peptide (95.3%, or fluoride resistant acid phosphatase (55.0% labeled cells. In the spinal cord, it was found that SSeCKS-immunoreactive axon collaterals terminate in the dorsal third of lamina II outer in a region similar to that of unmyelinated C-, or small diameter myelinated Aδ-, fibers. However, the precise characterization of the anatomical profile of the primary sensory neurons containing SSeCKS remains to be determined. Here, immunohistochemical labeling at the light and ultrastructural level is used to clarify the myelination status of SSeCKS-containing sensory neuron axons and to further clarify the morphometric, and provide insight into the functional, classification of SSeCKS-IR sensory neurons. Methods Colocalization studies of SSeCKS with myelination markers, ultrastructural localization of SSeCKS labeling and ablation of largely unmyelinated sensory fibers by neonatal capsaicin administration were all used to establish whether SSeCKS containing sensory neurons represent a subpopulation of unmyelinated primary sensory C-fibers. Results Double labeling studies of SSeCKS with CNPase in the dorsal horn and Pzero in the periphery showed that SSeCKS immunoreactivity was observed predominantly in association with unmyelinated primary sensory fibers. At the ultrastructural level, SSeCKS immunoreactivity was most commonly associated with axonal membrane margins of unmyelinated fibers. In capsaicin treated rats, SSeCKS immunoreactivity was essentially obliterated in the dorsal horn while in dorsal root ganglia quantitative analysis revealed a 43

  8. Epac activation sensitizes rat sensory neurons via activation of Ras

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    Shariati, Behzad; Thompson, Eric L.; Nicol, Grant D.; Vasko, Michael R.

    2015-01-01

    Guanine nucleotide exchange factors directly activated by cAMP (Epacs) have emerged as important signaling molecules mediating persistent hypersensitivity in animal models of inflammation, by augmenting the excitability of sensory neurons. Although Epacs activate numerous downstream signaling cascades, the intracellular signaling which mediates Epac-induced sensitization of capsaicin-sensitive sensory neurons remains unknown. Here, we demonstrate that selective activation of Epacs with 8-CPT-2′-O-Me-cAMP-AM (8CPT-AM) increases the number of action potentials (APs) generated by a ramp of depolarizing current and augments the evoked release of calcitonin gene-related peptide (CGRP) from isolated rat sensory neurons. Internal perfusion of capsaicin-sensitive sensory neurons with GDP-βS, substituted for GTP, blocks the ability of 8CPT-AM to increase AP firing, demonstrating that Epac-induced sensitization is G-protein dependent. Treatment with 8CPT-AM activates the small G-proteins Rap1 and Ras in cultures of sensory neurons. Inhibition of Rap1, by internal perfusion of a Rap1-neutralizing antibody or through a reduction in the expression of the protein using shRNA does not alter the Epac-induced enhancement of AP generation or CGRP release, despite the fact that in most other cell types, Epacs act as Rap-GEFs. In contrast, inhibition of Ras through expression of a dominant negative Ras (DN-Ras) or through internal perfusion of a Ras-neutralizing antibody blocks the increase in AP firing and attenuates the increase in the evoked release of CGRP induced by Epac activation. Thus, in this subpopulation of nociceptive sensory neurons, it is the novel interplay between Epacs and Ras, rather than the canonical Epacs and Rap1 pathway, that is critical for mediating Epac-induced sensitization. PMID:26596174

  9. Epac activation sensitizes rat sensory neurons through activation of Ras.

    Science.gov (United States)

    Shariati, Behzad; Thompson, Eric L; Nicol, Grant D; Vasko, Michael R

    2016-01-01

    Guanine nucleotide exchange factors directly activated by cAMP (Epacs) have emerged as important signaling molecules mediating persistent hypersensitivity in animal models of inflammation, by augmenting the excitability of sensory neurons. Although Epacs activate numerous downstream signaling cascades, the intracellular signaling which mediates Epac-induced sensitization of capsaicin-sensitive sensory neurons remains unknown. Here, we demonstrate that selective activation of Epacs with 8-CPT-2'-O-Me-cAMP-AM (8CPT-AM) increases the number of action potentials (APs) generated by a ramp of depolarizing current and augments the evoked release of calcitonin gene-related peptide (CGRP) from isolated rat sensory neurons. Internal perfusion of capsaicin-sensitive sensory neurons with GDP-βS, substituted for GTP, blocks the ability of 8CPT-AM to increase AP firing, demonstrating that Epac-induced sensitization is G-protein dependent. Treatment with 8CPT-AM activates the small G-proteins Rap1 and Ras in cultures of sensory neurons. Inhibition of Rap1, by internal perfusion of a Rap1-neutralizing antibody or through a reduction in the expression of the protein using shRNA does not alter the Epac-induced enhancement of AP generation or CGRP release, despite the fact that in most other cell types, Epacs act as Rap-GEFs. In contrast, inhibition of Ras through expression of a dominant negative Ras (DN-Ras) or through internal perfusion of a Ras-neutralizing antibody blocks the increase in AP firing and attenuates the increase in the evoked release of CGRP induced by Epac activation. Thus, in this subpopulation of nociceptive sensory neurons, it is the novel interplay between Epacs and Ras, rather than the canonical Epacs and Rap1 pathway, that is critical for mediating Epac-induced sensitization. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Diverse coupling of neurons to populations in sensory cortex.

    Science.gov (United States)

    Okun, Michael; Steinmetz, Nicholas; Cossell, Lee; Iacaruso, M Florencia; Ko, Ho; Barthó, Péter; Moore, Tirin; Hofer, Sonja B; Mrsic-Flogel, Thomas D; Carandini, Matteo; Harris, Kenneth D

    2015-05-28

    A large population of neurons can, in principle, produce an astronomical number of distinct firing patterns. In cortex, however, these patterns lie in a space of lower dimension, as if individual neurons were "obedient members of a huge orchestra". Here we use recordings from the visual cortex of mouse (Mus musculus) and monkey (Macaca mulatta) to investigate the relationship between individual neurons and the population, and to establish the underlying circuit mechanisms. We show that neighbouring neurons can differ in their coupling to the overall firing of the population, ranging from strongly coupled 'choristers' to weakly coupled 'soloists'. Population coupling is largely independent of sensory preferences, and it is a fixed cellular attribute, invariant to stimulus conditions. Neurons with high population coupling are more strongly affected by non-sensory behavioural variables such as motor intention. Population coupling reflects a causal relationship, predicting the response of a neuron to optogenetically driven increases in local activity. Moreover, population coupling indicates synaptic connectivity; the population coupling of a neuron, measured in vivo, predicted subsequent in vitro estimates of the number of synapses received from its neighbours. Finally, population coupling provides a compact summary of population activity; knowledge of the population couplings of n neurons predicts a substantial portion of their n(2) pairwise correlations. Population coupling therefore represents a novel, simple measure that characterizes the relationship of each neuron to a larger population, explaining seemingly complex network firing patterns in terms of basic circuit variables.

  11. 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

  12. [The mirror neuron system in motor and sensory rehabilitation].

    Science.gov (United States)

    Oouchida, Yutaka; Izumi, Shinichi

    2014-06-01

    The discovery of the mirror neuron system has dramatically changed the study of motor control in neuroscience. The mirror neuron system provides a conceptual framework covering the aspects of motor as well as sensory functions in motor control. Previous studies of motor control can be classified as studies of motor or sensory functions, and these two classes of studies appear to have advanced independently. In rehabilitation requiring motor learning, such as relearning movement after limb paresis, however, sensory information of feedback for motor output as well as motor command are essential. During rehabilitation from chronic pain, motor exercise is one of the most effective treatments for pain caused by dysfunction in the sensory system. In rehabilitation where total intervention unifying the motor and sensory aspects of motor control is important, learning through imitation, which is associated with the mirror neuron system can be effective and suitable. In this paper, we introduce the clinical applications of imitated movement in rehabilitation from motor impairment after brain damage and phantom limb pain after limb amputation.

  13. Activation of Six1 Expression in Vertebrate Sensory Neurons.

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    Shigeru Sato

    Full Text Available SIX1 homeodomain protein is one of the essential key regulators of sensory organ development. Six1-deficient mice lack the olfactory epithelium, vomeronasal organs, cochlea, vestibule and vestibuloacoustic ganglion, and also show poor neural differentiation in the distal part of the cranial ganglia. Simultaneous loss of both Six1 and Six4 leads to additional abnormalities such as small trigeminal ganglion and abnormal dorsal root ganglia (DRG. The aim of this study was to understand the molecular mechanism that controls Six1 expression in sensory organs, particularly in the trigeminal ganglion and DRG. To this end, we focused on the sensory ganglia-specific Six1 enhancer (Six1-8 conserved between chick and mouse. In vivo reporter assays using both animals identified an important core region comprising binding consensus sequences for several transcription factors including nuclear hormone receptors, TCF/LEF, SMAD, POU homeodomain and basic-helix-loop-helix proteins. The results provided information on upstream factors and signals potentially relevant to Six1 regulation in sensory neurons. We also report the establishment of a new transgenic mouse line (mSix1-8-NLSCre that expresses Cre recombinase under the control of mouse Six1-8. Cre-mediated recombination was detected specifically in ISL1/2-positive sensory neurons of Six1-positive cranial sensory ganglia and DRG. The unique features of the mSix1-8-NLSCre line are the absence of Cre-mediated recombination in SOX10-positive glial cells and central nervous system and ability to induce recombination in a subset of neurons derived from the olfactory placode/epithelium. This mouse model can be potentially used to advance research on sensory development.

  14. A role for Runx transcription factor signaling in dorsal root ganglion sensory neuron diversification.

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    Kramer, Ina; Sigrist, Markus; de Nooij, Joriene C; Taniuchi, Ichiro; Jessell, Thomas M; Arber, Silvia

    2006-02-02

    Subpopulations of sensory neurons in the dorsal root ganglion (DRG) can be characterized on the basis of sensory modalities that convey distinct peripheral stimuli, but the molecular mechanisms that underlie sensory neuronal diversification remain unclear. Here, we have used genetic manipulations in the mouse embryo to examine how Runx transcription factor signaling controls the acquisition of distinct DRG neuronal subtype identities. Runx3 acts to diversify an Ngn1-independent neuronal cohort by promoting the differentiation of proprioceptive sensory neurons through erosion of TrkB expression in prospective TrkC+ sensory neurons. In contrast, Runx1 controls neuronal diversification within Ngn1-dependent TrkA+ neurons by repression of neuropeptide CGRP expression and controlling the fine pattern of laminar termination in the dorsal spinal cord. Together, our findings suggest that Runx transcription factor signaling plays a key role in sensory neuron diversification.

  15. Sensory Prioritization in Rats: Behavioral Performance and Neuronal Correlates.

    Science.gov (United States)

    Lee, Conrad C Y; Diamond, Mathew E; Arabzadeh, Ehsan

    2016-03-16

    Operating with some finite quantity of processing resources, an animal would benefit from prioritizing the sensory modality expected to provide key information in a particular context. The present study investigated whether rats dedicate attentional resources to the sensory modality in which a near-threshold event is more likely to occur. We manipulated attention by controlling the likelihood with which a stimulus was presented from one of two modalities. In a whisker session, 80% of trials contained a brief vibration stimulus applied to whiskers and the remaining 20% of trials contained a brief change of luminance. These likelihoods were reversed in a visual session. When a stimulus was presented in the high-likelihood context, detection performance increased and was faster compared with the same stimulus presented in the low-likelihood context. Sensory prioritization was also reflected in neuronal activity in the vibrissal area of primary somatosensory cortex: single units responded differentially to the whisker vibration stimulus when presented with higher probability compared with lower probability. Neuronal activity in the vibrissal cortex displayed signatures of multiplicative gain control and enhanced response to vibration stimuli during the whisker session. In conclusion, rats allocate priority to the more likely stimulus modality and the primary sensory cortex may participate in the redistribution of resources. Detection of low-amplitude events is critical to survival; for example, to warn prey of predators. To formulate a response, decision-making systems must extract minute neuronal signals from the sensory modality that provides key information. Here, we identify the behavioral and neuronal correlates of sensory prioritization in rats. Rats were trained to detect whisker vibrations or visual flickers. Stimuli were embedded in two contexts in which either visual or whisker modality was more likely to occur. When a stimulus was presented in the high

  16. Involvement of sensory neurons in bone defect repair in rats

    International Nuclear Information System (INIS)

    Henmi, Akiko; Nakamura, Megumi; Echigo, Seishi; Sasano, Yasuyuki

    2011-01-01

    We investigated bone repair in sensory-denervated rats, compared with controls, to elucidate the involvement of sensory neurons. Nine-week-old male Wistar rats received subcutaneous injections of capsaicin to denervate sensory neurons. Rats treated with the same amount of vehicle served as controls. A standardized bone defect was created on the parietal bone. We measured the amount of repaired bone with quantitative radiographic analysis and the mRNA expressions of osteocalcin and cathepsin K with real-time polymerase chain reaction (PCR). Quantitative radiographic analysis showed that the standard deviations and coefficients of variation for the amount of repaired bone were much higher in the capsaicin-treated group than in the control group at any time point, which means that larger individual differences in the amount of repaired bone were found in capsaicin-treated rats than controls. Furthermore, radiographs showed radiolucency in pre-existing bone surrounding the standardized defect only in the capsaicin-treated group, and histological observation demonstrated some multinuclear cells corresponding to the radiolucent area. Real-time PCR indicated that there was no significant difference in the mRNA expression levels of osteocalcin and cathepsin K between the control group and the capsaicin-treated group. These results suggest that capsaicin-induced sensory denervation affects the bone defect repair. (author)

  17. Effects of Colored Noise on Stochastic Resonance in Sensory Neurons

    International Nuclear Information System (INIS)

    Nozaki, D.; Mar, D.J.; Collins, J.J.; Grigg, P.

    1999-01-01

    Noise can assist neurons in the detection of weak signals via a mechanism known as stochastic resonance (SR). We demonstrate experimentally that SR-type effects can be obtained in rat sensory neurons with white noise, 1/f noise, or 1/f 2 noise. For low-frequency input noise, we show that the optimal noise intensity is the lowest and the output signal-to-noise ratio the highest for conventional white noise. We also show that under certain circumstances, 1/f noise can be better than white noise for enhancing the response of a neuron to a weak signal. We present a theory to account for these results and discuss the biological implications of 1/f noise. copyright 1999 The American Physical Society

  18. Odor-evoked inhibition of olfactory sensory neurons drives olfactory perception in Drosophila.

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    Cao, Li-Hui; Yang, Dong; Wu, Wei; Zeng, Xiankun; Jing, Bi-Yang; Li, Meng-Tong; Qin, Shanshan; Tang, Chao; Tu, Yuhai; Luo, Dong-Gen

    2017-11-07

    Inhibitory response occurs throughout the nervous system, including the peripheral olfactory system. While odor-evoked excitation in peripheral olfactory cells is known to encode odor information, the molecular mechanism and functional roles of odor-evoked inhibition remain largely unknown. Here, we examined Drosophila olfactory sensory neurons and found that inhibitory odors triggered outward receptor currents by reducing the constitutive activities of odorant receptors, inhibiting the basal spike firing in olfactory sensory neurons. Remarkably, this odor-evoked inhibition of olfactory sensory neurons elicited by itself a full range of olfactory behaviors from attraction to avoidance, as did odor-evoked olfactory sensory neuron excitation. These results indicated that peripheral inhibition is comparable to excitation in encoding sensory signals rather than merely regulating excitation. Furthermore, we demonstrated that a bidirectional code with both odor-evoked inhibition and excitation in single olfactory sensory neurons increases the odor-coding capacity, providing a means of efficient sensory encoding.

  19. Visualization of Sensory Neurons and Their Projections in an Upper Motor Neuron Reporter Line.

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    Genç, Barış; Lagrimas, Amiko Krisa Bunag; Kuru, Pınar; Hess, Robert; Tu, Michael William; Menichella, Daniela Maria; Miller, Richard J; Paller, Amy S; Özdinler, P Hande

    2015-01-01

    Visualization of peripheral nervous system axons and cell bodies is important to understand their development, target recognition, and integration into complex circuitries. Numerous studies have used protein gene product (PGP) 9.5 [a.k.a. ubiquitin carboxy-terminal hydrolase L1 (UCHL1)] expression as a marker to label sensory neurons and their axons. Enhanced green fluorescent protein (eGFP) expression, under the control of UCHL1 promoter, is stable and long lasting in the UCHL1-eGFP reporter line. In addition to the genetic labeling of corticospinal motor neurons in the motor cortex and degeneration-resistant spinal motor neurons in the spinal cord, here we report that neurons of the peripheral nervous system are also fluorescently labeled in the UCHL1-eGFP reporter line. eGFP expression is turned on at embryonic ages and lasts through adulthood, allowing detailed studies of cell bodies, axons and target innervation patterns of all sensory neurons in vivo. In addition, visualization of both the sensory and the motor neurons in the same animal offers many advantages. In this report, we used UCHL1-eGFP reporter line in two different disease paradigms: diabetes and motor neuron disease. eGFP expression in sensory axons helped determine changes in epidermal nerve fiber density in a high-fat diet induced diabetes model. Our findings corroborate previous studies, and suggest that more than five months is required for significant skin denervation. Crossing UCHL1-eGFP with hSOD1G93A mice generated hSOD1G93A-UeGFP reporter line of amyotrophic lateral sclerosis, and revealed sensory nervous system defects, especially towards disease end-stage. Our studies not only emphasize the complexity of the disease in ALS, but also reveal that UCHL1-eGFP reporter line would be a valuable tool to visualize and study various aspects of sensory nervous system development and degeneration in the context of numerous diseases.

  20. Phospholipid Homeostasis Regulates Dendrite Morphogenesis in Drosophila Sensory Neurons

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    Shan Meltzer

    2017-10-01

    Full Text Available Disruptions in lipid homeostasis have been observed in many neurodevelopmental disorders that are associated with dendrite morphogenesis defects. However, the molecular mechanisms of how lipid homeostasis affects dendrite morphogenesis are unclear. We find that easily shocked (eas, which encodes a kinase with a critical role in phospholipid phosphatidylethanolamine (PE synthesis, and two other enzymes in this synthesis pathway are required cell autonomously in sensory neurons for dendrite growth and stability. Furthermore, we show that the level of Sterol Regulatory Element-Binding Protein (SREBP activity is important for dendrite development. SREBP activity increases in eas mutants, and decreasing the level of SREBP and its transcriptional targets in eas mutants largely suppresses the dendrite growth defects. Furthermore, reducing Ca2+ influx in neurons of eas mutants ameliorates the dendrite morphogenesis defects. Our study uncovers a role for EAS kinase and reveals the in vivo function of phospholipid homeostasis in dendrite morphogenesis.

  1. Sensory neurons do not induce motor neuron loss in a human stem cell model of spinal muscular atrophy.

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    Schwab, Andrew J; Ebert, Allison D

    2014-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive disorder leading to paralysis and early death due to reduced SMN protein. It is unclear why there is such a profound motor neuron loss, but recent evidence from fly and mouse studies indicate that cells comprising the whole sensory-motor circuit may contribute to motor neuron dysfunction and loss. Here, we used induced pluripotent stem cells derived from SMA patients to test whether sensory neurons directly contribute to motor neuron loss. We generated sensory neurons from SMA induced pluripotent stem cells and found no difference in neuron generation or survival, although there was a reduced calcium response to depolarizing stimuli. Using co-culture of SMA induced pluripotent stem cell derived sensory neurons with control induced pluripotent stem cell derived motor neurons, we found no significant reduction in motor neuron number or glutamate transporter boutons on motor neuron cell bodies or neurites. We conclude that SMA sensory neurons do not overtly contribute to motor neuron loss in this human stem cell system.

  2. PERIPHERAL SENSORY NEURONS EXPRESSING MELANOPSIN RESPOND TO LIGHT

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    Anna Matynia

    2016-08-01

    Full Text Available The ability of light to cause pain is paradoxical. The retina detects light but is devoid of nociceptors while the trigeminal sensory ganglia (TG contain nociceptors but not photoreceptors. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs are thought to mediate light-induced pain but recent evidence raises the possibility of an alternative light responsive pathway independent of the retina and optic nerve. Here, we show that melanopsin is expressed in both human and mouse TG neurons. In mice, they represent 3% of small TG neurons that are preferentially localized in the ophthalmic branch of the trigeminal nerve and are likely nociceptive C fibers and high-threshold mechanoreceptor Aδ fibers based on a strong size-function association. These isolated neurons respond to blue light stimuli with a delayed onset and sustained firing, similar to the melanopsin-dependent intrinsic photosensitivity observed in ipRGCs. Mice with severe bilateral optic nerve crush exhibit no light-induced responses including behavioral light aversion until treated with nitroglycerin, an inducer of migraine in people and migraine-like symptoms in mice. With nitroglycerin, these same mice with optic nerve crush exhibit significant light aversion. Furthermore, this retained light aversion remains dependent on melanopsin-expressing neurons. Our results demonstrate a novel light-responsive neural function independent of the optic nerve that may originate in the peripheral nervous system to provide the first direct mechanism for an alternative light detection pathway that influences motivated behavior.

  3. Multiple sensory G proteins in the olfactory, gustatory and nociceptive neurons modulate longevity in Caenorhabditis elegans

    NARCIS (Netherlands)

    H. Lans (Hannes); G. Jansen (Gert)

    2007-01-01

    textabstractThe life span of the nematode Caenorhabditis elegans is under control of sensory signals detected by the amphid neurons. In these neurons, C. elegans expresses at least 13 Galpha subunits and a Ggamma subunit, which are involved in the transduction and modulation of sensory signals.

  4. Morphology and intrinsic excitability of regenerating sensory and motor neurons grown on a line micropattern.

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    Ouafa Benzina

    Full Text Available Axonal regeneration is one of the greatest challenges in severe injuries of peripheral nerve. To provide the bridge needed for regeneration, biological or synthetic tubular nerve constructs with aligned architecture have been developed. A key point for improving axonal regeneration is assessing the effects of substrate geometry on neuronal behavior. In the present study, we used an extracellular matrix-micropatterned substrate comprising 3 µm wide lines aimed to physically mimic the in vivo longitudinal axonal growth of mice peripheral sensory and motor neurons. Adult sensory neurons or embryonic motoneurons were seeded and processed for morphological and electrical activity analyses after two days in vitro. We show that micropattern-guided sensory neurons grow one or two axons without secondary branching. Motoneurons polarity was kept on micropattern with a long axon and small dendrites. The micro-patterned substrate maintains the growth promoting effects of conditioning injury and demonstrates, for the first time, that neurite initiation and extension could be differentially regulated by conditioning injury among DRG sensory neuron subpopulations. The micro-patterned substrate impacts the excitability of sensory neurons and promotes the apparition of firing action potentials characteristic for a subclass of mechanosensitive neurons. The line pattern is quite relevant for assessing the regenerative and developmental growth of sensory and motoneurons and offers a unique model for the analysis of the impact of geometry on the expression and the activity of mechanosensitive channels in DRG sensory neurons.

  5. Morphology and nanomechanics of sensory neurons growth cones following peripheral nerve injury.

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    Marta Martin

    Full Text Available A prior peripheral nerve injury in vivo, promotes a rapid elongated mode of sensory neurons neurite regrowth in vitro. This in vitro model of conditioned axotomy allows analysis of the cellular and molecular mechanisms leading to an improved neurite re-growth. Our differential interference contrast microscopy and immunocytochemistry results show that conditioned axotomy, induced by sciatic nerve injury, did not increase somatic size of adult lumbar sensory neurons from mice dorsal root ganglia sensory neurons but promoted the appearance of larger neurites and growth cones. Using atomic force microscopy on live neurons, we investigated whether membrane mechanical properties of growth cones of axotomized neurons were modified following sciatic nerve injury. Our data revealed that neurons having a regenerative growth were characterized by softer growth cones, compared to control neurons. The increase of the growth cone membrane elasticity suggests a modification in the ratio and the inner framework of the main structural proteins.

  6. touché is required for touch evoked generator potentials within vertebrate sensory neurons

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    Low, Sean E.; Ryan, Joel; Sprague, Shawn M.; Hirata, Hiromi; Cui, Wilson W.; Zhou, Weibin; Hume, Richard I.; Kuwada, John Y.; Saint-Amant, Louis

    2010-01-01

    The process by which light-touch in vertebrates is transformed into an electrical response in cutaneous mechanosensitive neurons is a largely unresolved question. To address this question we undertook a forward genetic screen in zebrafish (Danio rerio) to identify mutants exhibiting abnormal touch-evoked behaviors, despite the presence of sensory neurons and peripheral neurites. One family, subsequently named touché, was found to harbor a recessive mutation which produced offspring that were unresponsive to light-touch, but responded to a variety of other sensory stimuli. The optogenetic activation of motor behaviors by touché mutant sensory neurons expressing ChannelRhodopsin-2 suggested that the synaptic output of sensory neurons was intact, consistent with a defect in sensory neuron activation. To explore sensory neuron activation we developed an in vivo preparation permitting the precise placement of a combined electrical and tactile stimulating probe upon eGFP positive peripheral neurites. In wild type larva electrical and tactile stimulation of peripheral neurites produced action potentials detectable within the cell body. In a subset of these sensory neurons an underlying generator potential could be observed in response to subthreshold tactile stimuli. A closer examination revealed that the amplitude of the generator potential was proportional to the stimulus amplitude. When assayed touché mutant sensory neurons also responded to electrical stimulation of peripheral neurites similar to wild type larvae, however tactile stimulation of these neurites failed to uncover a subset of sensory neurons possessing generator potentials. These findings suggest that touché is required for generator potentials, and that generator potentials underlie responsiveness to light-touch in zebrafish. PMID:20631165

  7. Optogenetically enhanced axon regeneration: motor versus sensory neuron-specific stimulation.

    Science.gov (United States)

    Ward, Patricia J; Clanton, Scott L; English, Arthur W

    2018-02-01

    Brief neuronal activation in injured peripheral nerves is both necessary and sufficient to enhance motor axon regeneration, and this effect is specific to the activated motoneurons. It is less clear whether sensory neurons respond in a similar manner to neuronal activation following peripheral axotomy. Further, it is unknown to what extent enhancement of axon regeneration with increased neuronal activity relies on a reflexive interaction within the spinal circuitry. We used mouse genetics and optical tools to evaluate the precision and selectivity of system-specific neuronal activation to enhance axon regeneration in a mixed nerve. We evaluated sensory and motor axon regeneration in two different mouse models expressing the light-sensitive cation channel, channelrhodopsin (ChR2). We selectively activated either sensory or motor axons using light stimulation combined with transection and repair of the sciatic nerve. Regardless of genotype, the number of ChR2-positive neurons whose axons had regenerated successfully was greater following system-specific optical treatment, with no effect on the number of ChR2-negative neurons (whether motor or sensory neurons). We conclude that acute system-specific neuronal activation is sufficient to enhance both motor and sensory axon regeneration. This regeneration-enhancing effect is likely cell autonomous. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  8. Sensory experience regulates cortical inhibition by inducing IGF1 in VIP neurons.

    Science.gov (United States)

    Mardinly, A R; Spiegel, I; Patrizi, A; Centofante, E; Bazinet, J E; Tzeng, C P; Mandel-Brehm, C; Harmin, D A; Adesnik, H; Fagiolini, M; Greenberg, M E

    2016-03-17

    Inhibitory neurons regulate the adaptation of neural circuits to sensory experience, but the molecular mechanisms by which experience controls the connectivity between different types of inhibitory neuron to regulate cortical plasticity are largely unknown. Here we show that exposure of dark-housed mice to light induces a gene program in cortical vasoactive intestinal peptide (VIP)-expressing neurons that is markedly distinct from that induced in excitatory neurons and other subtypes of inhibitory neuron. We identify Igf1 as one of several activity-regulated genes that are specific to VIP neurons, and demonstrate that IGF1 functions cell-autonomously in VIP neurons to increase inhibitory synaptic input onto these neurons. Our findings further suggest that in cortical VIP neurons, experience-dependent gene transcription regulates visual acuity by activating the expression of IGF1, thus promoting the inhibition of disinhibitory neurons and affecting inhibition onto cortical pyramidal neurons.

  9. 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.

  10. Untuned But Not Irrelevant: The Role of Untuned Neurons In Sensory Information Coding

    OpenAIRE

    Zylberberg, Joel

    2017-01-01

    In the sensory systems, most neurons' firing rates are tuned to at least one aspect of the stimulus. Other neurons are appear to be untuned, meaning that their firing rates do not depend on the stimulus. Previous work on information coding in neural populations has ignored untuned neurons, based on the tacit assumption that they are unimportant. Recent experimental work has questioned this assumption, showing that in some circumstances, neurons with no apparent stimulus tuning can contribute ...

  11. Diabetic polyneuropathy, sensory neurons, nuclear structure and spliceosome alterations: a role for CWC22

    Directory of Open Access Journals (Sweden)

    Masaki Kobayashi

    2017-03-01

    Full Text Available Unique deficits in the function of adult sensory neurons as part of their early neurodegeneration might account for progressive polyneuropathy during chronic diabetes mellitus. Here, we provide structural and functional evidence for aberrant pre-mRNA splicing in a chronic type 1 model of experimental diabetic polyneuropathy (DPN. Cajal bodies (CBs, unique nuclear substructures involved in RNA splicing, increased in number in diabetic sensory neurons, but their expected colocalization with survival motor neuron (SMN proteins was reduced – a mislocalization described in motor neurons of spinal muscular atrophy. Small nuclear ribonucleoprotein particles (snRNPs, also participants in the spliceosome, had abnormal multiple nuclear foci unassociated with CBs, and their associated snRNAs were reduced. CWC22, a key spliceosome protein, was aberrantly upregulated in diabetic dorsal root ganglia (DRG, and impaired neuronal function. CWC22 attenuated sensory neuron plasticity, with knockdown in vitro enhancing their neurite outgrowth. Further, axonal delivery of CWC22 siRNA unilaterally to locally knock down the aberrant protein in diabetic nerves improved aspects of sensory function in diabetic mice. Collectively, our findings identify subtle but significant alterations in spliceosome structure and function, including dysregulated CBs and CWC22 overexpression, in diabetic sensory neurons that offer new ideas regarding diabetic sensory neurodegeneration in polyneuropathy.

  12. En masse in vitro functional profiling of the axonal mechanosensitivity of sensory neurons.

    Science.gov (United States)

    Usoskin, Dmitry; Zilberter, Misha; Linnarsson, Sten; Hjerling-Leffler, Jens; Uhlén, Per; Harkany, Tibor; Ernfors, Patrik

    2010-09-14

    Perception of the environment relies on somatosensory neurons. Mechanosensory, proprioceptor and many nociceptor subtypes of these neurons have specific mechanosensitivity profiles to adequately differentiate stimulus patterns. Nevertheless, the cellular basis of differential mechanosensation remains largely elusive. Successful transduction of sensory information relies on the recruitment of sensory neurons and mechanosensation occurring at their peripheral axonal endings in vivo. Conspicuously, existing in vitro models aimed to decipher molecular mechanisms of mechanosensation test single sensory neuron somata at any one time. Here, we introduce a compartmental in vitro chamber design to deliver precisely controlled mechanical stimulation of sensory axons with synchronous real-time imaging of Ca(2+) transients in neuronal somata that reliably reflect action potential firing patterns. We report of three previously not characterized types of mechanosensitive neuron subpopulations with distinct intrinsic axonal properties tuned specifically to static indentation or vibration stimuli, showing that different classes of sensory neurons are tuned to specific types of mechanical stimuli. Primary receptor currents of vibration neurons display rapidly adapting conductance reliably detected for every single stimulus during vibration and are consistently converted into action potentials. This result allows for the characterization of two critical steps of mechanosensation in vivo: primary signal detection and signal conversion into specific action potential firing patterns in axons.

  13. Slack channels expressed in sensory neurons control neuropathic pain in mice.

    Science.gov (United States)

    Lu, Ruirui; Bausch, Anne E; Kallenborn-Gerhardt, Wiebke; Stoetzer, Carsten; Debruin, Natasja; Ruth, Peter; Geisslinger, Gerd; Leffler, Andreas; Lukowski, Robert; Schmidtko, Achim

    2015-01-21

    Slack (Slo2.2) is a sodium-activated potassium channel that regulates neuronal firing activities and patterns. Previous studies identified Slack in sensory neurons, but its contribution to acute and chronic pain in vivo remains elusive. Here we generated global and sensory neuron-specific Slack mutant mice and analyzed their behavior in various animal models of pain. Global ablation of Slack led to increased hypersensitivity in models of neuropathic pain, whereas the behavior in models of inflammatory and acute nociceptive pain was normal. Neuropathic pain behaviors were also exaggerated after ablation of Slack selectively in sensory neurons. Notably, the Slack opener loxapine ameliorated persisting neuropathic pain behaviors. In conclusion, Slack selectively controls the sensory input in neuropathic pain states, suggesting that modulating its activity might represent a novel strategy for management of neuropathic pain. Copyright © 2015 the authors 0270-6474/15/351125-11$15.00/0.

  14. Vasodilatation in the rat dorsal hindpaw induced by activation of sensory neurons is reduced by Paclitaxel

    OpenAIRE

    Gracias, N.G.; Cummins, T.R.; Kelley, M.R.; Basile, D.P.; Iqbal, T.; Vasko, M.R.

    2010-01-01

    Peripheral neuropathy is a major side effect following treatment with the cancer chemotherapeutic drug paclitaxel. Whether paclitaxel-induced peripheral neuropathy is secondary to altered function of small diameter sensory neurons remains controversial. To ascertain whether the function of the small diameter sensory neurons was altered following systemic administration of paclitaxel, we injected male Sprague Dawley rats with 1 mg/kg paclitaxel every other day for a total of four doses and exa...

  15. The critical period for peripheral specification of dorsal root ganglion neurons is related to the period of sensory neurogenesis

    International Nuclear Information System (INIS)

    Smith, C.L.

    1990-01-01

    Thoracic sensory neurons in bullfrog tadpoles can be induced to form connections typical of brachial sensory neurons by transplanting thoracic ganglia to the branchial level at stages when some thoracic sensory neurons already have formed connections. In order to find out how many postmitotic sensory neurons survive transplantation, [ 3 H]thymidine was administered to tadpoles in which thoracic ganglia were transplanted to the brachial level unilaterally at stages VII to IX. Between 16 and 37% of the neurons in transplanted ganglia were unlabeled, as compared to 46 to 60% in unoperated ganglia. Transplanted ganglia contained fewer unlabeled neurons than corresponding unoperated ganglia, indicating that transplantation caused degeneration of postmitotic neurons. Therefore, a large fraction of the neurons that formed connections typical of brachial sensory neurons probably differentiated while they were at the brachial level

  16. Immunization Elicits Antigen-Specific Antibody Sequestration in Dorsal Root Ganglia Sensory Neurons

    Science.gov (United States)

    Gunasekaran, Manojkumar; Chatterjee, Prodyot K.; Shih, Andrew; Imperato, Gavin H.; Addorisio, Meghan; Kumar, Gopal; Lee, Annette; Graf, John F.; Meyer, Dan; Marino, Michael; Puleo, Christopher; Ashe, Jeffrey; Cox, Maureen A.; Mak, Tak W.; Bouton, Chad; Sherry, Barbara; Diamond, Betty; Andersson, Ulf; Coleman, Thomas R.; Metz, Christine N.; Tracey, Kevin J.; Chavan, Sangeeta S.

    2018-01-01

    The immune and nervous systems are two major organ systems responsible for host defense and memory. Both systems achieve memory and learning that can be retained, retrieved, and utilized for decades. Here, we report the surprising discovery that peripheral sensory neurons of the dorsal root ganglia (DRGs) of immunized mice contain antigen-specific antibodies. Using a combination of rigorous molecular genetic analyses, transgenic mice, and adoptive transfer experiments, we demonstrate that DRGs do not synthesize these antigen-specific antibodies, but rather sequester primarily IgG1 subtype antibodies. As revealed by RNA-seq and targeted quantitative PCR (qPCR), dorsal root ganglion (DRG) sensory neurons harvested from either naïve or immunized mice lack enzymes (i.e., RAG1, RAG2, AID, or UNG) required for generating antibody diversity and, therefore, cannot make antibodies. Additionally, transgenic mice that express a reporter fluorescent protein under the control of Igγ1 constant region fail to express Ighg1 transcripts in DRG sensory neurons. Furthermore, neural sequestration of antibodies occurs in mice rendered deficient in neuronal Rag2, but antibody sequestration is not observed in DRG sensory neurons isolated from mice that lack mature B cells [e.g., Rag1 knock out (KO) or μMT mice]. Finally, adoptive transfer of Rag1-deficient bone marrow (BM) into wild-type (WT) mice or WT BM into Rag1 KO mice revealed that antibody sequestration was observed in DRG sensory neurons of chimeric mice with WT BM but not with Rag1-deficient BM. Together, these results indicate that DRG sensory neurons sequester and retain antigen-specific antibodies released by antibody-secreting plasma cells. Coupling this work with previous studies implicating DRG sensory neurons in regulating antigen trafficking during immunization raises the interesting possibility that the nervous system collaborates with the immune system to regulate antigen-mediated responses. PMID:29755449

  17. Immunization Elicits Antigen-Specific Antibody Sequestration in Dorsal Root Ganglia Sensory Neurons

    Directory of Open Access Journals (Sweden)

    Manojkumar Gunasekaran

    2018-04-01

    Full Text Available The immune and nervous systems are two major organ systems responsible for host defense and memory. Both systems achieve memory and learning that can be retained, retrieved, and utilized for decades. Here, we report the surprising discovery that peripheral sensory neurons of the dorsal root ganglia (DRGs of immunized mice contain antigen-specific antibodies. Using a combination of rigorous molecular genetic analyses, transgenic mice, and adoptive transfer experiments, we demonstrate that DRGs do not synthesize these antigen-specific antibodies, but rather sequester primarily IgG1 subtype antibodies. As revealed by RNA-seq and targeted quantitative PCR (qPCR, dorsal root ganglion (DRG sensory neurons harvested from either naïve or immunized mice lack enzymes (i.e., RAG1, RAG2, AID, or UNG required for generating antibody diversity and, therefore, cannot make antibodies. Additionally, transgenic mice that express a reporter fluorescent protein under the control of Igγ1 constant region fail to express Ighg1 transcripts in DRG sensory neurons. Furthermore, neural sequestration of antibodies occurs in mice rendered deficient in neuronal Rag2, but antibody sequestration is not observed in DRG sensory neurons isolated from mice that lack mature B cells [e.g., Rag1 knock out (KO or μMT mice]. Finally, adoptive transfer of Rag1-deficient bone marrow (BM into wild-type (WT mice or WT BM into Rag1 KO mice revealed that antibody sequestration was observed in DRG sensory neurons of chimeric mice with WT BM but not with Rag1-deficient BM. Together, these results indicate that DRG sensory neurons sequester and retain antigen-specific antibodies released by antibody-secreting plasma cells. Coupling this work with previous studies implicating DRG sensory neurons in regulating antigen trafficking during immunization raises the interesting possibility that the nervous system collaborates with the immune system to regulate antigen-mediated responses.

  18. Painful nerve injury decreases resting cytosolic calcium concentrations in sensory neurons of rats

    NARCIS (Netherlands)

    Fuchs, Andreas; Lirk, Philipp; Stucky, Cheryl; Abram, Stephen E.; Hogan, Quinn H.

    2005-01-01

    Neuropathic pain is difficult to treat and poorly understood at the cellular level. Although cytoplasmic calcium ([Ca]c) critically regulates neuronal function, the effects of peripheral nerve injury on resting sensory neuronal [Ca]c are unknown. Resting [Ca]c was determined by microfluorometry in

  19. Neto2 Assembles with Kainate Receptors in DRG Neurons during Development and Modulates Neurite Outgrowth in Adult Sensory Neurons.

    Science.gov (United States)

    Vernon, Claire G; Swanson, Geoffrey T

    2017-03-22

    Peripheral sensory neurons in the dorsal root ganglia (DRG) are the initial transducers of sensory stimuli, including painful stimuli, from the periphery to central sensory and pain-processing centers. Small- to medium-diameter non-peptidergic neurons in the neonatal DRG express functional kainate receptors (KARs), one of three subfamilies of ionotropic glutamate receptors, as well as the putative KAR auxiliary subunit Neuropilin- and tolloid-like 2 (Neto2). Neto2 alters recombinant KAR function markedly but has yet to be confirmed as an auxiliary subunit that assembles with and alters the function of endogenous KARs. KARs in neonatal DRG require the GluK1 subunit as a necessary constituent, but it is unclear to what extent other KAR subunits contribute to the function and proposed roles of KARs in sensory ganglia, which include promotion of neurite outgrowth and modulation of glutamate release at the DRG-dorsal horn synapse. In addition, KARs containing the GluK1 subunit are implicated in modes of persistent but not acute pain signaling. We show here that the Neto2 protein is highly expressed in neonatal DRG and modifies KAR gating in DRG neurons in a developmentally regulated fashion in mice. Although normally at very low levels in adult DRG neurons, Neto2 protein expression can be upregulated via MEK/ERK signaling and after sciatic nerve crush and Neto2 -/- neurons from adult mice have stunted neurite outgrowth. These data confirm that Neto2 is a bona fide KAR auxiliary subunit that is an important constituent of KARs early in sensory neuron development and suggest that Neto2 assembly is critical to KAR modulation of DRG neuron process outgrowth. SIGNIFICANCE STATEMENT Pain-transducing peripheral sensory neurons of the dorsal root ganglia (DRG) express kainate receptors (KARs), a subfamily of glutamate receptors that modulate neurite outgrowth and regulate glutamate release at the DRG-dorsal horn synapse. The putative KAR auxiliary subunit Neuropilin- and

  20. The evolutionarily conserved transcription factor PRDM12 controls sensory neuron development and pain perception.

    Science.gov (United States)

    Nagy, Vanja; Cole, Tiffany; Van Campenhout, Claude; Khoung, Thang M; Leung, Calvin; Vermeiren, Simon; Novatchkova, Maria; Wenzel, Daniel; Cikes, Domagoj; Polyansky, Anton A; Kozieradzki, Ivona; Meixner, Arabella; Bellefroid, Eric J; Neely, G Gregory; Penninger, Josef M

    2015-01-01

    PR homology domain-containing member 12 (PRDM12) belongs to a family of conserved transcription factors implicated in cell fate decisions. Here we show that PRDM12 is a key regulator of sensory neuronal specification in Xenopus. Modeling of human PRDM12 mutations that cause hereditary sensory and autonomic neuropathy (HSAN) revealed remarkable conservation of the mutated residues in evolution. Expression of wild-type human PRDM12 in Xenopus induced the expression of sensory neuronal markers, which was reduced using various human PRDM12 mutants. In Drosophila, we identified Hamlet as the functional PRDM12 homolog that controls nociceptive behavior in sensory neurons. Furthermore, expression analysis of human patient fibroblasts with PRDM12 mutations uncovered possible downstream target genes. Knockdown of several of these target genes including thyrotropin-releasing hormone degrading enzyme (TRHDE) in Drosophila sensory neurons resulted in altered cellular morphology and impaired nociception. These data show that PRDM12 and its functional fly homolog Hamlet are evolutionary conserved master regulators of sensory neuronal specification and play a critical role in pain perception. Our data also uncover novel pathways in multiple species that regulate evolutionary conserved nociception.

  1. Temporal-pattern recognition by single neurons in a sensory pathway devoted to social communication behavior.

    Science.gov (United States)

    Carlson, Bruce A

    2009-07-29

    Sensory systems often encode stimulus information into the temporal pattern of action potential activity. However, little is known about how the information contained within these patterns is extracted by postsynaptic neurons. Similar to temporal coding by sensory neurons, social information in mormyrid fish is encoded into the temporal patterning of an electric organ discharge. In the current study, sensitivity to temporal patterns of electrosensory stimuli was found to arise within the midbrain posterior exterolateral nucleus (ELp). Whole-cell patch recordings from ELp neurons in vivo revealed three patterns of interpulse interval (IPI) tuning: low-pass neurons tuned to long intervals, high-pass neurons tuned to short intervals, and bandpass neurons tuned to intermediate intervals. Many neurons within each class also responded preferentially to either increasing or decreasing IPIs. Playback of electric signaling patterns recorded from freely behaving fish revealed that the IPI and direction tuning of ELp neurons resulted in selective responses to particular social communication displays characterized by distinct IPI patterns. The postsynaptic potential responses of many neurons indicated a combination of excitatory and inhibitory synaptic input, and the IPI tuning of ELp neurons was directly related to rate-dependent changes in the direction and amplitude of postsynaptic potentials. These results suggest that differences in the dynamics of short-term synaptic plasticity in excitatory and inhibitory pathways may tune central sensory neurons to particular temporal patterns of presynaptic activity. This may represent a general mechanism for the processing of behaviorally relevant stimulus information encoded into temporal patterns of activity by sensory neurons.

  2. Polysensory response characteristics of dorsal root ganglion neurones that may serve sensory functions during myocardial ischaemia.

    Science.gov (United States)

    Huang, M H; Horackova, M; Negoescu, R M; Wolf, S; Armour, J A

    1996-09-01

    To determine the response characteristics of dorsal root ganglion neurones that may serve sensory functions during myocardial ischaemia. Extracellular recordings were made from 54 spontaneously active and 5 normally quiescent dorsal root ganglion neurones (T2-T5) in 22 anaesthetized open-chest dogs under control conditions and during epicardial mechanical or chemical stimulation and myocardial ischaemia. The activity of 78% of spontaneously active and all quiescent neurones with left ventricular sensory fields was modified by left ventricular ischaemia. Forty-six spontaneously active neurones (85%) were polysensory with respect to mechanical and chemical stimuli. The 5 quiescent neurones responded only to chemical stimuli. Spontaneously active neurones associated with left ventricular mechanosensory endings (37 neurones) generated four different activity patterns in response to similar mechanical stimuli (high or low pressure active, high-low pressure active, high-low pressure inactive). A fifth group generated activity which was not related to chamber dynamics. Adenosine, adenosine 5'-triphosphate, substance P and bradykinin modified 72, 61, 65 and 63% of the spontaneously active neurones, respectively. Maximum local mechanical or chemical stimuli enhanced activity to similar degrees, as did ischaemia. Each ischaemia-sensitive neurone displayed unique activity patterns in response to similar mechanical or chemical stimuli. Most myocardial ischemia-sensitive dorsal root ganglion neurones associated with epicardial neurites sense mechanical and multiple chemical stimuli, a small population sensing only mechanical or chemical stimuli. Activity patterns generated by these neurones depend on their primary sensory characteristics or those of other neurones that may converge on them, as well as the type and magnitude of the stimuli that impinge upon their sensory fields, both normally and during ischaemia.

  3. Opening of pannexin and connexin based-channels increases the excitability of nodose ganglion sensory neurons.

    Directory of Open Access Journals (Sweden)

    Mauricio Antonio Retamal

    2014-06-01

    Full Text Available Satellite glial cells (SGCs are the main glia in sensory ganglia. They surround neuronal bodies and form a cap that prevents the formation of chemical or electrical synapses between neighboring neurons. SGCs have been suggested to establish bidirectional paracrine communication with sensory neurons. However, the molecular mechanism involved in this cellular communication is unknown. In the central nervous system, astrocytes present connexin43 (Cx43 hemichannels and pannexin1 (Panx1 channels, and their opening allows the release of signal molecules, such as ATP and glutamate. We propose that these channels could play a role in the glia-neuron communication in sensory ganglia. Therefore, we studied the expression and function of Cx43 and Panx1 in rat and mouse nodose-petrosal-jugular complex (NPJc by confocal immunofluorescence, molecular and electrophysiological techniques. Cx43 and Panx1 were detected in SGCs and sensory neurons, respectively. In the rat and mouse, the electrical activity of vagal nerve increased significantly after nodose neurons were exposed to Ca2+/ Mg2+-free solution, a condition that increases the open probability of Cx hemichannels. This response was partially mimicked by a cell-permeable peptide corresponding to the last 10 amino acids of Cx43 (TAT-Cx43CT. Enhanced neuronal activity was reduced by Cx hemichannel, Panx1 channel and P2X7 receptor blockers. Moreover, the role of Panx1 was confirmed in NPJc, because Panx1 knockout mouse showed a reduced increase of neuronal activity induced by Ca2+/Mg2+-free extracellular conditions. Data suggest that Cx hemichannels and Panx channels serve as paracrine communication pathways between SGCs and neurons by modulating the excitability of sensory neurons.

  4. Neuronal substrates of sensory gating within the human brain.

    NARCIS (Netherlands)

    Grunwald, T.; Boutros, N.N.; Pezer, N.; Oertzen, J. von; Fernandez, G.S.E.; Schaller, C.; Elger, C.E.

    2003-01-01

    BACKGROUND: For the human brain, habituation to irrelevant sensory input is an important function whose failure is associated with behavioral disturbances. Sensory gating can be studied by recording the brain's electrical responses to repeated clicks: the P50 potential is normally reduced to the

  5. Spinal sensory projection neuron responses to spinal cord stimulation are mediated by circuits beyond gate control.

    Science.gov (United States)

    Zhang, Tianhe C; Janik, John J; Peters, Ryan V; Chen, Gang; Ji, Ru-Rong; Grill, Warren M

    2015-07-01

    Spinal cord stimulation (SCS) is a therapy used to treat intractable pain with a putative mechanism of action based on the Gate Control Theory. We hypothesized that sensory projection neuron responses to SCS would follow a single stereotyped response curve as a function of SCS frequency, as predicted by the Gate Control circuit. We recorded the responses of antidromically identified sensory projection neurons in the lumbar spinal cord during 1- to 150-Hz SCS in both healthy rats and neuropathic rats following chronic constriction injury (CCI). The relationship between SCS frequency and projection neuron activity predicted by the Gate Control circuit accounted for a subset of neuronal responses to SCS but could not account for the full range of observed responses. Heterogeneous responses were classifiable into three additional groups and were reproduced using computational models of spinal microcircuits representing other interactions between nociceptive and nonnociceptive sensory inputs. Intrathecal administration of bicuculline, a GABAA receptor antagonist, increased spontaneous and evoked activity in projection neurons, enhanced excitatory responses to SCS, and reduced inhibitory responses to SCS, suggesting that GABAA neurotransmission plays a broad role in regulating projection neuron activity. These in vivo and computational results challenge the Gate Control Theory as the only mechanism underlying SCS and refine our understanding of the effects of SCS on spinal sensory neurons within the framework of contemporary understanding of dorsal horn circuitry. Copyright © 2015 the American Physiological Society.

  6. 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.

  7. 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.

  8. Long-term memory in Aplysia modulates the total number of varicosities of single identified sensory neurons.

    OpenAIRE

    Bailey, C H; Chen, M

    1988-01-01

    The morphological consequences of long-term habituation and sensitization of the gill withdrawal reflex in Aplysia california were explored by examining the total number of presynaptic varicosities of single identified sensory neurons (a critical site of plasticity for the biochemical and biophysical changes that underlie both types of learning) in control and behaviorally trained animals. Sensory neurons from habituated animals had 35% fewer synaptic varicosities than did sensory neurons fro...

  9. Mathematical Relationships between Neuron Morphology and Neurite Growth Dynamics in Drosophila melanogaster Larva Class IV Sensory Neurons

    Science.gov (United States)

    Ganguly, Sujoy; Liang, Xin; Grace, Michael; Lee, Daniel; Howard, Jonathon

    The morphology of neurons is diverse and reflects the diversity of neuronal functions, yet the principles that govern neuronal morphogenesis are unclear. In an effort to better understand neuronal morphogenesis we will be focusing on the development of the dendrites of class IV sensory neuron in Drosophila melanogaster. In particular we attempt to determine how the the total length, and the number of branches of dendrites are mathematically related to the dynamics of neurite growth and branching. By imaging class IV neurons during early embryogenesis we are able to measure the change in neurite length l (t) as a function of time v (t) = dl / dt . We found that the distribution of v (t) is well characterized by a hyperbolic secant distribution, and that the addition of new branches per unit time is well described by a Poisson process. Combining these measurements with the assumption that branching occurs with equal probability anywhere along the dendrite we were able to construct a mathematical model that provides reasonable agreement with the observed number of branches, and total length of the dendrites of the class IV sensory neuron.

  10. Toxicity to sensory neurons and Schwann cells in experimental linezolid-induced peripheral neuropathy.

    Science.gov (United States)

    Bobylev, Ilja; Maru, Helina; Joshi, Abhijeet R; Lehmann, Helmar C

    2016-03-01

    Peripheral neuropathy is a common side effect of prolonged treatment with linezolid. This study aimed to explore injurious effects of linezolid on cells of the peripheral nervous system and to establish in vivo and in vitro models of linezolid-induced peripheral neuropathy. C57BL/6 mice were treated with linezolid or vehicle over a total period of 4 weeks. Animals were monitored by weight, nerve conduction studies and behavioural tests. Neuropathic changes were assessed by morphometry on sciatic nerves and epidermal nerve fibre density in skin sections. Rodent sensory neuron and Schwann cell cultures were exposed to linezolid in vitro and assessed for mitochondrial dysfunction. Prolonged treatment with linezolid induced a mild, predominantly small sensory fibre neuropathy in vivo. Exposure of Schwann cells and sensory neurons to linezolid in vitro caused mitochondrial dysfunction primarily in neurons (and less prominently in Schwann cells). Sensory axonopathy could be partially prevented by co-administration of the Na(+)/Ca(2+) exchanger blocker KB-R7943. Clinical and pathological features of linezolid-induced peripheral neuropathy can be replicated in in vivo and in vitro models. Mitochondrial dysfunction may contribute to the axonal damage to sensory neurons that occurs after linezolid exposure. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. 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.

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

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    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.

  13. RAGE-dependent potentiation of TRPV1 currents in sensory neurons exposed to high glucose.

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    Lam, Doris; Momeni, Zeinab; Theaker, Michael; Jagadeeshan, Santosh; Yamamoto, Yasuhiko; Ianowski, Juan P; Campanucci, Verónica A

    2018-01-01

    Diabetes mellitus is associated with sensory abnormalities, including exacerbated responses to painful (hyperalgesia) or non-painful (allodynia) stimuli. These abnormalities are symptoms of diabetic peripheral neuropathy (DPN), which is the most common complication that affects approximately 50% of diabetic patients. Yet, the underlying mechanisms linking hyperglycemia and symptoms of DPN remain poorly understood. The transient receptor potential vanilloid 1 (TRPV1) channel plays a central role in such sensory abnormalities and shows elevated expression levels in animal models of diabetes. Here, we investigated the function of TRPV1 channels in sensory neurons cultured from the dorsal root ganglion (DRG) of neonatal mice, under control (5mM) and high glucose (25mM) conditions. After maintaining DRG neurons in high glucose for 1 week, we observed a significant increase in capsaicin (CAP)-evoked currents and CAP-evoked depolarizations, independent of TRPV1 channel expression. These functional changes were largely dependent on the expression of the receptor for Advanced Glycation End-products (RAGE), calcium influx, cytoplasmic ROS accumulation, PKC, and Src kinase activity. Like cultured neurons from neonates, mature neurons from adult mice also displayed a similar potentiation of CAP-evoked currents in the high glucose condition. Taken together, our data demonstrate that under the diabetic condition, DRG neurons are directly affected by elevated levels of glucose, independent of vascular or glial signals, and dependent on RAGE expression. These early cellular and molecular changes to sensory neurons in vitro are potential mechanisms that might contribute to sensory abnormalities that can occur in the very early stages of diabetes.

  14. The chemokine CXCL1/growth related oncogene increases sodium currents and neuronal excitability in small diameter sensory neurons

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    Wick Dayna M

    2008-09-01

    Full Text Available Abstract Background Altered Na+ channel expression, enhanced excitability, and spontaneous activity occur in nerve-injury and inflammatory models of pathological pain, through poorly understood mechanisms. The cytokine GRO/KC (growth related oncogene; CXCL1 shows strong, rapid upregulation in dorsal root ganglion in both nerve injury and inflammatory models. Neurons and glia express its receptor (CXCR2. CXCL1 has well-known effects on immune cells, but little is known about its direct effects on neurons. Results We report that GRO/KC incubation (1.5 nM, overnight caused marked upregulation of Na+ currents in acutely isolated small diameter rat (adult sensory neurons in vitro. In both IB4-positive and IB4-negative sensory neurons, TTX-resistant and TTX-sensitive currents increased 2- to 4 fold, without altered voltage dependence or kinetic changes. These effects required long exposures, and were completely blocked by co-incubation with protein synthesis inhibitor cycloheximide. Amplification of cDNA from the neuronal cultures showed that 3 Na channel isoforms were predominant both before and after GRO/KC treatment (Nav 1.1, 1.7, and 1.8. TTX-sensitive isoforms 1.1 and 1.7 significantly increased 2 – 3 fold after GRO/KC incubation, while 1.8 showed a trend towards increased expression. Current clamp experiments showed that GRO/KC caused a marked increase in excitability, including resting potential depolarization, decreased rheobase, and lower action potential threshold. Neurons acquired a striking ability to fire repetitively; IB4-positive cells also showed marked broadening of action potentials. Immunohistochemical labelling confirmed that the CXCR2 receptor was present in most neurons both in dissociated cells and in DRG sections, as previously shown for neurons in the CNS. Conclusion Many studies on the role of chemokines in pain conditions have focused on their rapid and indirect effects on neurons, via release of inflammatory mediators

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

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    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.

  16. Rat model of cancer-induced bone pain: changes in nonnociceptive sensory neurons in vivo

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    Yong Fang Zhu

    2017-08-01

    Conclusion:. After induction of the CIBP model, Aβ-fiber LTMs at >2 weeks but not <1 week had undergone changes in electrophysiological properties. Importantly, changes observed are consistent with observations in models of peripheral neuropathy. Thus, Aβ-fiber nonnociceptive primary sensory neurons might be involved in the peripheral sensitization and tumor-induced tactile hypersensitivity in CIBP.

  17. Acute exposure to high‐induction electromagnetic field affects activity of model peripheral sensory neurons

    Czech Academy of Sciences Publication Activity Database

    Průcha, J.; Krůšek, Jan; Dittert, Ivan; Sinica, Viktor; Kádková, Anna; Vlachová, Viktorie

    2018-01-01

    Roč. 22, č. 2 (2018), s. 1355-1362 ISSN 1582-4934 R&D Projects: GA MZd(CZ) NV16-28784A Institutional support: RVO:67985823 Keywords : electromagnetic field * primary sensory neuron * ion channel * bradykinin receptor * transient receptor potential channel Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 4.499, year: 2016

  18. Zika Virus Persistently and Productively Infects Primary Adult Sensory Neurons In Vitro

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    Brianna K. Swartwout

    2017-10-01

    Full Text Available Zika virus (ZIKV has recently surged in human populations, causing an increase in congenital and Guillain-Barré syndromes. While sexual transmission and presence of ZIKV in urine, semen, vaginal secretions, and saliva have been established, the origin of persistent virus shedding into biological secretions is not clear. Using a primary adult murine neuronal culture model, we have determined that ZIKV persistently and productively infects sensory neurons of the trigeminal and dorsal root ganglia, which innervate glands and mucosa of the face and the genitourinary tract, respectively, without apparent injury. Autonomic neurons that innervate these regions are not permissive for infection. However, productive ZIKV infection of satellite glial cells that surround and support sensory and autonomic neurons in peripheral ganglia results in their destruction. Persistent infection of sensory neurons, without affecting their viability, provides a potential reservoir for viral shedding in biological secretions for extended periods of time after infection. Furthermore, viral destruction of satellite glial cells may contribute to the development of Guillain-Barré Syndrome via an alternative mechanism to the established autoimmune response.

  19. Zika Virus Persistently and Productively Infects Primary Adult Sensory Neurons In Vitro.

    Science.gov (United States)

    Swartwout, Brianna K; Zlotnick, Marta G; Saver, Ashley E; McKenna, Caroline M; Bertke, Andrea S

    2017-10-13

    Zika virus (ZIKV) has recently surged in human populations, causing an increase in congenital and Guillain-Barré syndromes. While sexual transmission and presence of ZIKV in urine, semen, vaginal secretions, and saliva have been established, the origin of persistent virus shedding into biological secretions is not clear. Using a primary adult murine neuronal culture model, we have determined that ZIKV persistently and productively infects sensory neurons of the trigeminal and dorsal root ganglia, which innervate glands and mucosa of the face and the genitourinary tract, respectively, without apparent injury. Autonomic neurons that innervate these regions are not permissive for infection. However, productive ZIKV infection of satellite glial cells that surround and support sensory and autonomic neurons in peripheral ganglia results in their destruction. Persistent infection of sensory neurons, without affecting their viability, provides a potential reservoir for viral shedding in biological secretions for extended periods of time after infection. Furthermore, viral destruction of satellite glial cells may contribute to the development of Guillain-Barré Syndrome via an alternative mechanism to the established autoimmune response.

  20. Morphological analysis of Drosophila larval peripheral sensory neuron dendrites and axons using genetic mosaics.

    Science.gov (United States)

    Karim, M Rezaul; Moore, Adrian W

    2011-11-07

    Nervous system development requires the correct specification of neuron position and identity, followed by accurate neuron class-specific dendritic development and axonal wiring. Recently the dendritic arborization (DA) sensory neurons of the Drosophila larval peripheral nervous system (PNS) have become powerful genetic models in which to elucidate both general and class-specific mechanisms of neuron differentiation. There are four main DA neuron classes (I-IV)(1). They are named in order of increasing dendrite arbor complexity, and have class-specific differences in the genetic control of their differentiation(2-10). The DA sensory system is a practical model to investigate the molecular mechanisms behind the control of dendritic morphology(11-13) because: 1) it can take advantage of the powerful genetic tools available in the fruit fly, 2) the DA neuron dendrite arbor spreads out in only 2 dimensions beneath an optically clear larval cuticle making it easy to visualize with high resolution in vivo, 3) the class-specific diversity in dendritic morphology facilitates a comparative analysis to find key elements controlling the formation of simple vs. highly branched dendritic trees, and 4) dendritic arbor stereotypical shapes of different DA neurons facilitate morphometric statistical analyses. DA neuron activity modifies the output of a larval locomotion central pattern generator(14-16). The different DA neuron classes have distinct sensory modalities, and their activation elicits different behavioral responses(14,16-20). Furthermore different classes send axonal projections stereotypically into the Drosophila larval central nervous system in the ventral nerve cord (VNC)(21). These projections terminate with topographic representations of both DA neuron sensory modality and the position in the body wall of the dendritic field(7,22,23). Hence examination of DA axonal projections can be used to elucidate mechanisms underlying topographic mapping(7,22,23), as well as

  1. Transcriptome Analysis of Chemically-Induced Sensory Neuron Ablation in Zebrafish.

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    Jane A Cox

    Full Text Available Peripheral glia are known to have a critical role in the initial response to axon damage and degeneration. However, little is known about the cellular responses of non-myelinating glia to nerve injury. In this study, we analyzed the transcriptomes of wild-type and mutant (lacking peripheral glia zebrafish larvae that were treated with metronidazole. This treatment allowed us to conditionally and selectively ablate cranial sensory neurons whose axons are ensheathed only by non-myelinating glia. While transcripts representing over 27,000 genes were detected by RNAseq, only a small fraction (~1% of genes were found to be differentially expressed in response to neuronal degeneration in either line at either 2 hrs or 5 hrs of metronidazole treatment. Analysis revealed that most expression changes (332 out of the total of 458 differentially expressed genes occurred over a continuous period (from 2 to 5 hrs of metronidazole exposure, with a small number of genes showing changes limited to only the 2 hr (55 genes or 5 hr (71 genes time points. For genes with continuous alterations in expression, some of the most meaningful sets of enriched categories in the wild-type line were those involving the inflammatory TNF-alpha and IL6 signaling pathways, oxidoreductase activities and response to stress. Intriguingly, these changes were not observed in the mutant line. Indeed, cluster analysis indicated that the effects of metronidazole treatment on gene expression was heavily influenced by the presence or absence of glia, indicating that the peripheral non-myelinating glia play a significant role in the transcriptional response to sensory neuron degeneration. This is the first transcriptome study of metronidazole-induced neuronal death in zebrafish and the response of non-myelinating glia to sensory neuron degeneration. We believe this study provides important insight into the mechanisms by which non-myelinating glia react to neuronal death and degeneration in

  2. Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy.

    Science.gov (United States)

    Altmann, Christine; Hardt, Stefanie; Fischer, Caroline; Heidler, Juliana; Lim, Hee-Young; Häussler, Annett; Albuquerque, Boris; Zimmer, Béla; Möser, Christine; Behrends, Christian; Koentgen, Frank; Wittig, Ilka; Schmidt, Mirko H H; Clement, Albrecht M; Deller, Thomas; Tegeder, Irmgard

    2016-12-01

    Peripheral or central nerve injury is a frequent cause of chronic pain and the mechanisms are not fully understood. Using newly generated transgenic mice we show that progranulin overexpression in sensory neurons attenuates neuropathic pain after sciatic nerve injury and accelerates nerve healing. A yeast-2-hybrid screen revealed putative interactions of progranulin with autophagy-related proteins, ATG12 and ATG4b. This was supported by colocalization and proteomic studies showing regulations of ATG13 and ATG4b and other members of the autophagy network, lysosomal proteins and proteins involved in endocytosis. The association of progranulin with the autophagic pathway was functionally confirmed in primary sensory neurons. Autophagy and survival were impaired in progranulin-deficient neurons and improved in progranulin overexpressing neurons. Nerve injury in vivo caused an accumulation of LC3b-EGFP positive bodies in neurons of the dorsal root ganglia and nerves suggesting an impairment of autophagic flux. Overexpression of progranulin in these neurons was associated with a reduction of the stress marker ATF3, fewer protein aggregates in the injured nerve and enhanced stump healing. At the behavioral level, further inhibition of the autophagic flux by hydroxychloroquine intensified cold and heat nociception after sciatic nerve injury and offset the pain protection provided by progranulin. We infer that progranulin may assist in removal of protein waste and thereby helps to resolve neuropathic pain after nerve injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Role of motoneuron-derived neurotrophin 3 in survival and axonal projection of sensory neurons during neural circuit formation.

    Science.gov (United States)

    Usui, Noriyoshi; Watanabe, Keisuke; Ono, Katsuhiko; Tomita, Koichi; Tamamaki, Nobuaki; Ikenaka, Kazuhiro; Takebayashi, Hirohide

    2012-03-01

    Sensory neurons possess the central and peripheral branches and they form unique spinal neural circuits with motoneurons during development. Peripheral branches of sensory axons fasciculate with the motor axons that extend toward the peripheral muscles from the central nervous system (CNS), whereas the central branches of proprioceptive sensory neurons directly innervate motoneurons. Although anatomically well documented, the molecular mechanism underlying sensory-motor interaction during neural circuit formation is not fully understood. To investigate the role of motoneuron on sensory neuron development, we analyzed sensory neuron phenotypes in the dorsal root ganglia (DRG) of Olig2 knockout (KO) mouse embryos, which lack motoneurons. We found an increased number of apoptotic cells in the DRG of Olig2 KO embryos at embryonic day (E) 10.5. Furthermore, abnormal axonal projections of sensory neurons were observed in both the peripheral branches at E10.5 and central branches at E15.5. To understand the motoneuron-derived factor that regulates sensory neuron development, we focused on neurotrophin 3 (Ntf3; NT-3), because Ntf3 and its receptors (Trk) are strongly expressed in motoneurons and sensory neurons, respectively. The significance of motoneuron-derived Ntf3 was analyzed using Ntf3 conditional knockout (cKO) embryos, in which we observed increased apoptosis and abnormal projection of the central branch innervating motoneuron, the phenotypes being apparently comparable with that of Olig2 KO embryos. Taken together, we show that the motoneuron is a functional source of Ntf3 and motoneuron-derived Ntf3 is an essential pre-target neurotrophin for survival and axonal projection of sensory neurons.

  4. Different requirements for GFRα2-signaling in three populations of cutaneous sensory neurons.

    Science.gov (United States)

    Kupari, Jussi; Airaksinen, Matti S

    2014-01-01

    Many primary sensory neurons in mouse dorsal root ganglia (DRG) express one or several GFRα's, the ligand-binding receptors of the GDNF family, and their common signaling receptor Ret. GFRα2, the principal receptor for neurturin, is expressed in most of the small nonpeptidergic DRG neurons, but also in some large DRG neurons that start to express Ret earlier. Previously, GFRα2 has been shown to be crucial for the soma size of small nonpeptidergic nociceptors and for their target innervation of glabrous epidermis. However, little is known about this receptor in other Ret-expressing DRG neuron populations. Here we have investigated two populations of Ret-positive low-threshold mechanoreceptors that innervate different types of hair follicles on mouse back skin: the small C-LTMRs and the large Aβ-LTMRs. Using GFRα2-KO mice and immunohistochemistry we found that, similar to the nonpeptidergic nociceptors, GFRα2 controls the cell size but not the survival of both C-LTMRs and Aβ-LTMRs. In contrast to the nonpeptidergic neurons, GFRα2 is not required for the target innervation of C-LTMRs and Aβ-LTMRs in the back skin. These results suggest that different factors drive target innervation in these three populations of neurons. In addition, the observation that the large Ret-positive DRG neurons lack GFRα2 immunoreactivity in mature animals suggests that these neurons switch their GFRα signaling pathways during postnatal development.

  5. Sensory Neuron Fates Are Distinguished by a Transcriptional Switch that Regulates Dendrite Branch Stabilization

    Science.gov (United States)

    Smith, Cody J.; O’Brien, Timothy; Chatzigeorgiou, Marios; Spencer, W. Clay; Feingold-Link, Elana; Husson, Steven J.; Hori, Sayaka; Mitani, Shohei; Gottschalk, Alexander; Schafer, William R.; Miller, David M.

    2013-01-01

    SUMMARY Sensory neurons adopt distinct morphologies and functional modalities to mediate responses to specific stimuli. Transcription factors and their downstream effectors orchestrate this outcome but are incompletely defined. Here, we show that different classes of mechanosensory neurons in C. elegans are distinguished by the combined action of the transcription factors MEC-3, AHR-1, and ZAG-1. Low levels of MEC-3 specify the elaborate branching pattern of PVD nociceptors, whereas high MEC-3 is correlated with the simple morphology of AVM and PVM touch neurons. AHR-1 specifies AVM touch neuron fate by elevating MEC-3 while simultaneously blocking expression of nociceptive genes such as the MEC-3 target, the claudin-like membrane protein HPO-30, that promotes the complex dendritic branching pattern of PVD. ZAG-1 exercises a parallel role to prevent PVM from adopting the PVD fate. The conserved dendritic branching function of the Drosophila AHR-1 homolog, Spineless, argues for similar pathways in mammals. PMID:23889932

  6. Dynamics of human subthalamic neuron phase-locking to motor and sensory cortical oscillations during movement.

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    Lipski, Witold J; Wozny, Thomas A; Alhourani, Ahmad; Kondylis, Efstathios D; Turner, Robert S; Crammond, Donald J; Richardson, Robert Mark

    2017-09-01

    Coupled oscillatory activity recorded between sensorimotor regions of the basal ganglia-thalamocortical loop is thought to reflect information transfer relevant to movement. A neuronal firing-rate model of basal ganglia-thalamocortical circuitry, however, has dominated thinking about basal ganglia function for the past three decades, without knowledge of the relationship between basal ganglia single neuron firing and cortical population activity during movement itself. We recorded activity from 34 subthalamic nucleus (STN) neurons, simultaneously with cortical local field potentials and motor output, in 11 subjects with Parkinson's disease (PD) undergoing awake deep brain stimulator lead placement. STN firing demonstrated phase synchronization to both low- and high-beta-frequency cortical oscillations, and to the amplitude envelope of gamma oscillations, in motor cortex. We found that during movement, the magnitude of this synchronization was dynamically modulated in a phase-frequency-specific manner. Importantly, we found that phase synchronization was not correlated with changes in neuronal firing rate. Furthermore, we found that these relationships were not exclusive to motor cortex, because STN firing also demonstrated phase synchronization to both premotor and sensory cortex. The data indicate that models of basal ganglia function ultimately will need to account for the activity of populations of STN neurons that are bound in distinct functional networks with both motor and sensory cortices and code for movement parameters independent of changes in firing rate. NEW & NOTEWORTHY Current models of basal ganglia-thalamocortical networks do not adequately explain simple motor functions, let alone dysfunction in movement disorders. Our findings provide data that inform models of human basal ganglia function by demonstrating how movement is encoded by networks of subthalamic nucleus (STN) neurons via dynamic phase synchronization with cortex. The data also

  7. Co-cultures provide a new tool to probe communication between adult sensory neurons and urothelium.

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    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.

  8. Recovery of function, peripheral sensitization and sensory neurone activation by novel pathways following axonal injury in Aplysia californica.

    Science.gov (United States)

    Dulin, M F; Steffensen, I; Morris, C E; Walters, E T

    1995-10-01

    Recovery of behavioural and sensory function was examined following unilateral pedal nerve crush in Aplysia californica. Nerve crush that transected all axons connecting the tail to the central nervous system (CNS) eliminated the ipsilateral tail-evoked siphon reflex, whose sensory input travels in the crushed tail nerve (p9). The first reliable signs of recovery of this reflex were observed within 1 week, and most animals displayed tail-evoked siphon responses within 2 weeks. Wide-dynamic-range mechanosensory neurons with somata in the ventrocaudal (VC) cluster of the ipsilateral pleural ganglion exhibited a few receptive fields (RFs) on the tail 3 weeks after unilateral pedal nerve crush, indicating that the RFs had either regenerated or been reconnected to the central somata. These RFs were smaller and sensitized compared with corresponding RFs on the contralateral, uncrushed side. Centrally conducted axon responses of VC sensory neurones to electrical stimulation distal to the nerve crush site did not reappear until at least 10 days after the crush. Because the crush site was much closer to the CNS than to the tail, the failure of axon responses to be restored earlier than the behavioural responses indicates that early stages of reflex recovery are not due to regeneration of VC sensory neurone axons into the tail. Following nerve crush, VC sensory neurones often could be activated by stimulating central connectives or peripheral nerves that do not normally contain the sensory neurone's axons. These results suggest that recovery of behavioral function after nerve injury involves complex mechanisms, including regenerative growth of axotomized VC sensory neurones, sensitization of regenerating RFs and sprouting of VC sensory neurone fibres within the CNS. Furthermore, the rapidity of behavioural recovery indicates that its initial phases are mediated by additional mechanisms, perhaps centripetal regeneration of unidentified sensory neurones having peripheral

  9. Expression Patterns of Odorant Receptors and Response Properties of Olfactory Sensory Neurons in Aged Mice

    OpenAIRE

    Lee, Anderson C.; Tian, Huikai; Grosmaitre, Xavier; Ma, Minghong

    2009-01-01

    The sense of smell deteriorates in normal aging, but the underling mechanisms are still elusive. Here we investigated age-related alterations in expression patterns of odorant receptor (OR) genes and functional properties of olfactory sensory neurons (OSNs)—2 critical factors that define the odor detection threshold in the olfactory epithelium. Using in situ hybridization for 9 representative OR genes, we compared the cell densities of each OR in coronal nose sections at different ages (3–27 ...

  10. Active signal conduction through the sensory dendrite of a spider mechanoreceptor neuron.

    Science.gov (United States)

    Gingl, Ewald; French, Andrew S

    2003-07-09

    Rapid responses to sensory stimulation are crucial for survival. This must be especially true for mechanical stimuli containing temporal information, such as vibration. Sensory transduction occurs at the tips of relatively long sensory dendrites in many mechanoreceptors of both vertebrates and invertebrates, but little is known about the electrical properties of these crucial links between transduction and action potential generation. The VS-3 slit-sense organ of the spider Cupiennius salei contains bipolar mechanosensory neurons that allow voltage-clamp recording from the somata, whereas mechanotransduction occurs at the tips of 100- to 200-microm-long sensory dendrites. We studied the properties of VS-3 sensory dendrites using three approaches. Voltage-jump experiments measured the spread of voltage outward from the soma by observing total mechanically transduced charge recovered at the soma as a function of time after a voltage jump. Frequency-response measurements between pseudorandom mechanical stimulation and somatic membrane potential estimated the passive cable properties of the dendrite for voltage spread in the opposite direction. Both of these sets of data indicated that the dendritic cable would significantly attenuate and retard a passively propagated receptor potential. Finally, current-clamp observations of receptor potentials and action potentials indicated that action potentials normally start at the distal dendrites and propagate regeneratively to the soma, reducing the temporal delay of passive conduction.

  11. Inflammatory mediator bradykinin increases population of sensory neurons expressing functional T-type Ca(2+) channels.

    Science.gov (United States)

    Huang, Dongyang; Liang, Ce; Zhang, Fan; Men, Hongchao; Du, Xiaona; Gamper, Nikita; Zhang, Hailin

    2016-04-29

    T-type Ca(2+) channels are important regulators of peripheral sensory neuron excitability. Accordingly, T-type Ca(2+) currents are often increased in various pathological pain conditions, such as inflammation or nerve injury. Here we investigated effects of inflammation on functional expression of T-type Ca(2+) channels in small-diameter cultured dorsal root ganglion (DRG) neurons. We found that overnight treatment of DRG cultures with a cocktail of inflammatory mediators bradykinin (BK), adenosine triphosphate (ATP), norepinephrine (NE) and prostaglandin E2 (PGE2) strongly increased the population size of the small-diameter neurons displaying low-voltage activated (LVA, T-type) Ca(2+) currents while having no effect on the peak LVA current amplitude. When applied individually, BK and ATP also increased the population size of LVA-positive neurons while NE and PGE2 had no effect. The PLC inhibitor U-73122 and B2 receptor antagonist, Hoe-140, both abolished the increase of the population of LVA-positive DRG neurons. Inflammatory treatment did not affect CaV3.2 mRNA or protein levels in DRG cultures. Furthermore, an ubiquitination inhibitor, MG132, did not increase the population of LVA-positive neurons. Our data suggest that inflammatory mediators BK and ATP increase the abundance of LVA-positive DRG neurons in total neuronal population by stimulating the recruitment of a 'reserve pool' of CaV3.2 channels, particularly in neurons that do not display measurable LVA currents under control conditions. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Developmental emergence of different forms of neuromodulation in Aplysia sensory neurons.

    Science.gov (United States)

    Marcus, E A; Carew, T J

    1998-04-14

    The capacity for neuromodulation and biophysical plasticity is a defining feature of most mature neuronal cell types. In several cases, modulation at the level of the individual neuron has been causally linked to changes in the functional output of a neuronal circuit and subsequent adaptive changes in the organism's behavioral responses. Understanding how such capacity for neuromodulation develops therefore may provide insights into the mechanisms both of neuronal development and learning and memory. We have examined the development of multiple forms of neuromodulation triggered by a common neurotransmitter, serotonin, in the pleural sensory neurons of Aplysia californica. We have found that multiple signaling cascades within a single neuron develop sequentially, with some being expressed only very late in development. In addition, our data suggest a model in which, within a single neuromodulatory pathway, the elements of the signaling cascade are developmentally expressed in a "retrograde" manner with the ionic channel that is modulated appearing early in development, functional elements in the second messenger cascade appearing later, and finally, coupling of the second messenger cascade to the serotonin receptor appearing quite late. These studies provide the characterization of the development of neuromodulation at the level of an identified cell type and offer insights into the potential roles of neuromodulatory processes in development and adult plasticity.

  13. Ebi/AP-1 suppresses pro-apoptotic genes expression and permits long-term survival of Drosophila sensory neurons.

    Directory of Open Access Journals (Sweden)

    Young-Mi Lim

    Full Text Available Sensory organs are constantly exposed to physical and chemical stresses that collectively threaten the survival of sensory neurons. Failure to protect stressed neurons leads to age-related loss of neurons and sensory dysfunction in organs in which the supply of new sensory neurons is limited, such as the human auditory system. Transducin β-like protein 1 (TBL1 is a candidate gene for ocular albinism with late-onset sensorineural deafness, a form of X-linked age-related hearing loss. TBL1 encodes an evolutionarily conserved F-box-like and WD40 repeats-containing subunit of the nuclear receptor co-repressor/silencing mediator for retinoid and thyroid hormone receptor and other transcriptional co-repressor complexes. Here we report that a Drosophila homologue of TBL1, Ebi, is required for maintenance of photoreceptor neurons. Loss of ebi function caused late-onset neuronal apoptosis in the retina and increased sensitivity to oxidative stress. Ebi formed a complex with activator protein 1 (AP-1 and was required for repression of Drosophila pro-apoptotic and anti-apoptotic genes expression. These results suggest that Ebi/AP-1 suppresses basal transcription levels of apoptotic genes and thereby protects sensory neurons from degeneration.

  14. Error-based analysis of optimal tuning functions explains phenomena observed in sensory neurons

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    Steve Yaeli

    2010-10-01

    Full Text Available Biological systems display impressive capabilities in effectively responding to environmental signals in real time. There is increasing evidence that organisms may indeed be employing near optimal Bayesian calculations in their decision-making. An intriguing question relates to the properties of optimal encoding methods, namely determining the properties of neural populations in sensory layers that optimize performance, subject to physiological constraints. Within an ecological theory of neural encoding/decoding, we show that optimal Bayesian performance requires neural adaptation which reflects environmental changes. Specifically, we predict that neuronal tuning functions possess an optimal width, which increases with prior uncertainty and environmental noise, and decreases with the decoding time window. Furthermore, even for static stimuli, we demonstrate that dynamic sensory tuning functions, acting at relatively short time scales, lead to improved performance. Interestingly, the narrowing of tuning functions as a function of time was recently observed in several biological systems. Such results set the stage for a functional theory which may explain the high reliability of sensory systems, and the utility of neuronal adaptation occurring at multiple time scales.

  15. Error-based analysis of optimal tuning functions explains phenomena observed in sensory neurons.

    Science.gov (United States)

    Yaeli, Steve; Meir, Ron

    2010-01-01

    Biological systems display impressive capabilities in effectively responding to environmental signals in real time. There is increasing evidence that organisms may indeed be employing near optimal Bayesian calculations in their decision-making. An intriguing question relates to the properties of optimal encoding methods, namely determining the properties of neural populations in sensory layers that optimize performance, subject to physiological constraints. Within an ecological theory of neural encoding/decoding, we show that optimal Bayesian performance requires neural adaptation which reflects environmental changes. Specifically, we predict that neuronal tuning functions possess an optimal width, which increases with prior uncertainty and environmental noise, and decreases with the decoding time window. Furthermore, even for static stimuli, we demonstrate that dynamic sensory tuning functions, acting at relatively short time scales, lead to improved performance. Interestingly, the narrowing of tuning functions as a function of time was recently observed in several biological systems. Such results set the stage for a functional theory which may explain the high reliability of sensory systems, and the utility of neuronal adaptation occurring at multiple time scales.

  16. Conserved RNA-Binding Proteins Required for Dendrite Morphogenesis in Caenorhabditis elegans Sensory Neurons

    Science.gov (United States)

    Antonacci, Simona; Forand, Daniel; Wolf, Margaret; Tyus, Courtney; Barney, Julia; Kellogg, Leah; Simon, Margo A.; Kerr, Genevieve; Wells, Kristen L.; Younes, Serena; Mortimer, Nathan T.; Olesnicky, Eugenia C.; Killian, Darrell J.

    2015-01-01

    The regulation of dendritic branching is critical for sensory reception, cell−cell communication within the nervous system, learning, memory, and behavior. Defects in dendrite morphology are associated with several neurologic disorders; thus, an understanding of the molecular mechanisms that govern dendrite morphogenesis is important. Recent investigations of dendrite morphogenesis have highlighted the importance of gene regulation at the posttranscriptional level. Because RNA-binding proteins mediate many posttranscriptional mechanisms, we decided to investigate the extent to which conserved RNA-binding proteins contribute to dendrite morphogenesis across phyla. Here we identify a core set of RNA-binding proteins that are important for dendrite morphogenesis in the PVD multidendritic sensory neuron in Caenorhabditis elegans. Homologs of each of these genes were previously identified as important in the Drosophila melanogaster dendritic arborization sensory neurons. Our results suggest that RNA processing, mRNA localization, mRNA stability, and translational control are all important mechanisms that contribute to dendrite morphogenesis, and we present a conserved set of RNA-binding proteins that regulate these processes in diverse animal species. Furthermore, homologs of these genes are expressed in the human brain, suggesting that these RNA-binding proteins are candidate regulators of dendrite development in humans. PMID:25673135

  17. Excitability of Aβ sensory neurons is altered in an animal model of peripheral neuropathy

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    Zhu Yong

    2012-01-01

    Full Text Available Abstract Background Causes of neuropathic pain following nerve injury remain unclear, limiting the development of mechanism-based therapeutic approaches. Animal models have provided some directions, but little is known about the specific sensory neurons that undergo changes in such a way as to induce and maintain activation of sensory pain pathways. Our previous studies implicated changes in the Aβ, normally non-nociceptive neurons in activating spinal nociceptive neurons in a cuff-induced animal model of neuropathic pain and the present study was directed specifically at determining any change in excitability of these neurons. Thus, the present study aimed at recording intracellularly from Aβ-fiber dorsal root ganglion (DRG neurons and determining excitability of the peripheral receptive field, of the cell body and of the dorsal roots. Methods A peripheral neuropathy was induced in Sprague Dawley rats by inserting two thin polyethylene cuffs around the right sciatic nerve. All animals were confirmed to exhibit tactile hypersensitivity to von Frey filaments three weeks later, before the acute electrophysiological experiments. Under stable intracellular recording conditions neurons were classified functionally on the basis of their response to natural activation of their peripheral receptive field. In addition, conduction velocity of the dorsal roots, configuration of the action potential and rate of adaptation to stimulation were also criteria for classification. Excitability was measured as the threshold to activation of the peripheral receptive field, the response to intracellular injection of depolarizing current into the soma and the response to electrical stimulation of the dorsal roots. Results In control animals mechanical thresholds of all neurons were within normal ranges. Aβ DRG neurons in neuropathic rats demonstrated a mean mechanical threshold to receptive field stimulation that were significantly lower than in control rats, a

  18. 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.

  19. EGL-13/SoxD Specifies Distinct O2 and CO2 Sensory Neuron Fates in Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Gramstrup Petersen, Jakob; Rojo Romanos, Teresa; Juozaityte, Vaida

    2013-01-01

    that EGL-13 is sufficient to induce O2- and CO2-sensing cell fates in some cellular contexts. Thus, the same core regulatory factor, egl-13, is required and sufficient to specify the distinct fates of O2- and CO2-sensing neurons in C. elegans. These findings extend our understanding of mechanisms......Animals harbor specialized neuronal systems that are used for sensing and coordinating responses to changes in oxygen (O2) and carbon dioxide (CO2). In Caenorhabditis elegans, the O2/CO2 sensory system comprises functionally and morphologically distinct sensory neurons that mediate rapid behavioral...

  20. Competition model for aperiodic stochastic resonance in a Fitzhugh-Nagumo model of cardiac sensory neurons.

    Science.gov (United States)

    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.

  1. Segmental distribution and morphometric features of primary sensory neurons projecting to the tibial periosteum in the rat.

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    Tadeusz Cichocki

    2004-07-01

    Full Text Available Previous reports have demonstrated very rich innervation pattern in the periosteum. Most of the periosteal fibers were found to be sensory in nature. The aim of this study was to identify the primary sensory neurons that innervate the tibial periosteum in the adult rat and to describe the morphometric features of their perikarya. To this end, an axonal fluorescent carbocyanine tracer, DiI, was injected into the periosteum on the medial surface of the tibia. The perikarya of the sensory fibers were traced back in the dorsal root ganglia (DRG L1-L6 by means of fluorescent microscopy on cryosections. DiI-containing neurons were counted in each section and their segmental distribution was determined. Using PC-assisted image analysis system, the size and shape of the traced perikarya were analyzed. DiI-labeled sensory neurons innervating the periosteum of the tibia were located in the DRG ipsilateral to the injection site, with the highest distribution in L3 and L4 (57% and 23%, respectively. The majority of the traced neurons were of small size (area < 850 microm2, which is consistent with the size distribution of CGRP- and SP-containing cells, regarded as primary sensory neurons responsible for perception of pain and temperature. A small proportion of labeled cells had large perikarya and probably supplied corpuscular sense receptors observed in the periosteum. No differences were found in the shape distribution of neurons belonging to different size classes.

  2. Differential response of olfactory sensory neuron populations to copper ion exposure in zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Lazzari, Maurizio, E-mail: maurizio.lazzari@unibo.it; Bettini, Simone; Milani, Liliana; Maurizii, Maria Gabriella; Franceschini, Valeria

    2017-02-15

    Highlights: • Copper exposure affects ciliated olfactory receptors more than microvillar cells. • Crypt olfactory sensory neurons are not affected by copper exposure. • Copper exposure induces an increase in the amount of sensory epithelium. - Abstract: The peripheral olfactory system of fish is in direct contact with the external aqueous environment, so dissolved contaminants can easily impair sensory functions and cause neurobehavioral injuries. The olfactory epithelium of fish is arranged in lamellae forming a rosette in the olfactory cavity and contains three main types of olfactory sensory neurons (OSNs): ciliated (cOSNs) and microvillous olfactory sensory neurons (mOSNs), common to all vertebrates, and a third minor group of olfactory neurons, crypt cells, absent in tetrapods. Since copper is a ubiquitously diffusing olfactory toxicant and a spreading contaminant in urban runoff, we investigated the effect of low copper concentration on the three different OSNs in the olfactory epithelium of zebrafish, a model system widely used in biological research. Image analysis was applied for morphometry and quantification of immunohistochemically detected OSNs. Copper exposure resulted in an evident decrease in olfactory epithelium thickness. Moreover, after exposure, the lamellae of the dorsal and ventral halves of the olfactory rosettes showed a different increase in their sensory areas, suggesting a lateral migration of new cells into non-sensory regions. The results of the present study provide clear evidence of a differential response of the three neural cell populations of zebrafish olfactory mucosa after 96 h of exposure to copper ions at the sublethal concentration of 30 μg L{sup −1}. Densitometric values of cONS, immunostained with anti-G {sub αolf}, decreased of about 60% compared to the control. When the fish were transferred to water without copper addition and examined after 3, 10 and 30 days, we observed a partial restoration of anti-G {sub

  3. Differential response of olfactory sensory neuron populations to copper ion exposure in zebrafish

    International Nuclear Information System (INIS)

    Lazzari, Maurizio; Bettini, Simone; Milani, Liliana; Maurizii, Maria Gabriella; Franceschini, Valeria

    2017-01-01

    Highlights: • Copper exposure affects ciliated olfactory receptors more than microvillar cells. • Crypt olfactory sensory neurons are not affected by copper exposure. • Copper exposure induces an increase in the amount of sensory epithelium. - Abstract: The peripheral olfactory system of fish is in direct contact with the external aqueous environment, so dissolved contaminants can easily impair sensory functions and cause neurobehavioral injuries. The olfactory epithelium of fish is arranged in lamellae forming a rosette in the olfactory cavity and contains three main types of olfactory sensory neurons (OSNs): ciliated (cOSNs) and microvillous olfactory sensory neurons (mOSNs), common to all vertebrates, and a third minor group of olfactory neurons, crypt cells, absent in tetrapods. Since copper is a ubiquitously diffusing olfactory toxicant and a spreading contaminant in urban runoff, we investigated the effect of low copper concentration on the three different OSNs in the olfactory epithelium of zebrafish, a model system widely used in biological research. Image analysis was applied for morphometry and quantification of immunohistochemically detected OSNs. Copper exposure resulted in an evident decrease in olfactory epithelium thickness. Moreover, after exposure, the lamellae of the dorsal and ventral halves of the olfactory rosettes showed a different increase in their sensory areas, suggesting a lateral migration of new cells into non-sensory regions. The results of the present study provide clear evidence of a differential response of the three neural cell populations of zebrafish olfactory mucosa after 96 h of exposure to copper ions at the sublethal concentration of 30 μg L"−"1. Densitometric values of cONS, immunostained with anti-G _α_o_l_f, decreased of about 60% compared to the control. When the fish were transferred to water without copper addition and examined after 3, 10 and 30 days, we observed a partial restoration of anti-G _

  4. Associative Memory Extinction Is Accompanied by Decayed Plasticity at Motor Cortical Neurons and Persistent Plasticity at Sensory Cortical Neurons.

    Science.gov (United States)

    Guo, Rui; Ge, Rongjing; Zhao, Shidi; Liu, Yulong; Zhao, Xin; Huang, Li; Guan, Sodong; Lu, Wei; Cui, Shan; Wang, Shirlene; Wang, Jin-Hui

    2017-01-01

    Associative memory is essential for cognition, in which associative memory cells and their plasticity presumably play important roles. The mechanism underlying associative memory extinction vs. maintenance remains unclear, which we have studied in a mouse model of cross-modal associative learning. Paired whisker and olfaction stimulations lead to a full establishment of odorant-induced whisker motion in training day 10, which almost disappears if paired stimulations are not given in a week, and then recovers after paired stimulation for an additional day. In mice that show associative memory, extinction and recovery, we have analyzed the dynamical plasticity of glutamatergic neurons in layers II-III of the barrel cortex and layers IV-V of the motor cortex. Compared with control mice, the rate of evoked spikes as well as the amplitude and frequency of excitatory postsynaptic currents increase, whereas the amplitude and frequency of inhibitory postsynaptic currents (IPSC) decrease at training day 10 in associative memory mice. Without paired training for a week, these plastic changes are persistent in the barrel cortex and decayed in the motor cortex. If paired training is given for an additional day to revoke associative memory, neuronal plasticity recovers in the motor cortex. Our study indicates persistent neuronal plasticity in the barrel cortex for cross-modal memory maintenance as well as the dynamical change of neuronal plasticity in the motor cortex for memory retrieval and extinction. In other words, the sensory cortices are essential for long-term memory while the behavior-related cortices with the inability of memory retrieval are correlated to memory extinction.

  5. Associative Memory Extinction Is Accompanied by Decayed Plasticity at Motor Cortical Neurons and Persistent Plasticity at Sensory Cortical Neurons

    Directory of Open Access Journals (Sweden)

    Rui Guo

    2017-06-01

    Full Text Available Associative memory is essential for cognition, in which associative memory cells and their plasticity presumably play important roles. The mechanism underlying associative memory extinction vs. maintenance remains unclear, which we have studied in a mouse model of cross-modal associative learning. Paired whisker and olfaction stimulations lead to a full establishment of odorant-induced whisker motion in training day 10, which almost disappears if paired stimulations are not given in a week, and then recovers after paired stimulation for an additional day. In mice that show associative memory, extinction and recovery, we have analyzed the dynamical plasticity of glutamatergic neurons in layers II–III of the barrel cortex and layers IV–V of the motor cortex. Compared with control mice, the rate of evoked spikes as well as the amplitude and frequency of excitatory postsynaptic currents increase, whereas the amplitude and frequency of inhibitory postsynaptic currents (IPSC decrease at training day 10 in associative memory mice. Without paired training for a week, these plastic changes are persistent in the barrel cortex and decayed in the motor cortex. If paired training is given for an additional day to revoke associative memory, neuronal plasticity recovers in the motor cortex. Our study indicates persistent neuronal plasticity in the barrel cortex for cross-modal memory maintenance as well as the dynamical change of neuronal plasticity in the motor cortex for memory retrieval and extinction. In other words, the sensory cortices are essential for long-term memory while the behavior-related cortices with the inability of memory retrieval are correlated to memory extinction.

  6. Predicting the response of olfactory sensory neurons to odor mixtures from single odor response

    Science.gov (United States)

    Marasco, Addolorata; de Paris, Alessandro; Migliore, Michele

    2016-04-01

    The response of olfactory receptor neurons to odor mixtures is not well understood. Here, using experimental constraints, we investigate the mathematical structure of the odor response space and its consequences. The analysis suggests that the odor response space is 3-dimensional, and predicts that the dose-response curve of an odor receptor can be obtained, in most cases, from three primary components with specific properties. This opens the way to an objective procedure to obtain specific olfactory receptor responses by manipulating mixtures in a mathematically predictable manner. This result is general and applies, independently of the number of odor components, to any olfactory sensory neuron type with a response curve that can be represented as a sigmoidal function of the odor concentration.

  7. Aging in Sensory and Motor Neurons Results in Learning Failure in Aplysia californica.

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    Andrew T Kempsell

    Full Text Available The physiological and molecular mechanisms of age-related memory loss are complicated by the complexity of vertebrate nervous systems. This study takes advantage of a simple neural model to investigate nervous system aging, focusing on changes in learning and memory in the form of behavioral sensitization in vivo and synaptic facilitation in vitro. The effect of aging on the tail withdrawal reflex (TWR was studied in Aplysia californica at maturity and late in the annual lifecycle. We found that short-term sensitization in TWR was absent in aged Aplysia. This implied that the neuronal machinery governing nonassociative learning was compromised during aging. Synaptic plasticity in the form of short-term facilitation between tail sensory and motor neurons decreased during aging whether the sensitizing stimulus was tail shock or the heterosynaptic modulator serotonin (5-HT. Together, these results suggest that the cellular mechanisms governing behavioral sensitization are compromised during aging, thereby nearly eliminating sensitization in aged Aplysia.

  8. Connectivity from OR37 expressing olfactory sensory neurons to distinct cell types in the hypothalamus

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    Andrea eBader

    2012-11-01

    Full Text Available Olfactory sensory neurons which express a member from the OR37 subfamily of odorant receptor genes are wired to the main olfactory bulb in a unique monoglomerular fashion; from these glomeruli an untypical connectivity into higher brain centers exists. In the present study we have investigated by DiI and transsynaptic tracing approaches how the connection pattern from these glomeruli into distinct hypothalamic nuclei is organized. The application of DiI onto the ventral domain of the bulb which harbors the OR37 glomeruli resulted in the labeling of fibers within the paraventricular and supraoptic nucleus of the hypothalamus; some of these fibers were covered with varicose-like structures. No DiI-labeled cell somata were detectable in these nuclei. The data indicate that projection neurons which originate in the OR37 region of the main olfactory bulb form direct connections into these nuclei. The cells that were labeled by the transsynaptic tracer WGA in these nuclei were further characterized. Their distribution pattern in the paraventricular nucleus was reminiscent of cells which produce distinct neuropeptides. Double labeling experiments confirmed that they contained vasopressin, but not the related neuropeptide oxytocin. Morphological analysis revealed that they comprise of magno- and parvocellular cells. A comparative investigation of the WGA-positive cells in the supraoptic nucleus demonstrated that these were vasopressin-positive, as well, whereas oxytocin-producing cells of this nucleus also contained no transsynaptic tracer. Together, the data demonstrate a connectivity from OR37 expressing sensory neurons to distinct hypothalamic neurons with the same neuropeptide content.

  9. Rapid Integration of Artificial Sensory Feedback during Operant Conditioning of Motor Cortex Neurons.

    Science.gov (United States)

    Prsa, Mario; Galiñanes, Gregorio L; Huber, Daniel

    2017-02-22

    Neuronal motor commands, whether generating real or neuroprosthetic movements, are shaped by ongoing sensory feedback from the displacement being produced. Here we asked if cortical stimulation could provide artificial feedback during operant conditioning of cortical neurons. Simultaneous two-photon imaging and real-time optogenetic stimulation were used to train mice to activate a single neuron in motor cortex (M1), while continuous feedback of its activity level was provided by proportionally stimulating somatosensory cortex. This artificial signal was necessary to rapidly learn to increase the conditioned activity, detect correct performance, and maintain the learned behavior. Population imaging in M1 revealed that learning-related activity changes are observed in the conditioned cell only, which highlights the functional potential of individual neurons in the neocortex. Our findings demonstrate the capacity of animals to use an artificially induced cortical channel in a behaviorally relevant way and reveal the remarkable speed and specificity at which this can occur. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Noise Enhances Action Potential Generation in Mouse Sensory Neurons via Stochastic Resonance.

    Science.gov (United States)

    Onorato, Irene; D'Alessandro, Giuseppina; Di Castro, Maria Amalia; Renzi, Massimiliano; Dobrowolny, Gabriella; Musarò, Antonio; Salvetti, Marco; Limatola, Cristina; Crisanti, Andrea; Grassi, Francesca

    2016-01-01

    Noise can enhance perception of tactile and proprioceptive stimuli by stochastic resonance processes. However, the mechanisms underlying this general phenomenon remain to be characterized. Here we studied how externally applied noise influences action potential firing in mouse primary sensory neurons of dorsal root ganglia, modelling a basic process in sensory perception. Since noisy mechanical stimuli may cause stochastic fluctuations in receptor potential, we examined the effects of sub-threshold depolarizing current steps with superimposed random fluctuations. We performed whole cell patch clamp recordings in cultured neurons of mouse dorsal root ganglia. Noise was added either before and during the step, or during the depolarizing step only, to focus onto the specific effects of external noise on action potential generation. In both cases, step + noise stimuli triggered significantly more action potentials than steps alone. The normalized power norm had a clear peak at intermediate noise levels, demonstrating that the phenomenon is driven by stochastic resonance. Spikes evoked in step + noise trials occur earlier and show faster rise time as compared to the occasional ones elicited by steps alone. These data suggest that external noise enhances, via stochastic resonance, the recruitment of transient voltage-gated Na channels, responsible for action potential firing in response to rapid step-wise depolarizing currents.

  11. Systemic Chemical Desensitization of Peptidergic Sensory Neurons with Resiniferatoxin Inhibits Experimental Periodontitis

    Science.gov (United States)

    Breivik, Torbjørn; Gundersen, Yngvar; Gjermo, Per; Fristad, Inge; Opstad, Per Kristian

    2011-01-01

    Background and objective: The immune system is an important player in the pathophysiology of periodontitis. The brain controls immune responses via neural and hormonal pathways, and brain-neuro-endocrine dysregulation may be a central determinant for pathogenesis. Our current knowledge also emphasizes the central role of sensory nerves. In line with this, we wanted to investigate how desensitization of peptidergic sensory neurons influences the progression of ligature-induced periodontitis, and, furthermore, how selected cytokine and stress hormone responses to Gram-negative bacterial lipopolysaccharide (LPS) stimulation are affected. Material and methods: Resiniferatoxin (RTX; 50 μg/kg) or vehicle was injected subcutaneously on days 1, 2, and 3 in stress high responding and periodontitis-susceptible Fischer 344 rats. Periodontitis was induced 2 days thereafter. Progression of the disease was assessed after the ligatures had been in place for 20 days. Two h before decapitation all rats received LPS (150 μg/kg i.p.) to induce a robust immune and stress response. Results: Desensitization with RTX significantly reduced bone loss as measured by digital X-rays. LPS provoked a significantly higher increase in serum levels of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α, but lower serum levels of the anti-inflammatory cytokine interleukin (IL)-10 and the stress hormone corticosterone. Conclusions: In this model RTX-induced chemical desensitization of sensory peptidergic neurons attenuated ligature-induced periodontitis and promoted a shift towards stronger pro-inflammatory cytokine and weaker stress hormone responses to LPS. The results may partly be explained by the attenuated transmission of immuno-inflammatory signals to the brain. In turn, this may weaken the anti-inflammatory brain-derived pathways. PMID:21339860

  12. Functional crosstalk in culture between macrophages and trigeminal sensory neurons of a mouse genetic model of migraine

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    Franceschini Alessia

    2012-11-01

    Full Text Available Abstract Background Enhanced activity of trigeminal ganglion neurons is thought to underlie neuronal sensitization facilitating the onset of chronic pain attacks, including migraine. Recurrent headache attacks might establish a chronic neuroinflammatory ganglion profile contributing to the hypersensitive phenotype. Since it is difficult to study this process in vivo, we investigated functional crosstalk between macrophages and sensory neurons in primary cultures from trigeminal sensory ganglia of wild-type (WT or knock-in (KI mice expressing the Cacna1a gene mutation (R192Q found in familial hemiplegic migraine-type 1. After studying the number and morphology of resident macrophages in culture, the consequences of adding host macrophages on macrophage phagocytosis and membrane currents mediated by pain-transducing P2X3 receptors on sensory neurons were examined. Results KI ganglion cultures constitutively contained a larger number of active macrophages, although no difference in P2X3 receptor expression was found. Co-culturing WT or KI ganglia with host macrophages (active as much as resident cells strongly stimulated single cell phagocytosis. The same protocol had no effect on P2X3 receptor expression in WT or KI co-cultures, but it largely enhanced WT neuron currents that grew to the high amplitude constitutively seen for KI neurons. No further potentiation of KI neuronal currents was observed. Conclusions Trigeminal ganglion cultures from a genetic mouse model of migraine showed basal macrophage activation together with enhanced neuronal currents mediated by P2X3 receptors. This phenotype could be replicated in WT cultures by adding host macrophages, indicating an important functional crosstalk between macrophages and sensory neurons.

  13. Functional crosstalk in culture between macrophages and trigeminal sensory neurons of a mouse genetic model of migraine.

    Science.gov (United States)

    Franceschini, Alessia; Nair, Asha; Bele, Tanja; van den Maagdenberg, Arn Mjm; Nistri, Andrea; Fabbretti, Elsa

    2012-11-21

    Enhanced activity of trigeminal ganglion neurons is thought to underlie neuronal sensitization facilitating the onset of chronic pain attacks, including migraine. Recurrent headache attacks might establish a chronic neuroinflammatory ganglion profile contributing to the hypersensitive phenotype. Since it is difficult to study this process in vivo, we investigated functional crosstalk between macrophages and sensory neurons in primary cultures from trigeminal sensory ganglia of wild-type (WT) or knock-in (KI) mice expressing the Cacna1a gene mutation (R192Q) found in familial hemiplegic migraine-type 1. After studying the number and morphology of resident macrophages in culture, the consequences of adding host macrophages on macrophage phagocytosis and membrane currents mediated by pain-transducing P2X3 receptors on sensory neurons were examined. KI ganglion cultures constitutively contained a larger number of active macrophages, although no difference in P2X3 receptor expression was found. Co-culturing WT or KI ganglia with host macrophages (active as much as resident cells) strongly stimulated single cell phagocytosis. The same protocol had no effect on P2X3 receptor expression in WT or KI co-cultures, but it largely enhanced WT neuron currents that grew to the high amplitude constitutively seen for KI neurons. No further potentiation of KI neuronal currents was observed. Trigeminal ganglion cultures from a genetic mouse model of migraine showed basal macrophage activation together with enhanced neuronal currents mediated by P2X3 receptors. This phenotype could be replicated in WT cultures by adding host macrophages, indicating an important functional crosstalk between macrophages and sensory neurons.

  14. EGL-13/SoxD specifies distinct O2 and CO2 sensory neuron fates in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Jakob Gramstrup Petersen

    2013-05-01

    Full Text Available Animals harbor specialized neuronal systems that are used for sensing and coordinating responses to changes in oxygen (O2 and carbon dioxide (CO2. In Caenorhabditis elegans, the O2/CO2 sensory system comprises functionally and morphologically distinct sensory neurons that mediate rapid behavioral responses to exquisite changes in O2 or CO2 levels via different sensory receptors. How the diversification of the O2- and CO2-sensing neurons is established is poorly understood. We show here that the molecular identity of both the BAG (O2/CO2-sensing and the URX (O2-sensing neurons is controlled by the phylogenetically conserved SoxD transcription factor homolog EGL-13. egl-13 mutant animals fail to fully express the distinct terminal gene batteries of the BAG and URX neurons and, as such, are unable to mount behavioral responses to changes in O2 and CO2. We found that the expression of egl-13 is regulated in the BAG and URX neurons by two conserved transcription factors-ETS-5(Ets factor in the BAG neurons and AHR-1(bHLH factor in the URX neurons. In addition, we found that EGL-13 acts in partially parallel pathways with both ETS-5 and AHR-1 to direct BAG and URX neuronal fate respectively. Finally, we found that EGL-13 is sufficient to induce O2- and CO2-sensing cell fates in some cellular contexts. Thus, the same core regulatory factor, egl-13, is required and sufficient to specify the distinct fates of O2- and CO2-sensing neurons in C. elegans. These findings extend our understanding of mechanisms of neuronal diversification and the regulation of molecular factors that may be conserved in higher organisms.

  15. Characterizing human stem cell-derived sensory neurons at the single-cell level reveals their ion channel expression and utility in pain research.

    Science.gov (United States)

    Young, Gareth T; Gutteridge, Alex; Fox, Heather DE; Wilbrey, Anna L; Cao, Lishuang; Cho, Lily T; Brown, Adam R; Benn, Caroline L; Kammonen, Laura R; Friedman, Julia H; Bictash, Magda; Whiting, Paul; Bilsland, James G; Stevens, Edward B

    2014-08-01

    The generation of human sensory neurons by directed differentiation of pluripotent stem cells opens new opportunities for investigating the biology of pain. The inability to generate this cell type has meant that up until now their study has been reliant on the use of rodent models. Here, we use a combination of population and single-cell techniques to perform a detailed molecular, electrophysiological, and pharmacological phenotyping of sensory neurons derived from human embryonic stem cells. We describe the evolution of cell populations over 6 weeks of directed differentiation; a process that results in the generation of a largely homogeneous population of neurons that are both molecularly and functionally comparable to human sensory neurons derived from mature dorsal root ganglia. This work opens the prospect of using pluripotent stem-cell-derived sensory neurons to study human neuronal physiology and as in vitro models for drug discovery in pain and sensory disorders.

  16. Characterizing Human Stem Cell–derived Sensory Neurons at the Single-cell Level Reveals Their Ion Channel Expression and Utility in Pain Research

    Science.gov (United States)

    Young, Gareth T; Gutteridge, Alex; Fox, Heather DE; Wilbrey, Anna L; Cao, Lishuang; Cho, Lily T; Brown, Adam R; Benn, Caroline L; Kammonen, Laura R; Friedman, Julia H; Bictash, Magda; Whiting, Paul; Bilsland, James G; Stevens, Edward B

    2014-01-01

    The generation of human sensory neurons by directed differentiation of pluripotent stem cells opens new opportunities for investigating the biology of pain. The inability to generate this cell type has meant that up until now their study has been reliant on the use of rodent models. Here, we use a combination of population and single-cell techniques to perform a detailed molecular, electrophysiological, and pharmacological phenotyping of sensory neurons derived from human embryonic stem cells. We describe the evolution of cell populations over 6 weeks of directed differentiation; a process that results in the generation of a largely homogeneous population of neurons that are both molecularly and functionally comparable to human sensory neurons derived from mature dorsal root ganglia. This work opens the prospect of using pluripotent stem-cell–derived sensory neurons to study human neuronal physiology and as in vitro models for drug discovery in pain and sensory disorders. PMID:24832007

  17. Modulation of Specific Sensory Cortical Areas by Segregated Basal Forebrain Cholinergic Neurons Demonstrated by Neuronal Tracing and Optogenetic Stimulation in Mice.

    Science.gov (United States)

    Chaves-Coira, Irene; Barros-Zulaica, Natali; Rodrigo-Angulo, Margarita; Núñez, Ángel

    2016-01-01

    Neocortical cholinergic activity plays a fundamental role in sensory processing and cognitive functions. Previous results have suggested a refined anatomical and functional topographical organization of basal forebrain (BF) projections that may control cortical sensory processing in a specific manner. We have used retrograde anatomical procedures to demonstrate the existence of specific neuronal groups in the BF involved in the control of specific sensory cortices. Fluoro-Gold (FlGo) and Fast Blue (FB) fluorescent retrograde tracers were deposited into the primary somatosensory (S1) and primary auditory (A1) cortices in mice. Our results revealed that the BF is a heterogeneous area in which neurons projecting to different cortical areas are segregated into different neuronal groups. Most of the neurons located in the horizontal limb of the diagonal band of Broca (HDB) projected to the S1 cortex, indicating that this area is specialized in the sensory processing of tactile stimuli. However, the nucleus basalis magnocellularis (B) nucleus shows a similar number of cells projecting to the S1 as to the A1 cortices. In addition, we analyzed the cholinergic effects on the S1 and A1 cortical sensory responses by optogenetic stimulation of the BF neurons in urethane-anesthetized transgenic mice. We used transgenic mice expressing the light-activated cation channel, channelrhodopsin-2, tagged with a fluorescent protein (ChR2-YFP) under the control of the choline-acetyl transferase promoter (ChAT). Cortical evoked potentials were induced by whisker deflections or by auditory clicks. According to the anatomical results, optogenetic HDB stimulation induced more extensive facilitation of tactile evoked potentials in S1 than auditory evoked potentials in A1, while optogenetic stimulation of the B nucleus facilitated either tactile or auditory evoked potentials equally. Consequently, our results suggest that cholinergic projections to the cortex are organized into segregated

  18. Increased Nerve Growth Factor Signaling in Sensory Neurons of Early Diabetic Rats Is Corrected by Electroacupuncture

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    Stefania Lucia Nori

    2013-01-01

    Full Text Available Diabetic polyneuropathy (DPN, characterized by early hyperalgesia and increased nerve growth factor (NGF, evolves in late irreversible neuropathic symptoms with reduced NGF support to sensory neurons. Electroacupuncture (EA modulates NGF in the peripheral nervous system, being effective for the treatment of DPN symptoms. We hypothesize that NGF plays an important pathogenic role in DPN development, while EA could be useful in the therapy of DPN by modulating NGF expression/activity. Diabetes was induced in rats by streptozotocin (STZ injection. One week after STZ, EA was started and continued for three weeks. NGF system and hyperalgesia-related mediators were analyzed in the dorsal root ganglia (DRG and in their spinal cord and skin innervation territories. Our results show that four weeks long diabetes increased NGF and NGF receptors and deregulated intracellular signaling mediators of DRG neurons hypersensitization; EA in diabetic rats decreased NGF and NGF receptors, normalized c-Jun N-terminal and p38 kinases activation, decreased transient receptor potential vanilloid-1 ion channel, and possibly activated the nuclear factor kappa-light-chain-enhancer of activated B cells (Nf-κB. In conclusion, NGF signaling deregulation might play an important role in the development of DPN. EA represents a supportive tool to control DPN development by modulating NGF signaling in diabetes-targeted neurons.

  19. Bilateral Neuropathy of Primary Sensory Neurons by the Chronic Compression of Multiple Unilateral DRGs

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    Ya-Bin Xie

    2016-01-01

    Full Text Available To mimic multilevel nerve root compression and intervertebral foramina stenosis in human, we established a new animal model of the chronic compression of unilateral multiple lumbar DRGs (mCCD in the rat. A higher occurrence of signs of spontaneous pain behaviors, such as wet-dog shaking and spontaneous hind paw shrinking behaviors, was firstly observed from day 1 onward. In the meantime, the unilateral mCCD rat exhibited significant bilateral hind paw mechanical and cold allodynia and hyperalgesia, as well as a thermal preference to 30°C plate between 30 and 35°C. The expression of activating transcription factor 3 (ATF3 was significantly increased in the ipsilateral and contralateral all-sized DRG neurons after the mCCD. And the expression of CGRP was significantly increased in the ipsilateral and contralateral large- and medium-sized DRG neurons. ATF3 and CGRP expressions correlated to evoked pain hypersensitivities such as mechanical and cold allodynia on postoperative day 1. The results suggested that bilateral neuropathy of primary sensory neurons might contribute to bilateral hypersensitivity in the mCCD rat.

  20. Generation of Otic Sensory Neurons from Mouse Embryonic Stem Cells in 3D Culture

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    Michael Perny

    2017-12-01

    Full Text Available The peripheral hearing process taking place in the cochlea mainly depends on two distinct sensory cell types: the mechanosensitive hair cells and the spiral ganglion neurons (SGNs. The first respond to the mechanical stimulation exerted by sound pressure waves on their hair bundles by releasing neurotransmitters and thereby activating the latter. Loss of these sensorineural cells is associated with permanent hearing loss. Stem cell-based approaches aiming at cell replacement or in vitro drug testing to identify potential ototoxic, otoprotective, or regenerative compounds have lately gained attention as putative therapeutic strategies for hearing loss. Nevertheless, they rely on efficient and reliable protocols for the in vitro generation of cochlear sensory cells for their implementation. To this end, we have developed a differentiation protocol based on organoid culture systems, which mimics the most important steps of in vivo otic development, robustly guiding mouse embryonic stem cells (mESCs toward otic sensory neurons (OSNs. The stepwise differentiation of mESCs toward ectoderm was initiated using a quick aggregation method in presence of Matrigel in serum-free conditions. Non-neural ectoderm was induced via activation of bone morphogenetic protein (BMP signaling and concomitant inhibition of transforming growth factor beta (TGFβ signaling to prevent mesendoderm induction. Preplacodal and otic placode ectoderm was further induced by inhibition of BMP signaling and addition of fibroblast growth factor 2 (FGF2. Delamination and differentiation of SGNs was initiated by plating of the organoids on a 2D Matrigel-coated substrate. Supplementation with brain-derived neurotrophic factor (BDNF and neurotrophin-3 (NT-3 was used for further maturation until 15 days of in vitro differentiation. A large population of neurons with a clear bipolar morphology and functional excitability was derived from these cultures. Immunostaining and gene expression

  1. Oncostatin M induces heat hypersensitivity by gp130-dependent sensitization of TRPV1 in sensory neurons

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    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.

  2. Spike propagation through the dorsal root ganglia in an unmyelinated sensory neuron: a modeling study.

    Science.gov (United States)

    Sundt, Danielle; Gamper, Nikita; Jaffe, David B

    2015-12-01

    Unmyelinated C-fibers are a major type of sensory neurons conveying pain information. Action potential conduction is regulated by the bifurcation (T-junction) of sensory neuron axons within the dorsal root ganglia (DRG). Understanding how C-fiber signaling is influenced by the morphology of the T-junction and the local expression of ion channels is important for understanding pain signaling. In this study we used biophysical computer modeling to investigate the influence of axon morphology within the DRG and various membrane conductances on the reliability of spike propagation. As expected, calculated input impedance and the amplitude of propagating action potentials were both lowest at the T-junction. Propagation reliability for single spikes was highly sensitive to the diameter of the stem axon and the density of voltage-gated Na(+) channels. A model containing only fast voltage-gated Na(+) and delayed-rectifier K(+) channels conducted trains of spikes up to frequencies of 110 Hz. The addition of slowly activating KCNQ channels (i.e., KV7 or M-channels) to the model reduced the following frequency to 30 Hz. Hyperpolarization produced by addition of a much slower conductance, such as a Ca(2+)-dependent K(+) current, was needed to reduce the following frequency to 6 Hz. Attenuation of driving force due to ion accumulation or hyperpolarization produced by a Na(+)-K(+) pump had no effect on following frequency but could influence the reliability of spike propagation mutually with the voltage shift generated by a Ca(2+)-dependent K(+) current. These simulations suggest how specific ion channels within the DRG may contribute toward therapeutic treatments for chronic pain. Copyright © 2015 the American Physiological Society.

  3. Changes in Olfactory Sensory Neuron Physiology and Olfactory Perceptual Learning After Odorant Exposure in Adult Mice.

    Science.gov (United States)

    Kass, Marley D; Guang, Stephanie A; Moberly, Andrew H; McGann, John P

    2016-02-01

    The adult olfactory system undergoes experience-dependent plasticity to adapt to the olfactory environment. This plasticity may be accompanied by perceptual changes, including improved olfactory discrimination. Here, we assessed experience-dependent changes in the perception of a homologous aldehyde pair by testing mice in a cross-habituation/dishabituation behavioral paradigm before and after a week-long ester-odorant exposure protocol. In a parallel experiment, we used optical neurophysiology to observe neurotransmitter release from olfactory sensory neuron (OSN) terminals in vivo, and thus compared primary sensory representations of the aldehydes before and after the week-long ester-odorant exposure in individual animals. Mice could not discriminate between the aldehydes during pre-exposure testing, but ester-exposed subjects spontaneously discriminated between the homologous pair after exposure, whereas home cage control mice cross-habituated. Ester exposure did not alter the spatial pattern, peak magnitude, or odorant-selectivity of aldehyde-evoked OSN input to olfactory bulb glomeruli, but did alter the temporal dynamics of that input to make the time course of OSN input more dissimilar between odorants. Together, these findings demonstrate that odor exposure can induce both physiological and perceptual changes in odor processing, and suggest that changes in the temporal patterns of OSN input to olfactory bulb glomeruli could induce differences in odor quality. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Adipose-derived stromal cells enhance auditory neuron survival in an animal model of sensory hearing loss.

    Science.gov (United States)

    Schendzielorz, Philipp; Vollmer, Maike; Rak, Kristen; Wiegner, Armin; Nada, Nashwa; Radeloff, Katrin; Hagen, Rudolf; Radeloff, Andreas

    2017-10-01

    A cochlear implant (CI) is an electronic prosthesis that can partially restore speech perception capabilities. Optimum information transfer from the cochlea to the central auditory system requires a proper functioning auditory nerve (AN) that is electrically stimulated by the device. In deafness, the lack of neurotrophic support, normally provided by the sensory cells of the inner ear, however, leads to gradual degeneration of auditory neurons with undesirable consequences for CI performance. We evaluated the potential of adipose-derived stromal cells (ASCs) that are known to produce neurotrophic factors to prevent neural degeneration in sensory hearing loss. For this, co-cultures of ASCs with auditory neurons have been studied, and autologous ASC transplantation has been performed in a guinea pig model of gentamicin-induced sensory hearing loss. In vitro ASCs were neuroprotective and considerably increased the neuritogenesis of auditory neurons. In vivo transplantation of ASCs into the scala tympani resulted in an enhanced survival of auditory neurons. Specifically, peripheral AN processes that are assumed to be the optimal activation site for CI stimulation and that are particularly vulnerable to hair cell loss showed a significantly higher survival rate in ASC-treated ears. ASC transplantation into the inner ear may restore neurotrophic support in sensory hearing loss and may help to improve CI performance by enhanced AN survival. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  5. TRPM7 is required within zebrafish sensory neurons for the activation of touch-evoked escape behaviors

    Science.gov (United States)

    Low, Sean E.; Amburgey, Kimberly; Horstick, Eric; Linsley, Jeremy; Sprague, Shawn M.; Cui, Wilson W.; Zhou, Weibin; Hirata, Hiromi; Saint-Amant, Louis; Hume, Richard I.; Kuwada, John Y.

    2011-01-01

    Mutations in the gene encoding TRPM7 (trpm7), a member of the TRP superfamily of cation channels that possesses an enzymatically active kinase at its carboxyl terminus, cause the touch-unresponsive zebrafish mutant touchdown. We identified and characterized a new allele of touchdown, as well as two previously reported alleles, and found that all three alleles harbor mutations which abolish channel activity. Through the selective restoration of TRPM7 expression in sensory neurons we found that TRPM7’s kinase activity, and selectivity for divalent cations over monovalent cations, were dispensable for touch-evoked activation of escape behaviors in zebrafish. Additional characterization revealed that sensory neurons were present and capable of responding to tactile stimuli in touchdown mutants, indicating that TRPM7 is not required for sensory neuron survival or mechanosensation. Finally, exposure to elevated concentrations of divalent cations was found to restore touch-evoked behaviors in touchdown mutants. Collectively these findings are consistent with a role for zebrafish TRPM7 within sensory neurons in the modulation of neurotransmitter release at central synapses, similar to that proposed for mammalian TRPM7 at peripheral synapses. PMID:21832193

  6. Spindle-F Is the Central Mediator of Ik2 Kinase-Dependent Dendrite Pruning in Drosophila Sensory Neurons.

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    Tzu Lin

    2015-11-01

    Full Text Available During development, certain Drosophila sensory neurons undergo dendrite pruning that selectively eliminates their dendrites but leaves the axons intact. How these neurons regulate pruning activity in the dendrites remains unknown. Here, we identify a coiled-coil protein Spindle-F (Spn-F that is required for dendrite pruning in Drosophila sensory neurons. Spn-F acts downstream of IKK-related kinase Ik2 in the same pathway for dendrite pruning. Spn-F exhibits a punctate pattern in larval neurons, whereas these Spn-F puncta become redistributed in pupal neurons, a step that is essential for dendrite pruning. The redistribution of Spn-F from puncta in pupal neurons requires the phosphorylation of Spn-F by Ik2 kinase to decrease Spn-F self-association, and depends on the function of microtubule motor dynein complex. Spn-F is a key component to link Ik2 kinase to dynein motor complex, and the formation of Ik2/Spn-F/dynein complex is critical for Spn-F redistribution and for dendrite pruning. Our findings reveal a novel regulatory mechanism for dendrite pruning achieved by temporal activation of Ik2 kinase and dynein-mediated redistribution of Ik2/Spn-F complex in neurons.

  7. Expression patterns of odorant receptors and response properties of olfactory sensory neurons in aged mice.

    Science.gov (United States)

    Lee, Anderson C; Tian, Huikai; Grosmaitre, Xavier; Ma, Minghong

    2009-10-01

    The sense of smell deteriorates in normal aging, but the underling mechanisms are still elusive. Here we investigated age-related alterations in expression patterns of odorant receptor (OR) genes and functional properties of olfactory sensory neurons (OSNs)-2 critical factors that define the odor detection threshold in the olfactory epithelium. Using in situ hybridization for 9 representative OR genes, we compared the cell densities of each OR in coronal nose sections at different ages (3-27 months). The cell density for different ORs peaked at different time points and a decline was observed for 6 of 9 ORs at advanced ages. Using patch clamp recordings, we then examined the odorant responses of individual OSNs coexpressing a defined OR (MOR23) and green fluorescent protein. The MOR23 neurons recorded from aged animals maintained a similar sensitivity and dynamic range in response to the cognate odorant (lyral) as those from younger mice. The results indicate that although the cell densities of OSNs expressing certain types of ORs decline at advanced ages, individual OSNs can retain their sensitivity. The implications of these findings in age-related olfactory deterioration are discussed.

  8. Anatomical and molecular consequences of Unilateral Naris Closure on two populations of olfactory sensory neurons expressing defined odorant receptors.

    Science.gov (United States)

    Molinas, Adrien; Aoudé, Imad; Soubeyre, Vanessa; Tazir, Bassim; Cadiou, Hervé; Grosmaitre, Xavier

    2016-07-28

    Mammalian olfactory sensory neurons (OSNs), the primary elements of the olfactory system, are located in the olfactory epithelium lining the nasal cavity. Exposed to the environment, their lifespan is short. Consequently, OSNs are regularly regenerated and several reports show that activity strongly modulates their development and regeneration: the peripheral olfactory system can adjust to the amount of stimulus through compensatory mechanisms. Unilateral naris occlusion (UNO) was frequently used to investigate this mechanism at the entire epithelium level. However, there is little data regarding the effects of UNO at the cellular level, especially on individual neuronal populations expressing a defined odorant receptor. Here, using UNO during the first three postnatal weeks, we analyzed the anatomical and molecular consequences of sensory deprivation in OSNs populations expressing the MOR23 and M71 receptors. The density of MOR23-expressing neurons is decreased in the closed side while UNO does not affect the density of M71-expressing neurons. Using Real Time qPCR on isolated neurons, we observed that UNO modulates the transcript levels for transduction pathway proteins (odorant receptors, CNGA2, PDE1c). The transcripts modulated by UNO will differ between populations depending on the receptor expressed. These results suggest that sensory deprivation will have different effects on different OSNs' populations. As a consequence, early experience will shape the functional properties of OSNs differently depending on the type of odorant receptor they express. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  11. APE1, the DNA base excision repair protein, regulates the removal of platinum adducts in sensory neuronal cultures by NER

    International Nuclear Information System (INIS)

    Kim, Hyun-Suk; Guo, Chunlu; Thompson, Eric L.; Jiang, Yanlin; Kelley, Mark R.; Vasko, Michael R.; Lee, Suk-Hee

    2015-01-01

    Peripheral neuropathy is one of the major side effects of treatment with the anticancer drug, cisplatin. One proposed mechanism for this neurotoxicity is the formation of platinum adducts in sensory neurons that could contribute to DNA damage. Although this damage is largely repaired by nuclear excision repair (NER), our previous findings suggest that augmenting the base excision repair pathway (BER) by overexpressing the repair protein APE1 protects sensory neurons from cisplatin-induced neurotoxicity. The question remains whether APE1 contributes to the ability of the NER pathway to repair platinum-damage in neuronal cells. To examine this, we manipulated APE1 expression in sensory neuronal cultures and measured Pt-removal after exposure to cisplatin. When neuronal cultures were treated with increasing concentrations of cisplatin for two or three hours, there was a concentration-dependent increase in Pt-damage that peaked at four hours and returned to near baseline levels after 24 h. In cultures where APE1 expression was reduced by ∼80% using siRNA directed at APE1, there was a significant inhibition of Pt-removal over eight hours which was reversed by overexpressing APE1 using a lentiviral construct for human wtAPE1. Overexpressing a mutant APE1 (C65 APE1), which only has DNA repair activity, but not its other significant redox-signaling function, mimicked the effects of wtAPE1. Overexpressing DNA repair activity mutant APE1 (226 + 177APE1), with only redox activity was ineffective suggesting it is the DNA repair function of APE1 and not its redox-signaling, that restores the Pt-damage removal. Together, these data provide the first evidence that a critical BER enzyme, APE1, helps regulate the NER pathway in the repair of cisplatin damage in sensory neurons

  12. APE1, the DNA base excision repair protein, regulates the removal of platinum adducts in sensory neuronal cultures by NER

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun-Suk [Department of Biochemistry and Molecular Biology, Indianapolis, IN 46202 (United States); Guo, Chunlu; Thompson, Eric L. [Department of Pharmacology and Toxicology, Indianapolis, IN 46202 (United States); Jiang, Yanlin [Department of Pediatrics and Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202 (United States); Kelley, Mark R. [Department of Biochemistry and Molecular Biology, Indianapolis, IN 46202 (United States); Department of Pharmacology and Toxicology, Indianapolis, IN 46202 (United States); Department of Pediatrics and Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202 (United States); Vasko, Michael R. [Department of Pharmacology and Toxicology, Indianapolis, IN 46202 (United States); Lee, Suk-Hee, E-mail: slee@iu.edu [Department of Biochemistry and Molecular Biology, Indianapolis, IN 46202 (United States)

    2015-09-15

    Peripheral neuropathy is one of the major side effects of treatment with the anticancer drug, cisplatin. One proposed mechanism for this neurotoxicity is the formation of platinum adducts in sensory neurons that could contribute to DNA damage. Although this damage is largely repaired by nuclear excision repair (NER), our previous findings suggest that augmenting the base excision repair pathway (BER) by overexpressing the repair protein APE1 protects sensory neurons from cisplatin-induced neurotoxicity. The question remains whether APE1 contributes to the ability of the NER pathway to repair platinum-damage in neuronal cells. To examine this, we manipulated APE1 expression in sensory neuronal cultures and measured Pt-removal after exposure to cisplatin. When neuronal cultures were treated with increasing concentrations of cisplatin for two or three hours, there was a concentration-dependent increase in Pt-damage that peaked at four hours and returned to near baseline levels after 24 h. In cultures where APE1 expression was reduced by ∼80% using siRNA directed at APE1, there was a significant inhibition of Pt-removal over eight hours which was reversed by overexpressing APE1 using a lentiviral construct for human wtAPE1. Overexpressing a mutant APE1 (C65 APE1), which only has DNA repair activity, but not its other significant redox-signaling function, mimicked the effects of wtAPE1. Overexpressing DNA repair activity mutant APE1 (226 + 177APE1), with only redox activity was ineffective suggesting it is the DNA repair function of APE1 and not its redox-signaling, that restores the Pt-damage removal. Together, these data provide the first evidence that a critical BER enzyme, APE1, helps regulate the NER pathway in the repair of cisplatin damage in sensory neurons.

  13. Reproductive experience modified dendritic spines on cortical pyramidal neurons to enhance sensory perception and spatial learning in rats.

    Science.gov (United States)

    Chen, Jeng-Rung; Lim, Seh Hong; Chung, Sin-Cun; Lee, Yee-Fun; Wang, Yueh-Jan; Tseng, Guo-Fang; Wang, Tsyr-Jiuan

    2017-01-27

    Behavioral adaptations during motherhood are aimed at increasing reproductive success. Alterations of hormones during motherhood could trigger brain morphological changes to underlie behavioral alterations. Here we investigated whether motherhood changes a rat's sensory perception and spatial memory in conjunction with cortical neuronal structural changes. Female rats of different statuses, including virgin, pregnant, lactating, and primiparous rats were studied. Behavioral test showed that the lactating rats were most sensitive to heat, while rats with motherhood and reproduction experience outperformed virgin rats in a water maze task. By intracellular dye injection and computer-assisted 3-dimensional reconstruction, the dendritic arbors and spines of the layer III and V pyramidal neurons of the somatosensory cortex and CA1 hippocampal pyramidal neurons were revealed for closer analysis. The results showed that motherhood and reproductive experience increased dendritic spines but not arbors or the lengths of the layer III and V pyramidal neurons of the somatosensory cortex and CA1 hippocampal pyramidal neurons. In addition, lactating rats had a higher incidence of spines than pregnant or primiparous rats. The increase of dendritic spines was coupled with increased expression of the glutamatergic postsynaptic marker protein (PSD-95), especially in lactating rats. On the basis of the present results, it is concluded that motherhood enhanced rat sensory perception and spatial memory and was accompanied by increases in dendritic spines on output neurons of the somatosensory cortex and CA1 hippocampus. The effect was sustained for at least 6 weeks after the weaning of the pups.

  14. Tissue engineering the mechanosensory circuit of the stretch reflex arc: sensory neuron innervation of intrafusal muscle fibers.

    Science.gov (United States)

    Rumsey, John W; Das, Mainak; Bhalkikar, Abhijeet; Stancescu, Maria; Hickman, James J

    2010-11-01

    The sensory circuit of the stretch reflex arc, composed of specialized intrafusal muscle fibers and type Ia proprioceptive sensory neurons, converts mechanical information regarding muscle length and stretch to electrical action potentials and relays them to the central nervous system. Utilizing a non-biological substrate, surface patterning photolithography and a serum-free medium formulation a co-culture system was developed that facilitated functional interactions between intrafusal muscle fibers and sensory neurons. The presence of annulospiral wrappings (ASWs) and flower-spray endings (FSEs), both physiologically relevant morphologies in sensory neuron-intrafusal fiber interactions, were demonstrated and quantified using immunocytochemistry. Furthermore, two proposed components of the mammalian mechanosensory transduction system, BNaC1 and PICK1, were both identified at the ASWs and FSEs. To verify functionality of the mechanoreceptor elements the system was integrated with a MEMS cantilever device, and Ca(2+) currents were imaged along the length of an axon innervating an intrafusal fiber when stretched by cantilever deflection. This system provides a platform for examining the role of this mechanosensory complex in the pathology of myotonic and muscular dystrophies, peripheral neuropathy, and spasticity inducing diseases like Parkinson's. These studies will also assist in engineering fine motor control for prosthetic devices by improving our understanding of mechanosensitive feedback. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  15. The mummified corpse in a domestic setting.

    Science.gov (United States)

    Campobasso, Carlo P; Falamingo, Rosa; Grattagliano, Ignazio; Vinci, Francesco

    2009-09-01

    A mummified body of an 86-year-old white man with a history of coronary atherosclerosis was found in the reception-room of his apartment located in a condominium of the city-center of Bari (Southern Italy) approximately 7 years after disappearance. Unpaid electricity bills caused the power stations to turn off electricity while unpaid condominium bills forced the manager of the condominium to open the apartment where the body was found. The corpse was well preserved through the mummification process and no external injuries were observed. Signs of a very low insect activity were also present, reasonably consistent with a rapid skin dehydration. The body was sitting on the carpet in front of an easy-chair, fully clothed by a woollen vest with dark paints and shoes. The head was lying face down on the easy-chair. The corpse was very light in weight, fixed in the sitting position by the brittle dehydrated tissues. The carpet on which the body was sitting and the covering tissue of the easy-chair on which the head was lying absorbed most of the early putrefactive fluids coming from the corpse. The internal organs were grossly identifiable but essentially unremarkable. On histologic examination most of the tissues were found to be autolyzed. Toxicology studies revealed only decompositional products. The cause of death was undetermined but presumed natural. Based on the ante-mortem data available the corpse was soon identified by dental comparison to be that one of the apartment owner missing 7 years before. The delayed recovery of elderly people who lived alone, incapacitated or unable to get help, or even of lonely deaths of nobody seems to miss are often explained by the isolation os such people even in urban areas in addition to a deficient family support, missing social and neighborly relationships, worsening of the health and financial conditions.

  16. Integration of Plasticity Mechanisms within a Single Sensory Neuron of C. elegans Actuates a Memory.

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    Hawk, Josh D; Calvo, Ana C; Liu, Ping; Almoril-Porras, Agustin; Aljobeh, Ahmad; Torruella-Suárez, María Luisa; Ren, Ivy; Cook, Nathan; Greenwood, Joel; Luo, Linjiao; Wang, Zhao-Wen; Samuel, Aravinthan D T; Colón-Ramos, Daniel A

    2018-01-17

    Neural plasticity, the ability of neurons to change their properties in response to experiences, underpins the nervous system's capacity to form memories and actuate behaviors. How different plasticity mechanisms act together in vivo and at a cellular level to transform sensory information into behavior is not well understood. We show that in Caenorhabditis elegans two plasticity mechanisms-sensory adaptation and presynaptic plasticity-act within a single cell to encode thermosensory information and actuate a temperature preference memory. Sensory adaptation adjusts the temperature range of the sensory neuron (called AFD) to optimize detection of temperature fluctuations associated with migration. Presynaptic plasticity in AFD is regulated by the conserved kinase nPKCε and transforms thermosensory information into a behavioral preference. Bypassing AFD presynaptic plasticity predictably changes learned behavioral preferences without affecting sensory responses. Our findings indicate that two distinct neuroplasticity mechanisms function together through a single-cell logic system to enact thermotactic behavior. VIDEO ABSTRACT. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Asymmetric localization of natural antisense RNA of neuropeptide sensorin in Aplysia sensory neurons during aging and activity

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    Beena eKadakkuzha

    2014-04-01

    Full Text Available Despite the advances in our understanding of transcriptome, regulation and function of its noncoding components continue to be poorly understood. Here we searched for natural antisense transcript for sensorin (NAT-SRN, a neuropeptide expressed in the presynaptic sensory neurons of gill-withdrawal reflex of the marine snail Aplysia californica. Sensorin (SRN has a key role in learning and long-term memory storage in Aplysia. We have identified NAT-SRN in the central nervous system (CNS and have confirmed its expression by northern blotting and fluorescent RNA in situ hybridization. Quantitative analysis of NAT-SRN in micro dissected cell bodies and processes of sensory neurons suggest that NAT-SRN is present in the distal neuronal processes along with sense transcripts. Importantly, aging is associated with reduced levels of NAT-SRN in sensory neuron processes. Furthermore, we find that forskolin, an activator of CREB signaling, differentially alters the distribution of SRN and NAT-SRN. These studies reveal novel insights into physiological regulation of natural antisense RNAs.

  18. Asymmetric localization of natural antisense RNA of neuropeptide sensorin in Aplysia sensory neurons during aging and activity.

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    Kadakkuzha, Beena M; Liu, Xin-An; Narvaez, Maria; Kaye, Alexandra; Akhmedov, Komolitdin; Puthanveettil, Sathyanarayanan V

    2014-01-01

    Despite the advances in our understanding of transcriptome, regulation and function of its non-coding components continue to be poorly understood. Here we searched for natural antisense transcript for sensorin (NAT-SRN), a neuropeptide expressed in the presynaptic sensory neurons of gill-withdrawal reflex of the marine snail Aplysia californica. Sensorin (SRN) has a key role in learning and long-term memory storage in Aplysia. We have now identified NAT-SRN in the central nervous system (CNS) and have confirmed its expression by northern blotting and fluorescent RNA in situ hybridization. Quantitative analysis of NAT-SRN in micro-dissected cell bodies and processes of sensory neurons suggest that NAT-SRN is present in the distal neuronal processes along with sense transcripts. Importantly, aging is associated with reduction in levels of NAT-SRN in sensory neuron processes. Furthermore, we find that forskolin, an activator of CREB signaling, differentially alters the distribution of SRN and NAT-SRN. These studies reveal novel insights into physiological regulation of natural antisense RNAs.

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

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    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.

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

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    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.

  1. C. elegans ciliated sensory neurons release extracellular vesicles that function in animal communication.

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    Wang, Juan; Silva, Malan; Haas, Leonard A; Morsci, Natalia S; Nguyen, Ken C Q; Hall, David H; Barr, Maureen M

    2014-03-03

    Cells release extracellular vesicles (ECVs) that play important roles in intercellular communication and may mediate a broad range of physiological and pathological processes. Many fundamental aspects of ECV biogenesis and signaling have yet to be determined, with ECV detection being a challenge and obstacle due to the small size (100 nm) of the ECVs. We developed an in vivo system to visualize the dynamic release of GFP-labeled ECVs. We show here that specific Caenorhabdidits elegans ciliated sensory neurons shed and release ECVs containing GFP-tagged polycystins LOV-1 and PKD-2. These ECVs are also abundant in the lumen surrounding the cilium. Electron tomography and genetic analysis indicate that ECV biogenesis occurs via budding from the plasma membrane at the ciliary base and not via fusion of multivesicular bodies. Intraflagellar transport and kinesin-3 KLP-6 are required for environmental release of PKD-2::GFP-containing ECVs. ECVs isolated from wild-type animals induce male tail-chasing behavior, while ECVs isolated from klp-6 animals and lacking PKD-2::GFP do not. We conclude that environmentally released ECVs play a role in animal communication and mating-related behaviors. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Intracellular recording, sensory field mapping, and culturing identified neurons in the leech, Hirudo medicinalis.

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    Titlow, Josh; Majeed, Zana R; Nicholls, John G; Cooper, Robin L

    2013-11-04

    The freshwater leech, Hirudo medicinalis, is a versatile model organism that has been used to address scientific questions in the fields of neurophysiology, neuroethology, and developmental biology. The goal of this report is to consolidate experimental techniques from the leech system into a single article that will be of use to physiologists with expertise in other nervous system preparations, or to biology students with little or no electrophysiology experience. We demonstrate how to dissect the leech for recording intracellularly from identified neural circuits in the ganglion. Next we show how individual cells of known function can be removed from the ganglion to be cultured in a Petri dish, and how to record from those neurons in culture. Then we demonstrate how to prepare a patch of innervated skin to be used for mapping sensory or motor fields. These leech preparations are still widely used to address basic electrical properties of neural networks, behavior, synaptogenesis, and development. They are also an appropriate training module for neuroscience or physiology teaching laboratories.

  3. Highly localized interactions between sensory neurons and sprouting sympathetic fibers observed in a transgenic tyrosine hydroxylase reporter mouse

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    Zhang Jun-Ming

    2011-07-01

    Full Text Available Abstract Background Sprouting of sympathetic fibers into sensory ganglia occurs in many preclinical pain models, providing a possible anatomical substrate for sympathetically enhanced pain. However, the functional consequences of this sprouting have been controversial. We used a transgenic mouse in which sympathetic fibers expressed green fluorescent protein, observable in live tissue. Medium and large diameter lumbar sensory neurons with and without nearby sympathetic fibers were recorded in whole ganglion preparations using microelectrodes. Results After spinal nerve ligation, sympathetic sprouting was extensive by 3 days. Abnormal spontaneous activity increased to 15% and rheobase was reduced. Spontaneously active cells had Aαβ conduction velocities but were clustered near the medium/large cell boundary. Neurons with sympathetic basket formations had a dramatically higher incidence of spontaneous activity (71% and had lower rheobase than cells with no sympathetic fibers nearby. Cells with lower density nearby fibers had intermediate phenotypes. Immunohistochemistry of sectioned ganglia showed that cells surrounded by sympathetic fibers were enriched in nociceptive markers TrkA, substance P, or CGRP. Spontaneous activity began before sympathetic sprouting was observed, but blocking sympathetic sprouting on day 3 by cutting the dorsal ramus in addition to the ventral ramus of the spinal nerve greatly reduced abnormal spontaneous activity. Conclusions The data suggest that early sympathetic sprouting into the sensory ganglia may have highly localized, excitatory effects. Quantitatively, neurons with sympathetic basket formations may account for more than half of the observed spontaneous activity, despite being relatively rare. Spontaneous activity in sensory neurons and sympathetic sprouting may be mutually re-enforcing.

  4. Brn3a regulates neuronal subtype specification in the trigeminal ganglion by promoting Runx expression during sensory differentiation

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    Raisa Eng S

    2010-01-01

    Full Text Available Abstract The transcription factor Brn3a, product of the pou4f1 gene, is expressed in most sensory neurons throughout embryogenesis. Prior work has demonstrated a role for Brn3a in the repression of early neurogenic genes; here we describe a second major role for Brn3a in the specification of sensory subtypes in the trigeminal ganglion (TG. Sensory neurons initially co-express multiple Trk-family neurotrophin receptors, but are later marked by the unique expression of TrkA, TrkB or TrkC. Maturation of these sensory subtypes is known to depend on the expression of Runx transcription factors. Newborn Brn3a knockout mice fail to express TrkC, which is associated in the TG with mechanoreceptors, plus a set of functional genes associated with nociceptor subtypes. In embryonic Brn3a-/- ganglia, the normal expression of Runx3 is never initiated in TrkC+ neurons, and Runx1 expression is greatly attenuated in TrkA+ nociceptors. These changes are accompanied by expanded expression of TrkB in neurons that abnormally express multiple Trks, followed by the loss of TrkC and TrkA expression. In transgenic embryos expressing a Brn3a-VP16 dominant transactivator, Runx3 mRNA expression is increased, suggesting that it is a direct regulatory target of Brn3a. Chromatin immunoprecipitation confirms that Brn3a binds in vivo to a conserved upstream enhancer element within histone H3-acetylated chromatin in the Runx3 locus. Together these data show that Brn3a acts upstream of the Runx factors, which then repress TrkB expression to allow establishment of the non-overlapping Trk receptor profiles and correct terminally differentiated phenotypes.

  5. Increased levels of SV2A botulinum neurotoxin receptor in clinical sensory disorders and functional effects of botulinum toxins A and E in cultured human sensory neurons

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    Yiangou Y

    2011-10-01

    Full Text Available Yiangos Yiangou1 Uma Anand1,2, William R. Otto2, Marco Sinisi3, Michael Fox3, Rolfe Birch3 Keith A. Foster4, Gaurav Mukerji1,5, Ayesha Akbar1,6, Sanjiv K. Agarwal5, Praveen Anand11Department of Clinical Neuroscience, Imperial College London, Hammersmith Hospital, London; 2Histopathology Laboratory, Cancer Research UK, London Research Institute, London; 3Peripheral Nerve Injury Unit, Royal National Orthopaedic Hospital, Stanmore; 4Syntaxin Ltd, Oxford; 5Department of Urology; 6Department of Gastroenterology, Imperial College London, Hammersmith Hospital, London, United Kingdom Background: There is increasing evidence that botulinum neurotoxin A may affect sensory nociceptor fibers, but the expression of its receptors in clinical pain states, and its effects in human sensory neurons, are largely unknown.Methods: We studied synaptic vesicle protein subtype SV2A, a receptor for botulinum neurotoxin A, by immunostaining in a range of clinical tissues, including human dorsal root ganglion sensory neurons, peripheral nerves, the urinary bladder, and the colon. We also determined the effects of botulinum neurotoxins A and E on localization of the capsaicin receptor, TRPV1, and functional sensitivity to capsaicin stimuli in cultured human dorsal root ganglion neurons.Results: Image analysis showed that SV2A immunoreactive nerve fibers were increased in injured nerves proximal to the injury (P = 0.002, and in painful neuromas (P = 0.0027; the ratio of percentage area SV2A to neurofilaments (a structural marker was increased proximal to injury (P = 0.0022 and in neuromas (P = 0.0001, indicating increased SV2A levels in injured nerve fibers. In the urinary bladder, SV2A nerve fibers were found in detrusor muscle and associated with blood vessels, with a significant increase in idiopathic detrusor overactivity (P = 0.002 and painful bladder syndrome (P = 0.0087. Colon biopsies showed numerous SV2A-positive nerve fibers, which were increased in quiescent

  6. Regulation of ASIC channels by a stomatin/STOML3 complex located in a mobile vesicle pool in sensory neurons.

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    Lapatsina, Liudmila; Jira, Julia A; Smith, Ewan St J; Poole, Kate; Kozlenkov, Alexey; Bilbao, Daniel; Lewin, Gary R; Heppenstall, Paul A

    2012-06-01

    A complex of stomatin-family proteins and acid-sensing (proton-gated) ion channel (ASIC) family members participate in sensory transduction in invertebrates and vertebrates. Here, we have examined the role of the stomatin-family protein stomatin-like protein-3 (STOML3) in this process. We demonstrate that STOML3 interacts with stomatin and ASIC subunits and that this occurs in a highly mobile vesicle pool in dorsal root ganglia (DRG) neurons and Chinese hamster ovary cells. We identify a hydrophobic region in the N-terminus of STOML3 that is required for vesicular localization of STOML3 and regulates physical and functional interaction with ASICs. We further characterize STOML3-containing vesicles in DRG neurons and show that they are Rab11-positive, but not part of the early-endosomal, lysosomal or Rab14-dependent biosynthetic compartment. Moreover, uncoupling of vesicles from microtubules leads to incorporation of STOML3 into the plasma membrane and increased acid-gated currents. Thus, STOML3 defines a vesicle pool in which it associates with molecules that have critical roles in sensory transduction. We suggest that the molecular features of this vesicular pool may be characteristic of a 'transducosome' in sensory neurons.

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

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    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.

  8. Genes that act downstream of sensory neurons to influence longevity, dauer formation, and pathogen responses in Caenorhabditis elegans.

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    Marta M Gaglia

    Full Text Available The sensory systems of multicellular organisms are designed to provide information about the environment and thus elicit appropriate changes in physiology and behavior. In the nematode Caenorhabditis elegans, sensory neurons affect the decision to arrest during development in a diapause state, the dauer larva, and modulate the lifespan of the animals in adulthood. However, the mechanisms underlying these effects are incompletely understood. Using whole-genome microarray analysis, we identified transcripts whose levels are altered by mutations in the intraflagellar transport protein daf-10, which result in impaired development and function of many sensory neurons in C. elegans. In agreement with existing genetic data, the expression of genes regulated by the transcription factor DAF-16/FOXO was affected by daf-10 mutations. In addition, we found altered expression of transcriptional targets of the DAF-12/nuclear hormone receptor in the daf-10 mutants and showed that this pathway influences specifically the dauer formation phenotype of these animals. Unexpectedly, pathogen-responsive genes were repressed in daf-10 mutant animals, and these sensory mutants exhibited altered susceptibility to and behavioral avoidance of bacterial pathogens. Moreover, we found that a solute transporter gene mct-1/2, which was induced by daf-10 mutations, was necessary and sufficient for longevity. Thus, sensory input seems to influence an extensive transcriptional network that modulates basic biological processes in C. elegans. This situation is reminiscent of the complex regulation of physiology by the mammalian hypothalamus, which also receives innervations from sensory systems, most notably the visual and olfactory systems.

  9. Two different avian cold-sensitive sensory neurons: Transient receptor potential melastatin 8 (TRPM8)-dependent and -independent activation mechanisms.

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    Yamamoto, A; Takahashi, K; Saito, S; Tominaga, M; Ohta, T

    2016-12-01

    Sensing the ambient temperature is an important function for survival in animals. Some TRP channels play important roles as detectors of temperature and irritating chemicals. There are functional differences of TRP channels among species. TRPM8 in mammals is activated by cooling compounds and cold temperature, but less information is available on the functional role of TRPM8 in avian species. Here we investigated the pharmacological properties and thermal sensitivities of chicken TRPM8 (cTRPM8) and cold-sensitive mechanisms in avian sensory neurons. In heterologously expressed cTRPM8, menthol and its derivative, WS-12 elicited [Ca 2+ ] i increases, but icilin did not. In chicken sensory neurons, icilin increased [Ca 2+ ] i, in a TRPA1-dependent manner. Icilin selectively stimulated heterologously expressed chicken TRPA1 (cTRPA1). Similar to mammalian orthologue, cTRPM8 was activated by cold. Both heterologous and endogenous expressed cTRPM8 were sensitive to mammalian TRPM8 antagonists. There are two types of cold-sensitive cells regarding menthol sensitivity in chicken sensory neurons. The temperature threshold of menthol-insensitive neurons was significantly lower than that of menthol-sensitive ones. The population of menthol-insensitive neurons was large in chicken but almost little in mammals. The cold-induced [Ca 2+ ] i increases were not abolished by the external Ca 2+ removal or by blockades of PLC-IP 3 pathways and ryanodine channels. The cold stimulation failed to evoke [Ca 2+ ] i increases after intracellular Ca 2+ store-depletion. These results indicate that cTRPM8 acts as a cold-sensor similar to mammals. It is noteworthy that TRPM8-independent cold-sensitive neurons are abundant in chicken sensory neurons. Our results suggest that most of the cold-induced [Ca 2+ ] i increases are mediated via Ca 2+ release from intracellular stores and that these mechanisms may be specific to avian species. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Diversity of Internal Sensory Neuron Axon Projection Patterns Is Controlled by the POU-Domain Protein Pdm3 in Drosophila Larvae.

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    Qian, Cheng Sam; Kaplow, Margarita; Lee, Jennifer K; Grueber, Wesley B

    2018-02-21

    Internal sensory neurons innervate body organs and provide information about internal state to the CNS to maintain physiological homeostasis. Despite their conservation across species, the anatomy, circuitry, and development of internal sensory systems are still relatively poorly understood. A largely unstudied population of larval Drosophila sensory neurons, termed tracheal dendrite (td) neurons, innervate internal respiratory organs and may serve as a model for understanding the sensing of internal states. Here, we characterize the peripheral anatomy, central axon projection, and diversity of td sensory neurons. We provide evidence for prominent expression of specific gustatory receptor genes in distinct populations of td neurons, suggesting novel chemosensory functions. We identify two anatomically distinct classes of td neurons. The axons of one class project to the subesophageal zone (SEZ) in the brain, whereas the other terminates in the ventral nerve cord (VNC). We identify expression and a developmental role of the POU-homeodomain transcription factor Pdm3 in regulating the axon extension and terminal targeting of SEZ-projecting td neurons. Remarkably, ectopic Pdm3 expression is alone sufficient to switch VNC-targeting axons to SEZ targets, and to induce the formation of putative synapses in these ectopic target zones. Our data thus define distinct classes of td neurons, and identify a molecular factor that contributes to diversification of axon targeting. These results introduce a tractable model to elucidate molecular and circuit mechanisms underlying sensory processing of internal body status and physiological homeostasis. SIGNIFICANCE STATEMENT How interoceptive sensory circuits develop, including how sensory neurons diversify and target distinct central regions, is still poorly understood, despite the importance of these sensory systems for maintaining physiological homeostasis. Here, we characterize classes of Drosophila internal sensory neurons (td

  11. Reversible Axonal Dystrophy by Calcium Modulation in Frataxin-Deficient Sensory Neurons of YG8R Mice

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    Belén Mollá

    2017-08-01

    Full Text Available Friedreich’s ataxia (FRDA is a peripheral neuropathy involving a loss of proprioceptive sensory neurons. Studies of biopsies from patients suggest that axonal dysfunction precedes the death of proprioceptive neurons in a dying-back process. We observed that the deficiency of frataxin in sensory neurons of dorsal root ganglia (DRG of the YG8R mouse model causes the formation of axonal spheroids which retain dysfunctional mitochondria, shows alterations in the cytoskeleton and it produces impairment of axonal transport and autophagic flux. The homogenous distribution of axonal spheroids along the neurites supports the existence of continues focal damages. This lead us to propose for FRDA a model of distal axonopathy based on axonal focal damages. In addition, we observed the involvement of oxidative stress and dyshomeostasis of calcium in axonal spheroid formation generating axonal injury as a primary cause of pathophysiology. Axonal spheroids may be a consequence of calcium imbalance, thus we propose the quenching or removal extracellular Ca2+ to prevent spheroids formation. In our neuronal model, treatments with BAPTA and o-phenanthroline reverted the axonal dystrophy and the mitochondrial dysmorphic parameters. These results support the hypothesis that axonal pathology is reversible in FRDA by pharmacological manipulation of intracellular Ca2+ with Ca2+ chelators or metalloprotease inhibitors, preventing Ca2+-mediated axonal injury. Thus, the modulation of Ca2+ levels may be a relevant therapeutic target to develop early axonal protection and prevent dying-back neurodegeneration.

  12. Accumulation of Misfolded SOD1 in Dorsal Root Ganglion Degenerating Proprioceptive Sensory Neurons of Transgenic Mice with Amyotrophic Lateral Sclerosis

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    Javier Sábado

    2014-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is an adult-onset progressive neurodegenerative disease affecting upper and lower motoneurons (MNs. Although the motor phenotype is a hallmark for ALS, there is increasing evidence that systems other than the efferent MN system can be involved. Mutations of superoxide dismutase 1 (SOD1 gene cause a proportion of familial forms of this disease. Misfolding and aggregation of mutant SOD1 exert neurotoxicity in a noncell autonomous manner, as evidenced in studies using transgenic mouse models. Here, we used the SOD1G93A mouse model for ALS to detect, by means of conformational-specific anti-SOD1 antibodies, whether misfolded SOD1-mediated neurotoxicity extended to neuronal types other than MNs. We report that large dorsal root ganglion (DRG proprioceptive neurons accumulate misfolded SOD1 and suffer a degenerative process involving the inflammatory recruitment of macrophagic cells. Degenerating sensory axons were also detected in association with activated microglial cells in the spinal cord dorsal horn of diseased animals. As large proprioceptive DRG neurons project monosynaptically to ventral horn MNs, we hypothesise that a prion-like mechanism may be responsible for the transsynaptic propagation of SOD1 misfolding from ventral horn MNs to DRG sensory neurons.

  13. PROS-1/Prospero Is a Major Regulator of the Glia-Specific Secretome Controlling Sensory-Neuron Shape and Function in C. elegans.

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    Wallace, Sean W; Singhvi, Aakanksha; Liang, Yupu; Lu, Yun; Shaham, Shai

    2016-04-19

    Sensory neurons are an animal's gateway to the world, and their receptive endings, the sites of sensory signal transduction, are often associated with glia. Although glia are known to promote sensory-neuron functions, the molecular bases of these interactions are poorly explored. Here, we describe a post-developmental glial role for the PROS-1/Prospero/PROX1 homeodomain protein in sensory-neuron function in C. elegans. Using glia expression profiling, we demonstrate that, unlike previously characterized cell fate roles, PROS-1 functions post-embryonically to control sense-organ glia-specific secretome expression. PROS-1 functions cell autonomously to regulate glial secretion and membrane structure, and non-cell autonomously to control the shape and function of the receptive endings of sensory neurons. Known glial genes controlling sensory-neuron function are PROS-1 targets, and we identify additional PROS-1-dependent genes required for neuron attributes. Drosophila Prospero and vertebrate PROX1 are expressed in post-mitotic sense-organ glia and astrocytes, suggesting conserved roles for this class of transcription factors. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Long-Range Regulatory Synergy Is Required to Allow Control of the TAC1 Locus by MEK/ERK Signalling in Sensory Neurones

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    Lynne Shanley

    2010-12-01

    Full Text Available Changes in the expression of the neuropeptide substance P (SP in different populations of sensory neurones are associated with the progression of chronic inflammatory disease. Thus, understanding the genomic and cellular mechanisms driving the expression of the TAC1 gene, which encodes SP, in sensory neurones is essential to understanding its role in inflammatory disease. We used a novel combination of computational genomics, primary-cell culture and mouse transgenics to determine the genomic and cellular mechanisms that control the expression of TAC1 in sensory neurones. Intriguingly, we demonstrated that the promoter of the TAC1 gene must act in synergy with a remote enhancer, identified using comparative genomics, to respond to MAPK signalling that modulates the expression of TAC1 in sensory neurones. We also reveal that noxious stimulation of sensory neurones triggers this synergy in larger diameter sensory neurones – an expression of SP associated with hyperalgesia. This noxious stimulation of TAC1 enhancer-promotor synergy could be strongly blocked by antagonism of the MEK pathway. This study provides a unique insight into the role of long-range enhancer-promoter synergy and selectivity in the tissue-specific response of promoters to specific signal transduction pathways and suggests a possible new avenue for the development of novel anti-inflammatory therapies.

  15. Age-related deficits in synaptic plasticity rescued by activating PKA or PKC in sensory neurons of Aplysia californica

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    Andrew T Kempsell

    2015-09-01

    Full Text Available Brain aging is associated with declines in synaptic function that contribute to memory loss, including reduced postsynaptic response to neurotransmitters and decreased neuronal excitability. To understand how aging affects memory in a simple neural circuit, we studied neuronal proxies of memory for sensitization in mature versus advanced age Aplysia. Glutamate- (L-Glu- evoked excitatory currents were facilitated by the neuromodulator serotonin (5-HT in sensory neurons (SN isolated from mature but not aged animals. Activation of PKA and PKC signaling rescued facilitation of L-Glu currents in aged SN. Similarly, PKA and PKC activators restored increased excitability in aged tail SN. These results suggest that altered synaptic plasticity during aging involves defects in second messenger systems

  16. Age-related deficits in synaptic plasticity rescued by activating PKA or PKC in sensory neurons of Aplysia californica.

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    Kempsell, Andrew T; Fieber, Lynne A

    2015-01-01

    Brain aging is associated with declines in synaptic function that contribute to memory loss, including reduced postsynaptic response to neurotransmitters and decreased neuronal excitability. To understand how aging affects memory in a simple neural circuit, we studied neuronal proxies of memory for sensitization in mature vs. advanced age Aplysia californica (Aplysia). L-Glutamate- (L-Glu-) evoked excitatory currents were facilitated by the neuromodulator serotonin (5-HT) in sensory neurons (SN) isolated from mature but not aged animals. Activation of protein kinase A (PKA) and protein kinase C (PKC) signaling rescued facilitation of L-Glu currents in aged SN. Similarly, PKA and PKC activators restored increased excitability in aged tail SN. These results suggest that altered synaptic plasticity during aging involves defects in second messenger systems.

  17. Expression of ionotropic receptors in terrestrial hermit crab’s olfactory sensory neurons

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    Katrin Christine Groh-Lunow

    2015-02-01

    Full Text Available Coenobitidae are one out of at least five crustacean lineages which independently succeeded in the transition from water to land. This change in lifestyle required adaptation of the peripheral olfactory organs, the antennules, in order to sense chemical cues in the new terrestrial habitat. Hermit crab olfactory aesthetascs are arranged in a field on the distal segment of the antennular flagellum. Aesthetascs house approximately 300 dendrites with their cell bodies arranged in spindle-like complexes of ca. 150 cell bodies each. While the aesthetascs of aquatic crustaceans have been shown to be the place of odor uptake and previous studies identified ionotropic receptors (IRs as the putative chemosensory receptors expressed in decapod antennules, the expression of IRs besides the IR co-receptors IR25a and IR93a in olfactory sensory neurons (OSNs has not been documented yet. Our goal was to reveal the expression and distribution pattern of non-co-receptor IRs in OSNs of Coenobita clypeatus, a terrestrial hermit crab, with RNA in situ hybridization. We expanded our previously published RNAseq dataset, and revealed 22 novel IR candidates in the Coenobita antennules. We then used RNA probes directed against three different IRs to visualize their expression within the OSN cell body complexes. Furthermore we aimed to characterize ligand spectra of single aesthetascs by recording local field potentials and responses from individual dendrites. This also allowed comparison to functional data from insect OSNs expressing antennal IRs. We show that this orphan receptor subgroup with presumably non-olfactory function in insects is likely the basis of olfaction in terrestrial hermit crabs.

  18. Blood oxygenation level dependent signal and neuronal adaptation to optogenetic and sensory stimulation in somatosensory cortex in awake animals.

    Science.gov (United States)

    Aksenov, Daniil P; Li, Limin; Miller, Michael J; Wyrwicz, Alice M

    2016-11-01

    The adaptation of neuronal responses to stimulation, in which a peak transient response is followed by a sustained plateau, has been well-studied. The blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal has also been shown to exhibit adaptation on a longer time scale. However, some regions such as the visual and auditory cortices exhibit significant BOLD adaptation, whereas other such as the whisker barrel cortex may not adapt. In the sensory cortex a combination of thalamic inputs and intracortical activity drives hemodynamic changes, although the relative contributions of these components are not entirely understood. The aim of this study is to assess the role of thalamic inputs vs. intracortical processing in shaping BOLD adaptation during stimulation in the somatosensory cortex. Using simultaneous fMRI and electrophysiology in awake rabbits, we measured BOLD, local field potentials (LFPs), single- and multi-unit activity in the cortex during whisker and optogenetic stimulation. This design allowed us to compare BOLD and haemodynamic responses during activation of the normal thalamocortical sensory pathway (i.e., both inputs and intracortical activity) vs. the direct optical activation of intracortical circuitry alone. Our findings show that whereas LFP and multi-unit (MUA) responses adapted, neither optogenetic nor sensory stimulation produced significant BOLD adaptation. We observed for both paradigms a variety of excitatory and inhibitory single unit responses. We conclude that sensory feed-forward thalamic inputs are not primarily responsible for shaping BOLD adaptation to stimuli; but the single-unit results point to a role in this behaviour for specific excitatory and inhibitory neuronal sub-populations, which may not correlate with aggregate neuronal activity. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  19. TRPA1 is functionally expressed primarily by IB4-binding, non-peptidergic mouse and rat sensory neurons.

    Directory of Open Access Journals (Sweden)

    Marie E Barabas

    Full Text Available Subpopulations of somatosensory neurons are characterized by functional properties and expression of receptor proteins and surface markers. CGRP expression and IB4-binding are commonly used to define peptidergic and non-peptidergic subpopulations. TRPA1 is a polymodal, plasma membrane ion channel that contributes to mechanical and cold hypersensitivity during tissue injury, making it a key target for pain therapeutics. Some studies have shown that TRPA1 is predominantly expressed by peptidergic sensory neurons, but others indicate that TRPA1 is expressed extensively within non-peptidergic, IB4-binding neurons. We used FURA-2 calcium imaging to define the functional distribution of TRPA1 among peptidergic and non-peptidergic adult mouse (C57BL/6J DRG neurons. Approximately 80% of all small-diameter (<27 µm neurons from lumbar 1-6 DRGs that responded to TRPA1 agonists allyl isothiocyanate (AITC; 79% or cinnamaldehyde (84% were IB4-positive. Retrograde labeling via plantar hind paw injection of WGA-Alexafluor594 showed similarly that most (81% cutaneous neurons responding to TRPA1 agonists were IB4-positive. Additionally, we cultured DRG neurons from a novel CGRP-GFP mouse where GFP expression is driven by the CGRPα promoter, enabling identification of CGRP-expressing live neurons. Interestingly, 78% of TRPA1-responsive neurons were CGRP-negative. Co-labeling with IB4 revealed that the majority (66% of TRPA1 agonist responders were IB4-positive but CGRP-negative. Among TRPA1-null DRGs, few small neurons (2-4% responded to either TRPA1 agonist, indicating that both cinnamaldehyde and AITC specifically target TRPA1. Additionally, few large neurons (≥27 µm diameter responded to AITC (6% or cinnamaldehyde (4%, confirming that most large-diameter somata lack functional TRPA1. Comparison of mouse and rat DRGs showed that the majority of TRPA1-responsive neurons in both species were IB4-positive. Together, these data demonstrate that TRPA1 is

  20. Multidendritic sensory neurons in the adult Drosophila abdomen: origins, dendritic morphology, and segment- and age-dependent programmed cell death

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    Sugimura Kaoru

    2009-10-01

    Full Text Available Abstract Background For the establishment of functional neural circuits that support a wide range of animal behaviors, initial circuits formed in early development have to be reorganized. One way to achieve this is local remodeling of the circuitry hardwiring. To genetically investigate the underlying mechanisms of this remodeling, one model system employs a major group of Drosophila multidendritic sensory neurons - the dendritic arborization (da neurons - which exhibit dramatic dendritic pruning and subsequent growth during metamorphosis. The 15 da neurons are identified in each larval abdominal hemisegment and are classified into four categories - classes I to IV - in order of increasing size of their receptive fields and/or arbor complexity at the mature larval stage. Our knowledge regarding the anatomy and developmental basis of adult da neurons is still fragmentary. Results We identified multidendritic neurons in the adult Drosophila abdomen, visualized the dendritic arbors of the individual neurons, and traced the origins of those cells back to the larval stage. There were six da neurons in abdominal hemisegment 3 or 4 (A3/4 of the pharate adult and the adult just after eclosion, five of which were persistent larval da neurons. We quantitatively analyzed dendritic arbors of three of the six adult neurons and examined expression in the pharate adult of key transcription factors that result in the larval class-selective dendritic morphologies. The 'baseline design' of A3/4 in the adult was further modified in a segment-dependent and age-dependent manner. One of our notable findings is that a larval class I neuron, ddaE, completed dendritic remodeling in A2 to A4 and then underwent caspase-dependent cell death within 1 week after eclosion, while homologous neurons in A5 and in more posterior segments degenerated at pupal stages. Another finding is that the dendritic arbor of a class IV neuron, v'ada, was immediately reshaped during post

  1. TRPA1 Is Functionally Expressed Primarily by IB4-Binding, Non-Peptidergic Mouse and Rat Sensory Neurons

    Science.gov (United States)

    Stucky, Cheryl L.

    2012-01-01

    Subpopulations of somatosensory neurons are characterized by functional properties and expression of receptor proteins and surface markers. CGRP expression and IB4-binding are commonly used to define peptidergic and non-peptidergic subpopulations. TRPA1 is a polymodal, plasma membrane ion channel that contributes to mechanical and cold hypersensitivity during tissue injury, making it a key target for pain therapeutics. Some studies have shown that TRPA1 is predominantly expressed by peptidergic sensory neurons, but others indicate that TRPA1 is expressed extensively within non-peptidergic, IB4-binding neurons. We used FURA-2 calcium imaging to define the functional distribution of TRPA1 among peptidergic and non-peptidergic adult mouse (C57BL/6J) DRG neurons. Approximately 80% of all small-diameter (neurons from lumbar 1–6 DRGs that responded to TRPA1 agonists allyl isothiocyanate (AITC; 79%) or cinnamaldehyde (84%) were IB4-positive. Retrograde labeling via plantar hind paw injection of WGA-Alexafluor594 showed similarly that most (81%) cutaneous neurons responding to TRPA1 agonists were IB4-positive. Additionally, we cultured DRG neurons from a novel CGRP-GFP mouse where GFP expression is driven by the CGRPα promoter, enabling identification of CGRP-expressing live neurons. Interestingly, 78% of TRPA1-responsive neurons were CGRP-negative. Co-labeling with IB4 revealed that the majority (66%) of TRPA1 agonist responders were IB4-positive but CGRP-negative. Among TRPA1-null DRGs, few small neurons (2–4%) responded to either TRPA1 agonist, indicating that both cinnamaldehyde and AITC specifically target TRPA1. Additionally, few large neurons (≥27 µm diameter) responded to AITC (6%) or cinnamaldehyde (4%), confirming that most large-diameter somata lack functional TRPA1. Comparison of mouse and rat DRGs showed that the majority of TRPA1-responsive neurons in both species were IB4-positive. Together, these data demonstrate that TRPA1 is functionally expressed

  2. 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

  3. Block of voltage-gated potassium channels by Pacific ciguatoxin-1 contributes to increased neuronal excitability in rat sensory neurons

    International Nuclear Information System (INIS)

    Birinyi-Strachan, Liesl C.; Gunning, Simon J.; Lewis, Richard J.; Nicholson, Graham M.

    2005-01-01

    The present study investigated the actions of the polyether marine toxin Pacific ciguatoxin-1 (P-CTX-1) on neuronal excitability in rat dorsal root ganglion (DRG) neurons using patch-clamp recording techniques. Under current-clamp conditions, bath application of 2-20 nM P-CTX-1 caused a rapid, concentration-dependent depolarization of the resting membrane potential in neurons expressing tetrodotoxin (TTX)-sensitive voltage-gated sodium (Na v ) channels. This action was completely suppressed by the addition of 200 nM TTX to the external solution, indicating that this effect was mediated through TTX-sensitive Na v channels. In addition, P-CTX-1 also prolonged action potential and afterhyperpolarization (AHP) duration. In a subpopulation of neurons, P-CTX-1 also produced tonic action potential firing, an effect that was not accompanied by significant oscillation of the resting membrane potential. Conversely, in neurons expressing TTX-resistant Na v currents, P-CTX-1 failed to alter any parameter of neuronal excitability examined in this study. Under voltage-clamp conditions in rat DRG neurons, P-CTX-1 inhibited both delayed-rectifier and 'A-type' potassium currents in a dose-dependent manner, actions that occurred in the absence of alterations to the voltage dependence of activation. These actions appear to underlie the prolongation of the action potential and AHP, and contribute to repetitive firing. These data indicate that a block of potassium channels contributes to the increase in neuronal excitability, associated with a modulation of Na v channel gating, observed clinically in response to ciguatera poisoning

  4. SAD kinases sculpt axonal arbors of sensory neurons through long and short-term responses to neurotrophin signals

    Science.gov (United States)

    Lilley, Brendan N.; Pan, Y. Albert; Sanes, Joshua R.

    2013-01-01

    SUMMARY Extrinsic cues activate intrinsic signaling mechanisms to pattern neuronal shape and connectivity. We showed previously that three cytoplasmic Ser/Thr kinases, LKB1, SAD-A and SAD-B, control early axon-dendrite polarization in forebrain neurons. Here we assess their role in other neuronal types. We found that all three kinases are dispensable for axon formation outside of the cortex, but that SAD kinases are required for formation of central axonal arbors by subsets of sensory neurons. The requirement for SAD kinases is most prominent in NT-3 dependent neurons. SAD kinases transduce NT-3 signals in two ways through distinct pathways. First, sustained NT-3/TrkC signaling increases SAD protein levels. Second, short duration NT-3/TrkC signals transiently activate SADs by inducing dephosphorylation of C-terminal domains, thereby allowing activating phosphorylation of the kinase domain. We propose that SAD kinases integrate long- and short duration signals from extrinsic cues to sculpt axon arbors within the CNS. PMID:23790753

  5. SAD kinases sculpt axonal arbors of sensory neurons through long- and short-term responses to neurotrophin signals.

    Science.gov (United States)

    Lilley, Brendan N; Pan, Y Albert; Sanes, Joshua R

    2013-07-10

    Extrinsic cues activate intrinsic signaling mechanisms to pattern neuronal shape and connectivity. We showed previously that three cytoplasmic Ser/Thr kinases, LKB1, SAD-A, and SAD-B, control early axon-dendrite polarization in forebrain neurons. Here, we assess their role in other neuronal types. We found that all three kinases are dispensable for axon formation outside of the cortex but that SAD kinases are required for formation of central axonal arbors by subsets of sensory neurons. The requirement for SAD kinases is most prominent in NT-3 dependent neurons. SAD kinases transduce NT-3 signals in two ways through distinct pathways. First, sustained NT-3/TrkC signaling increases SAD protein levels. Second, short-duration NT-3/TrkC signals transiently activate SADs by inducing dephosphorylation of C-terminal domains, thereby allowing activating phosphorylation of the kinase domain. We propose that SAD kinases integrate long- and short-duration signals from extrinsic cues to sculpt axon arbors within the CNS. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Structural and Functional Substitution of Deleted Primary Sensory Neurons by New Growth from Intrinsic Spinal Cord Nerve Cells: An Alternative Concept in Reconstruction of Spinal Cord Circuits

    Directory of Open Access Journals (Sweden)

    Nicholas D. James

    2017-07-01

    Full Text Available In a recent clinical report, return of the tendon stretch reflex was demonstrated after spinal cord surgery in a case of total traumatic brachial plexus avulsion injury. Peripheral nerve grafts had been implanted into the spinal cord to reconnect to the peripheral nerves for motor and sensory function. The dorsal root ganglia (DRG containing the primary sensory nerve cells had been surgically removed in order for secondary or spinal cord sensory neurons to extend into the periphery and replace the deleted DRG neurons. The present experimental study uses a rat injury model first to corroborate the clinical finding of a re-established spinal reflex arch, and second, to elucidate some of the potential mechanisms underlying these findings by means of morphological, immunohistochemical, and electrophysiological assessments. Our findings indicate that, after spinal cord surgery, the central nervous system sensory system could replace the traumatically detached original peripheral sensory connections through new neurite growth from dendrites.

  7. Anatomic and Physiologic Heterogeneity of Subgroup-A Auditory Sensory Neurons in Fruit Flies.

    Science.gov (United States)

    Ishikawa, Yuki; Okamoto, Natsuki; Nakamura, Mizuki; Kim, Hyunsoo; Kamikouchi, Azusa

    2017-01-01

    The antennal ear of the fruit fly detects acoustic signals in intraspecific communication, such as the courtship song and agonistic sounds. Among the five subgroups of mechanosensory neurons in the fly ear, subgroup-A neurons respond maximally to vibrations over a wide frequency range between 100 and 1,200 Hz. The functional organization of the neural circuit comprised of subgroup-A neurons, however, remains largely unknown. In the present study, we used 11 GAL4 strains that selectively label subgroup-A neurons and explored the diversity of subgroup-A neurons by combining single-cell anatomic analysis and Ca 2+ imaging. Our findings indicate that the subgroup-A neurons that project into various combinations of subareas in the brain are more anatomically diverse than previously described. Subgroup-A neurons were also physiologically diverse, and some types were tuned to a narrow frequency range, suggesting that the response of subgroup-A neurons to sounds of a wide frequency range is due to the existence of several types of subgroup-A neurons. Further, we found that an auditory behavioral response to the courtship song of flies was attenuated when most subgroup-A neurons were silenced. Together, these findings characterize the heterogeneous functional organization of subgroup-A neurons, which might facilitate species-specific acoustic signal detection.

  8. Thy1.2 YFP-16 transgenic mouse labels a subset of large-diameter sensory neurons that lack TRPV1 expression.

    Directory of Open Access Journals (Sweden)

    Thomas E Taylor-Clark

    Full Text Available The Thy1.2 YFP-16 mouse expresses yellow fluorescent protein (YFP in specific subsets of peripheral and central neurons. The original characterization of this model suggested that YFP was expressed in all sensory neurons, and this model has been subsequently used to study sensory nerve structure and function. Here, we have characterized the expression of YFP in the sensory ganglia (DRG, trigeminal and vagal of the Thy1.2 YFP-16 mouse, using biochemical, functional and anatomical analyses. Despite previous reports, we found that YFP was only expressed in approximately half of DRG and trigeminal neurons and less than 10% of vagal neurons. YFP-expression was only found in medium and large-diameter neurons that expressed neurofilament but not TRPV1. YFP-expressing neurons failed to respond to selective agonists for TRPV1, P2X(2/3 and TRPM8 channels in Ca2+ imaging assays. Confocal analysis of glabrous skin, hairy skin of the back and ear and skeletal muscle indicated that YFP was expressed in some peripheral terminals with structures consistent with their presumed non-nociceptive nature. In summary, the Thy1.2 YFP-16 mouse expresses robust YFP expression in only a subset of sensory neurons. But this mouse model is not suitable for the study of nociceptive nerves or the function of such nerves in pain and neuropathies.

  9. Lifespan decrease in a Caenorhabditis elegans mutant lacking TRX-1, a thioredoxin expressed in ASJ sensory neurons.

    Science.gov (United States)

    Miranda-Vizuete, Antonio; Fierro González, Juan Carlos; Gahmon, Gabriele; Burghoorn, Jan; Navas, Plácido; Swoboda, Peter

    2006-01-23

    Thioredoxins are a class of small proteins that play a key role in regulating many cellular redox processes. We report here the characterization of the first member of the thioredoxin family in metazoans that is mainly associated with neurons. The Caenorhabditis elegans gene B0228.5 encodes a thioredoxin (TRX-1) that is expressed in ASJ ciliated sensory neurons, and to some extent also in the posterior-most intestinal cells. TRX-1 is active at reducing protein disulfides in the presence of a heterologous thioredoxin reductase. A mutant worm strain carrying a null allele of the trx-1 gene displays a reproducible decrease in both mean and maximum lifespan when compared to wild-type. The identification and characterization of TRX-1 paves the way to use C. elegans as an in vivo model to study the role of thioredoxins in lifespan and nervous system physiology and pathology.

  10. Sensory signals and neuronal groups involved in guiding the sea-ward motor behavior in turtle hatchlings of Chelonia agassizi

    Science.gov (United States)

    Fuentes, A. L.; Camarena, V.; Ochoa, G.; Urrutia, J.; Gutierrez, G.

    2007-05-01

    Turtle hatchlings orient display sea-ward oriented movements as soon as they emerge from the nest. Although most studies have emphasized the role of the visual information in this process, less attention has been paid to other sensory modalities. Here, we evaluated the nature of sensory cues used by turtle hatchlings of Chelonia agassizi to orient their movements towards the ocean. We recorded the time they took to crawl from the nest to the beach front (120m long) in control conditions and in visually, olfactory and magnetically deprived circumstances. Visually-deprived hatchlings displayed a high degree of disorientation. Olfactory deprivation and magnetic field distortion impaired, but not abolished, sea-ward oriented movements. With regard to the neuronal mapping experiments, visual deprivation reduced dramatically c-fos expression in the whole brain. Hatchlings with their nares blocked revealed neurons with c-fos expression above control levels principally in the c and d areas, while those subjected to magnetic field distortion had a wide spread activation of neurons throughout the brain predominantly in the dorsal ventricular ridge The present results support that Chelonia agassizi hatchlings use predominantly visual cues to orient their movements towards the sea. Olfactory and magnetic cues may also be use but their influence on hatchlings oriented motor behavior is not as clear as it is for vision. This conclusion is supported by the fact that in the absence of olfactory and magnetic cues, the brain turns on the expression of c- fos in neuronal groups that, in the intact hatchling, are not normally involved in accomplishing the task.

  11. Notch is required in adult Drosophila sensory neurons for morphological and functional plasticity of the olfactory circuit.

    Directory of Open Access Journals (Sweden)

    Simon Kidd

    2015-05-01

    Full Text Available Olfactory receptor neurons (ORNs convey odor information to the central brain, but like other sensory neurons were thought to play a passive role in memory formation and storage. Here we show that Notch, part of an evolutionarily conserved intercellular signaling pathway, is required in adult Drosophila ORNs for the structural and functional plasticity of olfactory glomeruli that is induced by chronic odor exposure. Specifically, we show that Notch activity in ORNs is necessary for the odor specific increase in the volume of glomeruli that occurs as a consequence of prolonged odor exposure. Calcium imaging experiments indicate that Notch in ORNs is also required for the chronic odor induced changes in the physiology of ORNs and the ensuing changes in the physiological response of their second order projection neurons (PNs. We further show that Notch in ORNs acts by both canonical cleavage-dependent and non-canonical cleavage-independent pathways. The Notch ligand Delta (Dl in PNs switches the balance between the pathways. These data define a circuit whereby, in conjunction with odor, N activity in the periphery regulates the activity of neurons in the central brain and Dl in the central brain regulates N activity in the periphery. Our work highlights the importance of experience dependent plasticity at the first olfactory synapse.

  12. Cyclophosphamide-induced cystitis reduces ASIC channel but enhances TRPV1 receptor function in rat bladder sensory neurons.

    Science.gov (United States)

    Dang, Khoa; Bielefeldt, Klaus; Gebhart, G F

    2013-07-01

    Using patch-clamp techniques, we studied the plasticity of acid-sensing ion channels (ASIC) and transient receptor potential V1 (TRPV1) channel function in dorsal root ganglia (DRG) neurons retrogradely labeled from the bladder. Saline (control) or cyclophosphamide (CYP) was given intraperitoneally on days 1, 3, and 5. On day 6, lumbosacral (LS, L6-S2) or thoracolumbar (TL, T13-L2) DRG were removed and dissociated. Bladders and bladder DRG neurons from CYP-treated rats showed signs of inflammation (greater myeloperoxidase activity; lower intramuscular wall pH) and increased size (whole cell capacitance), respectively, compared with controls. Most bladder neurons (>90%) responded to protons and capsaicin. Protons produced multiphasic currents with distinct kinetics, whereas capsaicin always triggered a sustained response. The TRPV1 receptor antagonist A-425619 abolished capsaicin-triggered currents and raised the threshold of heat-activated currents. Prolonged exposure to an acidic environment (pH range: 7.2 to 6.6) inhibited proton-evoked currents, potentiated the capsaicin-evoked current, and reduced the threshold of heat-activated currents in LS and TL bladder neurons. CYP treatment reduced density but not kinetics of all current components triggered by pH 5. In contrast, CYP-treatment was associated with an increased current density in response to capsaicin in LS and TL bladder neurons. Correspondingly, heat triggered current at a significantly lower temperature in bladder neurons from CYP-treated rats compared with controls. These results reveal that cystitis differentially affects TRPV1- and ASIC-mediated currents in both bladder sensory pathways. Acidification of the bladder wall during inflammation may contribute to changes in nociceptive transmission mediated through the TRPV1 receptor, suggesting a role for TRPV1 in hypersensitivity associated with cystitis.

  13. Dync1h1 Mutation Causes Proprioceptive Sensory Neuron Loss and Impaired Retrograde Axonal Transport of Dorsal Root Ganglion Neurons.

    Science.gov (United States)

    Zhao, Jing; Wang, Yi; Xu, Huan; Fu, Yuan; Qian, Ting; Bo, Deng; Lu, Yan-Xin; Xiong, Yi; Wan, Jun; Zhang, Xiang; Dong, Qiang; Chen, Xiang-Jun

    2016-07-01

    Sprawling (Swl) is a radiation-induced mutation which has been identified to have a nine base pair deletion in dynein heavy chain 1 (DYNC1H1: encoded by a single gene Dync1h1). This study is to investigate the phenotype and the underlying mechanism of the Dync1h1 mutant. To display the phenotype of Swl mutant mice, we examined the embryos of homozygous (Swl/Swl) and heterozygous (Swl/+) mice and their postnatal dorsal root ganglion (DRG) of surviving Swl/+ mice. The Swl/+ mice could survive for a normal life span, while Swl/Swl could only survive till embryonic (E) 8.5 days. Excessive apoptosis of Swl/+ DRG neurons was revealed during E11.5-E15.5 days, and the peak rate was at E13.5 days. In vitro study of mutated DRG neurons showed impaired retrograde transport of dynein-driven nerve growth factor (NGF). Mitochondria, another dynein-driven cargo, demonstrated much slower retrograde transport velocity in Swl/+ neurons than in wild-type (WT) neurons. Nevertheless, the Swl, Loa, and Cra mutations did not affect homodimerization of DYNC1H1. The Swl/Swl mutation of Dync1h1 gene led to embryonic mal-development and lethality, whereas the Swl/+ DRG neurons demonstrated deficient retrograde transport in dynein-driven cargos and excessive apoptosis during mid- to late-developmental stages. The underlying mechanism of the mutation may not be due to impaired homodimerization of DYNC1H1. © 2016 John Wiley & Sons Ltd.

  14. Sensory Processing Dysfunction in the Personal Experience and Neuronal Machinery of Schizophrenia

    Science.gov (United States)

    Javitt, Daniel C.; Freedman, Robert

    2015-01-01

    Sensory processing deficits, first investigated by Kraeplin and Bleuler as possible pathophysiological mechanisms in schizophrenia, are now being re-characterized in the context of modern understanding of the involved molecular and neurobiological brain mechanisms. The National Institute of Mental Health Research Domain Criteria position these deficits as intermediaries between molecular and cellular mechanisms and clinical symptoms of schizophrenia such as hallucinations. The pre-pulse inhibition of startle responses by a weaker preceding tone, the inhibitory gating of response to paired sensory stimuli characterized using the auditory P50 evoked response, and the detection of slightly different stimuli that elicits the cortical Mismatch Negativity potential demonstrate deficits in early sensory processing mechanisms, whose molecular and neurobiological bases are increasingly well understood. Deficits in sensory processing underlie more complex cognitive dysfunction and, vice versa, are affected by higher-level cognitive difficulties. These deficits are now being used to identify genes involved in familial transmission of the illness and to monitor potentially therapeutic drug effects for both treatment and prevention. This research also provides a clinical reminder that patients’ sensory perception of the surrounding world, even during treatment sessions, may differ considerable from others’ perceptions. A person’s ability to understand and interact effectively with surrounding world ultimately depends upon an underlying sensory experience of it. PMID:25553496

  15. A BMP-mediated transcriptional cascade involving Cash1 and Tlx-3 specifies first-order relay sensory neurons in the developing hindbrain.

    Science.gov (United States)

    Hornbruch, Amata; Ma, Grace; Ballermann, Mark A; Tumova, Katerina; Liu, Dan; Cairine Logan, C

    2005-07-01

    The divergent homeobox-containing transcription factor, Tlx-3 (also known as Hox11L2/Rnx), is required for proper formation of first-order relay sensory neurons in the developing vertebrate brainstem. To date, however, the inductive signals and transcriptional regulatory cascade underlying their development are poorly understood. We previously isolated the chick Tlx-3 homologue and showed it is expressed early (i.e. beginning at HH15) in distinct subcomponents of both the trigeminal/solitary and vestibular nuclei. Here we show via in vivo rhombomere inversions that expression of Tlx-3 is under control of local environmental signals. Our RNA in situ analysis shows expression of the BMP-specific receptor, Bmpr-1b, correlates well with Tlx-3. Furthermore, manipulation of the BMP signaling pathway in vivo via electroporation of expression vectors encoding either BMP or NOGGIN coupled with MASH1 gain-of-function experiments demonstrate that a BMP-mediated transcriptional cascade involving Cash1 and Tlx-3 specifies first-order relay sensory neurons in the developing brainstem. Notably, high-level Noggin misexpression results in an increase in newly differentiated Tlx-3+ neurons that correlates with a corresponding increase in the number of Calretinin+ neurons in vestibular nuclei at later developmental stages strongly suggesting that Tlx-3, in addition to being required for proper formation of somatic as well as visceral sensory neurons in the trigeminal and solitary nuclei, respectively, is sufficient for proper formation of special somatic sensory neurons in vestibular nuclei.

  16. The expression of Toll-like receptor 4, 7 and co-receptors in neurochemical sub-populations of rat trigeminal ganglion sensory neurons.

    Science.gov (United States)

    Helley, M P; Abate, W; Jackson, S K; Bennett, J H; Thompson, S W N

    2015-12-03

    The recent discovery that mammalian nociceptors express Toll-like receptors (TLRs) has raised the possibility that these cells directly detect and respond to pathogens with implications for either direct nociceptor activation or sensitization. A range of neuronal TLRs have been identified, however a detailed description regarding the distribution of expression of these receptors within sub-populations of sensory neurons is lacking. There is also some debate as to the composition of the TLR4 receptor complex on sensory neurons. Here we use a range of techniques to quantify the expression of TLR4, TLR7 and some associated molecules within neurochemically-identified sub-populations of trigeminal (TG) and dorsal root (DRG) ganglion sensory neurons. We also detail the pattern of expression and co-expression of two isoforms of lysophosphatidylcholine acyltransferase (LPCAT), a phospholipid remodeling enzyme previously shown to be involved in the lipopolysaccharide-dependent TLR4 response in monocytes, within sensory ganglia. Immunohistochemistry shows that both TLR4 and TLR7 preferentially co-localize with transient receptor potential vallinoid 1 (TRPV1) and purinergic receptor P2X ligand-gated ion channel 3 (P2X3), markers of nociceptor populations, within both TG and DRG. A gene expression profile shows that TG sensory neurons express a range of TLR-associated molecules. LPCAT1 is expressed by a proportion of both nociceptors and non-nociceptive neurons. LPCAT2 immunostaining is absent from neuronal profiles within both TG and DRG and is confined to non-neuronal cell types under naïve conditions. Together, our results show that nociceptors express the molecular machinery required to directly respond to pathogenic challenge independently from the innate immune system. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. From Anticipatory Corpse to Posthuman God.

    Science.gov (United States)

    Bishop, Jeffrey P

    2016-12-01

    The essays in this issue of JMP are devoted to critical engagement of my book, The Anticipatory Corpse The essays, for the most part, accept the main thrust of my critique of medicine. The main thrust of the criticism is whether the scope of the critique is too totalizing, and whether the proposed remedy is sufficient. I greatly appreciate these interventions because they allow me this occasion to respond and clarify, and to even further extend the argument of my book. In this response essay, I maintain that the regnant social imaginary of medicine is the regnant social imaginary of our time. It is grounded in a specific ontotheology: where ontology is a power ontology; where material is malleable to the open-ended organization of power and dependent only on working out the efficient mechanisms of its enactment; where ethically it is oriented only to the immanent telos of utility maximization in the short run, and ultimately to some posthuman future in the long run. This ontotheology originates in the anticipatory corpse and is ordered toward some god-like posthuman being. The entire ontotheology finds enactment through the political economy of neoliberalism. This social imaginary constantly works to insulate itself from other social imaginaries through the use of its institutional power, through marginalization, circumscription, or absorption. The modern social imaginary of neoliberal societies marginalizes and politically isolates other social imaginaries, or transforms them into something acceptable to the neoliberal imaginary. Yet, these other social imaginaries could influence the larger social imaginary in novel ways, sometimes through withdrawal and sometimes through challenges. These other practices-again, usually practices ordered according to different ontological and teleological purposes-might serve as a source of renewal and transformation, but only if the practitioners of these other social imaginaries understand the ontotheological powers that they

  18. Education or business? - exhibition of human corpses

    Directory of Open Access Journals (Sweden)

    Grzegorz Wróbel

    2017-09-01

    Full Text Available Exhibition "BODY WORLDS" which are presented exhibits of human remains are presented all over the world and are a major problem for the modern man, as presented on the preparations of the human not only serve scientific research, are not transferred to the medical schools to educate future doctors, but they were made available to the general public in the form of commercial and ambiguous. The aim of this study was to assess the ethical commercialization of human corpses "BODY WORLDS" exhibitions. Individual approach to the problems presented the dignity and value of human remains after death, of course, strongly related to the professed worldview. In the exhibits can be seen in both the scientific interest anatomical structures, as well as desecrated human remains or beautiful by its functional perfection of the body, understood also in terms of art. The question of ethics determines the right to decide for themselves, on the other hand, allows you to protect bodily integrity even after death. "BODY WORLDS" exhibition goes for the moral and ethical boundaries. In terms of people Gunther von Hagens for plastination of human remains which became a very profitable business, and its current activities defined as "plastination business" should be firmly said about the lack of moral principles.

  19. Distribution of binding sites for the plant lectin Ulex europaeus agglutinin I on primary sensory neurones in seven different mammalian species.

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    Gerke, Michelle B; Plenderleith, Mark B

    2002-01-01

    There is an increasing body of evidence to suggest that different functional classes of neurones express characteristic cell-surface carbohydrates. Previous studies have shown that the plant lectin Ulex europaeus agglutinin-I (UEA) binds to a population of small to medium diameter primary sensory neurones in rabbits and humans. This suggests that a fucose-containing glycoconjugate may be expressed by nociceptive primary sensory neurones. In order to determine the extent to which this glycoconjugate is expressed by other species, in the current study, we have examined the distribution of UEA-binding sites on primary sensory neurones in seven different mammals. Binding sites for UEA were associated with the plasma membrane and cytoplasmic granules of small to medium dorsal root ganglion cells and their axon terminals in laminae I-III of the grey matter of the spinal cord, in the rabbit, cat and marmoset monkey. However, no binding was observed in either the dorsal root ganglia or spinal cord in the mouse, rat, guinea pig or flying fox. These results indicate an inter-species variation in the expression of cell-surface glycoconjugates on mammalian primary sensory neurones.

  20. Regulation of the Na,K-ATPase gamma-subunit FXYD2 by Runx1 and Ret signaling in normal and injured non-peptidergic nociceptive sensory neurons.

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    Stéphanie Ventéo

    Full Text Available Dorsal root ganglia (DRGs contain the cell bodies of sensory neurons which relay nociceptive, thermoceptive, mechanoceptive and proprioceptive information from peripheral tissues toward the central nervous system. These neurons establish constant communication with their targets which insures correct maturation and functioning of the somato-sensory nervous system. Interfering with this two-way communication leads to cellular, electrophysiological and molecular modifications that can eventually cause neuropathic conditions. In this study we reveal that FXYD2, which encodes the gamma-subunit of the Na,K-ATPase reported so far to be mainly expressed in the kidney, is induced in the mouse DRGs at postnatal stages where it is restricted specifically to the TrkB-expressing mechanoceptive and Ret-positive/IB4-binding non-peptidergic nociceptive neurons. In non-peptidergic nociceptors, we show that the transcription factor Runx1 controls FXYD2 expression during the maturation of the somato-sensory system, partly through regulation of the tyrosine kinase receptor Ret. Moreover, Ret signaling maintains FXYD2 expression in adults as demonstrated by the axotomy-induced down-regulation of the gene that can be reverted by in vivo delivery of GDNF family ligands. Altogether, these results establish FXYD2 as a specific marker of defined sensory neuron subtypes and a new target of the Ret signaling pathway during normal maturation of the non-peptidergic nociceptive neurons and after sciatic nerve injury.

  1. The Molecular Motor KIF1A Transports the TrkA Neurotrophin Receptor and Is Essential for Sensory Neuron Survival and Function.

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    Tanaka, Yosuke; Niwa, Shinsuke; Dong, Ming; Farkhondeh, Atena; Wang, Li; Zhou, Ruyun; Hirokawa, Nobutaka

    2016-06-15

    KIF1A is a major axonal transport motor protein, but its functional significance remains elusive. Here we show that KIF1A-haploinsufficient mice developed sensory neuropathy. We found progressive loss of TrkA(+) sensory neurons in Kif1a(+/-) dorsal root ganglia (DRGs). Moreover, axonal transport of TrkA was significantly disrupted in Kif1a(+/-) neurons. Live imaging and immunoprecipitation assays revealed that KIF1A bound to TrkA-containing vesicles through the adaptor GTP-Rab3, suggesting that TrkA is a cargo of the KIF1A motor. Physiological measurements revealed a weaker capsaicin response in Kif1a(+/-) DRG neurons. Moreover, these neurons were hyposensitive to nerve growth factor, which could explain the reduced neuronal survival and the functional deficiency of the pain receptor TRPV1. Because phosphatidylinositol 3-kinase (PI3K) signaling significantly rescued these phenotypes and also increased Kif1a mRNA, we propose that KIF1A is essential for the survival and function of sensory neurons because of the TrkA transport and its synergistic support of the NGF/TrkA/PI3K signaling pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Gastrodin Inhibits Allodynia and Hyperalgesia in Painful Diabetic Neuropathy Rats by Decreasing Excitability of Nociceptive Primary Sensory Neurons

    Science.gov (United States)

    Ye, Xin; Han, Wen-Juan; Wang, Wen-Ting; Luo, Ceng; Hu, San-Jue

    2012-01-01

    Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus and adversely affects the patients’ quality of life. Evidence has accumulated that PDN is associated with hyperexcitability of peripheral nociceptive primary sensory neurons. However, the precise cellular mechanism underlying PDN remains elusive. This may result in the lacking of effective therapies for the treatment of PDN. The phenolic glucoside, gastrodin, which is a main constituent of the Chinese herbal medicine Gastrodia elata Blume, has been widely used as an anticonvulsant, sedative, and analgesic since ancient times. However, the cellular mechanisms underlying its analgesic actions are not well understood. By utilizing a combination of behavioral surveys and electrophysiological recordings, the present study investigated the role of gastrodin in an experimental rat model of STZ-induced PDN and to further explore the underlying cellular mechanisms. Intraperitoneal administration of gastrodin effectively attenuated both the mechanical allodynia and thermal hyperalgesia induced by STZ injection. Whole-cell patch clamp recordings were obtained from nociceptive, capsaicin-sensitive small diameter neurons of the intact dorsal root ganglion (DRG). Recordings from diabetic rats revealed that the abnormal hyperexcitability of neurons was greatly abolished by application of GAS. To determine which currents were involved in the antinociceptive action of gastrodin, we examined the effects of gastrodin on transient sodium currents (I NaT) and potassium currents in diabetic small DRG neurons. Diabetes caused a prominent enhancement of I NaT and a decrease of potassium currents, especially slowly inactivating potassium currents (I AS); these effects were completely reversed by GAS in a dose-dependent manner. Furthermore, changes in activation and inactivation kinetics of I NaT and total potassium current as well as I AS currents induced by STZ were normalized by GAS. This study provides a

  3. TrpA1 activation in peripheral sensory neurons underlies the ionic basis of pain hypersensitivity in response to vinca alkaloids.

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    Nina Boiko

    Full Text Available Chemotherapy induced peripheral neuropathy (CIPN, a side effect of many anti-cancer drugs including the vinca alkaloids, is characterized by a severe pain syndrome that compromises treatment in many patients. Currently there are no effective treatments for this pain syndrome except for the reduction of anti-cancer drug dose. Existing data supports the model that the pain associated with CIPN is the result of anti-cancer drugs augmenting the function of the peripheral sensory nociceptors but the cellular mechanisms underlying the effects of anti-cancer drugs on sensory neuron function are not well described. Studies from animal models have suggested a number of disease etiologies including mitotoxicity, axonal degeneration, immune signaling, and reduced sensory innervations but these outcomes are the result of prolonged treatment paradigms and do not necessarily represent the early formative events associated with CIPN. Here we show that acute exposure to vinca alkaloids results in an immediate pain syndrome in both flies and mice. Furthermore, we demonstrate that exposure of isolated sensory neurons to vinca alkaloids results in the generation of an inward sodium current capable of depolarizing these neurons to threshold resulting in neuronal firing. These neuronal effects of vinca alkaloids require the transient receptor potential ankyrin-1 (TrpA1 channel, and the hypersensitization to painful stimuli in response to the acute exposure to vinca alkaloids is reduced in TrpA1 mutant flies and mice. These findings demonstrate the direct excitation of sensory neurons by CIPN-causing chemotherapy drugs, and identify TrpA1 as an important target during the pathogenesis of CIPN.

  4. Association between tetrodotoxin resistant channels and lipid rafts regulates sensory neuron excitability.

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    Alessandro Pristerà

    Full Text Available Voltage-gated sodium channels (VGSCs play a key role in the initiation and propagation of action potentials in neurons. Na(V1.8 is a tetrodotoxin (TTX resistant VGSC expressed in nociceptors, peripheral small-diameter neurons able to detect noxious stimuli. Na(V1.8 underlies the vast majority of sodium currents during action potentials. Many studies have highlighted a key role for Na(V1.8 in inflammatory and chronic pain models. Lipid rafts are microdomains of the plasma membrane highly enriched in cholesterol and sphingolipids. Lipid rafts tune the spatial and temporal organisation of proteins and lipids on the plasma membrane. They are thought to act as platforms on the membrane where proteins and lipids can be trafficked, compartmentalised and functionally clustered. In the present study we investigated Na(V1.8 sub-cellular localisation and explored the idea that it is associated with lipid rafts in nociceptors. We found that Na(V1.8 is distributed in clusters along the axons of DRG neurons in vitro and ex vivo. We also demonstrated, by biochemical and imaging studies, that Na(V1.8 is associated with lipid rafts along the sciatic nerve ex vivo and in DRG neurons in vitro. Moreover, treatments with methyl-β-cyclodextrin (MβCD and 7-ketocholesterol (7KC led to the dissociation between rafts and Na(V1.8. By calcium imaging we demonstrated that the lack of association between rafts and Na(V1.8 correlated with impaired neuronal excitability, highlighted by a reduction in the number of neurons able to conduct mechanically- and chemically-evoked depolarisations. These findings reveal the sub-cellular localisation of Na(V1.8 in nociceptors and highlight the importance of the association between Na(V1.8 and lipid rafts in the control of nociceptor excitability.

  5. Interactions of carbon dioxide and food odours in Drosophila: olfactory hedonics and sensory neuron properties.

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    Cécile P Faucher

    Full Text Available Behavioural responses of animals to volatiles in their environment are generally dependent on context. Most natural odours are mixtures of components that can each induce different behaviours when presented on their own. We have investigated how a complex of two olfactory stimuli is evaluated by Drosophila flies in a free-flying two-trap choice assay and how these stimuli are encoded in olfactory receptor neurons. We first observed that volatiles from apple cider vinegar attracted flies while carbon dioxide (CO2 was avoided, confirming their inherent positive and negative values. In contradiction with previous results obtained from walking flies in a four-field olfactometer, in the present assay the addition of CO2 to vinegar increased rather than decreased the attractiveness of vinegar. This effect was female-specific even though males and females responded similarly to CO2 and vinegar on their own. To test whether the female-specific behavioural response to the mixture correlated with a sexual dimorphism at the peripheral level we recorded from olfactory receptor neurons stimulated with vinegar, CO2 and their combination. Responses to vinegar were obtained from three neuron classes, two of them housed with the CO2-responsive neuron in ab1 sensilla. Sensitivity of these neurons to both CO2 and vinegar per se did not differ between males and females and responses from female neurons did not change when CO2 and vinegar were presented simultaneously. We also found that CO2-sensitive neurons are particularly well adapted to respond rapidly to small concentration changes irrespective of background CO2 levels. The ability to encode temporal properties of stimulations differs considerably between CO2- and vinegar-sensitive neurons. These properties may have important implications for in-flight navigation when rapid responses to fragmented odour plumes are crucial to locate odour sources. However, the flies' sex-specific response to the CO2-vinegar

  6. Searching for collective behavior in a large network of sensory neurons.

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    Gašper Tkačik

    2014-01-01

    Full Text Available Maximum entropy models are the least structured probability distributions that exactly reproduce a chosen set of statistics measured in an interacting network. Here we use this principle to construct probabilistic models which describe the correlated spiking activity of populations of up to 120 neurons in the salamander retina as it responds to natural movies. Already in groups as small as 10 neurons, interactions between spikes can no longer be regarded as small perturbations in an otherwise independent system; for 40 or more neurons pairwise interactions need to be supplemented by a global interaction that controls the distribution of synchrony in the population. Here we show that such "K-pairwise" models--being systematic extensions of the previously used pairwise Ising models--provide an excellent account of the data. We explore the properties of the neural vocabulary by: 1 estimating its entropy, which constrains the population's capacity to represent visual information; 2 classifying activity patterns into a small set of metastable collective modes; 3 showing that the neural codeword ensembles are extremely inhomogenous; 4 demonstrating that the state of individual neurons is highly predictable from the rest of the population, allowing the capacity for error correction.

  7. Dendritic development of Drosophila high order visual system neurons is independent of sensory experience

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    Reuter John E

    2003-06-01

    Full Text Available Abstract Background The complex and characteristic structures of dendrites are a crucial part of the neuronal architecture that underlies brain function, and as such, their development has been a focal point of recent research. It is generally believed that dendritic development is controlled by a combination of endogenous genetic mechanisms and activity-dependent mechanisms. Therefore, it is of interest to test the relative contributions of these two types of mechanisms towards the construction of specific dendritic trees. In this study, we make use of the highly complex Vertical System (VS of motion sensing neurons in the lobula plate of the Drosophila visual system to gauge the importance of visual input and synaptic activity to dendritic development. Results We find that the dendrites of VS1 neurons are unchanged in dark-reared flies as compared to control flies raised on a 12 hour light, 12 hour dark cycle. The dendrites of these flies show no differences from control in dendrite complexity, spine number, spine density, or axon complexity. Flies with genetically ablated eyes show a slight but significant reduction in the complexity and overall length of VS1 dendrites, although this effect may be due to a reduction in the overall size of the dendritic field in these flies. Conclusions Overall, our results indicate no role for visual experience in the development of VS dendrites, while spontaneous activity from photoreceptors may play at most a subtle role in the formation of fully complex dendrites in these high-order visual processing neurons.

  8. Identification of Chloride Channels CLCN3 and CLCN5 Mediating the Excitatory Cl− Currents Activated by Sphingosine-1-Phosphate in Sensory Neurons

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    Qi, Yanmei; Mair, Norbert; Kummer, Kai K.; Leitner, Michael G.; Camprubí-Robles, María; Langeslag, Michiel; Kress, Michaela

    2018-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid involved in numerous physiological and pathophysiological processes. We have previously reported a S1P-induced nocifensive response in mice by excitation of sensory neurons via activation of an excitatory chloride current. The underlying molecular mechanism for the S1P-induced chloride conductance remains elusive. In the present study, we identified two CLCN voltage-gated chloride channels, CLCN3 and CLCN5, which mediated a S1P-induced excitatory Cl− current in sensory neurons by combining RNA-seq, adenovirus-based gene silencing and whole-cell electrophysiological voltage-clamp recordings. Downregulation of CLCN3 and CLCN5 channels by adenovirus-mediated delivery of shRNA dramatically reduced S1P-induced Cl− current and membrane depolarization in sensory neurons. The mechanism of S1P-induced activation of the chloride current involved Rho GTPase but not Rho-associated protein kinase. Although S1P-induced potentiation of TRPV1-mediated ionic currents also involved Rho-dependent process, the lack of correlation of the S1P-activated Cl− current and the potentiation of TRPV1 by S1P suggests that CLCN3 and CLCN5 are necessary components for S1P-induced excitatory Cl− currents but not for the amplification of TRPV1-mediated currents in sensory neurons. This study provides a novel mechanistic insight into the importance of bioactive sphingolipids in nociception. PMID:29479306

  9. Identification of Chloride Channels CLCN3 and CLCN5 Mediating the Excitatory Cl− Currents Activated by Sphingosine-1-Phosphate in Sensory Neurons

    Directory of Open Access Journals (Sweden)

    Yanmei Qi

    2018-02-01

    Full Text Available Sphingosine-1-phosphate (S1P is a bioactive sphingolipid involved in numerous physiological and pathophysiological processes. We have previously reported a S1P-induced nocifensive response in mice by excitation of sensory neurons via activation of an excitatory chloride current. The underlying molecular mechanism for the S1P-induced chloride conductance remains elusive. In the present study, we identified two CLCN voltage-gated chloride channels, CLCN3 and CLCN5, which mediated a S1P-induced excitatory Cl− current in sensory neurons by combining RNA-seq, adenovirus-based gene silencing and whole-cell electrophysiological voltage-clamp recordings. Downregulation of CLCN3 and CLCN5 channels by adenovirus-mediated delivery of shRNA dramatically reduced S1P-induced Cl− current and membrane depolarization in sensory neurons. The mechanism of S1P-induced activation of the chloride current involved Rho GTPase but not Rho-associated protein kinase. Although S1P-induced potentiation of TRPV1-mediated ionic currents also involved Rho-dependent process, the lack of correlation of the S1P-activated Cl− current and the potentiation of TRPV1 by S1P suggests that CLCN3 and CLCN5 are necessary components for S1P-induced excitatory Cl− currents but not for the amplification of TRPV1-mediated currents in sensory neurons. This study provides a novel mechanistic insight into the importance of bioactive sphingolipids in nociception.

  10. ß-catenin, a transcription factor activated by canonical Wnt signaling, is expressed in sensory neurons of calves latently infected with bovine herpesvirus 1

    Science.gov (United States)

    Like many a-herpesvirinae subfamily members, bovine herpes virus 1 (BoHV-1) expresses an abundant transcript in latently infected sensory neurons: the latency-related (LR) RNA. LR-RNA encodes a protein (ORF2) that inhibits apoptosis, interacts with Notch family members, interferes with Notch mediate...

  11. An Iconography of the Flesh: How Corpses Mean As Matter

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    Margaret Shwartz

    2013-09-01

    Full Text Available The structuring relationship between the material world and the world of culture is variously embodied in the figure of the corpse. To ask how corpses mean as matter is to attend to them as “things themselves”—by bracketing the freighted assumptions and naturally mixed feelings we have when we encounter something that cannot but remind us of our own mortality. Corpses force us to think of putrefaction—and allow us, via a complex system of cultural and representational practices, to just as quickly disavow this unpleasantness. Wherever the corpse appears, then, it brings with it ideas about the relationship between representation and the real, or, more precisely, about the matter of subjectivity. This materiality also crucially constitutes the corpse’s difference from the identity of the deceased, and it is here where the corpse may thus do more than simply reference the past. The end point of the argument, then, is to work towards a vocabulary that allows this difference—this material remainder—to figure meaningfully in practices of grief and mourning that may not point exclusively back towards the deceased (and inevitably a particular version of that person’s legacy but towards the future and towards polysemic, even conflicting ideas of the responsibility placed upon us by this death. This paper opens a discussion of corpses as “vibrant matter” (to borrow Jane Bennett’s provocative term whose materiality is an equal partner to their cultural significance. My reading opens a conversation about the very real work of corpses as things capable of organizing diverse affect that in turn may become considered action. Following Bennett’s reading of Deleuze and Latour, I account for the corpse as both deceased subject and material object by framing it as a kind of assemblage. As remains, the corpse is essentially referential, the remains of someone. But remains are also material, matter that functions as an actant in concert with

  12. Nimesulide inhibits protein kinase C epsilon and substance P in sensory neurons – comparison with paracetamol

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    Vellani V

    2011-06-01

    Full Text Available Vittorio Vellani1, Silvia Franchi2, Massimiliano Prandini1, Sarah Moretti2, Giorgia Pavesi1, Chiara Giacomoni3, Paola Sacerdote21Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, Modena, Italy; 2Dipartimento di Farmacologia Chemioterapia e Tossicologia Medica, Università degli Studi di Milano, Italy; 3Dipartimento di Economia e Tecnologia, Università degli Studi della Repubblica di San Marino, Montegiardino, Repubblica di San MarinoAbstract: In this paper we describe new actions of nimesulide and paracetamol in cultured peripheral neurons isolated from rat dorsal root ganglia (DRG. Both drugs were able to decrease in a dose-dependent fashion the number of cultured DRG neurons showing translocation of protein kinase C epsilon (PKCε caused by exposure to 1 µM bradykinin or 100 nM thrombin. In addition, the level of substance P (SP released by DRG neurons and the level of preprotachykinin mRNA expression were measured in basal conditions and after 70 minutes or 36 hours of stimulation with nerve growth factor (NGF or with an inflammatory soup containing bradykinin, thrombin, endothelin-1, and KCl. Nimesulide (10 µM significantly decreased the mRNA levels of the SP precursor preprotachykinin in basal and in stimulated conditions, and decreased the amount of SP released in the medium during stimulation of neurons with NGF or with the inflammatory soup. The effects of paracetamol (10 µM on such response was lower. Nimesulide completely inhibited the release of prostaglandin E2 (PGE2 from DRG neurons, either basal or induced by NGF and by inflammatory soup, while paracetamol decreased PGE2 release only partially. Our data demonstrate, for the first time, a direct effect of two drugs largely used as analgesics on DRG neurons. The present results suggest that PKCε might be a target for the effect of nimesulide and paracetamol, while inhibition of SP synthesis and release is clearly more relevant for nimesulide than for

  13. Oscillatory neuronal activity reflects lexical-semantic feature integration within and across sensory modalities in distributed cortical networks.

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    van Ackeren, Markus J; Schneider, Till R; Müsch, Kathrin; Rueschemeyer, Shirley-Ann

    2014-10-22

    Research from the previous decade suggests that word meaning is partially stored in distributed modality-specific cortical networks. However, little is known about the mechanisms by which semantic content from multiple modalities is integrated into a coherent multisensory representation. Therefore we aimed to characterize differences between integration of lexical-semantic information from a single modality compared with two sensory modalities. We used magnetoencephalography in humans to investigate changes in oscillatory neuronal activity while participants verified two features for a given target word (e.g., "bus"). Feature pairs consisted of either two features from the same modality (visual: "red," "big") or different modalities (auditory and visual: "red," "loud"). The results suggest that integrating modality-specific features of the target word is associated with enhanced high-frequency power (80-120 Hz), while integrating features from different modalities is associated with a sustained increase in low-frequency power (2-8 Hz). Source reconstruction revealed a peak in the anterior temporal lobe for low-frequency and high-frequency effects. These results suggest that integrating lexical-semantic knowledge at different cortical scales is reflected in frequency-specific oscillatory neuronal activity in unisensory and multisensory association networks. Copyright © 2014 the authors 0270-6474/14/3314318-06$15.00/0.

  14. Gabapentin Inhibits Protein Kinase C Epsilon Translocation in Cultured Sensory Neurons with Additive Effects When Coapplied with Paracetamol (Acetaminophen).

    Science.gov (United States)

    Vellani, Vittorio; Giacomoni, Chiara

    2017-01-01

    Gabapentin is a well-established anticonvulsant drug which is also effective for the treatment of neuropathic pain. Although the exact mechanism leading to relief of allodynia and hyperalgesia caused by neuropathy is not known, the blocking effect of gabapentin on voltage-dependent calcium channels has been proposed to be involved. In order to further evaluate its analgesic mechanisms, we tested the efficacy of gabapentin on protein kinase C epsilon (PKC ε ) translocation in cultured peripheral neurons isolated from rat dorsal root ganglia (DRGs). We found that gabapentin significantly reduced PKC ε translocation induced by the pronociceptive peptides bradykinin and prokineticin 2, involved in both inflammatory and chronic pain. We recently showed that paracetamol (acetaminophen), a very commonly used analgesic drug, also produces inhibition of PKC ε . We tested the effect of the combined use of paracetamol and gabapentin, and we found that the inhibition of translocation adds up. Our study provides a novel mechanism of action for gabapentin in sensory neurons and suggests a mechanism of action for the combined use of paracetamol and gabapentin, which has recently been shown to be effective, with a cumulative behavior, in the control of postoperative pain in human patients.

  15. Gabapentin Inhibits Protein Kinase C Epsilon Translocation in Cultured Sensory Neurons with Additive Effects When Coapplied with Paracetamol (Acetaminophen

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    Vittorio Vellani

    2017-01-01

    Full Text Available Gabapentin is a well-established anticonvulsant drug which is also effective for the treatment of neuropathic pain. Although the exact mechanism leading to relief of allodynia and hyperalgesia caused by neuropathy is not known, the blocking effect of gabapentin on voltage-dependent calcium channels has been proposed to be involved. In order to further evaluate its analgesic mechanisms, we tested the efficacy of gabapentin on protein kinase C epsilon (PKCε translocation in cultured peripheral neurons isolated from rat dorsal root ganglia (DRGs. We found that gabapentin significantly reduced PKCε translocation induced by the pronociceptive peptides bradykinin and prokineticin 2, involved in both inflammatory and chronic pain. We recently showed that paracetamol (acetaminophen, a very commonly used analgesic drug, also produces inhibition of PKCε. We tested the effect of the combined use of paracetamol and gabapentin, and we found that the inhibition of translocation adds up. Our study provides a novel mechanism of action for gabapentin in sensory neurons and suggests a mechanism of action for the combined use of paracetamol and gabapentin, which has recently been shown to be effective, with a cumulative behavior, in the control of postoperative pain in human patients.

  16. Bovine Herpes Virus 1 (BHV-1) and Herpes Simplex Virus Type 1 (HSV-1) Promote Survival of Latently Infected Sensory Neurons, in Part by Inhibiting Apoptosis

    Science.gov (United States)

    Jones, Clinton

    2013-01-01

    α-Herpesvirinae subfamily members, including herpes simplex virus type 1 (HSV-1) and bovine herpes virus 1 (BHV-1), initiate infection in mucosal surfaces. BHV-1 and HSV-1 enter sensory neurons by cell-cell spread where a burst of viral gene expression occurs. When compared to non-neuronal cells, viral gene expression is quickly extinguished in sensory neurons resulting in neuronal survival and latency. The HSV-1 latency associated transcript (LAT), which is abundantly expressed in latently infected neurons, inhibits apoptosis, viral transcription, and productive infection, and directly or indirectly enhances reactivation from latency in small animal models. Three anti-apoptosis genes can be substituted for LAT, which will restore wild type levels of reactivation from latency to a LAT null mutant virus. Two small non-coding RNAs encoded by LAT possess anti-apoptosis functions in transfected cells. The BHV-1 latency related RNA (LR-RNA), like LAT, is abundantly expressed during latency. The LR-RNA encodes a protein (ORF2) and two microRNAs that are expressed in certain latently infected neurons. Wild-type expression of LR gene products is required for stress-induced reactivation from latency in cattle. ORF2 has anti-apoptosis functions and interacts with certain cellular transcription factors that stimulate viral transcription and productive infection. ORF2 is predicted to promote survival of infected neurons by inhibiting apoptosis and sequestering cellular transcription factors which stimulate productive infection. In addition, the LR encoded microRNAs inhibit viral transcription and apoptosis. In summary, the ability of BHV-1 and HSV-1 to interfere with apoptosis and productive infection in sensory neurons is crucial for the life-long latency-reactivation cycle in their respective hosts. PMID:25278776

  17. Predicting the response of olfactory sensory neurons to odor mixtures from single odor response

    OpenAIRE

    Marasco, Addolorata; De Paris, Alessandro; Migliore, Michele

    2016-01-01

    The response of olfactory receptor neurons to odor mixtures is not well understood. Here, using experimental constraints, we investigate the mathematical structure of the odor response space and its consequences. The analysis suggests that the odor response space is 3-dimensional, and predicts that the dose-response curve of an odor receptor can be obtained, in most cases, from three primary components with specific properties. This opens the way to an objective procedure to obtain specific o...

  18. Shifts in sensory neuron identity parallel differences in pheromone preference in the European corn borer

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    Fotini A Koutroumpa

    2014-10-01

    Full Text Available Pheromone communication relies on highly specific signals sent and received between members of the same species. However, how pheromone specificity is determined in moth olfactory circuits remains unknown. Here we provide the first glimpse into the mechanism that generates this specificity in Ostrinia nubilalis. In Ostrinia nubilalis it was found that a single locus causes strain-specific, diametrically opposed preferences for a 2-component pheromone blend. Previously we found pheromone preference to be correlated with the strain and hybrid-specific relative antennal response to both pheromone components. This led to the current study, in which we detail the underlying mechanism of this differential response, through chemotopically mapping of the pheromone detection circuit in the antenna. We determined that both strains and their hybrids have swapped the neuronal identity of the pheromone-sensitive neurons co-housed within a single sensillum. Furthermore, neurons that mediate behavioral antagonism surprisingly co-express up to five pheromone receptors, mirroring the concordantly broad tuning to heterospecific pheromones. This appears as possible evolutionary adaptation that could prevent cross attraction to a range of heterospecific signals, while keeping the pheromone detection system to its simplest tripartite setup.

  19. Neuronal correlates of a virtual-reality-based passive sensory P300 network.

    Science.gov (United States)

    Chen, Chun-Chuan; Syue, Kai-Syun; Li, Kai-Chiun; Yeh, Shih-Ching

    2014-01-01

    P300, a positive event-related potential (ERP) evoked at around 300 ms after stimulus, can be elicited using an active or passive oddball paradigm. Active P300 requires a person's intentional response, whereas passive P300 does not require an intentional response. Passive P300 has been used in incommunicative patients for consciousness detection and brain computer interface. Active and passive P300 differ in amplitude, but not in latency or scalp distribution. However, no study has addressed the mechanism underlying the production of passive P300. In particular, it remains unclear whether the passive P300 shares an identical active P300 generating network architecture when no response is required. This study aims to explore the hierarchical network of passive sensory P300 production using dynamic causal modelling (DCM) for ERP and a novel virtual reality (VR)-based passive oddball paradigm. Moreover, we investigated the causal relationship of this passive P300 network and the changes in connection strength to address the possible functional roles. A classical ERP analysis was performed to verify that the proposed VR-based game can reliably elicit passive P300. The DCM results suggested that the passive and active P300 share the same parietal-frontal neural network for attentional control and, underlying the passive network, the feed-forward modulation is stronger than the feed-back one. The functional role of this forward modulation may indicate the delivery of sensory information, automatic detection of differences, and stimulus-driven attentional processes involved in performing this passive task. To our best knowledge, this is the first study to address the passive P300 network. The results of this study may provide a reference for future clinical studies on addressing the network alternations under pathological states of incommunicative patients. However, caution is required when comparing patients' analytic results with this study. For example, the task

  20. Neuronal correlates of a virtual-reality-based passive sensory P300 network.

    Directory of Open Access Journals (Sweden)

    Chun-Chuan Chen

    Full Text Available P300, a positive event-related potential (ERP evoked at around 300 ms after stimulus, can be elicited using an active or passive oddball paradigm. Active P300 requires a person's intentional response, whereas passive P300 does not require an intentional response. Passive P300 has been used in incommunicative patients for consciousness detection and brain computer interface. Active and passive P300 differ in amplitude, but not in latency or scalp distribution. However, no study has addressed the mechanism underlying the production of passive P300. In particular, it remains unclear whether the passive P300 shares an identical active P300 generating network architecture when no response is required. This study aims to explore the hierarchical network of passive sensory P300 production using dynamic causal modelling (DCM for ERP and a novel virtual reality (VR-based passive oddball paradigm. Moreover, we investigated the causal relationship of this passive P300 network and the changes in connection strength to address the possible functional roles. A classical ERP analysis was performed to verify that the proposed VR-based game can reliably elicit passive P300. The DCM results suggested that the passive and active P300 share the same parietal-frontal neural network for attentional control and, underlying the passive network, the feed-forward modulation is stronger than the feed-back one. The functional role of this forward modulation may indicate the delivery of sensory information, automatic detection of differences, and stimulus-driven attentional processes involved in performing this passive task. To our best knowledge, this is the first study to address the passive P300 network. The results of this study may provide a reference for future clinical studies on addressing the network alternations under pathological states of incommunicative patients. However, caution is required when comparing patients' analytic results with this study. For example

  1. Conceptual Network Model From Sensory Neurons to Astrocytes of the Human Nervous System.

    Science.gov (United States)

    Yang, Yiqun; Yeo, Chai Kiat

    2015-07-01

    From a single-cell animal like paramecium to vertebrates like ape, the nervous system plays an important role in responding to the variations of the environment. Compared to animals, the nervous system in the human body possesses more intricate organization and utility. The nervous system anatomy has been understood progressively, yet the explanation at the cell level regarding complete information transmission is still lacking. Along the signal pathway toward the brain, an external stimulus first activates action potentials in the sensing neuron and these electric pulses transmit along the spinal nerve or cranial nerve to the neurons in the brain. Second, calcium elevation is triggered in the branch of astrocyte at the tripartite synapse. Third, the local calcium wave expands to the entire territory of the astrocyte. Finally, the calcium wave propagates to the neighboring astrocyte via gap junction channel. In our study, we integrate the existing mathematical model and biological experiments in each step of the signal transduction to establish a conceptual network model for the human nervous system. The network is composed of four layers and the communication protocols of each layer could be adapted to entities with different characterizations. We verify our simulation results against the available biological experiments and mathematical models and provide a test case of the integrated network. As the production of conscious episode in the human nervous system is still under intense research, our model serves as a useful tool to facilitate, complement and verify current and future study in human cognition.

  2. In Vitro Analysis of the Role of Schwann Cells on Axonal Degeneration and Regeneration Using Sensory Neurons from Dorsal Root Ganglia.

    Science.gov (United States)

    López-Leal, Rodrigo; Diaz, Paula; Court, Felipe A

    2018-01-01

    Sensory neurons from dorsal root ganglion efficiently regenerate after peripheral nerve injuries. These neurons are widely used as a model system to study degenerative mechanisms of the soma and axons, as well as regenerative axonal growth in the peripheral nervous system. This chapter describes techniques associated to the study of axonal degeneration and regeneration using explant cultures of dorsal root ganglion sensory neurons in vitro in the presence or absence of Schwann cells. Schwann cells are extremely important due to their involvement in tissue clearance during axonal degeneration as well as their known pro-regenerative effect during regeneration in the peripheral nervous system. We describe methods to induce and study axonal degeneration triggered by axotomy (mechanical separation of the axon from its soma) and treatment with vinblastine (which blocks axonal transport), which constitute clinically relevant mechanical and toxic models of axonal degeneration. In addition, we describe three different methods to evaluate axonal regeneration using quantitative methods. These protocols constitute a valuable tool to analyze in vitro mechanisms associated to axonal degeneration and regeneration of sensory neurons and the role of Schwann cells in these processes.

  3. Comparative analysis of behavioral and transcriptional variation underlying CO2 sensory neuron function and development in Drosophila.

    Science.gov (United States)

    Pan, Jia Wern; McLaughlin, Joi; Yang, Haining; Leo, Charles; Rambarat, Paula; Okuwa, Sumie; Monroy-Eklund, Anaïs; Clark, Sabrina; Jones, Corbin D; Volkan, Pelin Cayirlioglu

    2017-10-02

    Carbon dioxide is an important environmental cue for many insects, regulating many behaviors including some that have direct human impacts. To further improve our understanding of how this system varies among closely related insect species, we examined both the behavioral response to CO 2 as well as the transcriptional profile of key developmental regulators of CO 2 sensory neurons in the olfactory system across the Drosophila genus. We found that CO 2 generally evokes repulsive behavior across most of the Drosophilids we examined, but this behavior has been lost or reduced in several lineages. Comparisons of transcriptional profiles from the developing and adult antennae for subset these species suggest that behavioral differences in some species may be due to differences in the expression of the CO 2 co-receptor Gr63a. Furthermore, these differences in Gr63a expression are correlated with changes in the expression of a few genes known to be involved in the development of the CO 2 circuit, namely dac, an important regulator of sensilla fate for sensilla that house CO 2 ORNs, and mip120, a member of the MMB/dREAM epigenetic regulatory complex that regulates CO 2 receptor expression. In contrast, most of the other known structural, molecular, and developmental components of the peripheral Drosophila CO 2 olfactory system seem to be well-conserved across all examined lineages. These findings suggest that certain components of CO 2 sensory ORN development may be more evolutionarily labile, and may contribute to differences in CO 2 -evoked behavioral responses across species.

  4. Conversion of neurons and glia to external-cell fates in the external sensory organs of Drosophila hamlet mutants by a cousin-cousin cell-type respecification.

    Science.gov (United States)

    Moore, Adrian W; Roegiers, Fabrice; Jan, Lily Y; Jan, Yuh-Nung

    2004-03-15

    The Drosophila external sensory organ forms in a lineage elaborating from a single precursor cell via a stereotypical series of asymmetric divisions. HAMLET transcription factor expression demarcates the lineage branch that generates two internal cell types, the external sensory neuron and thecogen. In HAMLET mutant organs, these internal cells are converted to external cells via an unprecedented cousin-cousin cell-fate respecification event. Conversely, ectopic HAMLET expression in the external cell branch leads to internal cell production. The fate-determining signals NOTCH and PAX2 act at multiple stages of lineage elaboration and HAMLET acts to modulate their activity in a branch-specific manner.

  5. Irrelevant sensory stimuli interfere with working memory storage: evidence from a computational model of prefrontal neurons.

    Science.gov (United States)

    Bancroft, Tyler D; Hockley, William E; Servos, Philip

    2013-03-01

    The encoding of irrelevant stimuli into the memory store has previously been suggested as a mechanism of interference in working memory (e.g., Lange & Oberauer, Memory, 13, 333-339, 2005; Nairne, Memory & Cognition, 18, 251-269, 1990). Recently, Bancroft and Servos (Experimental Brain Research, 208, 529-532, 2011) used a tactile working memory task to provide experimental evidence that irrelevant stimuli were, in fact, encoded into working memory. In the present study, we replicated Bancroft and Servos's experimental findings using a biologically based computational model of prefrontal neurons, providing a neurocomputational model of overwriting in working memory. Furthermore, our modeling results show that inhibition acts to protect the contents of working memory, and they suggest a need for further experimental research into the capacity of vibrotactile working memory.

  6. Comparison of classifiers for decoding sensory and cognitive information from prefrontal neuronal populations.

    Directory of Open Access Journals (Sweden)

    Elaine Astrand

    Full Text Available Decoding neuronal information is important in neuroscience, both as a basic means to understand how neuronal activity is related to cerebral function and as a processing stage in driving neuroprosthetic effectors. Here, we compare the readout performance of six commonly used classifiers at decoding two different variables encoded by the spiking activity of the non-human primate frontal eye fields (FEF: the spatial position of a visual cue, and the instructed orientation of the animal's attention. While the first variable is exogenously driven by the environment, the second variable corresponds to the interpretation of the instruction conveyed by the cue; it is endogenously driven and corresponds to the output of internal cognitive operations performed on the visual attributes of the cue. These two variables were decoded using either a regularized optimal linear estimator in its explicit formulation, an optimal linear artificial neural network estimator, a non-linear artificial neural network estimator, a non-linear naïve Bayesian estimator, a non-linear Reservoir recurrent network classifier or a non-linear Support Vector Machine classifier. Our results suggest that endogenous information such as the orientation of attention can be decoded from the FEF with the same accuracy as exogenous visual information. All classifiers did not behave equally in the face of population size and heterogeneity, the available training and testing trials, the subject's behavior and the temporal structure of the variable of interest. In most situations, the regularized optimal linear estimator and the non-linear Support Vector Machine classifiers outperformed the other tested decoders.

  7. Immunohistochemical localization of two types of choline acetyltransferase in neurons and sensory cells of the octopus arm.

    Science.gov (United States)

    Sakaue, Yuko; Bellier, Jean-Pierre; Kimura, Shin; D'Este, Loredana; Takeuchi, Yoshihiro; Kimura, Hiroshi

    2014-01-01

    Cholinergic structures in the arm of the cephalopod Octopus vulgaris were studied by immunohistochemistry using specific antisera for two types (common and peripheral) of acetylcholine synthetic enzyme choline acetyltransferase (ChAT): antiserum raised against the rat common type ChAT (cChAT), which is cross-reactive with molluscan cChAT, and antiserum raised against the rat peripheral type ChAT (pChAT), which has been used to delineate peripheral cholinergic structures in vertebrates, but not previously in invertebrates. Western blot analysis of octopus extracts revealed a single pChAT-positive band, suggesting that pChAT antiserum is cross-reactive with an octopus counterpart of rat pChAT. In immunohistochemistry, only neuronal structures of the octopus arm were stained by cChAT and pChAT antisera, although the pattern of distribution clearly differed between the two antisera. cChAT-positive varicose nerve fibers were observed in both the cerebrobrachial tract and neuropil of the axial nerve cord, while pChAT-positive varicose fibers were detected only in the neuropil of the axial nerve cord. After epitope retrieval, pChAT-positive neuronal cells and their processes became visible in all ganglia of the arm, including the axial and intramuscular nerve cords, and in ganglia of suckers. Moreover, pChAT-positive structures also became detectable in nerve fibers connecting the different ganglia, in smooth nerve fibers among muscle layers and dermal connective tissues, and in sensory cells of the suckers. These results suggest that the octopus arm has two types of cholinergic nerves: cChAT-positive nerves from brain ganglia and pChAT-positive nerves that are intrinsic to the arm.

  8. DNA typing of Calliphorids collected from human corpses in Malaysia.

    Science.gov (United States)

    Kavitha, R; Tan, T C; Lee, H L; Nazni, W A; Sofian-Azirun, M

    2013-03-01

    Estimation of post-mortem interval (PMI) is crucial for time of death determination. The advent of DNA-based identification techniques forensic entomology saw the beginning of a proliferation of molecular studies into forensically important Calliphoridae (Diptera). The use of DNA to characterise morphologically indistinguishable immature calliphorids was recognised as a valuable molecular tool with enormous practical utility. The local entomofauna in most cases is important for the examination of entomological evidences. The survey of the local entomofauna has become a fundamental first step in forensic entomological studies, because different geographical distributions, seasonal and environmental factors may influence the decomposition process and the occurrence of different insect species on corpses. In this study, calliphorids were collected from 13 human corpses recovered from indoors, outdoors and aquatic conditions during the post-mortem examination by pathologists from the government hospitals in Malaysia. Only two species, Chrysomya megacephala and Chrysomya rufifacies were recovered from human corpses. DNA sequencing was performed to study the mitochondrial encoded COI gene and to evaluate the suitability of the 1300 base pairs of COI fragments for identification of blow fly species collected from real crime scene. The COI gene from blow fly specimens were sequenced and deposited in GenBank to expand local databases. The sequenced COI gene was useful in identifying calliphorids retrieved from human corpses.

  9. Odorant responsiveness of embryonic mouse olfactory sensory neurons expressing the odorant receptors S1 or MOR23.

    Science.gov (United States)

    Lam, Rebecca S; Mombaerts, Peter

    2013-07-01

    The mammalian olfactory system has developed some functionality by the time of birth. There is behavioral and limited electrophysiological evidence for prenatal olfaction in various mammalian species. However, there have been no reports, in any mammalian species, of recordings from prenatal olfactory sensory neurons (OSNs) that express a given odorant receptor (OR) gene. Here we have performed patch-clamp recordings from mouse OSNs that express the OR gene S1 or MOR23, using the odorous ligands 2-phenylethyl alcohol or lyral, respectively. We found that, out of a combined total of 20 OSNs from embryos of these two strains at embryonic day (E)16.5 or later, all responded to a cognate odorous ligand. By contrast, none of six OSNs responded to the ligand at E14.5 or E15.5. The kinetics of the odorant-evoked electrophysiological responses of prenatal OSNs are similar to those of postnatal OSNs. The S1 and MOR23 glomeruli in the olfactory bulb are formed postnatally, but the axon terminals of OSNs expressing these OR genes may be synaptically active in the olfactory bulb at embryonic stages. The upper limit of the acquisition of odorant responsiveness for S1 and MOR23 OSNs at E16.5 is consistent with the developmental expression patterns of components of the olfactory signaling pathway. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  10. Monosynaptic connections made by the sensory neurons of the gill- and siphon-withdrawal reflex in Aplysia participate in the storage of long-term memory for sensitization

    OpenAIRE

    Frost, William N.; Castellucci, Vincent F.; Hawkins, Robert D.; Kandel, Eric R.

    1985-01-01

    We have found that in the gill- and siphon- withdrawal reflex of Aplysia, the memory for short-term sensitization grades smoothly into long-term memory with increased amounts of sensitization training. One cellular locus for the storage of the memory underlying short-term sensitization is the set of monosynaptic connections between the siphon sensory cells and the gill and siphon motor neurons. We have now also found that these same monosynaptic connections participate in the storage of the m...

  11. Odorant responses of olfactory sensory neurons expressing the odorant receptor MOR23: A patch clamp analysis in gene-targeted mice

    OpenAIRE

    Grosmaitre, Xavier; Vassalli, Anne; Mombaerts, Peter; Shepherd, Gordon M.; Ma, Minghong

    2006-01-01

    A glomerulus in the mammalian olfactory bulb receives axonal inputs from olfactory sensory neurons (OSNs) that express the same odorant receptor (OR). Glomeruli are generally thought to represent functional units of olfactory coding, but there are no data on the electrophysiological properties of OSNs that express the same endogenous OR. Here, using patch clamp recordings in an intact epithelial preparation, we directly measured the transduction currents and receptor potentials from the dendr...

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

    Science.gov (United States)

    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.

  13. Processing of sub- and supra-second intervals in the primate brain results from the calibration of neuronal oscillators via sensory, motor, and feedback processes

    Science.gov (United States)

    Gupta, Daya S.

    2014-01-01

    The processing of time intervals in the sub- to supra-second range by the brain is critical for the interaction of primates with their surroundings in activities, such as foraging and hunting. For an accurate processing of time intervals by the brain, representation of physical time within neuronal circuits is necessary. I propose that time dimension of the physical surrounding is represented in the brain by different types of neuronal oscillators, generating spikes or spike bursts at regular intervals. The proposed oscillators include the pacemaker neurons, tonic inputs, and synchronized excitation and inhibition of inter-connected neurons. Oscillators, which are built inside various circuits of brain, help to form modular clocks, processing time intervals or other temporal characteristics specific to functions of a circuit. Relative or absolute duration is represented within neuronal oscillators by “neural temporal unit,” defined as the interval between regularly occurring spikes or spike bursts. Oscillator output is processed to produce changes in activities of neurons, named frequency modulator neuron, wired within a separate module, represented by the rate of change in frequency, and frequency of activities, proposed to encode time intervals. Inbuilt oscillators are calibrated by (a) feedback processes, (b) input of time intervals resulting from rhythmic external sensory stimulation, and (c) synchronous effects of feedback processes and evoked sensory activity. A single active clock is proposed per circuit, which is calibrated by one or more mechanisms. Multiple calibration mechanisms, inbuilt oscillators, and the presence of modular connections prevent a complete loss of interval timing functions of the brain. PMID:25136321

  14. Diminished superoxide generation is associated with respiratory chain dysfunction and changes in the mitochondrial proteome of sensory neurons from diabetic rats.

    Science.gov (United States)

    Akude, Eli; Zherebitskaya, Elena; Chowdhury, Subir K Roy; Smith, Darrell R; Dobrowsky, Rick T; Fernyhough, Paul

    2011-01-01

    Impairments in mitochondrial function have been proposed to play a role in the etiology of diabetic sensory neuropathy. We tested the hypothesis that mitochondrial dysfunction in axons of sensory neurons in type 1 diabetes is due to abnormal activity of the respiratory chain and an altered mitochondrial proteome. Proteomic analysis using stable isotope labeling with amino acids in cell culture (SILAC) determined expression of proteins in mitochondria from dorsal root ganglia (DRG) of control, 22-week-old streptozotocin (STZ)-diabetic rats, and diabetic rats treated with insulin. Rates of oxygen consumption and complex activities in mitochondria from DRG were measured. Fluorescence imaging of axons of cultured sensory neurons determined the effect of diabetes on mitochondrial polarization status, oxidative stress, and mitochondrial matrix-specific reactive oxygen species (ROS). Proteins associated with mitochondrial dysfunction, oxidative phosphorylation, ubiquinone biosynthesis, and the citric acid cycle were downregulated in diabetic samples. For example, cytochrome c oxidase subunit IV (COX IV; a complex IV protein) and NADH dehydrogenase Fe-S protein 3 (NDUFS3; a complex I protein) were reduced by 29 and 36% (P neurons exhibited oxidative stress and depolarized mitochondria, an aberrant adaption to oligomycin-induced mitochondrial membrane hyperpolarization, but reduced levels of intramitochondrial superoxide compared with control. Abnormal mitochondrial function correlated with a downregulation of mitochondrial proteins, with components of the respiratory chain targeted in lumbar DRG in diabetes. The reduced activity of the respiratory chain was associated with diminished superoxide generation within the mitochondrial matrix and did not contribute to oxidative stress in axons of diabetic neurons. Alternative pathways involving polyol pathway activity appear to contribute to raised ROS in axons of diabetic neurons under high glucose concentration.

  15. Microbial community assembly and metabolic function during mammalian corpse decomposition

    Energy Technology Data Exchange (ETDEWEB)

    Metcalf, J. L.; Xu, Z. Z.; Weiss, S.; Lax, S.; Van Treuren, W.; Hyde, E. R.; Song, S. J.; Amir, A.; Larsen, P.; Sangwan, N.; Haarmann, D.; Humphrey, G. C.; Ackermann, G.; Thompson, L. R.; Lauber, C.; Bibat, A.; Nicholas, C.; Gebert, M. J.; Petrosino, J. F.; Reed, S. C.; Gilbert, J. A.; Lynne, A. M.; Bucheli, S. R.; Carter, D. O.; Knight, R.

    2015-12-10

    Vertebrate corpse decomposition provides an important stage in nutrient cycling in most terrestrial habitats, yet microbially mediated processes are poorly understood. Here we combine deep microbial community characterization, community-level metabolic reconstruction, and soil biogeochemical assessment to understand the principles governing microbial community assembly during decomposition of mouse and human corpses on different soil substrates. We find a suite of bacterial and fungal groups that contribute to nitrogen cycling and a reproducible network of decomposers that emerge on predictable time scales. Our results show that this decomposer community is derived primarily from bulk soil, but key decomposers are ubiquitous in low abundance. Soil type was not a dominant factor driving community development, and the process of decomposition is sufficiently reproducible to offer new opportunities for forensic investigations.

  16. Microbial community assembly and metabolic function during mammalian corpse decomposition

    Science.gov (United States)

    Metcalf, Jessica L; Xu, Zhenjiang Zech; Weiss, Sophie; Lax, Simon; Van Treuren, Will; Hyde, Embriette R.; Song, Se Jin; Amir, Amnon; Larsen, Peter; Sangwan, Naseer; Haarmann, Daniel; Humphrey, Greg C; Ackermann, Gail; Thompson, Luke R; Lauber, Christian; Bibat, Alexander; Nicholas, Catherine; Gebert, Matthew J; Petrosino, Joseph F; Reed, Sasha C.; Gilbert, Jack A; Lynne, Aaron M; Bucheli, Sibyl R; Carter, David O; Knight, Rob

    2016-01-01

    Vertebrate corpse decomposition provides an important stage in nutrient cycling in most terrestrial habitats, yet microbially mediated processes are poorly understood. Here we combine deep microbial community characterization, community-level metabolic reconstruction, and soil biogeochemical assessment to understand the principles governing microbial community assembly during decomposition of mouse and human corpses on different soil substrates. We find a suite of bacterial and fungal groups that contribute to nitrogen cycling and a reproducible network of decomposers that emerge on predictable time scales. Our results show that this decomposer community is derived primarily from bulk soil, but key decomposers are ubiquitous in low abundance. Soil type was not a dominant factor driving community development, and the process of decomposition is sufficiently reproducible to offer new opportunities for forensic investigations.

  17. Natural Disasters, Corpses and the Risk of Infectious Diseases

    Directory of Open Access Journals (Sweden)

    JM Conly

    2005-01-01

    Full Text Available The recent occurrence of the category 4 Hurricane Katrina devastated the United States? Gulf Coast. The hurricane caused widespread destruction and flooding, and left hundreds of thousands of people homeless. The mounting death toll was reported at almost 300 deaths as of September 8, 2005 (1,2. The unfolding events and high death toll have left an unusual situation in which there are many decomposing corpses either lying on the streets or floating in the flood waters. The presence of these corpses in open settings, such as in public places and in the water that has inundated much of the city of New Orleans, naturally raises concerns about the occurrence of infectious disease epidemics (3. In the aftermath of large natural disasters, instinctive uncertainties arise among workers and the general population with respect to the appropriate handling and disposal of dead bodies and human remains. Given the recent occurrence of Hurricane Katrina as a large natural disaster and the unprecedented setting of the numerous corpses requiring disposal, it was considered timely to review the infectious disease risks associated with the handling of dead bodies.

  18. Inhibition of TRPA1 channel activity in sensory neurons by the glial cell line-derived neurotrophic factor family member, artemin

    Directory of Open Access Journals (Sweden)

    Wang Shenglan

    2011-05-01

    Full Text Available Abstract Background The transient receptor potential (TRP channel subtype A1 (TRPA1 is known to be expressed on sensory neurons and respond to changes in temperature, pH and local application of certain noxious chemicals such as allyl isothiocyanate (AITC. Artemin is a neuronal survival and differentiation factor and belongs to the glial cell line-derived neurotrophic factor (GDNF family. Both TRPA1 and artemin have been reported to be involved in pathological pain initiation and maintenance. In the present study, using whole-cell patch clamp recording technique, in situ hybridization and behavioral analyses, we examined the functional interaction between TRPA1 and artemin. Results We found that 85.8 ± 1.9% of TRPA1-expressing neurons also expressed GDNF family receptor alpha 3 (GFR α3, and 87.5 ± 4.1% of GFRα3-expressing neurons were TRPA1-positive. In whole-cell patch clamp analysis, a short-term treatment of 100 ng/ml artemin significantly suppressed the AITC-induced TRPA1 currents. A concentration-response curve of AITC resulting from the effect of artemin showed that this inhibition did not change EC50 but did lower the AITC-induced maximum response. In addition, pre-treatment of artemin significantly suppressed the number of paw lifts induced by intraplantar injection of AITC, as well as the formalin-induced pain behaviors. Conclusions These findings that a short-term application of artemin inhibits the TRPA1 channel's activity and the sequential pain behaviors suggest a role of artemin in regulation of sensory neurons.

  19. Regeneration of Drosophila sensory neuron axons and dendrites is regulated by the Akt pathway involving Pten and microRNA bantam

    Science.gov (United States)

    Song, Yuanquan; Ori-McKenney, Kassandra M.; Zheng, Yi; Han, Chun; Jan, Lily Yeh; Jan, Yuh Nung

    2012-01-01

    Both cell-intrinsic and extrinsic pathways govern axon regeneration, but only a limited number of factors have been identified and it is not clear to what extent axon regeneration is evolutionarily conserved. Whether dendrites also regenerate is unknown. Here we report that, like the axons of mammalian sensory neurons, the axons of certain Drosophila dendritic arborization (da) neurons are capable of substantial regeneration in the periphery but not in the CNS, and activating the Akt pathway enhances axon regeneration in the CNS. Moreover, those da neurons capable of axon regeneration also display dendrite regeneration, which is cell type-specific, developmentally regulated, and associated with microtubule polarity reversal. Dendrite regeneration is restrained via inhibition of the Akt pathway in da neurons by the epithelial cell-derived microRNA bantam but is facilitated by cell-autonomous activation of the Akt pathway. Our study begins to reveal mechanisms for dendrite regeneration, which depends on both extrinsic and intrinsic factors, including the PTEN–Akt pathway that is also important for axon regeneration. We thus established an important new model system—the fly da neuron regeneration model that resembles the mammalian injury model—with which to study and gain novel insights into the regeneration machinery. PMID:22759636

  20. 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.

  1. 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.

  2. IL-33/ST2 signaling excites sensory neurons and mediates itch response in a mouse model of poison ivy contact allergy.

    Science.gov (United States)

    Liu, Boyi; Tai, Yan; Achanta, Satyanarayana; Kaelberer, Melanie M; Caceres, Ana I; Shao, Xiaomei; Fang, Jianqiao; Jordt, Sven-Eric

    2016-11-22

    Poison ivy-induced allergic contact dermatitis (ACD) is the most common environmental allergic condition in the United States. Case numbers of poison ivy ACD are increasing due to growing biomass and geographical expansion of poison ivy and increasing content of the allergen, urushiol, likely attributable to rising atmospheric CO 2 Severe and treatment-resistant itch is the major complaint of affected patients. However, because of limited clinical data and poorly characterized models, the pruritic mechanisms in poison ivy ACD remain unknown. Here, we aim to identify the mechanisms of itch in a mouse model of poison ivy ACD by transcriptomics, neuronal imaging, and behavioral analysis. Using transcriptome microarray analysis, we identified IL-33 as a key cytokine up-regulated in the inflamed skin of urushiol-challenged mice. We further found that the IL-33 receptor, ST2, is expressed in small to medium-sized dorsal root ganglion (DRG) neurons, including neurons that innervate the skin. IL-33 induces Ca 2+ influx into a subset of DRG neurons through neuronal ST2. Neutralizing antibodies against IL-33 or ST2 reduced scratching behavior and skin inflammation in urushiol-challenged mice. Injection of IL-33 into urushiol-challenged skin rapidly exacerbated itch-related scratching via ST2, in a histamine-independent manner. Targeted silencing of neuronal ST2 expression by intrathecal ST2 siRNA delivery significantly attenuated pruritic responses caused by urushiol-induced ACD. These results indicate that IL-33/ST2 signaling is functionally present in primary sensory neurons and contributes to pruritus in poison ivy ACD. Blocking IL-33/ST2 signaling may represent a therapeutic approach to ameliorate itch and skin inflammation related to poison ivy ACD.

  3. Neuronal responses to tactile stimuli and tactile sensations evoked by microstimulation in the human thalamic principal somatic sensory nucleus (ventral caudal).

    Science.gov (United States)

    Schmid, Anne-Christine; Chien, Jui-Hong; Greenspan, Joel D; Garonzik, Ira; Weiss, Nirit; Ohara, Shinji; Lenz, Frederick Arthur

    2016-06-01

    The normal organization and plasticity of the cutaneous core of the thalamic principal somatosensory nucleus (ventral caudal, Vc) have been studied by single-neuron recordings and microstimulation in patients undergoing awake stereotactic operations for essential tremor (ET) without apparent somatic sensory abnormality and in patients with dystonia or chronic pain secondary to major nervous system injury. In patients with ET, most Vc neurons responded to one of the four stimuli, each of which optimally activates one mechanoreceptor type. Sensations evoked by microstimulation were similar to those evoked by the optimal stimulus only among rapidly adapting neurons. In patients with ET, Vc was highly segmented somatotopically, and vibration, movement, pressure, and sharp sensations were usually evoked by microstimulation at separate sites in Vc. In patients with conditions including spinal cord transection, amputation, or dystonia, RFs were mismatched with projected fields more commonly than in patients with ET. The representation of the border of the anesthetic area (e.g., stump) or of the dystonic limb was much larger than that of the same part of the body in patients with ET. This review describes the organization and reorganization of human Vc neuronal activity in nervous system injury and dystonia and then proposes basic mechanisms. Copyright © 2016 the American Physiological Society.

  4. Artificial Induction of Associative Olfactory Memory by Optogenetic and Thermogenetic Activation of Olfactory Sensory Neurons and Octopaminergic Neurons in Drosophila Larvae.

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    Honda, Takato; Lee, Chi-Yu; Honjo, Ken; Furukubo-Tokunaga, Katsuo

    2016-01-01

    The larval brain of Drosophila melanogaster provides an excellent system for the study of the neurocircuitry mechanism of memory. Recent development of neurogenetic techniques in fruit flies enables manipulations of neuronal activities in freely behaving animals. This protocol describes detailed steps for artificial induction of olfactory associative memory in Drosophila larvae. In this protocol, the natural reward signal is substituted by thermogenetic activation of octopaminergic neurons in the brain. In parallel, the odor signal is substituted by optogenetic activation of a specific class of olfactory receptor neurons. Association of reward and odor stimuli is achieved with the concomitant application of blue light and heat that leads to activation of both sets of neurons in living transgenic larvae. Given its operational simplicity and robustness, this method could be utilized to further our knowledge on the neurocircuitry mechanism of memory in the fly brain.

  5. Reduced sensory synaptic excitation impairs motor neuron function via Kv2.1 in spinal muscular atrophy.

    Science.gov (United States)

    Fletcher, Emily V; Simon, Christian M; Pagiazitis, John G; Chalif, Joshua I; Vukojicic, Aleksandra; Drobac, Estelle; Wang, Xiaojian; Mentis, George Z

    2017-07-01

    Behavioral deficits in neurodegenerative diseases are often attributed to the selective dysfunction of vulnerable neurons via cell-autonomous mechanisms. Although vulnerable neurons are embedded in neuronal circuits, the contributions of their synaptic partners to disease process are largely unknown. Here we show that, in a mouse model of spinal muscular atrophy (SMA), a reduction in proprioceptive synaptic drive leads to motor neuron dysfunction and motor behavior impairments. In SMA mice or after the blockade of proprioceptive synaptic transmission, we observed a decrease in the motor neuron firing that could be explained by the reduction in the expression of the potassium channel Kv2.1 at the surface of motor neurons. Chronically increasing neuronal activity pharmacologically in vivo led to a normalization of Kv2.1 expression and an improvement in motor function. Our results demonstrate a key role of excitatory synaptic drive in shaping the function of motor neurons during development and the contribution of its disruption to a neurodegenerative disease.

  6. From the Anticipatory Corpse to the Participatory Body.

    Science.gov (United States)

    Lysaught, M Therese

    2016-12-01

    Jeffrey Bishop's The Anticipatory Corpse demonstrates how death is present in and cloaked by contemporary practices of end-of-life care. A key to Bishop's argument is that for modern medicine the cadaver has become epistemologically normative and that a metaphysics shorn of formal and final causes now shapes contemporary healthcare practices. The essays of this symposium laud and interrogate Bishop's argument in three ways. First, they raise critical methodological challenges from the perspectives of human rights, Charles Taylor's concept of social imaginaries, and economics. Second, they demonstrate the analytical power of his argument by detailing how it might be extended to additional issues beyond simply end-of-life care and how it might be brought into conversation with sociology. Third, they engage the constructive turn Bishop takes at the end of the book. Bishop himself also updates readers on the reception of The Anticipatory Corpse, as well as the way his thinking has evolved over the past 5 years since its publication. He also engages the questions, challenges, and openings provided by our authors. © The Author 2016. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Sensory Neuroanatomy of Parastrongyloides trichosuri, a Nematode Parasite of Mammals: Amphidial Neurons of the First-Stage Larva

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    Zhu, He; Li, Jian; Nolan, Thomas J.; Schad, Gerhard A.; Lok, James B.

    2011-01-01

    Owing to its ability to switch between free-living and parasitic modes of development, Parastrongyloides trichosuri represents a valuable model with which to study the evolution of parasitism among the nematodes, especially aspects pertaining to morphogenesis of infective third-stage larvae. In the free-living nematode Caenorhabditis elegans, developmental fates of third-stage larvae are determined in part by environmental cues received by chemosensory neurons in the amphidial sensillae. As a basis for comparative study, we have described the neuroanatomy of the amphidial sensillae of P. trichosuri. Using computational methods we incorporated serial electron micrographs into a three-dimensional reconstruction of the amphidial neurons of this parasite. Each amphid is innervated by 13 neurons, and the dendritic processes of 10 of these extend nearly to the amphidial pore. Dendritic processes of two specialized neurons leave the amphidial channel and terminate within invaginations of the sheath cell. One of these is similar to the finger cell of C. elegans, terminating in digitiform projections. The other projects a single cilium into the sheath cell. The dendritic process of a third specialized neuron terminates within the tight junction of the amphid. Each amphidial neuron was traced from the tip of its dendrite(s) to its cell body in the lateral ganglion. Positions of these cell bodies approximate those of morphologically similar amphidial neurons in Caenorhabditis elegans, so the standard nomenclature for amphidial neurons in C. elegans was adopted. A map of cell bodies within the lateral ganglion of P. trichosuri was prepared to facilitate functional study of these neurons. PMID:21456026

  8. Inhibition of GluR Current in Microvilli of Sensory Neurons via Na+-Microdomain Coupling Among GluR, HCN Channel, and Na+/K+ Pump

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    Yasuhiro Kawasaki

    2018-04-01

    Full Text Available Glutamatergic dendritic EPSPs evoked in cortical pyramidal neurons are depressed by activation of hyperpolarization-activated cyclic nucleotide-gated (HCN channels expressed in dendritic spines. This depression has been attributed to shunting effects of HCN current (Ih on input resistance or Ih deactivation. Primary sensory neurons in the rat mesencephalic trigeminal nucleus (MTN have the somata covered by spine-like microvilli that express HCN channels. In rat MTN neurons, we demonstrated that Ih enhancement apparently diminished the glutamate receptor (GluR current (IGluR evoked by puff application of glutamate/AMPA and enhanced a transient outward current following IGluR (OT-IGluR. This suggests that some outward current opposes inward IGluR. The IGluR inhibition displayed a U-shaped voltage-dependence with a minimal inhibition around the resting membrane potential, suggesting that simple shunting effects or deactivation of Ih cannot explain the U-shaped voltage-dependence. Confocal imaging of Na+ revealed that GluR activation caused an accumulation of Na+ in the microvilli, which can cause a negative shift of the reversal potential for Ih (Eh. Taken together, it was suggested that IGluR evoked in MTN neurons is opposed by a transient decrease or increase in standing inward or outward Ih, respectively, both of which can be caused by negative shifts of Eh, as consistent with the U-shaped voltage-dependence of the IGluR inhibition and the OT-IGluR generation. An electron-microscopic immunohistochemical study revealed the colocalization of HCN channels and glutamatergic synapses in microvilli of MTN neurons, which would provide a morphological basis for the functional interaction between HCN and GluR channels. Mathematical modeling eliminated the possibilities of the involvements of Ih deactivation and/or shunting effect and supported the negative shift of Eh which causes the U-shaped voltage-dependent inhibition of IGluR.

  9. Repeated touch and needle-prick stimulation in the neonatal period increases the baseline mechanical sensitivity and postinjury hypersensitivity of adult spinal sensory neurons.

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    van den Hoogen, Nynke J; Patijn, Jacob; Tibboel, Dick; Joosten, Bert A; Fitzgerald, Maria; Kwok, Charlie H T

    2018-03-08

    Noxious stimulation at critical stages of development has long-term consequences on somatosensory processing in later life, but it is not known whether this developmental plasticity is restricted to nociceptive pathways. Here, we investigate the effect of repeated neonatal noxious or innocuous hind paw stimulation on adult spinal dorsal horn cutaneous mechanical sensitivity. Neonatal Sprague-Dawley rats of both sexes received 4 unilateral left hind paw needle pricks (NPs, n = 13) or 4 tactile (cotton swab touch) stimuli, per day (TC, n = 11) for the first 7 days of life. Control pups were left undisturbed (n = 17). When adult (6-8 weeks), lumbar wide-dynamic-range neuron activity in laminae III-V was recorded using in vivo extracellular single-unit electrophysiology. Spike activity evoked by cutaneous dynamic tactile (brush), pinch and punctate (von Frey hair) stimulation, and plantar receptive field areas were recorded, at baseline and 2 and 5 days after left plantar hind paw incision. Baseline brush receptive fields, von Frey hair, and pinch sensitivity were significantly enhanced in adult NP and TC animals compared with undisturbed controls, although effects were greatest in NP rats. After incision, injury sensitivity of adult wide-dynamic-range neurons to both noxious and dynamic tactile hypersensitivity was significantly greater in NP animals compared with TC and undisturbed controls. We conclude that both repeated touch and needle-prick stimulation in the neonatal period can alter adult spinal sensory neuron sensitivity to both innocuous and noxious mechanical stimulation. Thus, spinal sensory circuits underlying touch and pain processing are shaped by a range of early-life somatosensory experiences.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

  10. Dynein-dependent transport of nanos RNA in Drosophila sensory neurons requires Rumpelstiltskin and the germ plasm organizer Oskar.

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    Xu, Xin; Brechbiel, Jillian L; Gavis, Elizabeth R

    2013-09-11

    Intracellular mRNA localization is a conserved mechanism for spatially regulating protein production in polarized cells, such as neurons. The mRNA encoding the translational repressor Nanos (Nos) forms ribonucleoprotein (RNP) particles that are dendritically localized in Drosophila larval class IV dendritic arborization (da) neurons. In nos mutants, class IV da neurons exhibit reduced dendritic branching complexity, which is rescued by transgenic expression of wild-type nos mRNA but not by a localization-compromised nos derivative. While localization is essential for nos function in dendrite morphogenesis, the mechanism underlying the transport of nos RNP particles was unknown. We investigated the mechanism of dendritic nos mRNA localization by analyzing requirements for nos RNP particle motility in class IV da neuron dendrites through live imaging of fluorescently labeled nos mRNA. We show that dynein motor machinery components mediate transport of nos mRNA in proximal dendrites. Two factors, the RNA-binding protein Rumpelstiltskin and the germ plasm protein Oskar, which are required for diffusion/entrapment-mediated localization of nos during oogenesis, also function in da neurons for formation and transport of nos RNP particles. Additionally, we show that nos regulates neuronal function, most likely independent of its dendritic localization and function in morphogenesis. Our results reveal adaptability of localization factors for regulation of a target transcript in different cellular contexts.

  11. Nanos-mediated repression of hid protects larval sensory neurons after a global switch in sensitivity to apoptotic signals.

    Science.gov (United States)

    Bhogal, Balpreet; Plaza-Jennings, Amara; Gavis, Elizabeth R

    2016-06-15

    Dendritic arbor morphology is a key determinant of neuronal function. Once established, dendrite branching patterns must be maintained as the animal develops to ensure receptive field coverage. The translational repressors Nanos (Nos) and Pumilio (Pum) are required to maintain dendrite growth and branching of Drosophila larval class IV dendritic arborization (da) neurons, but their specific regulatory role remains unknown. We show that Nos-Pum-mediated repression of the pro-apoptotic gene head involution defective (hid) is required to maintain a balance of dendritic growth and retraction in class IV da neurons and that upregulation of hid results in decreased branching because of an increase in caspase activity. The temporal requirement for nos correlates with an ecdysone-triggered switch in sensitivity to apoptotic stimuli that occurs during the mid-L3 transition. We find that hid is required during pupariation for caspase-dependent pruning of class IV da neurons and that Nos and Pum delay pruning. Together, these results suggest that Nos and Pum provide a crucial neuroprotective regulatory layer to ensure that neurons behave appropriately in response to developmental cues. © 2016. Published by The Company of Biologists Ltd.

  12. Differential upregulation in DRG neurons of an α2δ-1 splice variant with a lower affinity for gabapentin after peripheral sensory nerve injury.

    Science.gov (United States)

    Lana, Beatrice; Schlick, Bettina; Martin, Stuart; Pratt, Wendy S; Page, Karen M; Goncalves, Leonor; Rahman, Wahida; Dickenson, Anthony H; Bauer, Claudia S; Dolphin, Annette C

    2014-03-01

    The α2δ-1 protein is an auxiliary subunit of voltage-gated calcium channels, critical for neurotransmitter release. It is upregulated in dorsal root ganglion (DRG) neurons following sensory nerve injury, and is also the therapeutic target of the gabapentinoid drugs, which are efficacious in both experimental and human neuropathic pain conditions. α2δ-1 has 3 spliced regions: A, B, and C. A and C are cassette exons, whereas B is introduced via an alternative 3' splice acceptor site. Here we have examined the presence of α2δ-1 splice variants in DRG neurons, and have found that although the main α2δ-1 splice variant in DRG is the same as that in brain (α2δ-1 ΔA+B+C), there is also another α2δ-1 splice variant (ΔA+BΔC), which is expressed in DRG neurons and is differentially upregulated compared to the main DRG splice variant α2δ-1 ΔA+B+C following spinal nerve ligation. Furthermore, this differential upregulation occurs preferentially in a small nonmyelinated DRG neuron fraction, obtained by density gradient separation. The α2δ-1 ΔA+BΔC splice variant supports CaV2 calcium currents with unaltered properties compared to α2δ-1 ΔA+B+C, but shows a significantly reduced affinity for gabapentin. This variant could therefore play a role in determining the efficacy of gabapentin in neuropathic pain. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  13. Stable Density and Dynamics of Dendritic Spines of Cortical Neurons Across the Estrous Cycle While Expressing Differential Levels of Sensory-Evoked Plasticity

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    Bailin H. Alexander

    2018-03-01

    Full Text Available Periodic oscillations of gonadal hormone levels during the estrous cycle exert effects on the female brain, impacting cognition and behavior. While previous research suggests that changes in hormone levels across the cycle affect dendritic spine dynamics in the hippocampus, little is known about the effects on cortical dendritic spines and previous studies showed contradictory results. In this in vivo imaging study, we investigated the impact of the estrous cycle on the density and dynamics of dendritic spines of pyramidal neurons in the primary somatosensory cortex of mice. We also examined if the induction of synaptic plasticity during proestrus, estrus, and metestrus/diestrus had differential effects on the degree of remodeling of synapses in this brain area. We used chronic two-photon excitation (2PE microscopy during steady-state conditions and after evoking synaptic plasticity by whisker stimulation at the different stages of the cycle. We imaged apical dendritic tufts of layer 5 pyramidal neurons of naturally cycling virgin young female mice. Spine density, turnover rate (TOR, survival fraction, morphology, and volume of mushroom spines remained unaltered across the estrous cycle, and the values of these parameters were comparable with those of young male mice. However, while whisker stimulation of female mice during proestrus and estrus resulted in increases in the TOR of spines (74.2 ± 14.9% and 75.1 ± 12.7% vs. baseline, respectively, sensory-evoked plasticity was significantly lower during metestrus/diestrus (32.3 ± 12.8%. In males, whisker stimulation produced 46.5 ± 20% increase in TOR compared with baseline—not significantly different from female mice at any stage of the cycle. These results indicate that, while steady-state density and dynamics of dendritic spines of layer 5 pyramidal neurons in the primary somatosensory cortex of female mice are constant during the estrous cycle, the susceptibility of these neurons to

  14. A developmental approach of imitation to study the emergence of mirror neurons in a sensory-motor controller

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    Gaussier Philippe

    2011-12-01

    Full Text Available Mirror neurons have often been considered as the explanation of how primates can imitate. In this paper, we show that a simple neural network architecture that learns visuo-motor associations can be enough to let low level imitation emerge without a priori mirror neurons. Adding sequence learning mechanisms and action inhibition allows to perform deferred imitation of gestures demonstrated visually or by body manipulation. With the building of a cognitive map giving the capability of learning plans, we can study in our model the emergence of both low level and high level resonances highlighted by Rizzolatti et al.

  15. Resveratrol engages AMPK to attenuate ERK and mTOR signaling in sensory neurons and inhibits incision-induced acute and chronic pain

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    Tillu Dipti V

    2012-01-01

    Full Text Available Abstract Background Despite advances in our understanding of basic mechanisms driving post-surgical pain, treating incision-induced pain remains a major clinical challenge. Moreover, surgery has been implicated as a major cause of chronic pain conditions. Hence, more efficacious treatments are needed to inhibit incision-induced pain and prevent the transition to chronic pain following surgery. We reasoned that activators of AMP-activated protein kinase (AMPK may represent a novel treatment avenue for the local treatment of incision-induced pain because AMPK activators inhibit ERK and mTOR signaling, two important pathways involved in the sensitization of peripheral nociceptors. Results To test this hypothesis we used a potent and efficacious activator of AMPK, resveratrol. Our results demonstrate that resveratrol profoundly inhibits ERK and mTOR signaling in sensory neurons in a time- and concentration-dependent fashion and that these effects are mediated by AMPK activation and independent of sirtuin activity. Interleukin-6 (IL-6 is thought to play an important role in incision-induced pain and resveratrol potently inhibited IL-6-mediated signaling to ERK in sensory neurons and blocked IL-6-mediated allodynia in vivo through a local mechanism of action. Using a model of incision-induced allodynia in mice, we further demonstrate that local injection of resveratrol around the surgical wound strongly attenuates incision-induced allodynia. Intraplantar IL-6 injection and plantar incision induces persistent nociceptive sensitization to PGE2 injection into the affected paw after the resolution of allodynia to the initial stimulus. We further show that resveratrol treatment at the time of IL-6 injection or plantar incision completely blocks the development of persistent nociceptive sensitization consistent with the blockade of a transition to a chronic pain state by resveratrol treatment. Conclusions These results highlight the importance of signaling

  16. Odorant responses of olfactory sensory neurons expressing the odorant receptor MOR23: a patch clamp analysis in gene-targeted mice.

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    Grosmaitre, Xavier; Vassalli, Anne; Mombaerts, Peter; Shepherd, Gordon M; Ma, Minghong

    2006-02-07

    A glomerulus in the mammalian olfactory bulb receives axonal inputs from olfactory sensory neurons (OSNs) that express the same odorant receptor (OR). Glomeruli are generally thought to represent functional units of olfactory coding, but there are no data on the electrophysiological properties of OSNs that express the same endogenous OR. Here, using patch clamp recordings in an intact epithelial preparation, we directly measured the transduction currents and receptor potentials from the dendritic knobs of mouse OSNs that express the odorant receptor MOR23 along with the green fluorescent protein. All of the 53 cells examined responded to lyral, a known ligand for MOR23. There were profound differences in response kinetics, particularly in the deactivation phase. The cells were very sensitive to lyral, with some cells responding to as little as 10 nM. The dynamic range was unexpectedly broad, with threshold and saturation in individual cells often covering three log units of lyral concentration. The potential causes and biological significance of this cellular heterogeneity are discussed. Patch clamp recording from OSNs that express a defined OR provides a powerful approach to investigate the sensory inputs to individual glomeruli.

  17. The Alzheimer's β-secretase enzyme BACE1 is required for accurate axon guidance of olfactory sensory neurons and normal glomerulus formation in the olfactory bulb

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    Rajapaksha Tharinda W

    2011-12-01

    Full Text Available Abstract Background The β-secretase, β-site amyloid precursor protein cleaving enzyme 1 (BACE1, is a prime therapeutic target for lowering cerebral β-amyloid (Aβ levels in Alzheimer's disease (AD. Clinical development of BACE1 inhibitors is being intensely pursued. However, little is known about the physiological functions of BACE1, and the possibility exists that BACE1 inhibition may cause mechanism-based side effects. Indeed, BACE1-/- mice exhibit a complex neurological phenotype. Interestingly, BACE1 co-localizes with presynaptic neuronal markers, indicating a role in axons and/or terminals. Moreover, recent studies suggest axon guidance molecules are potential BACE1 substrates. Here, we used a genetic approach to investigate the function of BACE1 in axon guidance of olfactory sensory neurons (OSNs, a well-studied model of axon targeting in vivo. Results We bred BACE1-/- mice with gene-targeted mice in which GFP is expressed from the loci of two odorant-receptors (ORs, MOR23 and M72, and olfactory marker protein (OMP to produce offspring that were heterozygous for MOR23-GFP, M72-GFP, or OMP-GFP and were either BACE1+/+ or BACE1-/-. BACE1-/- mice had olfactory bulbs (OBs that were smaller and weighed less than OBs of BACE1+/+ mice. In wild-type mice, BACE1 was present in OSN axon terminals in OB glomeruli. In whole-mount preparations and tissue sections, many OB glomeruli from OMP-GFP; BACE1-/- mice were malformed compared to wild-type glomeruli. MOR23-GFP; BACE1-/- mice had an irregular MOR23 glomerulus that was innervated by randomly oriented, poorly fasciculated OSN axons compared to BACE1+/+ mice. Most importantly, M72-GFP; BACE1-/- mice exhibited M72 OSN axons that were mis-targeted to ectopic glomeruli, indicating impaired axon guidance in BACE1-/- mice. Conclusions Our results demonstrate that BACE1 is required for the accurate targeting of OSN axons and the proper formation of glomeruli in the OB, suggesting a role for BACE1 in

  18. Multilayer perceptron classification of unknown volatile chemicals from the firing rates of insect olfactory sensory neurons and its application to biosensor design.

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    Bachtiar, Luqman R; Unsworth, Charles P; Newcomb, Richard D; Crampin, Edmund J

    2013-01-01

    In this letter, we use the firing rates from an array of olfactory sensory neurons (OSNs) of the fruit fly, Drosophila melanogaster, to train an artificial neural network (ANN) to distinguish different chemical classes of volatile odorants. Bootstrapping is implemented for the optimized networks, providing an accurate estimate of a network's predicted values. Initially a simple linear predictor was used to assess the complexity of the data and was found to provide low prediction performance. A nonlinear ANN in the form of a single multilayer perceptron (MLP) was also used, providing a significant increase in prediction performance. The effect of the number of hidden layers and hidden neurons of the MLP was investigated and found to be effective in enhancing network performance with both a single and a double hidden layer investigated separately. A hybrid array of MLPs was investigated and compared against the single MLP architecture. The hybrid MLPs were found to classify all vectors of the validation set, presenting the highest degree of prediction accuracy. Adjustment of the number of hidden neurons was investigated, providing further performance gain. In addition, noise injection was investigated, proving successful for certain network designs. It was found that the best-performing MLP was that of the double-hidden-layer hybrid MLP network without the use of noise injection. Furthermore, the level of performance was examined when different numbers of OSNs used were varied from the maximum of 24 to only 5 OSNs. Finally, the ideal OSNs were identified that optimized network performance. The results obtained from this study provide strong evidence of the usefulness of ANNs in the field of olfaction for the future realization of a signal processing back end for an artificial olfactory biosensor.

  19. C. elegans bicd-1, homolog of the Drosophila dynein accessory factor Bicaudal D, regulates the branching of PVD sensory neuron dendrites.

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    Aguirre-Chen, Cristina; Bülow, Hannes E; Kaprielian, Zaven

    2011-02-01

    The establishment of cell type-specific dendritic arborization patterns is a key phase in the assembly of neuronal circuitry that facilitates the integration and processing of synaptic and sensory input. Although studies in Drosophila and vertebrate systems have identified a variety of factors that regulate dendrite branch formation, the molecular mechanisms that control this process remain poorly defined. Here, we introduce the use of the Caenorhabditis elegans PVD neurons, a pair of putative nociceptors that elaborate complex dendritic arbors, as a tractable model for conducting high-throughput RNAi screens aimed at identifying key regulators of dendritic branch formation. By carrying out two separate RNAi screens, a small-scale candidate-based screen and a large-scale screen of the ~3000 genes on chromosome IV, we retrieved 11 genes that either promote or suppress the formation of PVD-associated dendrites. We present a detailed functional characterization of one of the genes, bicd-1, which encodes a microtubule-associated protein previously shown to modulate the transport of mRNAs and organelles in a variety of organisms. Specifically, we describe a novel role for bicd-1 in regulating dendrite branch formation and show that bicd-1 is likely to be expressed, and primarily required, in PVD neurons to control dendritic branching. We also present evidence that bicd-1 operates in a conserved pathway with dhc-1 and unc-116, components of the dynein minus-end-directed and kinesin-1 plus-end-directed microtubule-based motor complexes, respectively, and interacts genetically with the repulsive guidance receptor unc-5.

  20. Cultures of Death and Politics of Corpse Supply

    Science.gov (United States)

    Buklijas, Tatjana

    2008-01-01

    Summary Nineteenth-century Vienna is well known to medical historians as a leading centre of medical research and education, offering easy access to patients and corpses to students from all over the world. This article seeks to explain how this enviable supply with cadavers was achieved, why it provoked so little opposition at a time when Britain and the United States saw widespread protests against dissection, and how it was threatened from mid-century. To understand permissive Viennese attitudes we need to place them in a longue durée history of death and dissection, and to pay close attention to the city’s political geography as it was transformed into a major imperial capital. The tolerant stance of the Roman Catholic Church, strong links to Southern Europe and the weak position of individuals in the absolutist state all contributed to an idiosyncratic anatomical culture. But as the fame of the Vienna medical school peaked in the later 1800s, the increased demand created by rising student numbers combined with intensified interdisciplinary competition to produce a shortfall that professors found increasingly difficult to meet. Around 1900, new religious groups and mass political parties challenged the long-standing anatomical practice by refusing to supply cadavers and making dissection into an instrument of political struggle. This study of the material preconditions for anatomy at one of Europe’s most influential medical schools provides a contrast to the dominant Anglo-American histories of death and dissection. PMID:18791297

  1. Percutaneous vertebroplasty: an experimental study in adult corpses

    International Nuclear Information System (INIS)

    He Shicheng; Teng Gaojun; Zeng Shuilin; Guo Jinhe; Fang Wen; Zhu Guangyu; Liu Zhentian

    2002-01-01

    Objective: To investigate the key technique factors and the mechanisms of percutaneous vertebroplasty (PVP). Methods: PMMA was classified into three groups according to the ratio of powder/liquid as 1:1, 3:2 and 2:1. Polymerizing process in vitro was measured respectively in each group, which included 10 samples. Twenty vertebrae from T12-L4 in 4 adult corpses were randomly distributed into 2 groups. In one group, PVP was performed under monitoring by combined CT and C-arm X-ray machines. All vertebrae were dissected into individual vertebra and the ultimate compressive strength was measured in double-blind tests. Results: The period of the polymerizing process and the temperature changes during the polymerizing among 3 groups with different ratio of powder/liquid were significantly different. The ratio of 3/2 was the proper regimen for injection. Punctures were successfully reached in one set of puncture in all vertebrae but one, with 4.5 ml of PMMA in average injected in each vertebra. Pre-vertebral leakage of PMMA was demonstrated in 4 of 20 vertebrae. The ultimate compressive strength increased in 38% in the experimental group compared with that of the control group. Conclusions: Proper ratio of powder/liquid and injection time of PMMA is the key technique for PVP. The puncture route of trans-arch of vertebra is accessible for PVP. It is proven in this study that the ultimate compressive strength of vertebra enhances greatly after PVP

  2. Enhancement of delayed-rectifier potassium conductance by low concentrations of local anaesthetics in spinal sensory neurones

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    Olschewski, Andrea; Wolff, Matthias; Bräu, Michael E; Hempelmann, Gunter; Vogel, Werner; Safronov, Boris V

    2002-01-01

    Combining the patch-clamp recordings in slice preparation with the ‘entire soma isolation' method we studied action of several local anaesthetics on delayed-rectifier K+ currents in spinal dorsal horn neurones.Bupivacaine, lidocaine and mepivacaine at low concentrations (1–100 μM) enhanced delayed-rectifier K+ current in intact neurones within the spinal cord slice, while exhibiting a partial blocking effect at higher concentrations (>100 μM). In isolated somata 0.1–10 μM bupivacaine enhanced delayed-rectifier K+ current by shifting its steady-state activation characteristic and the voltage-dependence of the activation time constant to more negative potentials by 10–20 mV.Detailed analysis has revealed that bupivacaine also increased the maximum delayed-rectifier K+ conductance by changing the open probability, rather than the unitary conductance, of the channel.It is concluded that local anaesthetics show a dual effect on delayed-rectifier K+ currents by potentiating them at low concentrations and partially suppressing at high concentrations. The phenomenon observed demonstrated the complex action of local anaesthetics during spinal and epidural anaesthesia, which is not restricted to a suppression of Na+ conductance only. PMID:12055132

  3. Fast calcium transients translate the distribution and conduction of neural activity in different regions of a single sensory neuron.

    Science.gov (United States)

    Purali, Nuhan

    2017-09-01

    In the present study, cytosolic calcium concentration changes were recorded in response to various forms of excitations, using the fluorescent calcium indicator dye OG-BAPTA1 together with the current or voltage clamp methods in stretch receptor neurons of crayfish. A single action potential evoked a rise in the resting calcium level in the axon and axonal hillock, whereas an impulse train or a large saturating current injection would be required to evoke an equivalent response in the dendrite region. Under voltage clamp conditions, amplitude differences between axon and dendrite responses vanished completely. The fast activation time and the modulation of the response by extracellular calcium concentration changes indicated that the evoked calcium transients might be mediated by calcium entry into the cytosol through a voltage-gated calcium channel. The decay of the responses was slow and sensitive to extracellular sodium and calcium concentrations as well as exposure to 1-10 mM NiCl 2 and 10-500 µM lanthanum. Thus, a sodium calcium exchanger and a calcium ATPase might be responsible for calcium extrusion from the cytosol. Present results indicate that the calcium indicator OG-BAPTA1 might be an efficient but indirect way of monitoring regional membrane potential differences in a single neuron.

  4. Effects of NSAIDs and paracetamol (acetaminophen on protein kinase C epsilon translocation and on substance P synthesis and release in cultured sensory neurons

    Directory of Open Access Journals (Sweden)

    Vellani V

    2013-02-01

    Full Text Available Vittorio Vellani,1 Silvia Franchi,2 Massimiliano Prandini,1 Sarah Moretti,2 Mara Castelli,2 Chiara Giacomoni,3 Paola Sacerdote21Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; 2Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; 3Department of Economics and Technology, University of the Republic of San Marino, Republic of San MarinoAbstract: Celecoxib, diclofenac, ibuprofen, and nimesulide are nonsteroidal anti-inflammatory drugs (NSAIDs very commonly used for the treatment of moderate to mild pain, together with paracetamol (acetaminophen, a very widely used analgesic with a lesser anti-inflammatory effect. In the study reported here, we tested the efficacy of celecoxib, diclofenac, and ibuprofen on preprotachykinin mRNA synthesis, substance P (SP release, prostaglandin E2 (PGE2 release, and protein kinase C epsilon (PKCε translocation in rat cultured sensory neurons from dorsal root ganglia (DRGs. The efficacy of these NSAIDs was compared with the efficacy of paracetamol and nimesulide in in vitro models of hyperalgesia (investigated previously. While nimesulide and paracetamol, as in previous experiments, decreased the percentage of cultured DRG neurons showing translocation of PKCε caused by 100 nM thrombin or 1 µM bradykinin in a dose-dependent manner, the other NSAIDs tested did not have a significant effect. The amount of SP released by peptidergic neurons and the expression level of preprotachykinin mRNA were assessed in basal conditions and after 70 minutes or 36 hours of stimulation with an inflammatory soup (IS containing potassium chloride, thrombin, bradykinin, and endothelin-1. The release of SP at 70 minutes was inhibited only by nimesulide, while celecoxib and diclofenac were effective at 36 hours. The mRNA basal level of the SP precursor preprotachykinin expressed in DRG neurons was reduced only by nimesulide, while the

  5. H2S-induced HCO3- secretion in the rat stomach--involvement of nitric oxide, prostaglandins, and capsaicin-sensitive sensory neurons.

    Science.gov (United States)

    Takeuchi, Koji; Ise, Fumitaka; Takahashi, Kento; Aihara, Eitaro; Hayashi, Shusaku

    2015-04-30

    Hydrogen sulfide (H2S) is known to be an important gaseous mediator that affects various functions under physiological and pathological conditions. We examined the effects of NaHS, a H2S donor, on HCO3(-) secretion in rat stomachs and investigated the mechanism involved in this response. Under urethane anesthesia, rat stomachs were mounted on an ex vivo chamber and perfused with saline. Acid secretion had been inhibited by omeprazole. The secretion of HCO3(-) was measured at pH 7.0 using a pH-stat method and by the addition of 10 mM HCl. NaHS (0.5-10 mM) was perfused in the stomach for 5 min. Indomethacin or L-NAME was administered s.c. before NaHS treatment, while glibenclamide (a KATP channel blocker), ONO-8711 (an EP1 antagonist), or propargylglycine (a cystathionine γ-lyase inhibitor) was given i.p. before. The mucosal perfusion of NaHS dose-dependently increased the secretion of HCO3(-), and this effect was significantly attenuated by indomethacin, L-NAME, and sensory deafferentation, but not by glibenclamide or ONO-8711. The luminal output of nitric oxide, but not the mucosal production of prostaglandin E2, was increased by the perfusion of NaHS. Mucosal acidification stimulated HCO3(-) secretion, and this response was inhibited by sensory deafferentation, indomethacin, L-NAME, and ONO-8711, but not by propargylglycine. These results suggested that H2S increased HCO3(-) secretion in the stomach, and this effect was mediated by capsaicin-sensitive afferent neurons and dependent on nitric oxide and prostaglandins, but not ATP-sensitive K(+) channels. Further study is needed to define the role of endogenous H2S in the mechanism underlying acid-induced gastric HCO3(-) secretion. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Sea-anemone toxin ATX-II elicits A-fiber-dependent pain and enhances resurgent and persistent sodium currents in large sensory neurons

    Directory of Open Access Journals (Sweden)

    Klinger Alexandra B

    2012-09-01

    Full Text Available Abstract Background Gain-of-function mutations of the nociceptive voltage-gated sodium channel Nav1.7 lead to inherited pain syndromes, such as paroxysmal extreme pain disorder (PEPD. One characteristic of these mutations is slowed fast-inactivation kinetics, which may give rise to resurgent sodium currents. It is long known that toxins from Anemonia sulcata, such as ATX-II, slow fast inactivation and skin contact for example during diving leads to various symptoms such as pain and itch. Here, we investigated if ATX-II induces resurgent currents in sensory neurons of the dorsal root ganglion (DRGs and how this may translate into human sensations. Results In large A-fiber related DRGs ATX-II (5 nM enhances persistent and resurgent sodium currents, but failed to do so in small C-fiber linked DRGs when investigated using the whole-cell patch-clamp technique. Resurgent currents are thought to depend on the presence of the sodium channel β4-subunit. Using RT-qPCR experiments, we show that small DRGs express significantly less β4 mRNA than large sensory neurons. With the β4-C-terminus peptide in the pipette solution, it was possible to evoke resurgent currents in small DRGs and in Nav1.7 or Nav1.6 expressing HEK293/N1E115 cells, which were enhanced by the presence of extracellular ATX-II. When injected into the skin of healthy volunteers, ATX-II induces painful and itch-like sensations which were abolished by mechanical nerve block. Increase in superficial blood flow of the skin, measured by Laser doppler imaging is limited to the injection site, so no axon reflex erythema as a correlate for C-fiber activation was detected. Conclusion ATX-II enhances persistent and resurgent sodium currents in large diameter DRGs, whereas small DRGs depend on the addition of β4-peptide to the pipette recording solution for ATX-II to affect resurgent currents. Mechanical A-fiber blockade abolishes all ATX-II effects in human skin (e.g. painful and itch

  7. Auditory distance perception in humans: a review of cues, development, neuronal bases, and effects of sensory loss.

    Science.gov (United States)

    Kolarik, Andrew J; Moore, Brian C J; Zahorik, Pavel; Cirstea, Silvia; Pardhan, Shahina

    2016-02-01

    Auditory distance perception plays a major role in spatial awareness, enabling location of objects and avoidance of obstacles in the environment. However, it remains under-researched relative to studies of the directional aspect of sound localization. This review focuses on the following four aspects of auditory distance perception: cue processing, development, consequences of visual and auditory loss, and neurological bases. The several auditory distance cues vary in their effective ranges in peripersonal and extrapersonal space. The primary cues are sound level, reverberation, and frequency. Nonperceptual factors, including the importance of the auditory event to the listener, also can affect perceived distance. Basic internal representations of auditory distance emerge at approximately 6 months of age in humans. Although visual information plays an important role in calibrating auditory space, sensorimotor contingencies can be used for calibration when vision is unavailable. Blind individuals often manifest supranormal abilities to judge relative distance but show a deficit in absolute distance judgments. Following hearing loss, the use of auditory level as a distance cue remains robust, while the reverberation cue becomes less effective. Previous studies have not found evidence that hearing-aid processing affects perceived auditory distance. Studies investigating the brain areas involved in processing different acoustic distance cues are described. Finally, suggestions are given for further research on auditory distance perception, including broader investigation of how background noise and multiple sound sources affect perceived auditory distance for those with sensory loss.

  8. [Decomposition of corpses--a microbial degradation process with special reference to mummification, formation of adipocere and incomplete putrified corpes].

    Science.gov (United States)

    Schoenen, Dirk

    2013-01-01

    Decomposition of the human body is a microbial process. It is influenced by the environmental situation and it depends to a high degree on the exchange of substances between the corpse and the environment. Mummification occurs at low humidity or frost. Adipocere arises from lack of oxygen, incomplete putrified corpses develop when there is no exchange of air or water between the corpse and the environment.

  9. Super-resolution imaging of ciliary microdomains in isolated olfactory sensory neurons using a custom two-color stimulated emission depletion microscope

    Science.gov (United States)

    Meyer, Stephanie A.; Ozbay, Baris N.; Potcoava, Mariana; Salcedo, Ernesto; Restrepo, Diego; Gibson, Emily A.

    2016-06-01

    We performed stimulated emission depletion (STED) imaging of isolated olfactory sensory neurons (OSNs) using a custom-built microscope. The STED microscope uses a single pulsed laser to excite two separate fluorophores, Atto 590 and Atto 647N. A gated timing circuit combined with temporal interleaving of the different color excitation/STED laser pulses filters the two channel detection and greatly minimizes crosstalk. We quantified the instrument resolution to be ˜81 and ˜44 nm, for the Atto 590 and Atto 647N channels. The spatial separation between the two channels was measured to be under 10 nm, well below the resolution limit. The custom-STED microscope is incorporated onto a commercial research microscope allowing brightfield, differential interference contrast, and epifluorescence imaging on the same field of view. We performed immunolabeling of OSNs in mice to image localization of ciliary membrane proteins involved in olfactory transduction. We imaged Ca2+-permeable cyclic nucleotide gated (CNG) channel (Atto 594) and adenylyl cyclase type III (ACIII) (Atto 647N) in distinct cilia. STED imaging resolved well-separated subdiffraction limited clusters for each protein. We quantified the size of each cluster to have a mean value of 88±48 nm and 124±43 nm, for CNG and ACIII, respectively. STED imaging showed separated clusters that were not resolvable in confocal images.

  10. 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.

  11. 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)

  12. Temporal phases of activity-dependent plasticity and memory are mediated by compartmentalized routing of MAPK signaling in aplysia sensory neurons.

    Science.gov (United States)

    Shobe, Justin L; Zhao, Yali; Stough, Shara; Ye, Xiaojing; Hsuan, Vickie; Martin, Kelsey C; Carew, Thomas J

    2009-01-15

    An activity-dependent form of intermediate memory (AD-ITM) for sensitization is induced in Aplysia by a single tail shock that gives rise to plastic changes (AD-ITF) in tail sensory neurons (SNs) via the interaction of action potential firing in the SN coupled with the release of serotonin in the CNS. Activity-dependent long-term facilitation (AD-LTF, lasting >24hr) requires protein synthesis dependent persistent mitogen-activated protein kinase (MAPK) activation and translocation to the SN nucleus. We now show that the induction of the earlier temporal phase (AD-ITM and AD-ITF), which is translation and transcription independent, requires the activation of a compartmentally distinct novel signaling cascade that links second messengers, MAPK and PKC into a unified pathway within tail SNs. Since both AD-ITM and AD-LTM require MAPK activity, these collective findings suggest that presynaptic SNs route the flow of molecular information to distinct subcellular compartments during the induction of activity-dependent long-lasting memories.

  13. The requirement for enhanced CREB1 expression in consolidation of long-term synaptic facilitation and long-term excitability in sensory neurons of Aplysia

    Science.gov (United States)

    Liu, Rong-Yu; Cleary, Leonard J.; Byrne, John H.

    2011-01-01

    Accumulating evidence suggests that the transcriptional activator CREB1 is important for serotonin (5-HT)-induced long-term facilitation (LTF) of the sensorimotor synapse in Aplysia. Moreover, creb1 is among the genes activated by CREB1, suggesting a role for this protein beyond the induction phase of LTF. The time course of the requirement for CREB1 synthesis in the consolidation of long-term facilitation was examined using RNA interference (RNAi) techniques in sensorimotor co-cultures. Injection of CREB1 small-interfering RNA (siRNA) immediately or 10 h after 5-HT treatment blocked LTF when measured at 24 h and 48 h after treatment. In contrast, CREB1 siRNA did not block LTF when injected 16 h after 5-HT treatment. These results demonstrate that creb1 expression must be sustained for a relatively long time in order to support the consolidation of LTF. In addition, LTF is also accompanied by a long-term increase in the excitability (LTE) of sensory neurons (SNs). Because LTE was observed in the isolated SN after 5-HT treatment, this long-term change was intrinsic to that element of the circuit. LTE was blocked when CREB1 siRNA was injected into isolated SNs immediately after 5-HT treatment. These data suggest that 5-HT-induced CREB1 synthesis is required for consolidation of both LTF and LTE. PMID:21543617

  14. 17β-Estradiol Enhances ASIC Activity in Primary Sensory Neurons to Produce Sex Difference in Acidosis-Induced Nociception.

    Science.gov (United States)

    Qu, Zu-Wei; Liu, Ting-Ting; Ren, Cuixia; Gan, Xiong; Qiu, Chun-Yu; Ren, Ping; Rao, Zhiguo; Hu, Wang-Ping

    2015-12-01

    Sex differences have been reported in a number of pain conditions. Women are more sensitive to most types of painful stimuli than men, and estrogen plays a key role in the sex differences in pain perception. However, it is unclear whether there is a sex difference in acidosis-evoked pain. We report here that both male and female rats exhibit nociceptive behaviors in response to acetic acid, with females being more sensitive than males. Local application of exogenous 17β-estradiol (E2) exacerbated acidosis-evoked nociceptive response in male rats. E2 and estrogen receptor (ER)-α agonist 1,3,5-Tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole, but not ERβ agonist 2,3-bis(4-hydroxyphenyl)-propionitrile, replacement also reversed attenuation of the acetic acid-induced nociceptive response in ovariectomized females. Moreover, E2 can exert a rapid potentiating effect on the functional activity of acid-sensing ion channels (ASICs), which mediated the acidosis-induced events. E2 dose dependently increased the amplitude of ASIC currents with a 42.8 ± 1.6 nM of EC50. E2 shifted the concentration-response curve for proton upward with a 50.1% ± 6.2% increase of the maximal current response to proton. E2 potentiated ASIC currents via an ERα and ERK1/2 signaling pathway. E2 also altered acidosis-evoked membrane excitability of dorsal root ganglia neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acidic stimuli. E2 potentiation of the functional activity of ASICs revealed a peripheral mechanism underlying this sex difference in acetic acid-induced nociception.

  15. Detection of Metabolism Function of Microbial Community of Corpses by Biolog-Eco Method.

    Science.gov (United States)

    Jiang, X Y; Wang, J F; Zhu, G H; Ma, M Y; Lai, Y; Zhou, H

    2016-06-01

    To detect the changes of microbial community functional diversity of corpses with different postmortem interval (PMI) and to evaluate forensic application value for estimating PMI. The cultivation of microbial community from the anal swabs of a Sus scrofa and a human corpse placed in field environment from 0 to 240 h after death was performed using the Biolog-Eco Microplate and the variations of the absorbance values were also monitored. Combined with the technology of forensic pathology and flies succession, the metabolic characteristics and changes of microbial community on the decomposed corpse under natural environment were also observed. The diversity of microbial metabolism function was found to be negatively correlated with the number of maggots in the corpses. The freezing processing had the greatest impact on average well color development value at 0 h and the impact almost disappeared after 48 h. The diversity of microbial metabolism of the samples became relatively unstable after 192 h. The principal component analysis showed that 31 carbon sources could be consolidated for 5 principal components (accumulative contribution ratio >90%).The carbon source tsquare-analysis showed that N -acetyl- D -glucosamine and L -serine were the dominant carbon sources for estimating the PMI (0=240 h) of the Sus scrofa and human corpse. The Biolog-Eco method can be used to reveal the metabolic differences of the carbon resources utilization of the microbial community on the corpses during 0-240 h after death, which could provide a new basis for estimating the PMI. Copyright© by the Editorial Department of Journal of Forensic Medicine

  16. Octopamine regulates antennal sensory neurons via daytime-dependent changes in cAMP and IP3 levels in the hawkmoth Manduca sexta.

    Directory of Open Access Journals (Sweden)

    Thomas Schendzielorz

    Full Text Available The biogenic amine octopamine (OA mediates reward signals in olfactory learning and memory as well as circadian rhythms of sleep and activity. In the crepuscular hawkmoth Manduca sexta, OA changed pheromone detection thresholds daytime-dependently, suggesting that OA confers circadian control of olfactory transduction. Thus, with enzyme-linked immunosorbent assays we searched hawkmoth antennae for daytime-dependent changes in the concentration of OA and its respective second messengers. Antennal stimulation with OA raised cAMP- and IP3 levels. Furthermore, antennae expressed daytime-dependent changes in the concentration of OA, with maxima at Zeitgebertime (ZT 20 when moths were active and also maximal concentrations of cAMP occurred. Maximal IP3 levels at ZT 18 and 23 correlated with maximal flight activity of male moths, while minimal IP3 levels at dusk correlated with peaks of feeding activity. Half maximal effective concentration (EC50 for activation of the OA-receptor decreased during the moth's activity phase suggesting daytime-dependent changes in OA receptor sensitivity. With an antiserum against tyramine, the precursor of OA, two centrifugal neurons were detected projecting out into the sensory cell layer of the antenna, possibly mediating more rapid stimulus-dependent OA actions. Indeed, in fast kinetic assays OA receptor stimulation increased cAMP concentrations within 50 msec. Thus, we hypothesize that fast, stimulus-dependent centrifugal control of OA-release in the antenna occurs. Additional slow systemic OA actions might be based upon circadian release of OA into the hemolymph mediating circadian rhythms of antennal second messenger levels. The resulting rhythms of odor sensitivity are suggested to underlie circadian rhythms in odor-mediated behavior.

  17. A report on the pupae of Desmometopa sp. (Diptera: Milichiidae) recovered from a human corpse in Malaysia.

    Science.gov (United States)

    Kumara, T K; Abu Hassan, A; Che Salmah, M R; Bhupinder, S

    2010-04-01

    The pupae of Desmometopa sp. (Diptera: Milichiidae) were collected from a human corpse found indoor in active decay stage together with the larvae of Sarcophagidae, Synthesiomyia nudiseta (Wulp), Chrysomya megacephala (Fabricius) and Chrysomya rufifacies (Macquart). This research note is the first report of the Desmometopa sp. recovered from a human corpse in Malaysia.

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

    Science.gov (United States)

    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

  19. First survey of forensically important insects from human corpses in Shiraz, Iran.

    Science.gov (United States)

    Moemenbellah-Fard, Mohammad D; Keshavarzi, Davood; Fereidooni, Mehran; Soltani, Aboozar

    2018-02-01

    The presence of insects on human cadavers has potential judicial value in medicolegal cases. This research emphasized the important role of insects in postmortem decomposition. It was conducted to investigate the composition and abundance of insects from human corpses during autopsies in legal medicine. It was implemented in the city of Shiraz, south Iran. Insects associated with human corpses were carefully collected and put into labelled vials. They were then identified using valid taxonomic keys. Fifteen outdoor (67%) and indoor discovered cadavers were examined. All but one was covered at the time of discovery. From these several species of entomofauna played important roles in the minimum postmortem interval (minPMI) estimate. Insects included the orders of Diptera and Coleoptera. Overall, 14 different species of arthropods were identified. Within Diptera, 2 families of Sarcophagidae and Calliphoridae were present in 73% of the cases with Calliphora vicina Robineau-Desvoidy and Chrysomya albiceps Wiedemann accounting for about half of the cases. The latter family members, Calliphoridae, were more frequently (52%) collected in autumn and winter. Only 4/15 outdoor cadavers had beetles. Four species of Coleopterans; namely Dermestes frischii Kugelann, Nitidula flavomaculata Rossi, Creophilus maxillosus Linnaeus and Saprinus chalcites Illiger; were recorded for the first time from 3 corpses in Iran. The presence and diversity of different insects on human corpses could contribute to the advancement of forensic entomology knowledge and the refined estimates of minPMI in medicolegal cases. Copyright © 2017. Published by Elsevier Ltd.

  20. Mutated CaV2.1 channels dysregulate CASK/P2X3 signaling in mouse trigeminal sensory neurons of R192Q Cacna1a knock-in mice.

    Science.gov (United States)

    Gnanasekaran, Aswini; Bele, Tanja; Hullugundi, Swathi; Simonetti, Manuela; Ferrari, Michael D; van den Maagdenberg, Arn M J M; Nistri, Andrea; Fabbretti, Elsa

    2013-12-02

    ATP-gated P2X3 receptors of sensory ganglion neurons are important transducers of pain as they adapt their expression and function in response to acute and chronic nociceptive signals. The present study investigated the role of calcium/calmodulin-dependent serine protein kinase (CASK) in controlling P2X3 receptor expression and function in trigeminal ganglia from Cacna1a R192Q-mutated knock-in (KI) mice, a genetic model for familial hemiplegic migraine type-1. KI ganglion neurons showed more abundant CASK/P2X3 receptor complex at membrane level, a result that likely originated from gain-of-function effects of R192Q-mutated CaV2.1 channels and downstream enhanced CaMKII activity. The selective CaV2.1 channel blocker ω-Agatoxin IVA and the CaMKII inhibitor KN-93 were sufficient to return CASK/P2X3 co-expression to WT levels. After CASK silencing, P2X3 receptor expression was decreased in both WT and KI ganglia, supporting the role of CASK in P2X3 receptor stabilization. This process was functionally observed as reduced P2X3 receptor currents. We propose that, in trigeminal sensory neurons, the CASK/P2X3 complex has a dynamic nature depending on intracellular calcium and related signaling, that are enhanced in a transgenic mouse model of genetic hemiplegic migraine.

  1. Contribution of large-sized primary sensory neuronal sensitization to mechanical allodynia by upregulation of hyperpolarization-activated cyclic nucleotide gated channels via cyclooxygenase 1 cascade.

    Science.gov (United States)

    Sun, Wei; Yang, Fei; Wang, Yan; Fu, Han; Yang, Yan; Li, Chun-Li; Wang, Xiao-Liang; Lin, Qing; Chen, Jun

    2017-02-01

    Under physiological state, small- and medium-sized dorsal root ganglia (DRG) neurons are believed to mediate nociceptive behavioral responses to painful stimuli. However, recently it has been found that a number of large-sized neurons are also involved in nociceptive transmission under neuropathic conditions. Nonetheless, the underlying mechanisms that large-sized DRG neurons mediate nociception are poorly understood. In the present study, the role of large-sized neurons in bee venom (BV)-induced mechanical allodynia and the underlying mechanisms were investigated. Behaviorally, it was found that mechanical allodynia was still evoked by BV injection in rats in which the transient receptor potential vanilloid 1-positive DRG neurons were chemically deleted. Electrophysiologically, in vitro patch clamp recordings of large-sized neurons showed hyperexcitability in these neurons. Interestingly, the firing pattern of these neurons was changed from phasic to tonic under BV-inflamed state. It has been suggested that hyperpolarization-activated cyclic nucleotide gated channels (HCN) expressed in large-sized DRG neurons contribute importantly to repeatedly firing. So we examined the roles of HCNs in BV-induced mechanical allodynia. Consistent with the overexpression of HCN1/2 detected by immunofluorescence, HCNs-mediated hyperpolarization activated cation current (I h ) was significantly increased in the BV treated samples. Pharmacological experiments demonstrated that the hyperexcitability and upregulation of I h in large-sized neurons were mediated by cyclooxygenase-1 (COX-1)-prostaglandin E2 pathway. This is evident by the fact that the COX-1 inhibitor significantly attenuated the BV-induced mechanical allodynia. These results suggest that BV can excite the large-sized DRG neurons at least in part by increasing I h through activation of COX-1. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. A Computational Model Based on Multi-Regional Calcium Imaging Represents the Spatio-Temporal Dynamics in a Caenorhabditis elegans Sensory Neuron.

    Directory of Open Access Journals (Sweden)

    Masahiro Kuramochi

    Full Text Available Due to the huge number of neuronal cells in the brain and their complex circuit formation, computer simulation of neuronal activity is indispensable to understanding whole brain dynamics. Recently, various computational models have been developed based on whole-brain calcium imaging data. However, these analyses monitor only the activity of neuronal cell bodies and treat the cells as point unit. This point-neuron model is inexpensive in computational costs, but the model is unrealistically simplistic at representing intact neural activities in the brain. Here, we describe a novel three-unit Ordinary Differential Equation (ODE model based on the neuronal responses derived from a Caenorhabditis elegans salt-sensing neuron. We recorded calcium responses in three regions of the ASER neuron using a simple downstep of NaCl concentration. Our simple ODE model generated from a single recording can adequately reproduce and predict the temporal responses of each part of the neuron to various types of NaCl concentration changes. Our strategy which combines a simple recording data and an ODE mathematical model may be extended to realistically understand whole brain dynamics by computational simulation.

  3. Searching the soil: forensic importance of edaphic fauna after the removal of a corpse.

    Science.gov (United States)

    Saloña, Marta I; Moraza, M Lourdes; Carles-Tolrá, Miguel; Iraola, Victor; Bahillo, Pablo; Yélamos, Tomás; Outerelo, Raimundo; Alcaraz, Rafael

    2010-11-01

    Arthropods at different stages of development collected from human remains in an advanced stage of decomposition (following autopsy) and from the soil at the scene are reported. The corpse was found in a mixed deciduous forest of Biscay (northern Spain). Soil fauna was extracted by sieving the soil where the corpse lay and placing the remains in Berlese-Tullgren funnels. Necrophagous fauna on the human remains was dominated by the fly Piophilidae: Stearibia nigriceps (Meigen, 1826), mites Ascidae: Proctolaelaps epuraeae (Hirschmann, 1963), Laelapidae: Hypoaspis (Gaeolaelaps) aculeifer (Canestrini, 1884), and the beetle Cleridae: Necrobia rufipes (de Geer, 1775). We confirm the importance of edaphic fauna, especially if the deceased is discovered in natural environs. Related fauna may remain for days after corpse removal and reveal information related to the circumstances of death. The species Nitidulidae: Omosita depressa (Linnaeus, 1758), Acaridae: Sancassania berlesei (Michael, 1903), Ascidae: Zerconopsis remiger (Kramer, 1876) and P. epuraeae, Urodinychidae: Uroobovella pulchella (Berlese, 1904), and Macrochelidae: Glyptholaspis americana (Berlese, 1888) were recorded for the first time in the Iberian Peninsula. 2010 American Academy of Forensic Sciences. Published 2010. This article is a U.S. Government work and is in the public domain in the U.S.A.

  4. Experimental measurement of flexion-extension movement in normal and corpse prosthetic elbow joint.

    Science.gov (United States)

    TarniŢă, Daniela; TarniŢă, DănuŢ Nicolae

    2016-01-01

    This paper presents a comparative experimental study of flexion-extension movement in healthy elbow and in the prosthetic elbow joint fixed on an original experimental bench. Measurements were carried out in order to validate the functional morphology and a new elbow prosthesis type ball head. The three-dimensional (3D) model and the physical prototype of our experimental bench used to test elbow endoprosthesis at flexion-extension and pronation-supination movements is presented. The measurements were carried out on a group of nine healthy subjects and on the prosthetic corpse elbow, the experimental data being obtained for flexion-extension movement cycles. Experimental data for the two different flexion-extension tests for the nine subjects and for the corpse prosthetic elbow were acquired using SimiMotion video system. Experimental data were processed statistically. The corresponding graphs were obtained for all subjects in the experimental group, and for corpse prosthetic elbow for both flexion-extension tests. The statistical analysis has proved that the flexion angles of healthy elbows were significantly close to the values measured at the prosthetic elbow fixed on the experimental bench. The studied elbow prosthesis manages to re-establish the mobility for the elbow joint as close to the normal one.

  5. The mechanism of functional up-regulation of P2X3 receptors of trigeminal sensory neurons in a genetic mouse model of familial hemiplegic migraine type 1 (FHM-1.

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    Swathi K Hullugundi

    Full Text Available A knock-in (KI mouse model of FHM-1 expressing the R192Q missense mutation of the Cacna1a gene coding for the α1 subunit of CaV2.1 channels shows, at the level of the trigeminal ganglion, selective functional up-regulation of ATP -gated P2X3 receptors of sensory neurons that convey nociceptive signals to the brainstem. Why P2X3 receptors are constitutively more responsive, however, remains unclear as their membrane expression and TRPV1 nociceptor activity are the same as in wildtype (WT neurons. Using primary cultures of WT or KI trigeminal ganglia, we investigated whether soluble compounds that may contribute to initiating (or maintaining migraine attacks, such as TNFα, CGRP, and BDNF, might be responsible for increasing P2X3 receptor responses. Exogenous application of TNFα potentiated P2X3 receptor-mediated currents of WT but not of KI neurons, most of which expressed both the P2X3 receptor and the TNFα receptor TNFR2. However, sustained TNFα neutralization failed to change WT or KI P2X3 receptor currents. This suggests that endogenous TNFα does not regulate P2X3 receptor responses. Nonetheless, on cultures made from both genotypes, exogenous TNFα enhanced TRPV1 receptor-mediated currents expressed by a few neurons, suggesting transient amplification of TRPV1 nociceptor responses. CGRP increased P2X3 receptor currents only in WT cultures, although prolonged CGRP receptor antagonism or BDNF neutralization reduced KI currents to WT levels. Our data suggest that, in KI trigeminal ganglion cultures, constitutive up-regulation of P2X3 receptors probably is already maximal and is apparently contributed by basal CGRP and BDNF levels, thereby rendering these neurons more responsive to extracellular ATP.

  6. Nerve growth factor alters microtubule targeting agent-induced neurotransmitter release but not MTA-induced neurite retraction in sensory neurons.

    Science.gov (United States)

    Pittman, Sherry K; Gracias, Neilia G; Fehrenbacher, Jill C

    2016-05-01

    Peripheral neuropathy is a dose-limiting side effect of anticancer treatment with the microtubule-targeted agents (MTAs), paclitaxel and epothilone B (EpoB); however, the mechanisms by which the MTAs alter neuronal function and morphology are unknown. We previously demonstrated that paclitaxel alters neuronal sensitivity, in vitro, in the presence of nerve growth factor (NGF). Evidence in the literature suggests that NGF may modulate the neurotoxic effects of paclitaxel. Here, we examine whether NGF modulates changes in neuronal sensitivity and morphology induced by paclitaxel and EpoB. Neuronal sensitivity was assessed using the stimulated release of calcitonin gene-related peptide (CGRP), whereas morphology of established neurites was evaluated using a high content screening system. Dorsal root ganglion cultures, maintained in the absence or presence of NGF, were treated from day 7 to day 12 in culture with paclitaxel (300nM) or EpoB (30nM). Following treatment, the release of CGRP was stimulated using capsaicin or high extracellular potassium. In the presence of NGF, EpoB mimicked the effects of paclitaxel: capsaicin-stimulated release was attenuated, potassium-stimulated release was slightly enhanced and the total peptide content was unchanged. In the absence of NGF, both paclitaxel and EpoB decreased capsaicin- and potassium-stimulated release and the total peptide content, suggesting that NGF may reverse MTA-induced hyposensitivity. Paclitaxel and EpoB both decreased neurite length and branching, and this attenuation was unaffected by NGF in the growth media. These differential effects of NGF on neuronal sensitivity and morphology suggest that neurite retraction is not a causative factor to alter neuronal sensitivity. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Functional Reintegration of Sensory Neurons and Transitional Dendritic Reduction of Mitral/Tufted Cells during Injury-Induced Recovery of the Larval Xenopus Olfactory Circuit

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    Sara J. Hawkins

    2017-11-01

    Full Text Available Understanding the mechanisms involved in maintaining lifelong neurogenesis has a clear biological and clinical interest. In the present study, we performed olfactory nerve transection on larval Xenopus to induce severe damage to the olfactory circuitry. We surveyed the timing of the degeneration, subsequent rewiring and functional regeneration of the olfactory system following injury. A range of structural labeling techniques and functional calcium imaging were performed on both tissue slices and whole brain preparations. Cell death of olfactory receptor neurons and proliferation of stem cells in the olfactory epithelium were immediately increased following lesion. New olfactory receptor neurons repopulated the olfactory epithelium and once again showed functional responses to natural odorants within 1 week after transection. Reinnervation of the olfactory bulb (OB by newly formed olfactory receptor neuron axons also began at this time. Additionally, we observed a temporary increase in cell death in the OB and a subsequent loss in OB volume. Mitral/tufted cells, the second order neurons of the olfactory system, largely survived, but transiently lost dendritic tuft complexity. The first odorant-induced responses in the OB were observed 3 weeks after nerve transection and the olfactory network showed signs of major recovery, both structurally and functionally, after 7 weeks.

  8. Outdoor post-mortem bite injuries by Tapinoma nigerrimum (Hymenoptera, Formicidae) on a human corpse: Case report.

    Science.gov (United States)

    Bonacci, Teresa; Vercillo, Vannio

    2015-07-01

    Ants are among the insects that colonize exposed human and animal corpses during the early stage of decomposition. In Calabria, Italy (as well as in other countries), Formicidae have been observed preying on immature stages of Diptera and other insects, as well as causing irregular scalloped areas of superficial skin loss on human corpses and animal carcasses. We present a case of injuries on a human corpse caused by ant feeding. The macroscopic appearance is described and the results of a histochemical investigation of the skin lesions caused by worker ants are reported for the first time. The investigation was carried out on the fresh corpse of a 53-year-old man discovered in a rural area of Cosenza province (Calabria, southern Italy). Numerous irregular areas of superficial skin loss caused by the ant Tapinoma nigerrimum (Nylander 1856) (Hymenoptera, Formicidae) were observed on the body surface, inflicted very early in the post-mortem period. Because the classification of lesions is of crucial importance for forensic investigations, the macroscopic appearance and distribution pattern of the lesions on the corpse are illustrated. The histochemical investigation of the damaged skin explains, for the first time, the mechanism of production of the lesions. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  9. [Entomologic fauna and its importance in the determination of the age of corpses].

    Science.gov (United States)

    Dolný, A; Loyka, S

    1993-04-01

    The authors summarize results of research conducted in 1990-1992, the aim of which was to test the accuracy of practical application of forensic entomology in medical practice. Based on the results of laboratory breeding of necrophagic Diptera collected from corpses and based on time characteristics of subsequent stages, the authors assessed the assumed time of death. In all instances where there was the first generation of necrophagic species of Diptera in the first and second stage of succession the results were very accurate, in the remaining cases the data of death was estimated correctly but less accurately.

  10. Origins, actions and dynamic expression patterns of the neuropeptide VGF in rat peripheral and central sensory neurones following peripheral nerve injury

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    Costigan Michael

    2008-12-01

    Full Text Available Abstract Background The role of the neurotrophin regulated polypeptide, VGF, has been investigated in a rat spared injury model of neuropathic pain. This peptide has been shown to be associated with synaptic strengthening and learning in the hippocampus and while it is known that VGFmRNA is upregulated in dorsal root ganglia following peripheral nerve injury, the role of this VGF peptide in neuropathic pain has yet to be investigated. Results Prolonged upregulation of VGF mRNA and protein was observed in injured dorsal root ganglion neurons, central terminals and their target dorsal horn neurons. Intrathecal application of TLQP-62, the C-terminal active portion of VGF (5–50 nmol to naïve rats caused a long-lasting mechanical and cold behavioral allodynia. Direct actions of 50 nM TLQP-62 upon dorsal horn neuron excitability was demonstrated in whole cell patch recordings in spinal cord slices and in receptive field analysis in intact, anesthetized rats where significant actions of VGF were upon spontaneous activity and cold evoked responses. Conclusion VGF expression is therefore highly modulated in nociceptive pathways following peripheral nerve injury and can cause dorsal horn cell excitation and behavioral hypersensitivity in naïve animals. Together the results point to a novel and powerful role for VGF in neuropathic pain.

  11. A checklist of arthropods associated with pig carrion and human corpses in Southeastern Brazil

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    LML Carvalho

    2000-01-01

    Full Text Available Necrophagous insects, mainly Diptera and Coleoptera, are attracted to specific stages of carcass decomposition, in a process of faunistic succession. They are very important in estimating the postmortem interval, the time interval between the death and the discovery of the body. In studies done with pig carcasses exposed to natural conditions in an urban forest (Santa Genebra Reservation, located in Campinas, State of São Paulo, southeastern Brazil, 4 out of 36 families of insects collected - Calliphoridae, Sarcophagidae, Muscidae (Diptera and Dermestidae (Coleoptera - were considered of forensic importance, because several species were collected in large numbers both visiting and breeding in pig carcasses. Several species were also observed and collected on human corpses at the Institute of Legal Medicine. The species belonged to 17 different families, 6 being of forensic importance because they were reared from human corpses or pig carcasses: Calliphoridae, Sarcophagidae, Muscidae, Piophilidae (Diptera, Dermestidae, Silphidae and Cleridae (Coleoptera. The most important species were: Diptera - Chrysomya albiceps, Chrysomya putoria, Hemilucilia segmentaria, Hemilucilia semidiaphana (Calliphoridae, Pattonella intermutans (Sarcophagidae, Ophyra chalcogaster (Muscidae, Piophila casei (Piophilidae; Coleoptera - Dermestes maculatus (Dermestidae, Oxyletrum disciolle (Silphidae and Necrobia rufipes (Cleridae.

  12. Media and Propaganda: The Northcliffe Press and the Corpse Factory Story of World War I

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    Randal Marlin

    2010-01-01

    Full Text Available Demonization of Germans was an early feature of British propaganda in World War I, with numerous atrocities reported in the Bryce Report, 1915. But in April, 1917, a particularly gripping, gruesome, and odium-inducing tale was given credence by the press of Lord Northcliffe, notably The Times and The Daily Mail.These papers seemed to provide convincing proof that the Germans boiled down corpses of their own soldiers for the purpose of producing useful products such as fats, bone meal, pig food and the like. The story is well known, but significant details have been obscured or misrepresented with regard to the way in which it came to be so widely believed. Our purpose here is to straighten out key elements of the record, based on archival findings, and to draw attention to the techniques employed to ensure widespread credence in this false tale. These techniques, and the principles behind their use, have recent and contemporary parallels, some of which are drawn in this paper. The Corpse Factory story succeeded in its goal, but may have made a lasting peace more difficult. Also, official repudiation of the story in 1925 encouraged later disbelief when early reports circulated about the Holocaust under Hitler, thus contributing to the early lack of response by nations asked to accept Jewish refugees.

  13. Hominin skeletal part abundances and claims of deliberate disposal of corpses in the Middle Pleistocene.

    Science.gov (United States)

    Egeland, Charles P; Domínguez-Rodrigo, Manuel; Pickering, Travis Rayne; Menter, Colin G; Heaton, Jason L

    2018-05-01

    Humans are set apart from other organisms by the realization of their own mortality. Thus, determining the prehistoric emergence of this capacity is of significant interest to understanding the uniqueness of the human animal. Tracing that capacity chronologically is possible through archaeological investigations that focus on physical markers that reflect "mortality salience." Among these markers is the deliberate and culturally mediated disposal of corpses. Some Neandertal bone assemblages are among the earliest reasonable claims for the deliberate disposal of hominins, but even these are vigorously debated. More dramatic assertions center on the Middle Pleistocene sites of Sima de los Huesos (SH, Spain) and the Dinaledi Chamber (DC, South Africa), where the remains of multiple hominin individuals were found in deep caves, and under reported taphonomic circumstances that seem to discount the possibility that nonhominin actors and processes contributed to their formation. These claims, with significant implications for charting the evolution of the "human condition," deserve scrutiny. We test these assertions through machine-learning analyses of hominin skeletal part representation in the SH and DC assemblages. Our results indicate that nonanthropogenic agents and abiotic processes cannot yet be ruled out as significant contributors to the ultimate condition of both collections. This finding does not falsify hypotheses of deliberate disposal for the SH and DC corpses, but does indicate that the data also support partially or completely nonanthropogenic formational histories.

  14. The sensory system acts with a neuromedin U signaling pathway to mediate food type-dependent effects on lifespan

    OpenAIRE

    Adilov, Bakhtiyor

    2010-01-01

    In order to survive, the animal uses its sensory system to interpret the complexity of its environment. Interestingly, a subset of sensory neurons, which function in taste or olfaction, has been found to influence the lifespan of C. elegans and Drosophila. Although the mechanisms by which these neurons affect lifespan are unknown, the nature of these neurons suggest that the sensory influence on lifespan is mediated by food-derived cues. This thesis shows that sensory neurons r...

  15. Positron emission tomography studies of neuronal activity patterns during sensory and cognitive stimulations in Alzheimer's disease. A study of cortical attention sites in man

    International Nuclear Information System (INIS)

    Johannsen, Peter

    1997-01-01

    This Ph.D.-thesis describes different subtypes of attention, models for the organization of attention, and the attention deficits in Alzheimer's disease. The experimental part of the study is based on studies of sustained and divided attention to two different sensory modalities; a visual checkerboard stimulation reversing at 7 Hz, and a 110 Hz vibrotactile stimulation of the right hand in a group of healthy elderly subjects (n = 16) age-matched with a group of patients with mild to moderate Alzheimer's disease (n = 16). The cortical activations during the attention tasks have been mapped using O-15-water and positron emission tomography (PET) measurements of regional cerebral blood flow (rCBF) during rest and during performance of an attention task. After anatomical standardization and averaging over subjects, activation foci were assessed by a t-statistical evaluation of the differences of rCBF maps acquired before and during the execution of the attention tasks. The rCBF deficits in the Alzheimer patients were compared to rCBF pattern in the healthy elderly and assessed statistically on a voxel-by-voxel basis, revealing a distinct and localized pattern of rCBF deficits extending from the hippocampal area along the longitudinal fascicle to the temporo-parietal cortices with further deficits in the frontal regions. The resting rCBF deficits are distributed with the same pattern as described in neuropathological studies of lesions in Alzheimer's disease. In the healthy elderly, both sustained and divided attention elicited activation of the right inferior parietal lobule (Brodmann Area 19/40) and the right middle frontal gyrus (Brodmann Area 46). Divided attention favored activation of the right middle frontal gyrus and sustained attention activation of the right inferior parietal lobule. Both the frontal and the parietal attention sites were active during attention to both the visual and the vibrotactile stimuli. These results support a network hypothesis of

  16. Positron emission tomography studies of neuronal activity patterns during sensory and cognitive stimulations in Alzheimer`s disease. A study of cortical attention sites in man

    Energy Technology Data Exchange (ETDEWEB)

    Johannsen, Peter

    1997-12-31

    This Ph.D.-thesis describes different subtypes of attention, models for the organization of attention, and the attention deficits in Alzheimer`s disease. The experimental part of the study is based on studies of sustained and divided attention to two different sensory modalities; a visual checkerboard stimulation reversing at 7 Hz, and a 110 Hz vibrotactile stimulation of the right hand in a group of healthy elderly subjects (n = 16) age-matched with a group of patients with mild to moderate Alzheimer`s disease (n = 16). The cortical activations during the attention tasks have been mapped using O-15-water and positron emission tomography (PET) measurements of regional cerebral blood flow (rCBF) during rest and during performance of an attention task. After anatomical standardization and averaging over subjects, activation foci were assessed by a t-statistical evaluation of the differences of rCBF maps acquired before and during the execution of the attention tasks. The rCBF deficits in the Alzheimer patients were compared to rCBF pattern in the healthy elderly and assessed statistically on a voxel-by-voxel basis, revealing a distinct and localized pattern of rCBF deficits extending from the hippocampal area along the longitudinal fascicle to the temporo-parietal cortices with further deficits in the frontal regions. The resting rCBF deficits are distributed with the same pattern as described in neuropathological studies of lesions in Alzheimer`s disease. In the healthy elderly, both sustained and divided attention elicited activation of the right inferior parietal lobule (Brodmann Area 19/40) and the right middle frontal gyrus (Brodmann Area 46). Divided attention favored activation of the right middle frontal gyrus and sustained attention activation of the right inferior parietal lobule. Both the frontal and the parietal attention sites were active during attention to both the visual and the vibrotactile stimuli. These results support a network hypothesis of

  17. Physically disconnected non-diffusible cell-to-cell communication between neuroblastoma SH-SY5Y and DRG primary sensory neurons.

    Science.gov (United States)

    Chaban, Victor V; Cho, Taehoon; Reid, Christopher B; Norris, Keith C

    2013-01-01

    Cell-cell communication occurs via a variety of mechanisms, including long distances (hormonal), short distances (paracrine and synaptic) or direct coupling via gap junctions, antigen presentation, or ligand-receptor interactions. We evaluated the possibility of neuro-hormonal independent, non-diffusible, physically disconnected pathways for cell-cell communication using dorsal root ganglion (DRG) neurons. We assessed intracellular calcium ([Ca(2+)]) in primary culture DRG neurons that express ATP-sensitive P2X3, capsaicinsensitive TRPV1 receptors modulated by estradiol. Physically disconnected (dish-in-dish system; inner chamber enclosed) mouse DRG were cultured for 12 hours near: a) media alone (control 1), b) mouse DRG (control 2), c) human neuroblastoma SHSY-5Y cells (cancer intervention), or d) mouse DRG treated with KCl (apoptosis intervention). Chemosensitive receptors [Ca(2+)](i) signaling did not differ between control 1 and 2. ATP (10 μM) and capsaicin (100nM) increased [Ca(2+)](i) transients to 425.86 + 49.5 nM, and 399.21 ± 44.5 nM, respectively. 17β-estradiol (100 nM) exposure reduced ATP (171.17 ± 48.9 nM) and capsaicin (175.01±34.8 nM) [Ca(2+)](i) transients. The presence of cancer cells reduced ATP- and capsaicin-induced [Ca(2+)](i) by >50% (pcommunication.

  18. The sympathetic and sensory innervation of rat airways: origin and neurochemical characterisation

    OpenAIRE

    Radtke, Anne

    2010-01-01

    Sensory and sympathetic innervation of Brown Norway rat airways were investigated using retrograde neuronal tracing with fluorescent dyes and double labelling immunofluorescence. Sensory neurons projecting to the lung are located in nodose and jugular vagal ganglia. Sympathetic neuronal supply of the lung originates in the stellate ganglia and superior cervical ganglia. Concerning immuno-reactivity for the SP and NOS in sensory and NPY and TH in sympathetic neurons were investigated. IR for S...

  19. ‘We Demand Dignity for the Victims’ – Reflections on the Legal Qualification of the Indecent Disposal of Corpses

    NARCIS (Netherlands)

    Fournet, Caroline; Siller, Nicole

    2015-01-01

    ‘We demand dignity for the victims’. Such was the pledge of the Dutch Minister of Foreign Affairs following the crash of Malaysia Airlines flight mh17 in rebel-held territory in eastern Ukraine and the looting of the corpses of the 298 victims. Although not an isolated instance, the indecent

  20. A multi-ingredient dietary supplement abolishes large-scale brain cell loss, improves sensory function, and prevents neuronal atrophy in aging mice.

    Science.gov (United States)

    Lemon, J A; Aksenov, V; Samigullina, R; Aksenov, S; Rodgers, W H; Rollo, C D; Boreham, D R

    2016-06-01

    Transgenic growth hormone mice (TGM) are a recognized model of accelerated aging with characteristics including chronic oxidative stress, reduced longevity, mitochondrial dysfunction, insulin resistance, muscle wasting, and elevated inflammatory processes. Growth hormone/IGF-1 activate the Target of Rapamycin known to promote aging. TGM particularly express severe cognitive decline. We previously reported that a multi-ingredient dietary supplement (MDS) designed to offset five mechanisms associated with aging extended longevity, ameliorated cognitive deterioration and significantly reduced age-related physical deterioration in both normal mice and TGM. Here we report that TGM lose more than 50% of cells in midbrain regions, including the cerebellum and olfactory bulb. This is comparable to severe Alzheimer's disease and likely explains their striking age-related cognitive impairment. We also demonstrate that the MDS completely abrogates this severe brain cell loss, reverses cognitive decline and augments sensory and motor function in aged mice. Additionally, histological examination of retinal structure revealed markers consistent with higher numbers of photoreceptor cells in aging and supplemented mice. We know of no other treatment with such efficacy, highlighting the potential for prevention or amelioration of human neuropathologies that are similarly associated with oxidative stress, inflammation and cellular dysfunction. Environ. Mol. Mutagen. 57:382-404, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. May Ingestion of Leachate from Decomposed Corpses Cause Appendicitis? A Case Report

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    Maurício Domingues-Ferreira

    2011-01-01

    Full Text Available The general consensus is that appendicitis is basically provoked by fecaliths or lymphoid hyperplasic obstruction. Several studies based on histological diagnosis have not confirmed this hypothesis. On the contrary, obstruction has been proved in only a minority of cases. Diverse infections by parasites, bacteria, fungus, and noninfective agents have been associated with appendicitis in the medical literature. We describe a firefighter, who ingested a small quantity of leachate from decomposing corpses while working and developed enteritis a few hours later, which lasted several days and evolved to appendicitis. This case raises the possibility that the high quantity of bacteria concentration present in the leachate could have provoked enteritis and the subsequent appendicitis due to a direct effect of the bacteria on the appendix.

  2. Homicides with corpse dismemberment in the material collected by the Department of Forensic Medicine, Krakow, Poland.

    Science.gov (United States)

    Konopka, Tomasz; Bolechała, Filip; Strona, Marcin; Kopacz, Paweł

    2016-01-01

    Aim of the study: To determine the circumstances which can be useful for offenders profiling in homicide cases with victim's body dismemberment. Material and methods: Study of all homicide cases with victim's corpse dismemberment examined in Krakow Department of Forensic Medicine over the last 50 years. Results: Within the past 50 years, a total number of 30 cases of homicides with dismembered bodies were examined in Krakow. 22 cases represent defensive mutilations performed by offender, 3 cases can be classified as offensive muti-lations and 3 cases represent aggressive mutilations - decapitation as a method of committing homicide. In this period the only 1 case of necrophilic mutilations was examined, when the body was dismembered without murder. In most cases the background of homicide was the family conflict, 6 was cause of mental illness of perpetrator and in 3 was sexual motive. Only in 3 cases (from 25 when the offender was known) perpetrator kill a stranger. In the other the offender belonged to the family or friends of the victim. In all cases where the perpetrator was determined, homicide and dismemberment was performed in his place of residence. The findings of the Police investigations indicate that in most cases homicides were not planned, occurred under the influence of emotion, only two have been previously scheduled. Conclusions: Homicides with corpses dismemberment usually are committed by offenders who is in close relationship with victim (family or friend). Dismemberment is almost always performed in the same place as murder - home of perpetrator. This type of homicide usually is not planned.

  3. Homicides with corpse dismemberment in the material collected by the Department of Forensic Medicine, Krakow, Poland

    Directory of Open Access Journals (Sweden)

    Tomasz Konopka

    2017-06-01

    Full Text Available Aim of the study : To determine the circumstances which can be useful for offenders profiling in homicide cases with victim’s body dismemberment. Material and methods: Study of all homicide cases with victim’s corpse dismemberment examined in Krakow Department of Forensic Medicine over the last 50 years. Results : Within the past 50 years, a total number of 30 cases of homicides with dismembered bodies were examined in Krakow. 22 cases represent defensive mutilations performed by offender, 3 cases can be classified as offensive muti­lations and 3 cases represent aggressive mutilations – decapitation as a method of committing homicide. In this period the only 1 case of necrophilic mutilations was examined, when the body was dismembered without murder. In most cases the background of homicide was the family conflict, 6 was cause of mental illness of perpetrator and in 3 was sexual motive. Only in 3 cases (from 25 when the offender was known perpetrator kill a stranger. In the other the offender belonged to the family or friends of the victim. In all cases where the perpetrator was determined, homicide and dismemberment was performed in his place of residence. The findings of the Police investigations indicate that in most cases homicides were not planned, occurred under the influence of emotion, only two have been previously scheduled. Conclusions : Homicides with corpses dismemberment usually are committed by offenders who is in close relationship with victim (family or friend. Dismemberment is almost always performed in the same place as murder – home of perpetrator. This type of homicide usually is not planned.

  4. Sensory modulation disorders in childhood epilepsy.

    Science.gov (United States)

    van Campen, Jolien S; Jansen, Floor E; Kleinrensink, Nienke J; Joëls, Marian; Braun, Kees Pj; Bruining, Hilgo

    2015-01-01

    Altered sensory sensitivity is generally linked to seizure-susceptibility in childhood epilepsy but may also be associated to the highly prevalent problems in behavioral adaptation. This association is further suggested by the frequent overlap of childhood epilepsy with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), conditions in which altered behavioral responses to sensory stimuli have been firmly established. A continuum of sensory processing defects due to imbalanced neuronal inhibition and excitation across these disorders has been hypothesizedthat may lead to common symptoms of inadequate modulation of behavioral responses to sensory stimuli. Here, we investigated the prevalence of sensory modulation disorders among children with epilepsy and their relation with symptomatology of neurodevelopmental disorders. We used the Sensory Profile questionnaire to assess behavioral responses to sensory stimuli and categorize sensory modulation disorders in children with active epilepsy (aged 4-17 years). We related these outcomes to epilepsy characteristics and tested their association with comorbid symptoms of ASD (Social Responsiveness Scale) and ADHD (Strengths and Difficulties Questionnaire). Sensory modulation disorders were reported in 49 % of the 158 children. Children with epilepsy reported increased behavioral responses associated with sensory "sensitivity," "sensory avoidance," and "poor registration" but not "sensory seeking." Comorbidity of ASD and ADHD was associated with more severe sensory modulation problems, although 27 % of typically developing children with epilepsy also reported a sensory modulation disorder. Sensory modulation disorders are an under-recognized problem in children with epilepsy. The extent of the modulation difficulties indicates a substantial burden on daily functioning and may explain an important part of the behavioral distress associated with childhood epilepsy.

  5. [Biometric method for the description of the head of an unrecognized corpse for the purpose of personality individualization and identification].

    Science.gov (United States)

    Zviagin, V N; Galitskaia, O I; Negasheva, M A

    2012-01-01

    We have determined absolute dimensions of the head and the relationship between the dimensions of its selected parts. The study enrolled adult subjects (mostly of Russian ethnicity) at the age from 17 to 22 years (1108 men and 1153 women). We calculated the normal values for the estimation of real dimensional characteristics and the frequency of their occurrence in the population. The proposed approach makes it possible to reliably identify the dimensional features of human appearance in terms of the quantitative verbal description (categories 1-5) and to reveal its most characteristic features. The results of this biometric study of the heads of unrecognized corpses obtained by the specially developed technology may be used in operational and search investigations, in the procedure of corpse identification, and forensic medical personality identification of a missing subject.

  6. Genes for hereditary sensory and autonomic neuropathies : a genotype-phenotype correlation

    NARCIS (Netherlands)

    Rotthier, Annelies; Baets, Jonathan; De Vriendt, Els; Jacobs, An; Auer-Grumbach, Michaela; Levy, Nicolas; Bonello-Palot, Nathalie; Kilic, Sara Sebnem; Weis, Joachim; Nascimento, Andres; Swinkels, Marielle; Kruyt, Moyo C.; Jordanova, Albena; De Jonghe, Peter; Timmerman, Vincent

    2009-01-01

    Hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders characterized by axonal atrophy and degeneration, exclusively or predominantly affecting the sensory and autonomic neurons. So far, disease-associated mutations have been identified in seven

  7. ASIC3 channels in multimodal sensory perception.

    Science.gov (United States)

    Li, Wei-Guang; Xu, Tian-Le

    2011-01-19

    Acid-sensing ion channels (ASICs), which are members of the sodium-selective cation channels belonging to the epithelial sodium channel/degenerin (ENaC/DEG) family, act as membrane-bound receptors for extracellular protons as well as nonproton ligands. At least five ASIC subunits have been identified in mammalian neurons, which form both homotrimeric and heterotrimeric channels. The highly proton sensitive ASIC3 channels are predominantly distributed in peripheral sensory neurons, correlating with their roles in multimodal sensory perception, including nociception, mechanosensation, and chemosensation. Different from other ASIC subunit composing ion channels, ASIC3 channels can mediate a sustained window current in response to mild extracellular acidosis (pH 7.3-6.7), which often occurs accompanied by many sensory stimuli. Furthermore, recent evidence indicates that the sustained component of ASIC3 currents can be enhanced by nonproton ligands including the endogenous metabolite agmatine. In this review, we first summarize the growing body of evidence for the involvement of ASIC3 channels in multimodal sensory perception and then discuss the potential mechanisms underlying ASIC3 activation and mediation of sensory perception, with a special emphasis on its role in nociception. We conclude that ASIC3 activation and modulation by diverse sensory stimuli represent a new avenue for understanding the role of ASIC3 channels in sensory perception. Furthermore, the emerging implications of ASIC3 channels in multiple sensory dysfunctions including nociception allow the development of new pharmacotherapy.

  8. Economic, human and environmental health benefits of replacing formaldehyde in the preservation of corpses.

    Science.gov (United States)

    Rocha Ferreira, Jussara; Cardoso Rezende, Lorenna; Barbosa, Abel De Souza; De Carvalho, Phellip; De Lima, Natácia Evangelista; Assis Carvalho, Alexandre

    2017-11-01

    Formaldehyde has been prominent in preserving biological tissues since the nineteenth century. Despite being admittedly harmful to health and to the environment, it is still widely used. The Morphology Department of the University of Brasília - Brazil, applied the rethink, reduce, reuse, recycle and responsibility methodology to their activities in an effort to protect the health of laboratory workers and users, save resources and reduce damage to the environment. Here we evaluate the results obtained a decade after the implementation of this proposal (2005-2015). Formaldehyde was replaced by alcohol and glycerol solutions in corpse conservation. Over five thousand dollars in public funds that would have been destined to buying preserving substances were saved annually, and over a hundred thousand liters of water that would have been contaminated and thrown into the sewage system were spared. The environment used to implement the study was improved and anatomical parts kept for study had their lifespan extended. It is noteworthy that such simple adjustments could cause pronounced changes in laboratory activities. We would avoid contaminating billions of liters of water and it would be possible to save millions if similar practices were implemented in all educational institutions having similar routines. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Radioiodine Therapy: Care of the Helpless Patient and Handling of the Radioactive Corpse

    International Nuclear Information System (INIS)

    Geaves, C. D.; Tendale, W. B.

    2016-01-01

    Nurses caring for a helpless patient following a nominal 800 MBq administration of radioiodine were concerned about their radiation dose. Using published data, a nurse could receive an estimated 650 micro Sv per shift. A regime to restrict their dose was planned using a 500 micro Sv dose constraint. Thermoluminescent dosimeters indicated a maximum whole body effective dose of 250 micro Sv. Three days post 131 I administration the patient died (estimated activity in the body 400 MBq). A minimum delay of two weeks was advised prior to a post-mortem. Special precautions were issued to minimise contamination. Dose rates (micro Sv h-1), measured one day after the patient died, at the level of the thyroid, chest and bladder at 0.01 m from the corpse were 1800, 290 and 73 respectively. At 1.0 m the dose rate was 26 micro Sv h-1 at all levels. The pathologist was estimated to have received a maximum whole-body dose of 400 micro Sv during the postmortem. Contamination measurements (Bq cm-2) made following the postmortem were as follows: pathologist's hands 5, clothes 0, towels 1.8, saw 5, instruments 0.5, plastic sheet 0.8, scales 0.4 and floors/walls 1.1. These data indicate that with appropriate radiation protection guidelines, staff can be reassured that their doses in these circumstances are very low. (author)

  10. Fabrication of nonfouling, bactericidal, and bacteria corpse release multifunctional surface through surface-initiated RAFT polymerization.

    Science.gov (United States)

    Wang, Bailiang; Ye, Zi; Tang, Yihong; Han, Yuemei; Lin, Quankui; Liu, Huihua; Chen, Hao; Nan, Kaihui

    Infections after surgery or endophthalmitis are potentially blinding complications caused by bacterial adhesion and subsequent biofilm formation on the intraocular lens. Neither single-function anti-adhesion surface nor contacting killing surface can exhibit ideal antibacterial function. In this work, a novel (2-(dimethylamino)-ethyl methacrylate- co -2-methacryloyloxyethyl phosphorylcholine) (p (DMAEMA- co -MPC)) brush was synthesized by "grafting from" method through reversible-addition fragmentation chain transfer polymerization. 1-Bromoheptane was used to quaternize the p (DMAEMA- co -MPC) brush coating and to endow the surface with bactericidal function. The success of the surface functionalization was confirmed by atomic force microscopy, water contact angle, and spectroscopic ellipsometry. The quaternary ammonium salt units were employed as efficient disinfection that can eliminate bacteria through contact killing, whereas the 2-methacryloyloxyethyl phosphorylcholine units were introduced to suppress unwanted nonspecific adsorption. The functionalized poly(dimethyl siloxane) surfaces showed efficiency in reducing bovine serum albumin adsorption and in inhibiting bacteria adhesion and biofilm formation. The copolymer brushes also demonstrated excellent bactericidal function against gram-positive ( Staphylococcus aureus ) bacteria measured by bacteria live/dead staining and shake-flask culture methods. The surface biocompatibility was evaluated by morphology and activity measurement with human lens epithelial cells in vitro. The achievement of the p (DMAEMA + - co -MPC) copolymer brush coating with nonfouling, bactericidal, and bacteria corpse release properties can be used to modify intraocular lenses.

  11. Corpses of Metaphor. Images of Death in David Leavitt and Jamaica Kincaid

    Directory of Open Access Journals (Sweden)

    Fiorenzo Iuliano

    2010-10-01

    Full Text Available This essay analyzes two works, My Brother by Jamaica Kincaid, and "Saturn Street" by David Leavitt, investigating the construction of homosexuality as a process accomplished by resorting to illness (AIDS and death. In both works, indeed, the slow and dramatic course of AIDS amounts to the progressive unveiling of homosexuality as a social threat or a cause of anxiety and repulsion. The two works are set in different contexts: whereas Jamaica Kincaid refers to the problematic situation of homosexuality in the Caribbean, David Leavitt explores the social and cultural scenario of the 1990s Los Angeles, in the wake of a by now ended utopian confidence in science and technology.  This comparative approach helps us understand the political dynamics through which, in different and, to some extents, opposite realities, the social stigma of AIDS worked as a means to construct homosexual identity and set it apart from the sanitized spectrum of normal and sanctioned sexual behaviors. The point I want to make in this essay is that the corpse is used as an effective metaphor for a dehumanized depiction of male homosexual and ill subjects.

  12. Quality improvement of fingerprints of decayed corpses by local thanatopractical processing (Thanatoprint

    Directory of Open Access Journals (Sweden)

    Gahr, Britta

    2013-11-01

    Full Text Available Thanatopractical processing allows morphological reconstruction of even advanced decayed bodies. By extracting fluids from the body’s tissue antemortem tenseness and volume can be restored. If bodies are partly subject to thanatopractical processing in the hand region (“Thanatoprint”, fingerprints of high quality can be gathered even in cases of advanced decay. Without this treatment fingerprinting can be extremely difficult, if not impossible. Thanatopractical processing could be applied successfully in cases of partial to subtotal detachment of the epidermis as well. In an interdisciplinary study 400 fingerprints of bodies in various states of decay were examined after application of Thanatoprint. In 76.75% fingerprints were applicable for data entry into AFIS (Automated Fingerprint Identification System; another 11.00% of the fingerprints could be used for the process of non-elimination. Further advantages of the method are low invasivity while maintaining the integrity of the corpse, less time- and material requirement as well as its long-lasting effect.

  13. Distinction among the puparia of three blowfly species (Diptera: Calliphoridae frequently found on unburied corpses

    Directory of Open Access Journals (Sweden)

    JA Amorim

    2001-08-01

    Full Text Available Calliphorid larvae are important in the decomposition of carrion. Since these larvae are present in the primary stages of succession on carcasses, they may be important indicators of death time and the movement of corpses in homicide investigations. In this study we examined the morphological differences among puparia of Chrysomya megacephala, C. putoria and Cochliomyia macellaria. Puparia of the three species (N=30, each were obtained from the F2 generation bred in culture medium at 25° C, and 60% relative humidity on a 12 h photoperiod. The interspecific differences found were related to the conspicuousness of six tubercles located in the region near the posterior spiracles and to the distance between the two peritrema involving the spiracles. The latter were (mean ± SD 15.2 ± 3.1 mum for C. megacephala, 18.8 ± 2.8 mum for C. putoria and 16.5 ± 3.5 mum for C. macellaria. The results of the present study may be useful in forensic entomology.

  14. Cultures of death and politics of corpse supply: anatomy in Vienna, 1848-1914.

    Science.gov (United States)

    Buklijas, Tatjana

    2008-01-01

    Nineteenth-century Vienna is well known to medical historians as a leading center of medical research and education, offering easy access to patients and corpses to students from all over the world. The author seeks to explain how this enviable supply of cadavers was achieved, why it provoked so little opposition at a time when Britain and the United States saw widespread protests against dissection, and how it was threatened from mid-century onward. To understand permissive Viennese attitudes, we need to place them in a longue durée history of death and dissection and to pay close attention to the city's political geography as it was transformed into a major imperial capital. The tolerant stance of the Roman Catholic Church, strong links to Southern Europe, and the weak position of individuals in the absolutist state all contributed to an idiosyncratic anatomical culture. But as the fame of the Vienna medical school peaked in the later 1800s, the increased demand created by rising numbers of students combined with intensified interdisciplinary competition to produce a shortfall that professors found increasingly difficult to meet. Around 1900, new religious groups and mass political parties challenged long-standing anatomical practice by refusing to supply cadavers and making dissection into an instrument of political struggle. This study of the material preconditions for anatomy at one of Europe's most influential medical schools provides a contrast to the dominant Anglo-American histories of death and dissection.

  15. Sensory optimization by stochastic tuning.

    Science.gov (United States)

    Jurica, Peter; Gepshtein, Sergei; Tyukin, Ivan; van Leeuwen, Cees

    2013-10-01

    Individually, visual neurons are each selective for several aspects of stimulation, such as stimulus location, frequency content, and speed. Collectively, the neurons implement the visual system's preferential sensitivity to some stimuli over others, manifested in behavioral sensitivity functions. We ask how the individual neurons are coordinated to optimize visual sensitivity. We model synaptic plasticity in a generic neural circuit and find that stochastic changes in strengths of synaptic connections entail fluctuations in parameters of neural receptive fields. The fluctuations correlate with uncertainty of sensory measurement in individual neurons: The higher the uncertainty the larger the amplitude of fluctuation. We show that this simple relationship is sufficient for the stochastic fluctuations to steer sensitivities of neurons toward a characteristic distribution, from which follows a sensitivity function observed in human psychophysics and which is predicted by a theory of optimal allocation of receptive fields. The optimal allocation arises in our simulations without supervision or feedback about system performance and independently of coupling between neurons, making the system highly adaptive and sensitive to prevailing stimulation. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  16. Fabrication of nonfouling, bactericidal, and bacteria corpse release multifunctional surface through surface-initiated RAFT polymerization

    Directory of Open Access Journals (Sweden)

    Wang B

    2016-12-01

    bacteria corpse release properties can be used to modify intraocular lenses. Keywords: anti-fouling, poly(dimethylsiloxane, intraocular lenses, endophthalmitis, biofilms

  17. Emerging Role of Sensory Perception in Aging and Metabolism.

    Science.gov (United States)

    Riera, Celine E; Dillin, Andrew

    2016-05-01

    Sensory perception comprises gustatory (taste) and olfactory (smell) modalities as well as somatosensory (pain, heat, and tactile mechanosensory) inputs, which are detected by a multitude of sensory receptors. These sensory receptors are contained in specialized ciliated neurons where they detect changes in environmental conditions and participate in behavioral decisions ranging from food choice to avoiding harmful conditions, thus insuring basic survival in metazoans. Recent genetic studies, however, indicate that sensory perception plays additional physiological functions, notably influencing energy homeostatic processes and longevity through neuronal circuits originating from sensory tissues. Here we review how these findings are redefining metabolic signaling and establish a prominent role of sensory neuroendocrine processes in controlling health span and lifespan, with a goal of translating this knowledge towards managing age-associated diseases. Copyright © 2016. Published by Elsevier Ltd.

  18. First contribution of mites (Acari) to the forensic analysis of hanged corpses: a case study from Spain.

    Science.gov (United States)

    Saloña-Bordas, Marta I; Perotti, M Alejandra

    2014-11-01

    This case study from North Spain, highlights the importance of the collection of mites in addition to insects, from crime scenes or corpses subjected to environmental constraints that reduce or minimise insect activity, such as hanged corpses. In addition, this analysis highlights the relevance of arthropods' collection in the field, even after the corpse has been moved away for autopsy. Four species of mites, phoretic on carrion (Silphidae) and rove (Staphylinidae) beetles, complemented and reinforced the autopsy analysis as well as the scarce information provided by insect activity. Poecilochirus carabi Canestrini & Canestrini, 1882 and Poecilochirus (Physoparasitus) davydovae Hyatt, 1980 (Mesostigmata: Parasitidae) were found in association with two Silphidae, Nicrophorus Fabricius, 1775 and Necrodes Leach, 1815, only when sampled in the autopsy room; this is suggestive of host-switching of mites and was likely due to the lack of availability of specific carriers in the field. The interpretation of the activity of Parasitidae mites both in the field and the autopsy room allows a better understanding of the timing and circumstances of decomposition. Phoretic deutonymphs of Pelzneria Scheucher 1957 (Astigmata: Histiostomatidae) were highly abundant, mostly P. crenulata Oudemans, 1909 and are reported for the first time on a Staphylinidae rove beetle, Creophilus maxillosus (L., 1758). Surprisingly, in this case study no Pelzneria were associated with the Silphidae found, which are their most common hosts, such as Necrodes littoralis (L., 1758) and Nicrophorus interruptus (Stephens, 1830). All histiostomatids were removed from the staphylinid (rove beetle) collected from the soil, at the scene of death, suggesting a recent arrival of the beetle. The occurrence of Staphylinidae beetles and their associated mites, such as Parasitidae and Pelzneria, and the information they provided would have been easily overlooked or lost if only the autopsy sampling would have been

  19. Psychological Stress In First Year Medical Students In Response To The Dissection Of A Human Corpse

    Science.gov (United States)

    Bernhardt, Veronika; Rothkötter, Hermann Josef; Kasten, Erich

    2012-01-01

    the confrontation with corpses. Furthermore, personality tests were shown to be only partly reliable for selecting affected people in advance. With regard to these results capabilities to provide support to the first year medical students should be discussed. PMID:22403597

  20. The synaptic pharmacology underlying sensory processing in the superior colliculus.

    Science.gov (United States)

    Binns, K E

    1999-10-01

    The superior colliculus (SC) is one of the most ancient regions of the vertebrate central sensory system. In this hub afferents from several sensory pathways converge, and an extensive range of neural circuits enable primary sensory processing, multi-sensory integration and the generation of motor commands for orientation behaviours. The SC has a laminar structure and is usually considered in two parts; the superficial visual layers and the deep multi-modal/motor layers. Neurones in the superficial layers integrate visual information from the retina, cortex and other sources, while the deep layers draw together data from many cortical and sub-cortical sensory areas, including the superficial layers, to generate motor commands. Functional studies in anaesthetized subjects and in slice preparations have used pharmacological tools to probe some of the SC's interacting circuits. The studies reviewed here reveal important roles for ionotropic glutamate receptors in the mediation of sensory inputs to the SC and in transmission between the superficial and deep layers. N-methyl-D-aspartate receptors appear to have special responsibility for the temporal matching of retinal and cortical activity in the superficial layers and for the integration of multiple sensory data-streams in the deep layers. Sensory responses are shaped by intrinsic inhibitory mechanisms mediated by GABA(A) and GABA(B) receptors and influenced by nicotinic acetylcholine receptors. These sensory and motor-command activities of SC neurones are modulated by levels of arousal through extrinsic connections containing GABA, serotonin and other transmitters. It is possible to naturally stimulate many of the SC's sensory and non-sensory inputs either independently or simultaneously and this brain area is an ideal location in which to study: (a) interactions between inputs from the same sensory system; (b) the integration of inputs from several sensory systems; and (c) the influence of non-sensory systems on

  1. Neuronal involvement in cisplatin neuropathy

    DEFF Research Database (Denmark)

    Krarup-Hansen, A; Helweg-Larsen, Susanne Elisabeth; Schmalbruch, H

    2007-01-01

    of large dorsal root ganglion cells. Motor conduction studies, autonomic function and warm and cold temperature sensation remained unchanged at all doses of cisplatin treatment. The results of these studies are consistent with degeneration of large sensory neurons whereas there was no evidence of distal......Although it is well known that cisplatin causes a sensory neuropathy, the primary site of involvement is not established. The clinical symptoms localized in a stocking-glove distribution may be explained by a length dependent neuronopathy or by a distal axonopathy. To study whether the whole neuron...

  2. Desynchronizing electrical and sensory coordinated reset neuromodulation.

    Science.gov (United States)

    Popovych, Oleksandr V; Tass, Peter A

    2012-01-01

    Coordinated reset (CR) stimulation is a desynchronizing stimulation technique based on timely coordinated phase resets of sub-populations of a synchronized neuronal ensemble. It has initially been computationally developed for electrical deep brain stimulation (DBS), to enable an effective desynchronization and unlearning of pathological synchrony and connectivity (anti-kindling). Here we computationally show for ensembles of spiking and bursting model neurons interacting via excitatory and inhibitory adaptive synapses that a phase reset of neuronal populations as well as a desynchronization and an anti-kindling can robustly be achieved by direct electrical stimulation or indirect (synaptically-mediated) excitatory and inhibitory stimulation. Our findings are relevant for DBS as well as for sensory stimulation in neurological disorders characterized by pathological neuronal synchrony. Based on the obtained results, we may expect that the local effects in the vicinity of a depth electrode (realized by direct stimulation of the neurons' somata or stimulation of axon terminals) and the non-local CR effects (realized by stimulation of excitatory or inhibitory efferent fibers) of deep brain CR neuromodulation may be similar or even identical. Furthermore, our results indicate that an effective desynchronization and anti-kindling can even be achieved by non-invasive, sensory CR neuromodulation. We discuss the concept of sensory CR neuromodulation in the context of neurological disorders.

  3. European Council of Legal Medicine (ECLM) principles for on-site forensic and medico-legal scene and corpse investigation.

    Science.gov (United States)

    Cusack, D; Ferrara, S D; Keller, E; Ludes, B; Mangin, P; Väli, M; Vieira, N

    2017-07-01

    Forensic medical practitioners need to define the general principles governing procedures to be used for the on-site examination of a body where the death has occurred in unnatural, violent or suspicious circumstances. These principles should be followed whenever a medical expert is required to perform an on-site corpse inspection and should be utilised as a set of general guidelines to be adapted to the specific situation in hand and interpreted using common sense and scientific knowledge of the relevant procedures and facts of the case. The aim of these principles is to ensure that forensic evidence at the scene of a death is properly observed and assessed and all necessary relevant evidence gathered in order to ensure that a comprehensive report is available to the judicial authority (investigating judge or coroner) in the justice system. The on-site corpse inspection by a forensic practitioner is a mandatory and essential stage of the forensic and medico-legal autopsy, as it may provide important information for subsequent investigation stages.

  4. Processing of Sensory Information in the Olfactory System

    DEFF Research Database (Denmark)

    The olfactory system is an attractive model system due to the easy control of sensory input and the experimental accessibility in animal studies. The odorant signals are processed from receptor neurons to a neural network of mitral and granular cells while various types of nonlinear behaviour can...... and equation-free techniques allow for a better reproduction and understanding of recent experimental findings. Talks: Olfaction as a Model System for Sensory-Processing Neural Networks (Jens Midtgaard, University of Copenhagen, Denmark) Nonlinear Effects of Signal Transduction in Olfactory Sensory Neurons...

  5. [Biometric ranging of the corpses destroyed at the site of a catastrophe in terms of gender, longitudinal and circumferencial dimensions, and the degree of subcutaneous fat distribution].

    Science.gov (United States)

    Zviagin, V N; Galitskaia, O I; Negasheva, M A

    2012-01-01

    The quantitative criteria for biometric ranging of destroyed corpses in terms of anatomical localization, gender, longitudinal length, trunk circumference, and the folds of subcutaneous fat are proposed. The wealth of anthropometric materials obtained in the studies of various Caucasoid populations was used to calculate the normative tables for biometric ranging of the decomposed corpses. The proposed technology excludes the subjective assessments for the purpose of such classification at the sites of catastrophes. Moreover, it promotes the accumulation of the variety of valuable information, such as the size of the collar, headwear, and footwear, clothing size and height, and portrait features, that can be used for victim identification.

  6. Crocodylians evolved scattered multi-sensory micro-organs

    Science.gov (United States)

    2013-01-01

    Background During their evolution towards a complete life cycle on land, stem reptiles developed both an impermeable multi-layered keratinized epidermis and skin appendages (scales) providing mechanical, thermal, and chemical protection. Previous studies have demonstrated that, despite the presence of a particularly armored skin, crocodylians have exquisite mechanosensory abilities thanks to the presence of small integumentary sensory organs (ISOs) distributed on postcranial and/or cranial scales. Results Here, we analyze and compare the structure, innervation, embryonic morphogenesis and sensory functions of postcranial, cranial, and lingual sensory organs of the Nile crocodile (Crocodylus niloticus) and the spectacled caiman (Caiman crocodilus). Our molecular analyses indicate that sensory neurons of crocodylian ISOs express a large repertoire of transduction channels involved in mechano-, thermo-, and chemosensory functions, and our electrophysiological analyses confirm that each ISO exhibits a combined sensitivity to mechanical, thermal and pH stimuli (but not hyper-osmotic salinity), making them remarkable multi-sensorial micro-organs with no equivalent in the sensory systems of other vertebrate lineages. We also show that ISOs all exhibit similar morphologies and modes of development, despite forming at different stages of scale morphogenesis across the body. Conclusions The ancestral vertebrate diffused sensory system of the skin was transformed in the crocodylian lineages into an array of discrete multi-sensory micro-organs innervated by multiple pools of sensory neurons. This discretization of skin sensory expression sites is unique among vertebrates and allowed crocodylians to develop a highly-armored, but very sensitive, skin. PMID:23819918

  7. Analysis of the symmetric configuration of the circle of Willis in a series of autopsied corpses.

    Science.gov (United States)

    Stojanović, Nebojga; Stefanović, Ivica; Kostić, Aleksandar; Radisavejević, Misa; Stojanov, Dragan; Petrović, Sladjana

    2015-04-01

    The forming of the blood vessels network configuration at the base of the brain and interconnecting of blood vessels during the embryogenesis is directly related to the phylogenetic development of the brain and brain structures. A blood vessel configuration at the brain base, in the form of a ring or a hexagon, stands in direct relation to the perfusion needs of certain parts of the brain during its primary differentiation. The aim of this paper was to determine the incidence of certain blood vessel configurations at the base of the brain and understanding their symmetry or asymmetry. Analysis of the blood vessels at the base of the brain was performed on the autopsied subjects. The object of observation was the anterior segment of the circle of Willis consisting of C1- a. carotis interna (ICA), above a. communicaus posterior (PcoA), the segment A1 a. cerebri anterior (ACA) from a. carotis interna bifurcation to the a. communicans anterior (AcoA) and a communicans anterior itself, as well as the posterior segment consisting of PcoA and the segment P1--a. cerebri posterior (PCA) from the a. basilaris bifurcation to the PcoA. For the purpose of grouping the findings, the four basic configuration types of the circle of Willis were identified based on its symmetry or asymmetry. Type-A (symmetric circle of Willis), type-B (asymmetric circle of Willis' due to the unilateral hypoplastic A1-ACA); type-C (symmetric circle of Willis with bilateral symmetric changes on PcoA) and type-D (asymmetric circle of Willis due to the asymmetric changes on PcoA). Autosy was performed on 56 corpses. A total of 41 (73.2%) subjects were recorded with a symmetric configuration of the circle of Willis', of which 27 (48.2%) subjects had type A and 14 (25%) type C. The asymmetric configuration was present in 15 (26.8%) subjects, of whom 9 (16%) had type B and 6 (10.8%) subjects, of whom 9 (16%) had type B and 6 (10.8%) type D. The symmetric Willis group (73.2%) did not have a homogeneous

  8. Analysis of the symmetric configuration of the circle of Willis in a series of autopsied corpses

    Directory of Open Access Journals (Sweden)

    Stojanović Nebojša

    2015-01-01

    Full Text Available Introduction. The forming of the blood vessels network configuration at the base of the brain and interconnecting of blood vessels during the embryogenesis is directly related to the phylogenetic development of the brain and brain structures. A blood vessel configuration at the brain base, in the form of a ring or a hexagon, stands in direct relation to the perfusion needs of certain parts of the brain during its primary differentiation. The aim of this paper was to determine the incidence of certain blood vessel configurations at the base of the brain and understanding their symmetry or asymmetry. Methods. Analysis of the blood vessels at the base of the brain was performed on the autopsied subjects. The object of observation was the anterior segment of the circle of Willis consisting of C1- a. carotis interna (ICA, above a. communicaus posterior (PcoA, the segment A1 a. cerebri anterior (ACA from a. carotis interna bifurcation to the a. communicans anterior (AcoA and a. communicans anterior itself, as well as the posterior segment consisting of PcoA and the segment P1 - a. cerebri posterior (PCA from the a. basilaris bifurcation to the PcoA. For the purpose of grouping the findings, the four basic configuration types of the circle of Willis were identified based on its symmetry or asymmetry. Type-A (symmetric circle of Willis, type-B (asymmetric circle of Willis' due to the unilateral hypoplastic A1-ACA; type-C (symmetric circle of Willis with bilateral symmetric changes on PcoA and type-D (asymmetric circle of Willis due to the asymmetric changes on PcoA. Results. Autopsy was performed on 56 corpses. A total of 41 (73.2% subjects were recorded with a symmetric configuration of the circle of Willis', of which 27 (48.2% subjects had type A and 14 (25% type C. The asymmetric configuration was present in 15 (26.8% subjects, of whom 9 (16% had type B and 6 (10.8% type D. The symmetric Willis group (73.2% did not have a homogeneous finding that

  9. [Practicability of the mobile one-finger scanner Cross Match MV5 in fingerprinting of corpses: are mobile fingerprinting scanners suitable for use in mass disasters?].

    Science.gov (United States)

    Breitmeier, Dirk; Landmesser, Britta; Schulz, Yvonne; Albrecht, Knut

    2008-01-01

    Dactyloscopy is a special field in the police records department and a suitable means for identifying unknown dead persons as well as solving crimes by taking fingerprints from living persons. Apart from the conventional methods of dactyloscopy, mobile and more compact instruments are to facilitate taking prints of fingertips and palms also at the scene of mass disasters. In the presented study, living persons and corpses were examined to find out the possible uses and limits of mobile one-finger scanners. The concrete issue of the investigation was whether the mobile one-finger scanner Cross Match MV5 is suitable for application in mass disasters. The device was used in 12 corpses aged 5 weeks to 76 years (mean postmortem interval 5.5 days) and in 28 living persons aged 6 weeks to 87 years. In summary, the scanner produced qualitatively good prints in all age groups of the living individuals. In the corpses, the prints were only partly evaluable. In particular, fingers and fingertips with soot blackening and livid discoloration were difficult to analyse. Postmortem rigidity also complicated the handling of the scanner. In fresh corpses, the scanner can be recommended without reservation. Even if the epidermis was detached, the scanner was able to produce evaluable prints of the dermis of the hypothenar.

  10. Desynchronizing Electrical and Sensory Coordinated Reset Neuromodulation

    Directory of Open Access Journals (Sweden)

    Oleksandr V. Popovych

    2012-03-01

    Full Text Available Coordinated reset (CR stimulation is a desynchronizing stimulation technique based on timely coordinated phase resets of sub-populations of a synchronized neuronal ensemble. It has initially been computationally developed for electrical deep brain stimulation (DBS,to enable an effective desynchronization and unlearning of pathological synchrony and connectivity (anti-kindling. Here we computationally show for ensembles of spiking and bursting model neurons interacting via excitatory and inhibitory adaptive synapses that a phase reset of neuronal populations as well as a desynchronization and an anti-kindling can robustly be achieved by direct electrical stimulation or indirect (synaptically-mediated excitatory and inhibitory stimulation.Our findings are relevant for DBS as well as for sensory stimulation in neurological disorders characterized by pathological neuronalsynchrony. Based on the obtained results, we may expect that the local effects in the vicinity of a depth electrode (realized by direct stimulation of the neurons' somata or stimulation of axon terminals and the non-local CR effects (realized by stimulation of excitatory or inhibitory efferent fibers of deep brain CR neuromodulation may be similar or even identical. Furthermore, ourresults indicate that an effective desynchronization and anti-kindlingcan even be achieved by non-invasive, sensory CR neuromodulation. We discuss the concept of sensory CR neuromodulation in the context of neurological disorders.

  11. The meaning and classification of tattoos in the context of their suitability to identify corpses of unknown identity.

    Science.gov (United States)

    Sadowski, Wojciech A; Borowska-Solonynko, Aleksandra B

    2017-01-01

    To present the most popular types of tattoos, their meaning and classification, and to assess the suitability of different forms of tattoos in the process of identification of corpses of unknown identity. The tattoos found on 729 cadavers who underwent post mortem examinations at the Department of Forensic Medicine in Warsaw in the years 2012-2015 were analyzed. The tattoos were photographed and identified in terms of their meaning domain and classified into groups. Tattoos belonging to all groups were found, according to the most popular tattoo classification, which is based on their nature and includes: criminal and prison tattoos (defining the prison hierarchy, criminal profession as well as intentions and goals, erotic tattoos, environmental, penitentiary), military and artistic. The novel classification, focusing on the utility of certain kinds of tattoos for identyfying corpses of unknown identity, was also developed. According to the above mentioned classification the following kinds of tattoos are distinguished: individual (artistic), group (e.g. penitentiary - indicating the fact of being imprisoned in a penitentiary institution or belonging to a "prison kites" subculture, or presenting criminal profession; group confined tattoo (indicating a staying in a specific penitentiary institution), group tattoo with individual data (indicating the fact of staying in a penitentiary institution as well as dates of imprisonment), and others (e.g. names of relatives, military tattoo, etc.). Analysis of individual types of tattoo can accelerate the process of identification of the cadavers. The proposed classification allows to quickly determine whether a particular tattoo can be helpful in initial individual identification (in the case of individual tattoos) or whether it can be used to reduce the group of people considered (in cases of different types of group tattoos).

  12. Membrane potential correlates of sensory perception in mouse barrel cortex.

    Science.gov (United States)

    Sachidhanandam, Shankar; Sreenivasan, Varun; Kyriakatos, Alexandros; Kremer, Yves; Petersen, Carl C H

    2013-11-01

    Neocortical activity can evoke sensory percepts, but the cellular mechanisms remain poorly understood. We trained mice to detect single brief whisker stimuli and report perceived stimuli by licking to obtain a reward. Pharmacological inactivation and optogenetic stimulation demonstrated a causal role for the primary somatosensory barrel cortex. Whole-cell recordings from barrel cortex neurons revealed membrane potential correlates of sensory perception. Sensory responses depended strongly on prestimulus cortical state, but both slow-wave and desynchronized cortical states were compatible with task performance. Whisker deflection evoked an early (sensory response that was encoded through cell-specific reversal potentials. A secondary late (50-400 ms) depolarization was enhanced on hit trials compared to misses. Optogenetic inactivation revealed a causal role for late excitation. Our data reveal dynamic processing in the sensory cortex during task performance, with an early sensory response reliably encoding the stimulus and later secondary activity contributing to driving the subjective percept.

  13. The Sensory Neocortex and Associative Memory.

    Science.gov (United States)

    Aschauer, Dominik; Rumpel, Simon

    2018-01-01

    Most behaviors in mammals are directly or indirectly guided by prior experience and therefore depend on the ability of our brains to form memories. The ability to form an association between an initially possibly neutral sensory stimulus and its behavioral relevance is essential for our ability to navigate in a changing environment. The formation of a memory is a complex process involving many areas of the brain. In this chapter we review classic and recent work that has shed light on the specific contribution of sensory cortical areas to the formation of associative memories. We discuss synaptic and circuit mechanisms that mediate plastic adaptations of functional properties in individual neurons as well as larger neuronal populations forming topographically organized representations. Furthermore, we describe commonly used behavioral paradigms that are used to study the mechanisms of memory formation. We focus on the auditory modality that is receiving increasing attention for the study of associative memory in rodent model systems. We argue that sensory cortical areas may play an important role for the memory-dependent categorical recognition of previously encountered sensory stimuli.

  14. Population coding in sparsely connected networks of noisy neurons

    OpenAIRE

    Tripp, Bryan P.; Orchard, Jeff

    2012-01-01

    This study examines the relationship between population coding and spatial connection statistics in networks of noisy neurons. Encoding of sensory information in the neocortex is thought to require coordinated neural populations, because individual cortical neurons respond to a wide range of stimuli, and exhibit highly variable spiking in response to repeated stimuli. Population coding is rooted in network structure, because cortical neurons receive information only from other neurons, and be...

  15. Sensory Neuropathy Due to Loss of Bcl-w

    Science.gov (United States)

    Courchesne, Stephanie L.; Karch, Christoph; Pazyra-Murphy, Maria F.; Segal, Rosalind A.

    2010-01-01

    Small fiber sensory neuropathy is a common disorder in which progressive degeneration of small diameter nociceptors causes decreased sensitivity to thermal stimuli and painful sensations in the extremities. In the majority of patients, the cause of small fiber sensory neuropathy is unknown, and treatment options are limited. Here, we show that Bcl-w (Bcl-2l2) is required for the viability of small fiber nociceptive sensory neurons. Bcl-w −/− mice demonstrate an adult-onset progressive decline in thermosensation and a decrease in nociceptor innervation of the epidermis. This denervation occurs without cell body loss, indicating that lack of Bcl-w results in a primary axonopathy. Consistent with this phenotype, we show that Bcl-w, in contrast to the closely related Bcl-2 and Bcl-xL, is enriched in axons of sensory neurons and that Bcl-w prevents the dying back of axons. Bcl-w −/− sensory neurons exhibit mitochondrial abnormalities, including alterations in axonal mitochondrial size, axonal mitochondrial membrane potential, and cellular ATP levels. Collectively, these data establish bcl-w −/− mice as an animal model of small fiber sensory neuropathy, and provide new insight regarding the role of bcl-w and of mitochondria in preventing axonal degeneration. PMID:21289171

  16. [The coordination of the forensic medical service with the medical criminology subdivisions of internal affairs organs in the personal identification of unidentified corpses].

    Science.gov (United States)

    Pashinian, G A; Tuchik, E S

    1997-01-01

    In order to improve the cooperation between medical criminology departments of the organs of home affairs and forensic medical service in personality identification of unidentified corpses, the authors propose amendments to the routine procedure regulated by documents of the Ministry of Home Affairs of the Russian Federation, for these documents are in need of serious correction and revision, so that they conform to the judicial legislation and other documents.

  17. [Sensory integration: hierarchy and synchronization].

    Science.gov (United States)

    Kriukov, V I

    2005-01-01

    This is the first in the series of mini-reviews devoted to the basic problems and most important effects of attention in terms of neuronal modeling. We believe that the absence of the unified view on wealth of new date on attention is the main obstacle for further understanding of higher nervous activity. The present work deals with the main ground problem of reconciling two competing architectures designed to integrate the sensory information in the brain. The other mini-reviews will be concerned with the remaining five or six problems of attention, all of them to be ultimately resolved uniformly in the framework of small modification of dominant model of attention and memory.

  18. A New Population of Parvocellular Oxytocin Neurons Controlling Magnocellular Neuron Activity and Inflammatory Pain Processing.

    Science.gov (United States)

    Eliava, Marina; Melchior, Meggane; Knobloch-Bollmann, H Sophie; Wahis, Jérôme; da Silva Gouveia, Miriam; Tang, Yan; Ciobanu, Alexandru Cristian; Triana Del Rio, Rodrigo; Roth, Lena C; Althammer, Ferdinand; Chavant, Virginie; Goumon, Yannick; Gruber, Tim; Petit-Demoulière, Nathalie; Busnelli, Marta; Chini, Bice; Tan, Linette L; Mitre, Mariela; Froemke, Robert C; Chao, Moses V; Giese, Günter; Sprengel, Rolf; Kuner, Rohini; Poisbeau, Pierrick; Seeburg, Peter H; Stoop, Ron; Charlet, Alexandre; Grinevich, Valery

    2016-03-16

    Oxytocin (OT) is a neuropeptide elaborated by the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Magnocellular OT neurons of these nuclei innervate numerous forebrain regions and release OT into the blood from the posterior pituitary. The PVN also harbors parvocellular OT cells that project to the brainstem and spinal cord, but their function has not been directly assessed. Here, we identified a subset of approximately 30 parvocellular OT neurons, with collateral projections onto magnocellular OT neurons and neurons of deep layers of the spinal cord. Evoked OT release from these OT neurons suppresses nociception and promotes analgesia in an animal model of inflammatory pain. Our findings identify a new population of OT neurons that modulates nociception in a two tier process: (1) directly by release of OT from axons onto sensory spinal cord neurons and inhibiting their activity and (2) indirectly by stimulating OT release from SON neurons into the periphery. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Sensory perception in autism.

    Science.gov (United States)

    Robertson, Caroline E; Baron-Cohen, Simon

    2017-11-01

    Autism is a complex neurodevelopmental condition, and little is known about its neurobiology. Much of autism research has focused on the social, communication and cognitive difficulties associated with the condition. However, the recent revision of the diagnostic criteria for autism has brought another key domain of autistic experience into focus: sensory processing. Here, we review the properties of sensory processing in autism and discuss recent computational and neurobiological insights arising from attention to these behaviours. We argue that sensory traits have important implications for the development of animal and computational models of the condition. Finally, we consider how difficulties in sensory processing may relate to the other domains of behaviour that characterize autism.

  20. Programmes of cell death and autolysis in tracheary elements: when a suicidal cell arranges its own corpse removal.

    Science.gov (United States)

    Escamez, Sacha; Tuominen, Hannele

    2014-03-01

    Tracheary element (TE) differentiation represents a unique system to study plant developmental programmed cell death (PCD). TE PCD occurs after deposition of the secondary cell walls when an unknown signal induces tonoplast rupture and the arrest of cytoplasmic streaming. TE PCD is tightly followed by autolysis of the protoplast and partial hydrolysis of the primary cell walls. This review integrates TE differentiation, programmed cell death (PCD), and autolysis in a biological and evolutionary context. The collective evidence from the evolutionary and molecular studies suggests that TE differentiation consists primarily of a programme for cell death and autolysis under the direct control of the transcriptional master switches VASCULAR NAC DOMAIN 6 (VND6) and VND7. In this scenario, secondary cell walls represent a later innovation to improve the water transport capacity of TEs which necessitates transcriptional regulators downstream of VND6 and VND7. One of the most fascinating features of TEs is that they need to prepare their own corpse removal by expression and accumulation of hydrolases that are released from the vacuole after TE cell death. Therefore, TE differentiation involves, in addition to PCD, a programmed autolysis which is initiated before cell death and executed post-mortem. It has recently become clear that TE PCD and autolysis are separate processes with separate molecular regulation. Therefore, the importance of distinguishing between the cell death programme per se and autolysis in all plant PCD research and of careful description of the morphological, biochemical, and molecular sequences in each of these processes, is advocated.

  1. Thalamic control of sensory selection in divided attention.

    Science.gov (United States)

    Wimmer, Ralf D; Schmitt, L Ian; Davidson, Thomas J; Nakajima, Miho; Deisseroth, Karl; Halassa, Michael M

    2015-10-29

    How the brain selects appropriate sensory inputs and suppresses distractors is unknown. Given the well-established role of the prefrontal cortex (PFC) in executive function, its interactions with sensory cortical areas during attention have been hypothesized to control sensory selection. To test this idea and, more generally, dissect the circuits underlying sensory selection, we developed a cross-modal divided-attention task in mice that allowed genetic access to this cognitive process. By optogenetically perturbing PFC function in a temporally precise window, the ability of mice to select appropriately between conflicting visual and auditory stimuli was diminished. Equivalent sensory thalamocortical manipulations showed that behaviour was causally dependent on PFC interactions with the sensory thalamus, not sensory cortex. Consistent with this notion, we found neurons of the visual thalamic reticular nucleus (visTRN) to exhibit PFC-dependent changes in firing rate predictive of the modality selected. visTRN activity was causal to performance as confirmed by bidirectional optogenetic manipulations of this subnetwork. Using a combination of electrophysiology and intracellular chloride photometry, we demonstrated that visTRN dynamically controls visual thalamic gain through feedforward inhibition. Our experiments introduce a new subcortical model of sensory selection, in which the PFC biases thalamic reticular subnetworks to control thalamic sensory gain, selecting appropriate inputs for further processing.

  2. Encoding of Naturalistic Optic Flow by a Population of Blowfly Motion-Sensitive Neurons

    NARCIS (Netherlands)

    Karmeier, K.; Hateren, J.H. van; Kern, R.; Egelhaaf, M.

    In sensory systems information is encoded by the activity of populations of neurons. To analyze the coding properties of neuronal populations sensory stimuli have usually been used that were much simpler than those encountered in real life. It has been possible only recently to stimulate visual

  3. UNCOMMON SENSORY METHODOLOGIES

    Directory of Open Access Journals (Sweden)

    Vladimír Vietoris

    2015-02-01

    Full Text Available Sensory science is the young but the rapidly developing field of the food industry. Actually, the great emphasis is given to the production of rapid techniques of data collection, the difference between consumers and trained panel is obscured and the role of sensory methodologists is to prepare the ways for evaluation, by which a lay panel (consumers can achieve identical results as a trained panel. Currently, there are several conventional methods of sensory evaluation of food (ISO standards, but more sensory laboratories are developing methodologies that are not strict enough in the selection of evaluators, their mechanism is easily understandable and the results are easily interpretable. This paper deals with mapping of marginal methods used in sensory evaluation of food (new types of profiles, CATA, TDS, napping.

  4. Probabilistic sensory recoding.

    Science.gov (United States)

    Jazayeri, Mehrdad

    2008-08-01

    A hallmark of higher brain functions is the ability to contemplate the world rather than to respond reflexively to it. To do so, the nervous system makes use of a modular architecture in which sensory representations are dissociated from areas that control actions. This flexibility however necessitates a recoding scheme that would put sensory information to use in the control of behavior. Sensory recoding faces two important challenges. First, recoding must take into account the inherent variability of sensory responses. Second, it must be flexible enough to satisfy the requirements of different perceptual goals. Recent progress in theory, psychophysics, and neurophysiology indicate that cortical circuitry might meet these challenges by evaluating sensory signals probabilistically.

  5. Behavioral guides for sensory neurophysiology.

    Science.gov (United States)

    Konishi, M

    2006-06-01

    The study of natural behavior is important for understanding the coding schemes of sensory systems. The jamming avoidance response of the weakly electric fish Eigenmannia is an excellent example of a bottom-up approach, in which behavioral analyses guided neurophysiological studies. These studies started from the electroreceptive sense organs to the motor output consisting of pacemaker neurons. Going in the opposite direction, from the central nervous system to lower centers, is the characteristic of the top-down approach. Although this approach is perhaps more difficult than the bottom-up approach, it was successfully employed in the neuroethological analysis of sound localization in the barn owl. In the latter studies, high-order neurons selective for complex natural stimuli led to the discovery of neural pathways and networks responsible for the genesis of the stimulus selectivity. Comparison of Eigenmannia and barn owls, and their neural systems, has revealed similarities in network designs, such as parallel pathways and their convergence to produce stimulus selectivity necessary for detection of natural stimuli.

  6. Synaptic Circuit Organization of Motor Corticothalamic Neurons

    Science.gov (United States)

    Yamawaki, Naoki

    2015-01-01

    Corticothalamic (CT) neurons in layer 6 constitute a large but enigmatic class of cortical projection neurons. How they are integrated into intracortical and thalamo-cortico-thalamic circuits is incompletely understood, especially outside of sensory cortex. Here, we investigated CT circuits in mouse forelimb motor cortex (M1) using multiple circuit-analysis methods. Stimulating and recording from CT, intratelencephalic (IT), and pyramidal tract (PT) projection neurons, we found strong CT↔ CT and CT↔ IT connections; however, CT→IT connections were limited to IT neurons in layer 6, not 5B. There was strikingly little CT↔ PT excitatory connectivity. Disynaptic inhibition systematically accompanied excitation in these pathways, scaling with the amplitude of excitation according to both presynaptic (class-specific) and postsynaptic (cell-by-cell) factors. In particular, CT neurons evoked proportionally more inhibition relative to excitation (I/E ratio) than IT neurons. Furthermore, the amplitude of inhibition was tuned to match the amount of excitation at the level of individual neurons; in the extreme, neurons receiving no excitation received no inhibition either. Extending these studies to dissect the connectivity between cortex and thalamus, we found that M1-CT neurons and thalamocortical neurons in the ventrolateral (VL) nucleus were remarkably unconnected in either direction. Instead, VL axons in the cortex excited both IT and PT neurons, and CT axons in the thalamus excited other thalamic neurons, including those in the posterior nucleus, which additionally received PT excitation. These findings, which contrast in several ways with previous observations in sensory areas, illuminate the basic circuit organization of CT neurons within M1 and between M1 and thalamus. PMID:25653383

  7. 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.

  8. Genes for Hereditary Sensory and Autonomic Neuropathies: A Genotype-Phenotype Correlation

    Science.gov (United States)

    Rotthier, Annelies; Baets, Jonathan; De Vriendt, Els; Jacobs, An; Auer-Grumbach, Michaela; Levy, Nicolas; Bonello-Palot, Nathalie; Kilic, Sara Sebnem; Weis, Joachim; Nascimento, Andres; Swinkels, Marielle; Kruyt, Moyo C.; Jordanova, Albena; De Jonghe, Peter; Timmerman, Vincent

    2009-01-01

    Hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders characterized by axonal atrophy and degeneration, exclusively or predominantly affecting the sensory and autonomic neurons. So far, disease-associated mutations have been identified in seven genes: two genes for autosomal dominant ("SPTLC1"…

  9. The power of projectomes: genetic mosaic labeling in the larval zebrafish brain reveals organizing principles of sensory circuits.

    Science.gov (United States)

    Robles, Estuardo

    2017-09-01

    In no vertebrate species do we possess an accurate, comprehensive tally of neuron types in the brain. This is in no small part due to the vast diversity of neuronal types that comprise complex vertebrate nervous systems. A fundamental goal of neuroscience is to construct comprehensive catalogs of cell types defined by structure, connectivity, and physiological response properties. This type of information will be invaluable for generating models of how assemblies of neurons encode and distribute sensory information and correspondingly alter behavior. This review summarizes recent efforts in the larval zebrafish to construct sensory projectomes, comprehensive analyses of axonal morphologies in sensory axon tracts. Focusing on the olfactory and optic tract, these studies revealed principles of sensory information processing in the olfactory and visual systems that could not have been directly quantified by other methods. In essence, these studies reconstructed the optic and olfactory tract in a virtual manner, providing insights into patterns of neuronal growth that underlie the formation of sensory axon tracts. Quantitative analysis of neuronal diversity revealed organizing principles that determine information flow through sensory systems in the zebrafish that are likely to be conserved across vertebrate species. The generation of comprehensive cell type classifications based on structural, physiological, and molecular features will lead to testable hypotheses on the functional role of individual sensory neuron subtypes in controlling specific sensory-evoked behaviors.

  10. Npas4: Linking Neuronal Activity to Memory.

    Science.gov (United States)

    Sun, Xiaochen; Lin, Yingxi

    2016-04-01

    Immediate-early genes (IEGs) are rapidly activated after sensory and behavioral experience and are believed to be crucial for converting experience into long-term memory. Neuronal PAS domain protein 4 (Npas4), a recently discovered IEG, has several characteristics that make it likely to be a particularly important molecular link between neuronal activity and memory: it is among the most rapidly induced IEGs, is expressed only in neurons, and is selectively induced by neuronal activity. By orchestrating distinct activity-dependent gene programs in different neuronal populations, Npas4 affects synaptic connections in excitatory and inhibitory neurons, neural circuit plasticity, and memory formation. It may also be involved in circuit homeostasis through negative feedback and psychiatric disorders. We summarize these findings and discuss their implications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Accessibility and sensory experiences

    DEFF Research Database (Denmark)

    Ryhl, Camilla

    2010-01-01

    and accessibility. Sensory accessibility accommodates aspects of a sensory disability and describes architectural design requirements needed to ensure access to architectural experiences. In the context of architecture accessibility has become a design concept of its own. It is generally described as ensuring...... physical access to the built environment by accommodating physical disabilities. While the existing concept of accessibility ensures the physical access of everyone to a given space, sensory accessibility ensures the choice of everyone to stay and be able to participate and experience....

  12. Neuromorphic sensory systems.

    Science.gov (United States)

    Liu, Shih-Chii; Delbruck, Tobi

    2010-06-01

    Biology provides examples of efficient machines which greatly outperform conventional technology. Designers in neuromorphic engineering aim to construct electronic systems with the same efficient style of computation. This task requires a melding of novel engineering principles with knowledge gleaned from neuroscience. We discuss recent progress in realizing neuromorphic sensory systems which mimic the biological retina and cochlea, and subsequent sensor processing. The main trends are the increasing number of sensors and sensory systems that communicate through asynchronous digital signals analogous to neural spikes; the improved performance and usability of these sensors; and novel sensory processing methods which capitalize on the timing of spikes from these sensors. Experiments using these sensors can impact how we think the brain processes sensory information. 2010 Elsevier Ltd. All rights reserved.

  13. Sensory evaluation techniques

    National Research Council Canada - National Science Library

    Meilgaard, Morten; Civille, Gail Vance; Carr, B. Thomas

    1991-01-01

    ..., #2 as a textbook for courses at the academic level, it aims to provide just enough theoretical background to enable the student to understand which sensory methods are best suited to particular...

  14. Neuronal degeneration in autonomic nervous system of Dystonia musculorum mice

    Directory of Open Access Journals (Sweden)

    Liu Kang-Jen

    2011-01-01

    Full Text Available Abstract Background Dystonia musculorum (dt is an autosomal recessive hereditary neuropathy with a characteristic uncoordinated movement and is caused by a defect in the bullous pemphigoid antigen 1 (BPAG1 gene. The neural isoform of BPAG1 is expressed in various neurons, including those in the central and peripheral nerve systems of mice. However, most previous studies on neuronal degeneration in BPAG1-deficient mice focused on peripheral sensory neurons and only limited investigation of the autonomic system has been conducted. Methods In this study, patterns of nerve innervation in cutaneous and iridial tissues were examined using general neuronal marker protein gene product 9.5 via immunohistochemistry. To perform quantitative analysis of the autonomic neuronal number, neurons within the lumbar sympathetic and parasympathetic ciliary ganglia were calculated. In addition, autonomic neurons were cultured from embryonic dt/dt mutants to elucidate degenerative patterns in vitro. Distribution patterns of neuronal intermediate filaments in cultured autonomic neurons were thoroughly studied under immunocytochemistry and conventional electron microscopy. Results Our immunohistochemistry results indicate that peripheral sensory nerves and autonomic innervation of sweat glands and irises dominated degeneration in dt/dt mice. Quantitative results confirmed that the number of neurons was significantly decreased in the lumbar sympathetic ganglia as well as in the parasympathetic ciliary ganglia of dt/dt mice compared with those of wild-type mice. We also observed that the neuronal intermediate filaments were aggregated abnormally in cultured autonomic neurons from dt/dt embryos. Conclusions These results suggest that a deficiency in the cytoskeletal linker BPAG1 is responsible for dominant sensory nerve degeneration and severe autonomic degeneration in dt/dt mice. Additionally, abnormally aggregated neuronal intermediate filaments may participate in

  15. Observation of the human fetal corpses with maxillofacial malformations. 1. CT and MRI examinations of the fetal cleft lip and/or palate

    International Nuclear Information System (INIS)

    Saito, Chikara; Nakano, Yoko; Shigematsu, Shiro

    1999-01-01

    Of the various types of congenital malformations, the cleft lip and/or palate is one of the most frequent. Observation of human fetal corpses exhibiting cleft lip and palate is very important to research on its onset of its mechanism and development. In recent years, some of researchers have performed clinical studies on prenatal diagnosis and surgical treatment for the entirety. However, there have hardly been any reports on detailed observations of the maxillofacial structure of a fetus with cleft lip and palate. We seized an opportunity of observing the maxillofacial structure of fetuses with cleft lip and/or palate using three-dimensional CT (3D-CT) and MR imaging as non-disjunctive methods. In the present study, nine fetal corpses having cleft lip and/or palate were examined. The results were as follows: CT and MRI were useful for non-invasive observation of the maxillofacial structure, including soft tissues. Because the osseous tissues of young fetus tissue is not fully mature, observation of bone structures was slightly difficult. When corpses were immersed in formalin for a long time, osseous tissue was decalcified, thus making it difficult to obtain clear images. We could observe the details of the maxillofacial structures such as the alveolar process, the hard palate, the maxillary sinus, the nasal cavity, the nasal bone, and the vomer, in some of the cases. 3D-CT and MR findings observed in the fetuses with cleft lip and/or palate should provide some basement of the imaging diagnosis of congenital disorder. (author))

  16. Observation of the human fetal corpses with maxillofacial malformations. 1. CT and MRI examinations of the fetal cleft lip and/or palate

    Energy Technology Data Exchange (ETDEWEB)

    Saito, Chikara; Nakano, Yoko; Shigematsu, Shiro [Tokyo Dental Coll., Chiba (Japan)] (and others)

    1999-06-01

    Of the various types of congenital malformations, the cleft lip and/or palate is one of the most frequent. Observation of human fetal corpses exhibiting cleft lip and palate is very important to research on its onset of its mechanism and development. In recent years, some of researchers have performed clinical studies on prenatal diagnosis and surgical treatment for the entirey. However, there have hardly been any reports on detailed observations of the maxillofacial structure of a fetus with cleft lip and palate. We seized an opportunity of observing the maxillofacial structure of fetuses with cleft lip and/or palate using three-dimensional CT (3D-CT) and MR imaging as non-disjunctive methods. In the present study, nine fetal corpses having cleft lip and/or palate were examined. The results were as follows: CT and MRI were useful for non-invasive observation of the maxillofacial structure, including soft tissues. Because the osseous tissues of young fetus tissue is not fully mature, observation of bone structures was slightly difficult. When corpses were immersed in formalin for a long time, osseous tissue was decalcified, thus making it difficult to obtain clear images. We could observe the details of the maxillofacial structures such as the alveolar process, the hard palate, the maxillary sinus, the nasal cavity, the nasal bone, and the vomer, in some of the cases. 3D-CT and MR findings observed in the fetuses with cleft lip and/or palate should provide some basement of the imaging diagnosis of congenital disorder. (author)

  17. Sensory maps in the claustrum of the cat.

    Science.gov (United States)

    Olson, C R; Graybiel, A M

    1980-12-04

    The claustrum is a telencephalic cell group (Fig. 1A, B) possessing widespread reciprocal connections with the neocortex. In this regard, it bears a unique and striking resemblance to the thalamus. We have now examined the anatomical ordering of pathways linking the claustrum with sensory areas of the cat neocortex and, in parallel electrophysiological experiments, have studied the functional organization of claustral sensory zones so identified. Our findings indicate that there are discrete visual and somatosensory subdivisions in the claustrum interconnected with the corresponding primary sensory areas of the neocortex and that the respective zones contain orderly retinotopic and somatotopic maps. A third claustral region receiving fibre projections from the auditory cortex in or near area Ep was found to contain neurones responsive to auditory stimulation. We conclude that loops connecting sensory areas of the neocortex with satellite zones in the claustrum contribute to the early processing of exteroceptive information by the forebrain.

  18. Sensory Deprivation during Early Postnatal Period Alters the Density of Interneurons in the Mouse Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Hiroshi Ueno

    2015-01-01

    Full Text Available Early loss of one sensory system can cause improved function of other sensory systems. However, both the time course and neuronal mechanism of cross-modal plasticity remain elusive. Recent study using functional MRI in humans suggests a role of the prefrontal cortex (PFC in cross-modal plasticity. Since this phenomenon is assumed to be associated with altered GABAergic inhibition in the PFC, we have tested the hypothesis that early postnatal sensory deprivation causes the changes of inhibitory neuronal circuit in different regions of the PFC of the mice. We determined the effects of sensory deprivation from birth to postnatal day 28 (P28 or P58 on the density of parvalbumin (PV, calbindin (CB, and calretinin (CR neurons in the prelimbic, infralimbic, and dorsal anterior cingulate cortices. The density of PV and CB neurons was significantly increased in layer 5/6 (L5/6. Moreover, the density of CR neurons was higher in L2/3 in sensory deprived mice compared to intact mice. These changes were more prominent at P56 than at P28. These results suggest that long-term sensory deprivation causes the changes of intracortical inhibitory networks in the PFC and the changes of inhibitory networks in the PFC may contribute to cross-modal plasticity.

  19. Central auditory neurons have composite receptive fields.

    Science.gov (United States)

    Kozlov, Andrei S; Gentner, Timothy Q

    2016-02-02

    High-level neurons processing complex, behaviorally relevant signals are sensitive to conjunctions of features. Characterizing the receptive fields of such neurons is difficult with standard statistical tools, however, and the principles governing their organization remain poorly understood. Here, we demonstrate multiple distinct receptive-field features in individual high-level auditory neurons in a songbird, European starling, in response to natural vocal signals (songs). We then show that receptive fields with similar characteristics can be reproduced by an unsupervised neural network trained to represent starling songs with a single learning rule that enforces sparseness and divisive normalization. We conclude that central auditory neurons have composite receptive fields that can arise through a combination of sparseness and normalization in neural circuits. Our results, along with descriptions of random, discontinuous receptive fields in the central olfactory neurons in mammals and insects, suggest general principles of neural computation across sensory systems and animal classes.

  20. Motor Neurons

    DEFF Research Database (Denmark)

    Hounsgaard, Jorn

    2017-01-01

    Motor neurons translate synaptic input from widely distributed premotor networks into patterns of action potentials that orchestrate motor unit force and motor behavior. Intercalated between the CNS and muscles, motor neurons add to and adjust the final motor command. The identity and functional...... in in vitro preparations is far from complete. Nevertheless, a foundation has been provided for pursuing functional significance of intrinsic response properties in motoneurons in vivo during motor behavior at levels from molecules to systems....

  1. Prefrontal cortex and sensory cortices during working memory: quantity and quality.

    Science.gov (United States)

    Ku, Yixuan; Bodner, Mark; Zhou, Yong-Di

    2015-04-01

    The activity in sensory cortices and the prefrontal cortex (PFC) throughout the delay interval of working memory (WM) tasks reflect two aspects of WM-quality and quantity, respectively. The delay activity in sensory cortices is fine-tuned to sensory information and forms the neural basis of the precision of WM storage, while the delay activity in the PFC appears to represent behavioral goals and filters out irrelevant distractions, forming the neural basis of the quantity of task-relevant information in WM. The PFC and sensory cortices interact through different frequency bands of neuronal oscillation (theta, alpha, and gamma) to fulfill goal-directed behaviors.

  2. Runx transcription factors in neuronal development

    Directory of Open Access Journals (Sweden)

    Shiga Takashi

    2008-08-01

    Full Text Available Abstract Runt-related (Runx transcription factors control diverse aspects of embryonic development and are responsible for the pathogenesis of many human diseases. In recent years, the functions of this transcription factor family in the nervous system have just begun to be understood. In dorsal root ganglion neurons, Runx1 and Runx3 play pivotal roles in the development of nociceptive and proprioceptive sensory neurons, respectively. Runx appears to control the transcriptional regulation of neurotrophin receptors, numerous ion channels and neuropeptides. As a consequence, Runx contributes to diverse aspects of the sensory system in higher vertebrates. In this review, we summarize recent progress in determining the role of Runx in neuronal development.

  3. Merkel cells and neurons keep in touch

    Science.gov (United States)

    Woo, Seung-Hyun; Lumpkin, Ellen A.; Patapoutian, Ardem

    2014-01-01

    The Merkel cell-neurite complex is a unique vertebrate touch receptor comprising two distinct cell types in the skin. Its presence in touch-sensitive skin areas was recognized more than a century ago, but the functions of each cell type in sensory transduction have been unclear. Three recent studies demonstrate that Merkel cells are mechanosensitive cells that function in touch transduction via Piezo2. One study concludes that Merkel cells rather than sensory neurons are principal sites of mechanotransduction, whereas the other two studies report that both Merkel cells and neurons encode mechanical inputs. Together, these studies settle a longstanding debate on whether Merkel cells are mechanosensory cells, and enable future investigations of how these skin cells communicate with neurons. PMID:25480024

  4. Beyond The Anticipatory Corpse: Medicine, Power, and the Care of the Dying: A Theoretical and Methodological Intervention into the Sociology of Brain Implant Surgery.

    Science.gov (United States)

    Hancock, Black Hawk; Morrison, Daniel R

    2016-12-01

    Drawing on and extending the Foucaultian philosophical framework that Jeffrey Bishop develops in his masterful book, The Anticipatory Corpse: Medicine, Power, and the Care of the Dying, we undertake a sociological analysis of the neurological procedure-deep brain stimulation (DBS)-which implants electrodes in the brain, powered by a pacemaker-like device, for the treatment of movement disorders. Following Bishop's work, we carry out this analysis through a two-fold strategy. First, we examine how a multidisciplinary team evaluates candidates for this implant at a major medical center. We present excerpts from an ethnographic study of the "case conference" where disease entities are presented, contested, ratified, and made objects for intervention with this technology. The case conference becomes the key site in the transition from "person-with-illness" to "person-with-brain-implant" as a team of health professionals determines a plan of action by interpreting both statistical and "quality of life" data regarding their patients. Second, this article explores these decision-making processes through Bishop's conceptualization of evidence-based medicine, which relies on statistical approaches as the ultimate authority in knowledge production and medical decisions. We then reflect on Bishop's critique of the social sciences and the methodological, analytical, and substantive ramifications that The Anticipatory Corpse can offer future sociological work. © The Author 2016. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. hamlet, a binary genetic switch between single- and multiple- dendrite neuron morphology.

    Science.gov (United States)

    Moore, Adrian W; Jan, Lily Yeh; Jan, Yuh Nung

    2002-08-23

    The dendritic morphology of neurons determines the number and type of inputs they receive. In the Drosophila peripheral nervous system (PNS), the external sensory (ES) neurons have a single nonbranched dendrite, whereas the lineally related multidendritic (MD) neurons have extensively branched dendritic arbors. We report that hamlet is a binary genetic switch between these contrasting morphological types. In hamlet mutants, ES neurons are converted to an MD fate, whereas ectopic hamlet expression in MD precursors results in transformation of MD neurons into ES neurons. Moreover, hamlet expression induced in MD neurons undergoing dendrite outgrowth drastically reduces arbor branching.

  6. Sensory cortex underpinnings of traumatic brain injury deficits.

    Directory of Open Access Journals (Sweden)

    Dasuni S Alwis

    Full Text Available Traumatic brain injury (TBI can result in persistent sensorimotor and cognitive deficits including long-term altered sensory processing. The few animal models of sensory cortical processing effects of TBI have been limited to examination of effects immediately after TBI and only in some layers of cortex. We have now used the rat whisker tactile system and the cortex processing whisker-derived input to provide a highly detailed description of TBI-induced long-term changes in neuronal responses across the entire columnar network in primary sensory cortex. Brain injury (n=19 was induced using an impact acceleration method and sham controls received surgery only (n=15. Animals were tested in a range of sensorimotor behaviour tasks prior to and up to 6 weeks post-injury when there were still significant sensorimotor behaviour deficits. At 8-10 weeks post-trauma, in terminal experiments, extracellular recordings were obtained from barrel cortex neurons in response to whisker motion, including motion that mimicked whisker motion observed in awake animals undertaking different tasks. In cortex, there were lamina-specific neuronal response alterations that appeared to reflect local circuit changes. Hyper-excitation was found only in supragranular layers involved in intra-areal processing and long-range integration, and only for stimulation with complex, naturalistic whisker motion patterns and not for stimulation with simple trapezoidal whisker motion. Thus TBI induces long-term directional changes in integrative sensory cortical layers that depend on the complexity of the incoming sensory information. The nature of these changes allow predictions as to what types of sensory processes may be affected in TBI and contribute to post-trauma sensorimotor deficits.

  7. Changes in the Adult Vertebrate Auditory Sensory Epithelium After Trauma

    Science.gov (United States)

    Oesterle, Elizabeth C.

    2012-01-01

    Auditory hair cells transduce sound vibrations into membrane potential changes, ultimately leading to changes in neuronal firing and sound perception. This review provides an overview of the characteristics and repair capabilities of traumatized auditory sensory epithelium in the adult vertebrate ear. Injured mammalian auditory epithelium repairs itself by forming permanent scars but is unable to regenerate replacement hair cells. In contrast, injured non-mammalian vertebrate ear generates replacement hair cells to restore hearing functions. Non-sensory support cells within the auditory epithelium play key roles in the repair processes. PMID:23178236

  8. Studying Sensory Perception.

    Science.gov (United States)

    Ackerly, Spafford C.

    2001-01-01

    Explains the vestibular organ's role in balancing the body and stabilizing the visual world using the example of a hunter. Describes the relationship between sensory perception and learning. Recommends using optical illusions to illustrate the distinctions between external realities and internal perceptions. (Contains 13 references.) (YDS)

  9. Transcendence and Sensoriness

    DEFF Research Database (Denmark)

    Protestant theology and culture are known for a reserved, at times skeptical, attitude to the use of art and aesthetic forms of expression in a religious context. In Transcendence and Sensoriness, this attitude is analysed and discussed both theoretically and through case studies considered...

  10. Sensory matched filters.

    Science.gov (United States)

    Warrant, Eric J

    2016-10-24

    As animals move through their environments they are subjected to an endless barrage of sensory signals. Of these, some will be of utmost importance, such as the tell-tale aroma of a potential mate, the distinctive appearance of a vital food source or the unmistakable sound of an approaching predator. Others will be less important. Indeed some will not be important at all. There are, for instance, wide realms of the sensory world that remain entirely undetected, simply because an animal lacks the physiological capacity to detect and analyse the signals that characterise this realm. Take ourselves for example: we are completely insensitive to the Earth's magnetic field, a sensory cue of vital importance as a compass for steering the long distance migration of animals as varied as birds, lobsters and sea turtles. We are also totally oblivious to the rich palette of ultraviolet colours that exist all around us, colours seen by insects, crustaceans, birds, fish and lizards (in fact perhaps by most animals). Nor can we hear the ultrasonic sonar pulses emitted by bats in hot pursuit of flying insect prey. The simple reason for these apparent deficiencies is that we either lack the sensory capacity entirely (as in the case of magnetoreception) or that our existing senses are incapable of detecting specific ranges of the stimulus (such as the ultraviolet wavelength range of light). Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Information transmission with spiking Bayesian neurons

    International Nuclear Information System (INIS)

    Lochmann, Timm; Deneve, Sophie

    2008-01-01

    Spike trains of cortical neurons resulting from repeatedpresentations of a stimulus are variable and exhibit Poisson-like statistics. Many models of neural coding therefore assumed that sensory information is contained in instantaneous firing rates, not spike times. Here, we ask how much information about time-varying stimuli can be transmitted by spiking neurons with such input and output variability. In particular, does this variability imply spike generation to be intrinsically stochastic? We consider a model neuron that estimates optimally the current state of a time-varying binary variable (e.g. presence of a stimulus) by integrating incoming spikes. The unit signals its current estimate to other units with spikes whenever the estimate increased by a fixed amount. As shown previously, this computation results in integrate and fire dynamics with Poisson-like output spike trains. This output variability is entirely due to the stochastic input rather than noisy spike generation. As a result such a deterministic neuron can transmit most of the information about the time varying stimulus. This contrasts with a standard model of sensory neurons, the linear-nonlinear Poisson (LNP) model which assumes that most variability in output spike trains is due to stochastic spike generation. Although it yields the same firing statistics, we found that such noisy firing results in the loss of most information. Finally, we use this framework to compare potential effects of top-down attention versus bottom-up saliency on information transfer with spiking neurons

  12. [Mirror neurons].

    Science.gov (United States)

    Rubia Vila, Francisco José

    2011-01-01

    Mirror neurons were recently discovered in frontal brain areas of the monkey. They are activated when the animal makes a specific movement, but also when the animal observes the same movement in another animal. Some of them also respond to the emotional expression of other animals of the same species. These mirror neurons have also been found in humans. They respond to or "reflect" actions of other individuals in the brain and are thought to represent the basis for imitation and empathy and hence the neurobiological substrate for "theory of mind", the potential origin of language and the so-called moral instinct.

  13. Anterograde transneuronal viral tract tracing reveals central sensory circuits from brown fat and sensory denervation alters its thermogenic responses.

    Science.gov (United States)

    Vaughan, Cheryl H; Bartness, Timothy J

    2012-05-01

    Brown adipose tissue (BAT) thermogenic activity and growth are controlled by its sympathetic nervous system (SNS) innervation, but nerve fibers containing sensory-associated neuropeptides [substance P, calcitonin gene-related peptide (CGRP)] also suggest sensory innervation. The central nervous system (CNS) projections of BAT afferents are unknown. Therefore, we used the H129 strain of the herpes simplex virus-1 (HSV-1), an anterograde transneuronal viral tract tracer used to delineate sensory nerve circuits, to define these projections. HSV-1 was injected into interscapular BAT (IBAT) of Siberian hamsters and HSV-1 immunoreactivity (ir) was assessed 24, 48, 72, 96, and 114 h postinjection. The 96- and 114-h groups had the most HSV-1-ir neurons with marked infections in the hypothalamic paraventricular nucleus, periaqueductal gray, olivary areas, parabrachial nuclei, raphe nuclei, and reticular areas. These sites also are involved in sympathetic outflow to BAT suggesting possible BAT sensory-SNS thermogenesis feedback circuits. We tested the functional contribution of IBAT sensory innervation on thermogenic responses to an acute (24 h) cold exposure test by injecting the specific sensory nerve toxin capsaicin directly into IBAT pads and then measuring core (T(c)) and IBAT (T(IBAT)) temperature responses. CGRP content was significantly decreased in capsaicin-treated IBAT demonstrating successful sensory nerve destruction. T(IBAT) and T(c) were significantly decreased in capsaicin-treated hamsters compared with the saline controls at 2 h of cold exposure. Thus the central sensory circuits from IBAT have been delineated for the first time, and impairment of sensory feedback from BAT appears necessary for the appropriate, initial thermogenic response to acute cold exposure.

  14. Relating normalization to neuronal populations across cortical areas.

    Science.gov (United States)

    Ruff, Douglas A; Alberts, Joshua J; Cohen, Marlene R

    2016-09-01

    Normalization, which divisively scales neuronal responses to multiple stimuli, is thought to underlie many sensory, motor, and cognitive processes. In every study where it has been investigated, neurons measured in the same brain area under identical conditions exhibit a range of normalization, ranging from suppression by nonpreferred stimuli (strong normalization) to additive responses to combinations of stimuli (no normalization). Normalization has been hypothesized to arise from interactions between neuronal populations, either in the same or different brain areas, but current models of normalization are not mechanistic and focus on trial-averaged responses. To gain insight into the mechanisms underlying normalization, we examined interactions between neurons that exhibit different degrees of normalization. We recorded from multiple neurons in three cortical areas while rhesus monkeys viewed superimposed drifting gratings. We found that neurons showing strong normalization shared less trial-to-trial variability with other neurons in the same cortical area and more variability with neurons in other cortical areas than did units with weak normalization. Furthermore, the cortical organization of normalization was not random: neurons recorded on nearby electrodes tended to exhibit similar amounts of normalization. Together, our results suggest that normalization reflects a neuron's role in its local network and that modulatory factors like normalization share the topographic organization typical of sensory tuning properties. Copyright © 2016 the American Physiological Society.

  15. 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.

  16. Neurosemantics, neurons and system theory.

    Science.gov (United States)

    Breidbach, Olaf

    2007-08-01

    Following the concept of internal representations, signal processing in a neuronal system has to be evaluated exclusively based on internal system characteristics. Thus, this approach omits the external observer as a control function for sensory integration. Instead, the configuration of the system and its computational performance are the effects of endogenous factors. Such self-referential operation is due to a strictly local computation in a network and, thereby, computations follow a set of rules that constitute the emergent behaviour of the system. These rules can be shown to correspond to a "logic" that is intrinsic to the system, an idea which provides the basis for neurosemantics.

  17. Neuronal involvement in cisplatin neuropathy

    DEFF Research Database (Denmark)

    Krarup-Hansen, A; Helweg-Larsen, Susanne Elisabeth; Schmalbruch, H

    2007-01-01

    Although it is well known that cisplatin causes a sensory neuropathy, the primary site of involvement is not established. The clinical symptoms localized in a stocking-glove distribution may be explained by a length dependent neuronopathy or by a distal axonopathy. To study whether the whole neuron...... of the foot evoked by a tactile probe showed similar changes to those observed in SNAPs evoked by electrical stimulation. At these doses, somatosensory evoked potentials (SEPs) from the tibial nerve had increased latencies of peripheral, spinal and central responses suggesting loss of central processes...

  18. Electrophysiological Features of Neurons in the Mesencephalic Trigeminal Nuclei

    Directory of Open Access Journals (Sweden)

    Jun-Ling Xing

    2015-01-01

    Full Text Available Mesencephalic trigeminal nucleus (Mes V neurons represent an uncommon class of primary sensory neurons. Besides receiving somatosensory information, Mes V neurons are also involved in regulating multisensory information. The present review first describes the passive features as well as three important currents, followed by a distinct excitability classification and a description of the excitability transition of Mes V neurons. Furthermore, their resonance property, the existence of membrane oscillation and electrical coupling which may promote strong synchronization, as well as their function in controlling stretch reflex activity, are discussed.

  19. Descriptive sensory evaluations

    DEFF Research Database (Denmark)

    Dehlholm, Christian

    A recent trend in descriptive sensory evaluation methodology has been the application of rapid evaluation techniques. The ease in use makes the techniques extremely easy to implement by industry and university environments. Thus, one might not consider validity in the choice of method. The overall...... aim of this thesis is to compare and evaluate selected rapid evaluation techniques for sensory profiling. Method variations have been suggested for evaluations in product development and quality control, and method insight is provided. The thesis includes three original studies, designed...... as a consequence of the current practices and needs faced in the industry. Study I compared applicability and validity of rapid methods across several panels of trained assessors. Two rapid approaches were introduced for the evaluation of foods. The first method, ‘Free Multiple Sorting’, allows subjects to perform...

  20. Mirror neurons and motor intentionality.

    Science.gov (United States)

    Rizzolatti, Giacomo; Sinigaglia, Corrado

    2007-01-01

    Our social life rests to a large extent on our ability to understand the intentions of others. What are the bases of this ability? A very influential view is that we understand the intentions of others because we are able to represent them as having mental states. Without this meta-representational (mind-reading) ability their behavior would be meaningless to us. Over the past few years this view has been challenged by neurophysiological findings and, in particular, by the discovery of mirror neurons. The functional properties of these neurons indicate that intentional understanding is based primarily on a mechanism that directly matches the sensory representation of the observed actions with one's own motor representation of those same actions. These findings reveal how deeply motor and intentional components of action are intertwined, suggesting that both can be fully comprehended only starting from a motor approach to intentionality.

  1. Reply to 'Comments on 'Radioiodine therapy: care of the helpless patient and handling of the radioactive corpse' '

    Energy Technology Data Exchange (ETDEWEB)

    Tindale, Claire Greaves and Wendy

    2002-09-01

    The recently published medical and dental guidance notes provide advice on dealing with patients who die following the administration of a radioactive substance. The guidance notes deal with cremation of radioactive patients and provide limits above which special precautions (and advice from the radiation protection advisor) may be required. For Sr-89 special precautions are required once the administered activity exceeds 200 MBq. In 1989 an assessment of the radiological impact of cremating a corpse containing up to 500 MBq of Sr-89 was undertaken by the NRPB. The results were published by the Institute of Physical Sciences in Medicine and are also discussed in Mountford's 'Exposure of critical groups to nuclear medicine patients'. Cremation of one corpse contaminated at a reference level of 500 MBq resulted in a maximum individual dose equivalent to an adult member of the public of less than 0.1 {mu}Sv (mostly from inhalation). A skin dose of less than 2 {mu}Sv would be expected in conditions of moderate rain (mostly from direct deposition on the skin). A crematorium worker would receive a maximum individual effective dose equivalent of about 0.3 {mu}Sv from inhalation and 0.4 {mu}Sv from ingestion. The maximum doses to an adult members of the public scattering contaminated ashes are unknown but are extremely unlikely to exceed those calculated for the crematorium worker per cremation. The maximum dose equivalents to a child or infant who may come into contact with the ash shortly after being scattered is similarly unknown and subject to considerable uncertainty. Pessimistic estimates based on a reference intake (1 mg) are greatest for an infant ingesting ash inadvertently (3 {mu}Sv). It was noted that although a person may be exposed to an atmospheric discharge of Sr-89 on more than one occasion, direct exposure to contaminated ash is very unlikely to occur more than once. The conclusion was that the levels of dose likely to be encountered in

  2. Neural correlates of sensory prediction errors in monkeys: evidence for internal models of voluntary self-motion in the cerebellum.

    Science.gov (United States)

    Cullen, Kathleen E; Brooks, Jessica X

    2015-02-01

    During self-motion, the vestibular system makes essential contributions to postural stability and self-motion perception. To ensure accurate perception and motor control, it is critical to distinguish between vestibular sensory inputs that are the result of externally applied motion (exafference) and that are the result of our own actions (reafference). Indeed, although the vestibular sensors encode vestibular afference and reafference with equal fidelity, neurons at the first central stage of sensory processing selectively encode vestibular exafference. The mechanism underlying this reafferent suppression compares the brain's motor-based expectation of sensory feedback with the actual sensory consequences of voluntary self-motion, effectively computing the sensory prediction error (i.e., exafference). It is generally thought that sensory prediction errors are computed in the cerebellum, yet it has been challenging to explicitly demonstrate this. We have recently addressed this question and found that deep cerebellar nuclei neurons explicitly encode sensory prediction errors during self-motion. Importantly, in everyday life, sensory prediction errors occur in response to changes in the effector or world (muscle strength, load, etc.), as well as in response to externally applied sensory stimulation. Accordingly, we hypothesize that altering the relationship between motor commands and the actual movement parameters will result in the updating in the cerebellum-based computation of exafference. If our hypothesis is correct, under these conditions, neuronal responses should initially be increased--consistent with a sudden increase in the sensory prediction error. Then, over time, as the internal model is updated, response modulation should decrease in parallel with a reduction in sensory prediction error, until vestibular reafference is again suppressed. The finding that the internal model predicting the sensory consequences of motor commands adapts for new

  3. Conceptual Design and Simulation of a Semi-Automatic Cell for the Washing and Preparation of a Corpse Prior to an Islamic Burial

    Directory of Open Access Journals (Sweden)

    A. Meghdari

    2012-07-01

    Full Text Available Washing the corpse and dressing the body prior to burial is an act of love and necessity in many religions. Applying robotics and automation technologies for the washing and preparation of a deceased Muslim in accordance with the Islamic Shari'at laws has been the challenging foundation of this research. With an increasing annual population growth resulting in an increase in the number of deaths (historically and/or immediately after a national disaster, automating part of this procedure to increase the speed of operation, reducing the health risks to the personnel of washing rooms “Ghassalkhaneh” at the cemeteries and enhancing their quality of life have been the primary objectives of this project. We have named and patented this semi-automated corpse preparation machine as the “PaakShooy” or “پاک شوی” in Persian (Farsi which means purifying the deceased. The whole process is composed of three operational units lined up in a series; the automatic washing chamber, drying cell and the semi-automatic shrouding table. This paper covers an introductory concept of the subject in Islam, a conceptual design of various machines and mechanisms to automate the important tasks in accordance with Islamic laws, and the final detailed design, graphic simulation and animation of the PaakShooy machine. In doing so, consultation with Islamic scholars has been a priority from the beginning of the project to the end and a few Fatwa have been issued by some high ranking Ayatollahs in support of the project. With a few modifications, the semi-automated PaakShooy machine may now be updated to conform to other religions/customs.

  4. Seasonal Blowfly Distribution and Abundance in Fragmented Landscapes. Is It Useful in Forensic Inference about Where a Corpse Has Been Decaying?

    Science.gov (United States)

    Zabala, Jabi; Díaz, Beatriz; Saloña-Bordas, Marta I.

    2014-01-01

    Blowflies are insects of forensic interest as they may indicate characteristics of the environment where a body has been laying prior to the discovery. In order to estimate changes in community related to landscape and to assess if blowfly species can be used as indicators of the landscape where a corpse has been decaying, we studied the blowfly community and how it is affected by landscape in a 7,000 km2 region during a whole year. Using baited traps deployed monthly we collected 28,507 individuals of 10 calliphorid species, 7 of them well represented and distributed in the study area. Multiple Analysis of Variance found changes in abundance between seasons in the 7 analyzed species, and changes related to land use in 4 of them (Calliphora vomitoria, Lucilia ampullacea, L. caesar and L. illustris). Generalised Linear Model analyses of abundance of these species compared with landscape descriptors at different scales found only a clear significant relationship between summer abundance of C. vomitoria and distance to urban areas and degree of urbanisation. This relationship explained more deviance when considering the landscape composition at larger geographical scales (up to 2,500 m around sampling site). For the other species, no clear relationship between land uses and abundance was found, and therefore observed changes in their abundance patterns could be the result of other variables, probably small changes in temperature. Our results suggest that blowfly community composition cannot be used to infer in what kind of landscape a corpse has decayed, at least in highly fragmented habitats, the only exception being the summer abundance of C. vomitoria. PMID:24918607

  5. Neurons versus herpes simplex virus: the innate immune interactions that contribute to a host–pathogen standoff

    Science.gov (United States)

    Rosato, Pamela C; Leib, David A

    2015-01-01

    Herpes simplex virus (HSV) is a prevalent neurotropic virus, which establishes lifelong latent infections in the neurons of sensory ganglia. Despite our long-standing knowledge that HSV predominately infects sensory neurons during its life cycle, little is known about the neuronal antiviral response to HSV infection. Recent studies show that while sensory neurons have impaired intrinsic immunity to HSV infection, paracrine IFN signaling can potentiate a potent antiviral response. Additionally, antiviral autophagy plays an important role in neuronal control of HSV infection. Here we review the literature of antiviral signaling and autophagy in neurons, the mechanisms by which HSV can counteract these responses, and postulate how these two pathways may synergize to mediate neuronal control of HSV infection and yet result in lifelong persistence of the virus. PMID:26213562

  6. Identification and Characterization of Mouse Otic Sensory Lineage Genes

    Directory of Open Access Journals (Sweden)

    Byron H. Hartman

    2015-03-01

    Full Text Available Vertebrate embryogenesis gives rise to all cell types of an organism through the development of many unique lineages derived from the three primordial germ layers. The otic sensory lineage arises from the otic vesicle, a structure formed through invagination of placodal non-neural ectoderm. This developmental lineage possesses unique differentiation potential, giving rise to otic sensory cell populations including hair cells, supporting cells, and ganglion neurons of the auditory and vestibular organs. Here we present a systematic approach to identify transcriptional features that distinguish the otic sensory lineage (from early otic progenitors to otic sensory populations from other major lineages of vertebrate development. We used a microarray approach to analyze otic sensory lineage populations including microdissected otic vesicles (embryonic day 10.5 as well as isolated neonatal cochlear hair cells and supporting cells at postnatal day 3. Non-otic tissue samples including periotic tissues and whole embryos with otic regions removed were used as reference populations to evaluate otic specificity. Otic populations shared transcriptome-wide correlations in expression profiles that distinguish members of this lineage from non-otic populations. We further analyzed the microarray data using comparative and dimension reduction methods to identify individual genes that are specifically expressed in the otic sensory lineage. This analysis identified and ranked top otic sensory lineage-specific transcripts including Fbxo2, Col9a2, and Oc90, and additional novel otic lineage markers. To validate these results we performed expression analysis on select genes using immunohistochemistry and in situ hybridization. Fbxo2 showed the most striking pattern of specificity to the otic sensory lineage, including robust expression in the early otic vesicle and sustained expression in prosensory progenitors and auditory and vestibular hair cells and supporting

  7. Disruption of Transient Serotonin Accumulation by Non-Serotonin-Producing Neurons Impairs Cortical Map Development

    Directory of Open Access Journals (Sweden)

    Xiaoning Chen

    2015-01-01

    Full Text Available Polymorphisms that alter serotonin transporter SERT expression and functionality increase the risks for autism and psychiatric traits. Here, we investigate how SERT controls serotonin signaling in developing CNS in mice. SERT is transiently expressed in specific sets of glutamatergic neurons and uptakes extrasynaptic serotonin during perinatal CNS development. We show that SERT expression in glutamatergic thalamocortical axons (TCAs dictates sensory map architecture. Knockout of SERT in TCAs causes lasting alterations in TCA patterning, spatial organizations of cortical neurons, and dendritic arborization in sensory cortex. Pharmacological reduction of serotonin synthesis during the first postnatal week rescues sensory maps in SERTGluΔ mice. Furthermore, knockdown of SERT expression in serotonin-producing neurons does not impair barrel maps. We propose that spatiotemporal SERT expression in non-serotonin-producing neurons represents a determinant in early life genetic programming of cortical circuits. Perturbing this SERT function could be involved in the origin of sensory and cognitive deficits associated with neurodevelopmental disorders.

  8. Cross-Excitation in Peripheral Sensory Ganglia Associated with Pain Transmission

    Directory of Open Access Journals (Sweden)

    Katsuhiro Omoto

    2015-08-01

    Full Text Available Despite the absence of synaptic contacts, cross-excitation of neurons in sensory ganglia during signal transmission is considered to be chemically mediated and appears increased in chronic pain states. In this study, we modulated neurotransmitter release in sensory neurons by direct application of type A botulinum neurotoxin (BoNT/A to sensory ganglia in an animal model of neuropathic pain and evaluated the effect of this treatment on nocifensive. Unilateral sciatic nerve entrapment (SNE reduced the ipsilateral hindpaw withdrawal threshold to mechanical stimulation and reduced hindpaw withdrawal latency to thermal stimulation. Direct application of BoNT/A to the ipsilateral L4 dorsal root ganglion (DRG was localized in the cell bodies of the DRG and reversed the SNE-induced decreases in withdrawal thresholds within 2 days of BoNT/A administration. Results from this study suggest that neurotransmitter release within sensory ganglia is involved in the regulation of pain-related signal transmission.

  9. Chloride homeostasis and chemoreception in trigeminal sensory neurons of mice

    OpenAIRE

    Radtke, Debbie

    2012-01-01

    In der vorliegenden Arbeit konnte gezeigt werden, dass trigeminale Ganglienneurone (TGNs), im Gegensatz zu den meisten zentralen Neuronen, auch postnatal eine hohe intrazelluläre Chloridkonzentration vorweisen. Die intrazelluläre Akkumulation von Chlorid wird hauptsächlich durch den Na+-K+-2Cl- Cotransporter NKCC1 gewährleistet. Auf Grund der hohen intrazellulären Chloridkonzentration führt das Öffnen von Chlorid-leitenden GABAA Rezeptoren nicht zu einem Einstrom von Chlorid-Ionen...

  10. Pain-Causing Venom Peptides: Insights into Sensory Neuron Pharmacology

    Directory of Open Access Journals (Sweden)

    Sina Jami

    2017-12-01

    Full Text Available Venoms are produced by a wide variety of species including spiders, scorpions, reptiles, cnidarians, and fish for the purpose of harming or incapacitating predators or prey. While some venoms are of relatively simple composition, many contain hundreds to thousands of individual components with distinct pharmacological activity. Pain-inducing or “algesic” venom compounds have proven invaluable to our understanding of how physiological nociceptive neural networks operate. In this review, we present an overview of some of the diverse nociceptive pathways that can be modulated by specific venom components to evoke pain.

  11. Distinct membrane effects of spinal nerve ligation on injured and adjacent dorsal root ganglion neurons in rats

    NARCIS (Netherlands)

    Sapunar, Damir; Ljubkovic, Marko; Lirk, Philipp; McCallum, J. Bruce; Hogan, Quinn H.

    2005-01-01

    Painful peripheral nerve injury results in disordered sensory neuron function that contributes to the pathogenesis of neuropathic pain. However, the relative roles of neurons with transected axons versus intact adjacent neurons have not been resolved. An essential first step is identification of

  12. Immunohistochemical study of sensory nerve formations in human glabrous skin.

    Science.gov (United States)

    Haro, J J; Vega, J A; del Valle, M E; Calzada, B; Zaccheo, D; Malinovsky, L

    1991-01-01

    The sensory nerve formations (or corpuscles) of normal human glabrous skin from hand and fingers, obtained by punch biopsies, were studied by the streptavidin-biotin method using monoclonal antibodies directed against neurofilament protein (NFP), S-100 protein, glial fibrillary acidic protein (GFAP), cytokeratins, and vimentin. NFP immunoreactivity (IR) was observed in the central axons of most sensory formations, while S-100 protein IR was restricted to non-neuronal cells forming the so-called inner cells core or lamellar cells. Furthermore, vimentin IR was found in the same cells of Meissner's and glomerular corpuscles. None of the sensory nerve formations were stained for GFAP or keratin. The present results suggest that the main nature of the intermediate filaments of the non-neuronal cells of sensory nerve formations from human glabrous skin is represented by vimentin and not by GFAP. Thus, our findings suggest that lamellar and inner core cells of SNF are modified and specialized Schwann cells and not epithelial or perineurial derived cells.

  13. The Sensory Striatum Is Permanently Impaired by Transient Developmental Deprivation

    Directory of Open Access Journals (Sweden)

    Todd M. Mowery

    2017-06-01

    Full Text Available Corticostriatal circuits play a fundamental role in regulating many behaviors, and their dysfunction is associated with many neurological disorders. In contrast, sensory disorders, like hearing loss (HL, are commonly linked with processing deficits at or below the level of the auditory cortex (ACx. However, HL can be accompanied by non-sensory deficits, such as learning delays, suggesting the involvement of regions downstream of ACx. Here, we show that transient developmental HL differentially affected the ACx and its downstream target, the sensory striatum. Following HL, both juvenile ACx layer 5 and striatal neurons displayed an excitatory-inhibitory imbalance and lower firing rates. After hearing was restored, adult ACx neurons recovered balanced excitatory-inhibitory synaptic gain and control-like firing rates, but striatal neuron synapses and firing properties did not recover. Thus, a brief period of abnormal cortical activity may induce cellular impairments that persist into adulthood and contribute to neurological disorders that are striatal in origin.

  14. Layer 5 Callosal Parvalbumin-Expressing Neurons: A Distinct Functional Group of GABAergic Neurons.

    Science.gov (United States)

    Zurita, Hector; Feyen, Paul L C; Apicella, Alfonso Junior

    2018-01-01

    Previous studies have shown that parvalbumin-expressing neurons (CC-Parv neurons) connect the two hemispheres of motor and sensory areas via the corpus callosum, and are a functional part of the cortical circuit. Here we test the hypothesis that layer 5 CC-Parv neurons possess anatomical and molecular mechanisms which dampen excitability and modulate the gating of interhemispheric inhibition. In order to investigate this hypothesis we use viral tracing to determine the anatomical and electrophysiological properties of layer 5 CC-Parv and parvalbumin-expressing (Parv) neurons of the mouse auditory cortex (AC). Here we show that layer 5 CC-Parv neurons had larger dendritic fields characterized by longer dendrites that branched farther from the soma, whereas layer 5 Parv neurons had smaller dendritic fields characterized by shorter dendrites that branched nearer to the soma. The layer 5 CC-Parv neurons are characterized by delayed action potential (AP) responses to threshold currents, lower firing rates, and lower instantaneous frequencies compared to the layer 5 Parv neurons. Kv1.1 containing K + channels are the main source of the AP repolarization of the layer 5 CC-Parv and have a major role in determining both the spike delayed response, firing rate and instantaneous frequency of these neurons.

  15. Intrinsic neuromodulation: altering neuronal circuits from within.

    Science.gov (United States)

    Katz, P S; Frost, W N

    1996-02-01

    There are two sources of neuromodulation for neuronal circuits: extrinsic inputs and intrinsic components of the circuits themselves. Extrinsic neuromodulation is known to be pervasive in nervous systems, but intrinsic neuromodulation is less recognized, despite the fact that it has now been demonstrated in sensory and neuromuscular circuits and in central pattern generators. By its nature, intrinsic neuromodulation produces local changes in neuronal computation, whereas extrinsic neuromodulation can cause global changes, often affecting many circuits simultaneously. Studies in a number of systems are defining the different properties of these two forms of neuromodulation.

  16. Tlx3 exerts context-dependent transcriptional regulation and promotes neuronal differentiation from embryonic stem cells

    OpenAIRE

    Kondo, Takako; Sheets, Patrick L.; Zopf, David A.; Aloor, Heather L.; Cummins, Theodore R.; Chan, Rebecca J.; Hashino, Eri

    2008-01-01

    The T cell leukemia 3 (Tlx3) gene has been implicated in specification of glutamatergic sensory neurons in the spinal cord. In cranial sensory ganglia, Tlx3 is highly expressed in differentiating neurons during early embryogenesis. To study a role of Tlx3 during neural differentiation, mouse embryonic stem (ES) cells were transfected with a Tlx3 expression vector. ES cells stably expressing Tlx3 were grown in the presence or absence of a neural induction medium. In undifferentiated ES cells, ...

  17. Spiking irregularity and frequency modulate the behavioral report of single-neuron stimulation.

    Science.gov (United States)

    Doron, Guy; von Heimendahl, Moritz; Schlattmann, Peter; Houweling, Arthur R; Brecht, Michael

    2014-02-05

    The action potential activity of single cortical neurons can evoke measurable sensory effects, but it is not known how spiking parameters and neuronal subtypes affect the evoked sensations. Here, we examined the effects of spike train irregularity, spike frequency, and spike number on the detectability of single-neuron stimulation in rat somatosensory cortex. For regular-spiking, putative excitatory neurons, detectability increased with spike train irregularity and decreasing spike frequencies but was not affected by spike number. Stimulation of single, fast-spiking, putative inhibitory neurons led to a larger sensory effect compared to regular-spiking neurons, and the effect size depended only on spike irregularity. An ideal-observer analysis suggests that, under our experimental conditions, rats were using integration windows of a few hundred milliseconds or more. Our data imply that the behaving animal is sensitive to single neurons' spikes and even to their temporal patterning. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. 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.

  19. Charcot Marie Tooth 2B Peripheral Sensory Neuropathy: How Rab7 Mutations Impact NGF Signaling?

    Directory of Open Access Journals (Sweden)

    Harry Liu

    2017-02-01

    Full Text Available Charcot-Marie-Tooth 2B peripheral sensory neuropathy (CMT2B is a debilitating autosomal dominant hereditary sensory neuropathy. Patients with this disease lose pain sensation and frequently need amputation. Axonal dysfunction and degeneration of peripheral sensory neurons is a major clinical manifestation of CMT2B. However, the cellular and molecular pathogenic mechanisms remain undefined. CMT2B is caused by missense point mutations (L129F, K157N, N161T/I, V162M in Rab7 GTPase. Strong evidence suggests that the Rab7 mutation(s enhances the cellular levels of activated Rab7 proteins, thus resulting in increased lysosomal activity and autophagy. As a consequence, trafficking and signaling of neurotrophic factors such as nerve growth factor (NGF in the long axons of peripheral sensory neurons are particularly vulnerable to premature degradation. A “gain of toxicity” model has, thus, been proposed based on these observations. However, studies of fly photo-sensory neurons indicate that the Rab7 mutation(s causes a “loss of function”, resulting in haploinsufficiency. In the review, we summarize experimental evidence for both hypotheses. We argue that better models (rodent animals and human neurons of CMT2B are needed to precisely define the disease mechanisms.

  20. Charcot Marie Tooth 2B Peripheral Sensory Neuropathy: How Rab7 Mutations Impact NGF Signaling?

    Science.gov (United States)

    Liu, Harry; Wu, Chengbiao

    2017-02-04

    Charcot-Marie-Tooth 2B peripheral sensory neuropathy (CMT2B) is a debilitating autosomal dominant hereditary sensory neuropathy. Patients with this disease lose pain sensation and frequently need amputation. Axonal dysfunction and degeneration of peripheral sensory neurons is a major clinical manifestation of CMT2B. However, the cellular and molecular pathogenic mechanisms remain undefined. CMT2B is caused by missense point mutations (L129F, K157N, N161T/I, V162M) in Rab7 GTPase. Strong evidence suggests that the Rab7 mutation(s) enhances the cellular levels of activated Rab7 proteins, thus resulting in increased lysosomal activity and autophagy. As a consequence, trafficking and signaling of neurotrophic factors such as nerve growth factor (NGF) in the long axons of peripheral sensory neurons are particularly vulnerable to premature degradation. A "gain of toxicity" model has, thus, been proposed based on these observations. However, studies of fly photo-sensory neurons indicate that the Rab7 mutation(s) causes a "loss of function", resulting in haploinsufficiency. In the review, we summarize experimental evidence for both hypotheses. We argue that better models (rodent animals and human neurons) of CMT2B are needed to precisely define the disease mechanisms.

  1. Sensory Science Education

    DEFF Research Database (Denmark)

    Otrel-Cass, Kathrin

    2018-01-01

    little note of the body-mind interactions we have with the material world. Utilizing examples from primary schools, it is argued that a sensory pedagogy in science requires a deliberate sensitization and validation of the senses’ presence and that a sensor pedagogy approach may reveal the unique ways...... in how we all experience the world. Troubling science education pedagogy is therefore also a reconceptualization of who we are and how we make sense of the world and the acceptance that the body-mind is present, imbalanced and complex....

  2. The changing sensory room

    DEFF Research Database (Denmark)

    2018-01-01

    In 2017 the kindergarten The Milky Way in the city Vejle in Denmark made a sensory room that has the special ability change whenever wanted by the children and social educators. Kjetil Sandvik (to the right) from Copenhagen University and Klaus Thestrup from Aarhus University reflects upon what...... they saw, took part in and talked with the social educators about. Jacob Knudsen from VIFIN filmed the two gentlemen and organised the project. it is a room composed around common experiments, many self-made objects, open narrative structures. and a combination of digital and analogue elements....

  3. Neuronal network analyses: premises, promises and uncertainties

    OpenAIRE

    Parker, David

    2010-01-01

    Neuronal networks assemble the cellular components needed for sensory, motor and cognitive functions. Any rational intervention in the nervous system will thus require an understanding of network function. Obtaining this understanding is widely considered to be one of the major tasks facing neuroscience today. Network analyses have been performed for some years in relatively simple systems. In addition to the direct insights these systems have provided, they also illustrate some of the diffic...

  4. Mutations in the nervous system--specific HSN2 exon of WNK1 cause hereditary sensory neuropathy type II.

    Science.gov (United States)

    Shekarabi, Masoud; Girard, Nathalie; Rivière, Jean-Baptiste; Dion, Patrick; Houle, Martin; Toulouse, André; Lafrenière, Ronald G; Vercauteren, Freya; Hince, Pascale; Laganiere, Janet; Rochefort, Daniel; Faivre, Laurence; Samuels, Mark; Rouleau, Guy A

    2008-07-01

    Hereditary sensory and autonomic neuropathy type II (HSANII) is an early-onset autosomal recessive disorder characterized by loss of perception to pain, touch, and heat due to a loss of peripheral sensory nerves. Mutations in hereditary sensory neuropathy type II (HSN2), a single-exon ORF originally identified in affected families in Quebec and Newfoundland, Canada, were found to cause HSANII. We report here that HSN2 is a nervous system-specific exon of the with-no-lysine(K)-1 (WNK1) gene. WNK1 mutations have previously been reported to cause pseudohypoaldosteronism type II but have not been studied in the nervous system. Given the high degree of conservation of WNK1 between mice and humans, we characterized the structure and expression patterns of this isoform in mice. Immunodetections indicated that this Wnk1/Hsn2 isoform was expressed in sensory components of the peripheral nervous system and CNS associated with relaying sensory and nociceptive signals, including satellite cells, Schwann cells, and sensory neurons. We also demonstrate that the novel protein product of Wnk1/Hsn2 was more abundant in sensory neurons than motor neurons. The characteristics of WNK1/HSN2 point to a possible role for this gene in the peripheral sensory perception deficits characterizing HSANII.

  5. Mutations in the nervous system–specific HSN2 exon of WNK1 cause hereditary sensory neuropathy type II

    Science.gov (United States)

    Shekarabi, Masoud; Girard, Nathalie; Rivière, Jean-Baptiste; Dion, Patrick; Houle, Martin; Toulouse, André; Lafrenière, Ronald G.; Vercauteren, Freya; Hince, Pascale; Laganiere, Janet; Rochefort, Daniel; Faivre, Laurence; Samuels, Mark; Rouleau, Guy A.

    2008-01-01

    Hereditary sensory and autonomic neuropathy type II (HSANII) is an early-onset autosomal recessive disorder characterized by loss of perception to pain, touch, and heat due to a loss of peripheral sensory nerves. Mutations in hereditary sensory neuropathy type II (HSN2), a single-exon ORF originally identified in affected families in Quebec and Newfoundland, Canada, were found to cause HSANII. We report here that HSN2 is a nervous system–specific exon of the with-no-lysine(K)–1 (WNK1) gene. WNK1 mutations have previously been reported to cause pseudohypoaldosteronism type II but have not been studied in the nervous system. Given the high degree of conservation of WNK1 between mice and humans, we characterized the structure and expression patterns of this isoform in mice. Immunodetections indicated that this Wnk1/Hsn2 isoform was expressed in sensory components of the peripheral nervous system and CNS associated with relaying sensory and nociceptive signals, including satellite cells, Schwann cells, and sensory neurons. We also demonstrate that the novel protein product of Wnk1/Hsn2 was more abundant in sensory neurons than motor neurons. The characteristics of WNK1/HSN2 point to a possible role for this gene in the peripheral sensory perception deficits characterizing HSANII. PMID:18521183

  6. Modularity in Sensory Auditory Memory

    OpenAIRE

    Clement, Sylvain; Moroni, Christine; Samson, Séverine

    2004-01-01

    The goal of this paper was to review various experimental and neuropsychological studies that support the modular conception of auditory sensory memory or auditory short-term memory. Based on initial findings demonstrating that verbal sensory memory system can be dissociated from a general auditory memory store at the functional and anatomical levels. we reported a series of studies that provided evidence in favor of multiple auditory sensory stores specialized in retaining eit...

  7. SENSORY AND CONSUMER TESTING LABORATORY

    Data.gov (United States)

    Federal Laboratory Consortium — These laboratories conduct a wide range of studies to characterize the sensory properties of and consumer responses to foods, beverages, and other consumer products....

  8. Variable sensory perception in autism.

    Science.gov (United States)

    Haigh, Sarah M

    2018-03-01

    Autism is associated with sensory and cognitive abnormalities. Individuals with autism generally show normal or superior early sensory processing abilities compared to healthy controls, but deficits in complex sensory processing. In the current opinion paper, it will be argued that sensory abnormalities impact cognition by limiting the amount of signal that can be used to interpret and interact with environment. There is a growing body of literature showing that individuals with autism exhibit greater trial-to-trial variability in behavioural and cortical sensory responses. If multiple sensory signals that are highly variable are added together to process more complex sensory stimuli, then this might destabilise later perception and impair cognition. Methods to improve sensory processing have shown improvements in more general cognition. Studies that specifically investigate differences in sensory trial-to-trial variability in autism, and the potential changes in variability before and after treatment, could ascertain if trial-to-trial variability is a good mechanism to target for treatment in autism. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  9. Influence of Sensory Stimulation on Exhaled Volatile Organic Compounds.

    Science.gov (United States)

    Mazzatenta, A; Pokorski, M; Di Tano, A; Cacchio, M; Di Giulio, C

    2016-01-01

    The real-time exhaled volatile organic compounds (VOCs) have been suggested as a new biomarker to detect and monitor physiological processes in the respiratory system. The VOCs profile in exhaled breath reflects the biochemical alterations related to metabolic changes, organ failure, and neuronal activity, which are, at least in part, transmitted via the lungs to the alveolar exhaled breath. Breath analysis has been applied to investigate cancer, lung failure, and neurodegenerative diseases. There are by far no studies on the real-time monitoring of VOCs in sensory stimulation in healthy subjects. Therefore, in this study we investigated the breath parameters and exhaled VOCs in humans during sensory stimulation: smell, hearing, sight, and touch. Responses sensory stimulations were recorded in 12 volunteers using an iAQ-2000 sensor. We found significant effects of sensory stimulation. In particular, olfactory stimulation was the most effective stimulus that elicited the greatest VOCs variations in the exhaled breath. Since the olfactory pathway is distinctly driven by the hypothalamic and limbic circuitry, while other senses project first to the thalamic area and then re-project to other brain areas, the findings suggest the importance of olfaction and chemoreception in the regulation lung gas exchange. VOCs variations during sensory activation may become putative indicators of neural activity.

  10. HIV Associated Sensory Neuropathy.

    Science.gov (United States)

    G, Amruth; S, Praveen-Kumar; B, Nataraju; Bs, Nagaraja

    2014-07-01

    In the era of highly active antiretroviral therapy, sensory neuropathies have increased in prevalence. We have documented the frequency and profile of the two most common forms of sensory neuropathies associated with Human Immunodeficiency Virus (HIV) infection and looked into clinicoelectrophysiological correlates to differentiate the two entities. The study population comprised of all consecutive patients detected to be HIV positive and attending the Neurology outpatient department (from March 2011 to March 2012) who were aged ≥ 18 years and were able to give informed consent. The data were collected from the patient records (including CD4 counts and treatment details) and questionnaire based interview with each patient. All patients underwent detailed clinical examination and nerve conduction studies (NCSs). Among the total study population of 50 patients, there were 31 men and 19 women. Thirty two patients were in age range of 21 - 40 years and rest were above 40 years. 25 were on antiretroviral therapy (18 on regimen containing zidovudine; seven on regimen containing stavudine). The mean duration of antiretroviral therapy was 16.6±8.4 months. Low CD4 counts ( 40 years. Subclinical neuropathy was common in those on antiretroviral therapy. Axonal neuropathy was the commonest pattern noted in patients who were receiving antiretroviral therapy and demyelinating neuropathy in patients not on antiretroviral therapy. Surprisingly no significant correlation was found between low CD4 counts and symptomatic neuropathy.

  11. Cellular Links between Neuronal Activity and Energy Homeostasis

    OpenAIRE

    Shetty, Pavan K.; Galeffi, Francesca; Turner, Dennis A.

    2012-01-01

    Neuronal activity, astrocytic responses to this activity, and energy homeostasis are linked together during baseline, conscious conditions, and short-term rapid activation (as occurs with sensory or motor function). Nervous system energy homeostasis also varies during long-term physiological conditions (i.e., development and aging) and with adaptation to pathological conditions, such as ischemia or low glucose. Neuronal activation requires increased metabolism (i.e., ATP generation) which lea...

  12. Hunger neurons drive feeding through a sustained, positive reinforcement signal.

    Science.gov (United States)

    Chen, Yiming; Lin, Yen-Chu; Zimmerman, Christopher A; Essner, Rachel A; Knight, Zachary A

    2016-08-24

    The neural mechanisms underlying hunger are poorly understood. AgRP neurons are activated by energy deficit and promote voracious food consumption, suggesting these cells may supply the fundamental hunger drive that motivates feeding. However recent in vivo recording experiments revealed that AgRP neurons are inhibited within seconds by the sensory detection of food, raising the question of how these cells can promote feeding at all. Here we resolve this paradox by showing that brief optogenetic stimulation of AgRP neurons before food availability promotes intense appetitive and consummatory behaviors that persist for tens of minutes in the absence of continued AgRP neuron activation. We show that these sustained behavioral responses are mediated by a long-lasting potentiation of the rewarding properties of food and that AgRP neuron activity is positively reinforcing. These findings reveal that hunger neurons drive feeding by transmitting a positive valence signal that triggers a stable transition between behavioral states.

  13. Hereditary sensory ataxic neuropathy associated with proximal muscle weakness in the lower extremities.

    Science.gov (United States)

    Murakami, Tatsufumi; Fukai, Yuta; Rikimaru, Mitsue; Henmi, Shoji; Ohsawa, Yutaka; Sunada, Yoshihide

    2010-04-15

    We describe three patients from the same family with hereditary sensory ataxic neuropathy followed by proximal muscle weakness in the lower extremities. Sensory ataxic gait began as an initial symptom when patients were in their 50s. Mild proximal weakness in the lower extremities appeared several years later. Serum creatine kinase was mildly elevated. Nerve conduction studies revealed sensory dominant axonal neuropathy, and short sensory evoked potentials showed involvement of the sensory nerve axon, dorsal root ganglia and posterior funiculus of the spinal cord. Needle electromyography showed fibrillation, positive sharp waves, and multiple giant motor unit potentials, suggesting the involvement of anterior horn motor neurons or the anterior root. Autosomal recessive inheritance was considered, because of consanguinity. The disorder described here may be a new clinical entity with unique clinical manifestations. Copyright 2009 Elsevier B.V. All rights reserved.

  14. Simultaneous activation of parallel sensory pathways promotes a grooming sequence in Drosophila

    Science.gov (United States)

    Hampel, Stefanie; McKellar, Claire E

    2017-01-01

    A central model that describes how behavioral sequences are produced features a neural architecture that readies different movements simultaneously, and a mechanism where prioritized suppression between the movements determines their sequential performance. We previously described a model whereby suppression drives a Drosophila grooming sequence that is induced by simultaneous activation of different sensory pathways that each elicit a distinct movement (Seeds et al., 2014). Here, we confirm this model using transgenic expression to identify and optogenetically activate sensory neurons that elicit specific grooming movements. Simultaneous activation of different sensory pathways elicits a grooming sequence that resembles the naturally induced sequence. Moreover, the sequence proceeds after the sensory excitation is terminated, indicating that a persistent trace of this excitation induces the next grooming movement once the previous one is performed. This reveals a mechanism whereby parallel sensory inputs can be integrated and stored to elicit a delayed and sequential grooming response. PMID:28887878

  15. 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.

  16. Imbalance between sympathetic and sensory innervation in peritoneal endometriosis.

    Science.gov (United States)

    Arnold, Julia; Barcena de Arellano, Maria L; Rüster, Carola; Vercellino, Giuseppe F; Chiantera, Vito; Schneider, Achim; Mechsner, Sylvia

    2012-01-01

    To investigate possible mechanisms of pain pathophysiology in patients with peritoneal endometriosis, a clinical study on sensory and sympathetic nerve fibre sprouting in endometriosis was performed. Peritoneal lesions (n=40) and healthy peritoneum (n=12) were immunostained and analysed with anti-protein gene product 9.5 (PGP 9.5), anti-substance P (SP) and anti-tyrosine hydroxylase (TH), specific markers for intact nerve fibres, sensory nerve fibres and sympathetic nerve fibres, respectively, to identify the ratio of sympathetic and sensory nerve fibres. In addition, immune cell infiltrates in peritoneal endometriotic lesions were analysed and the nerve growth factor (NGF) and interleukin (IL)-1β expression was correlate with the nerve fibre density. Peritoneal fluids from patients with endometriosis (n=40) and without endometriosis (n=20) were used for the in vitro neuronal growth assay. Cultured chicken dorsal root ganglia (DRG) and sympathetic ganglia were stained with anti-growth associated protein 43 (anti-GAP 43), anti-SP and anti-TH. We could detect an increased sensory and decreased sympathetic nerve fibres density in peritoneal lesions compared to healthy peritoneum. Peritoneal fluids of patients with endometriosis compared to patients without endometriosis induced an increased sprouting of sensory neurites from DRG and decreased neurite outgrowth from sympathetic ganglia. In conclusion, this study demonstrates an imbalance between sympathetic and sensory nerve fibres in peritoneal endometriosis, as well as an altered modulation of peritoneal fluids from patients with endometriosis on sympathetic and sensory innervation which might directly be involved in the maintenance of inflammation and pain. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. A computational relationship between thalamic sensory neural responses and contrast perception.

    Science.gov (United States)

    Jiang, Yaoguang; Purushothaman, Gopathy; Casagrande, Vivien A

    2015-01-01

    Uncovering the relationship between sensory neural responses and perceptual decisions remains a fundamental problem in neuroscience. Decades of experimental and modeling work in the sensory cortex have demonstrated that a perceptual decision pool is usually composed of tens to hundreds of neurons, the responses of which are significantly correlated not only with each other, but also with the behavioral choices of an animal. Few studies, however, have measured neural activity in the sensory thalamus of awake, behaving animals. Therefore, it remains unclear how many thalamic neurons are recruited and how the information from these neurons is pooled at subsequent cortical stages to form a perceptual decision. In a previous study we measured neural activity in the macaque lateral geniculate nucleus (LGN) during a two alternative forced choice (2AFC) contrast detection task, and found that single LGN neurons were significantly correlated with the monkeys' behavioral choices, despite their relatively poor contrast sensitivity and a lack of overall interneuronal correlations. We have now computationally tested a number of specific hypotheses relating these measured LGN neural responses to the contrast detection behavior of the animals. We modeled the perceptual decisions with different numbers of neurons and using a variety of pooling/readout strategies, and found that the most successful model consisted of about 50-200 LGN neurons, with individual neurons weighted differentially according to their signal-to-noise ratios (quantified as d-primes). These results supported the hypothesis that in contrast detection the perceptual decision pool consists of multiple thalamic neurons, and that the response fluctuations in these neurons can influence contrast perception, with the more sensitive thalamic neurons likely to exert a greater influence.

  18. Successive neuron loss in the thalamus and cortex in a mouse model of infantile neuronal ceroid lipofuscinosis.

    Science.gov (United States)

    Kielar, Catherine; Maddox, Lucy; Bible, Ellen; Pontikis, Charlie C; Macauley, Shannon L; Griffey, Megan A; Wong, Michael; Sands, Mark S; Cooper, Jonathan D

    2007-01-01

    Infantile neuronal ceroid lipofuscinosis (INCL) is caused by deficiency of the lysosomal enzyme, palmitoyl protein thioesterase 1 (PPT1). We have investigated the onset and progression of pathological changes in Ppt1 deficient mice (Ppt1-/-) and the development of their seizure phenotype. Surprisingly, cortical atrophy and neuron loss occurred only late in disease progression but were preceded by localized astrocytosis within individual thalamic nuclei and the progressive loss of thalamic neurons that relay different sensory modalities to the cortex. This thalamic neuron loss occurred first within the visual system and only subsequently in auditory and somatosensory relay nuclei or the inhibitory reticular thalamic nucleus. The loss of granule neurons and GABAergic interneurons followed in each corresponding cortical region, before the onset of seizure activity. These findings provide novel evidence for successive neuron loss within the thalamus and cortex in Ppt1-/- mice, revealing the thalamus as an important early focus of INCL pathogenesis.

  19. Fine-scale topography in sensory systems: insights from Drosophila and vertebrates.

    Science.gov (United States)

    Kaneko, Takuya; Ye, Bing

    2015-09-01

    To encode the positions of sensory stimuli, sensory circuits form topographic maps in the central nervous system through specific point-to-point connections between pre- and postsynaptic neurons. In vertebrate visual systems, the establishment of topographic maps involves the formation of a coarse topography followed by that of fine-scale topography that distinguishes the axon terminals of neighboring neurons. It is known that intrinsic differences in the form of broad gradients of guidance molecules instruct coarse topography while neuronal activity is required for fine-scale topography. On the other hand, studies in the Drosophila visual system have shown that intrinsic differences in cell adhesion among the axon terminals of neighboring neurons instruct the fine-scale topography. Recent studies on activity-dependent topography in the Drosophila somatosensory system have revealed a role of neuronal activity in creating molecular differences among sensory neurons for establishing fine-scale topography, implicating a conserved principle. Here we review the findings in both Drosophila and vertebrates and propose an integrated model for fine-scale topography.

  20. Sensory adaptation for timing perception.

    Science.gov (United States)

    Roseboom, Warrick; Linares, Daniel; Nishida, Shin'ya

    2015-04-22

    Recent sensory experience modifies subjective timing perception. For example, when visual events repeatedly lead auditory events, such as when the sound and video tracks of a movie are out of sync, subsequent vision-leads-audio presentations are reported as more simultaneous. This phenomenon could provide insights into the fundamental problem of how timing is represented in the brain, but the underlying mechanisms are poorly understood. Here, we show that the effect of recent experience on timing perception is not just subjective; recent sensory experience also modifies relative timing discrimination. This result indicates that recent sensory history alters the encoding of relative timing in sensory areas, excluding explanations of the subjective phenomenon based only on decision-level changes. The pattern of changes in timing discrimination suggests the existence of two sensory components, similar to those previously reported for visual spatial attributes: a lateral shift in the nonlinear transducer that maps relative timing into perceptual relative timing and an increase in transducer slope around the exposed timing. The existence of these components would suggest that previous explanations of how recent experience may change the sensory encoding of timing, such as changes in sensory latencies or simple implementations of neural population codes, cannot account for the effect of sensory adaptation on timing perception.

  1. Sensory characteristics of camphor.

    Science.gov (United States)

    Green, B G

    1990-05-01

    The perceptual effects of camphor on hairy skin were measured in a psychophysical experiment. Subjects rated the intensity and quality of sensations produced when a solution of 20% camphor (in a vehicle of ethanol and deionized H2O) was applied topically to the volar forearm. Under conditions in which skin temperature was varied either from 33-43 degrees C or from 33-18 degrees C, it was found that camphor increased the perceived intensity of the cutaneous sensations produced during heating and cooling. Although camphor's effect appeared to be greater during warming, neither effect was large. Camphor also produced a significant increase in the frequency of reports of "burning." It is concluded that camphor is a relatively weak sensory irritant that may have a modest excitatory effect on thermosensitive (and perhaps nociceptive) cutaneous fibers.

  2. Gain control network conditions in early sensory coding.

    Directory of Open Access Journals (Sweden)

    Eduardo Serrano

    Full Text Available Gain control is essential for the proper function of any sensory system. However, the precise mechanisms for achieving effective gain control in the brain are unknown. Based on our understanding of the existence and strength of connections in the insect olfactory system, we analyze the conditions that lead to controlled gain in a randomly connected network of excitatory and inhibitory neurons. We consider two scenarios for the variation of input into the system. In the first case, the intensity of the sensory input controls the input currents to a fixed proportion of neurons of the excitatory and inhibitory populations. In the second case, increasing intensity of the sensory stimulus will both, recruit an increasing number of neurons that receive input and change the input current that they receive. Using a mean field approximation for the network activity we derive relationships between the parameters of the network that ensure that the overall level of activity of the excitatory population remains unchanged for increasing intensity of the external stimulation. We find that, first, the main parameters that regulate network gain are the probabilities of connections from the inhibitory population to the excitatory population and of the connections within the inhibitory population. Second, we show that strict gain control is not achievable in a random network in the second case, when the input recruits an increasing number of neurons. Finally, we confirm that the gain control conditions derived from the mean field approximation are valid in simulations of firing rate models and Hodgkin-Huxley conductance based models.

  3. Tic Modulation Using Sensory Tricks

    Directory of Open Access Journals (Sweden)

    Rebecca W. Gilbert

    2013-04-01

    Full Text Available Background: A sensory trick, or geste antagoniste, is defined as a physical gesture (such as a touch on a particular body part that mitigates the production of an involuntary movement. This phenomenon is most commonly described as a feature of dystonia. Here we present a case of successful modulation of tics using sensory tricks.Case Report:: A case report and video are presented. The case and video demonstrate a 19-year-old male who successfully controlled his tics with various sensory tricks.Discussion: It is underappreciated by movement disorder physicians that sensory tricks can play a role in tics. Introducing this concept to patients could potentially help in tic control. In addition, understanding the pathophysiological underpinnings of sensory tricks could help in the understanding of the pathophysiology of tics.

  4. Sensory analysis of pet foods.

    Science.gov (United States)

    Koppel, Kadri

    2014-08-01

    Pet food palatability depends first and foremost on the pet and is related to the pet food sensory properties such as aroma, texture and flavor. Sensory analysis of pet foods may be conducted by humans via descriptive or hedonic analysis, pets via acceptance or preference tests, and through a number of instrumental analysis methods. Sensory analysis of pet foods provides additional information on reasons behind palatable and unpalatable foods as pets lack linguistic capabilities. Furthermore, sensory analysis may be combined with other types of information such as personality and environment factors to increase understanding of acceptable pet foods. Most pet food flavor research is proprietary and, thus, there are a limited number of publications available. Funding opportunities for pet food studies would increase research and publications and this would help raise public awareness of pet food related issues. This mini-review addresses current pet food sensory analysis literature and discusses future challenges and possibilities. © 2014 Society of Chemical Industry.

  5. Respiratory Neuron Activity in the Mesencephalon, Diencephalon and Cerebellum of the Carp

    NARCIS (Netherlands)

    Ballintijn, C.M.; Luiten, P.G.M.; Jüch, P.J.W.

    1979-01-01

    The functional properties, localization and connections of neurons with a respiratory-rhythmic firing pattern in the mesencephalon, diencephalon and cerebellum of the carp were studied. Some neurons acquire respiratory rhythm only as a side effect of respiration via sensory stimulation by movements

  6. The L1-type cell adhesion molecule Neuroglian is necessary for maintenance of sensory axon advance in the Drosophila embryo

    Directory of Open Access Journals (Sweden)

    Martin Veronica

    2008-04-01

    Full Text Available Abstract Background Cell adhesion molecules have long been implicated in the regulation of axon growth, but the precise cellular roles played by individual cell adhesion molecules and the molecular basis for their action are still not well understood. We have used the sensory system of the Drosophila embryo to shed light on the mechanism by which the L1-type cell adhesion molecule Neuroglian regulates axon growth. Results We have found a highly penetrant sensory axon stalling phenotype in neuroglian mutant embryos. Axons stalled at a variety of positions along their normal trajectory, but most commonly in the periphery some distance along the peripheral nerve. All lateral and dorsal cluster sensory neurons examined, except for the dorsal cluster neuron dbd, showed stalling. Sensory axons were never seen to project along inappropriate pathways in neuroglian mutants and stalled axons showed normal patterns of fasciculation within nerves. The growth cones of stalled axons possessed a simple morphology, similar to their appearance in wild-type embryos when advancing along nerves. Driving expression of the wild-type form of Neuroglian in sensory neurons alone rescued the neuroglian mutant phenotype of both pioneering and follower neurons. A partial rescue was achieved by expressing the Neuroglian extracellular domain. Over/mis-expression of Neuroglian in all neurons, oenocytes or trachea had no apparent effect on sensory axon growth. Conclusion We conclude that Neuroglian is necessary to maintain axon advance along axonal substrates, but is not required for initiation of axon outgrowth, axon fasciculation or recognition of correct growth substrates. Expression of Neuroglian in sensory neurons alone is sufficient to promote axon advance and the intracellular region of the molecule is largely dispensable for this function. It is unlikely, therefore, that Nrg acts as a molecular 'clutch' to couple adhesion of F-actin within the growth cone to the

  7. Two distinct populations of projection neurons in the rat lateral parafascicular thalamic nucleus and their cholinergic responsiveness.

    Science.gov (United States)

    Beatty, J A; Sylwestrak, E L; Cox, C L

    2009-08-04

    The lateral parafascicular nucleus (lPf) is a member of the intralaminar thalamic nuclei, a collection of nuclei that characteristically provides widespread projections to the neocortex and basal ganglia and is associated with arousal, sensory, and motor functions. Recently, lPf neurons have been shown to possess different characteristics than other cortical-projecting thalamic relay neurons. We performed whole cell recordings from lPf neurons using an in vitro rat slice preparation and found two distinct neuronal subtypes that were differentiated by distinct morphological and physiological characteristics: diffuse and bushy. Diffuse neurons, which had been previously described, were the predominant neuronal subtype (66%). These neurons had few, poorly-branching, extended dendrites, and rarely displayed burst-like action potential discharge, a ubiquitous feature of thalamocortical relay neurons. Interestingly, we discovered a smaller population of bushy neurons (34%) that shared similar morphological and physiological characteristics with thalamocortical relay neurons of primary sensory thalamic nuclei. In contrast to other thalamocortical relay neurons, activation of muscarinic cholinergic receptors produced a membrane hyperpolarization via activation of M(2) receptors in most lPf neurons (60%). In a minority of lPf neurons (33%), muscarinic agonists produced a membrane depolarization via activation of predominantly M(3) receptors. The muscarinic receptor-mediated actions were independent of lPf neuronal subtype (i.e. diffuse or bushy neurons); however the cholinergic actions were correlated with lPf neurons with different efferent targets. Retrogradely-labeled lPf neurons from frontal cortical fluorescent bead injections primarily consisted of bushy type lPf neurons (78%), but more importantly, all of these neurons were depolarized by muscarinic agonists. On the other hand, lPf neurons labeled by striatal injections were predominantly hyperpolarized by muscarinic

  8. Mechanosensor Channels in Mammalian Somatosensory Neurons

    Directory of Open Access Journals (Sweden)

    Patrick Delmas

    2007-09-01

    Full Text Available Mechanoreceptive sensory neurons innervating the skin, skeletal muscles andviscera signal both innocuous and noxious information necessary for proprioception, touchand pain. These neurons are responsible for the transduction of mechanical stimuli intoaction potentials that propagate to the central nervous system. The ability of these cells todetect mechanical stimuli impinging on them relies on the presence of mechanosensitivechannels that transduce the external mechanical forces into electrical and chemical signals.Although a great deal of information regarding the molecular and biophysical properties ofmechanosensitive channels in prokaryotes has been accumulated over the past two decades,less is known about the mechanosensitive channels necessary for proprioception and thesenses of touch and pain. This review summarizes the most pertinent data onmechanosensitive channels of mammalian somatosensory neurons, focusing on theirproperties, pharmacology and putative identity.

  9. Assessing sensory versus optogenetic network activation by combining (o)fMRI with optical Ca2+ recordings

    Science.gov (United States)

    Schmid, Florian; Wachsmuth, Lydia; Schwalm, Miriam; Prouvot, Pierre-Hugues; Jubal, Eduardo Rosales; Fois, Consuelo; Pramanik, Gautam; Zimmer, Claus; Stroh, Albrecht

    2015-01-01

    Encoding of sensory inputs in the cortex is characterized by sparse neuronal network activation. Optogenetic stimulation has previously been combined with fMRI (ofMRI) to probe functional networks. However, for a quantitative optogenetic probing of sensory-driven sparse network activation, the level of similarity between sensory and optogenetic network activation needs to be explored. Here, we complement ofMRI with optic fiber-based population Ca2+ recordings for a region-specific readout of neuronal spiking activity in rat brain. Comparing Ca2+ responses to the blood oxygenation level-dependent signal upon sensory stimulation with increasing frequencies showed adaptation of Ca2+ transients contrasted by an increase of blood oxygenation level-dependent responses, indicating that the optical recordings convey complementary information on neuronal network activity to the corresponding hemodynamic response. To study the similarity of optogenetic and sensory activation, we quantified the density of cells expressing channelrhodopsin-2 and modeled light propagation in the tissue. We estimated the effectively illuminated volume and numbers of optogenetically stimulated neurons, being indicative of sparse activation. At the functional level, upon either sensory or optogenetic stimulation we detected single-peak short-latency primary Ca2+ responses with similar amplitudes and found that blood oxygenation level-dependent responses showed similar time courses. These data suggest that ofMRI can serve as a representative model for functional brain mapping. PMID:26661247

  10. Assessing sensory versus optogenetic network activation by combining (o)fMRI with optical Ca2+ recordings.

    Science.gov (United States)

    Schmid, Florian; Wachsmuth, Lydia; Schwalm, Miriam; Prouvot, Pierre-Hugues; Jubal, Eduardo Rosales; Fois, Consuelo; Pramanik, Gautam; Zimmer, Claus; Faber, Cornelius; Stroh, Albrecht

    2016-11-01

    Encoding of sensory inputs in the cortex is characterized by sparse neuronal network activation. Optogenetic stimulation has previously been combined with fMRI (ofMRI) to probe functional networks. However, for a quantitative optogenetic probing of sensory-driven sparse network activation, the level of similarity between sensory and optogenetic network activation needs to be explored. Here, we complement ofMRI with optic fiber-based population Ca 2+ recordings for a region-specific readout of neuronal spiking activity in rat brain. Comparing Ca 2+ responses to the blood oxygenation level-dependent signal upon sensory stimulation with increasing frequencies showed adaptation of Ca 2+ transients contrasted by an increase of blood oxygenation level-dependent responses, indicating that the optical recordings convey complementary information on neuronal network activity to the corresponding hemodynamic response. To study the similarity of optogenetic and sensory activation, we quantified the density of cells expressing channelrhodopsin-2 and modeled light propagation in the tissue. We estimated the effectively illuminated volume and numbers of optogenetically stimulated neurons, being indicative of sparse activation. At the functional level, upon either sensory or optogenetic stimulation we detected single-peak short-latency primary Ca 2+ responses with similar amplitudes and found that blood oxygenation level-dependent responses showed similar time courses. These data suggest that ofMRI can serve as a representative model for functional brain mapping. © The Author(s) 2015.

  11. [The distribution of NADPH-diaphorase and neuronal no synthase in rat medulla oblongata nuclei].

    Science.gov (United States)

    Chertok, V M; Kotsuba, A E

    2013-01-01

    The distribution of nitroxide ergic neurons in the medulla oblongata nuclei in Wistar rats (n = 8) was studied histochemically (NADPH-diaphorase) and using immunohistochemistry with an antiserum against neuronal form of nitric oxide synthase (nNOS). NADPH-diaphorase activity was found in large and small neurons of the sensory, autonomic and motor nuclei. The latter were especially rich in the cells demonstrating the activity of the enzyme. Unlike NADPH-diaphorase, nNOS in the corresponding nuclei was always detected in the fewer number of neurons, predominantly of small sizes. The sensory nuclei (nucleus of solitary tract, reticular parvocellular and lateral nuclei, spinal nucleus of the trigeminal nerve) contained 1.5-3 times more nNOS neurons than in motor nuclei. In some nuclei (nucleus ambiguus, hypoglossal nerve nucleus), containing numerous NADPH-diaphorase-positive neurons, immunoreactive cells were particularly rare.

  12. 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.

  13. The Effects of Motor Neurone Disease on Language: Further Evidence

    Science.gov (United States)

    Bak, Thomas H.; Hodges, John R.

    2004-01-01

    It might sound surprising that Motor Neurone Disease (MND), regarded still by many as the very example of a neurodegenerative disease affecting selectively the motor system and sparing the sensory functions as well as cognition, can have a significant influence on language. In this article we hope to demonstrate that language dysfunction is not…

  14. Corticothalamic Synaptic Noise as a Mechanism for Selective Attention in Thalamic Neurons

    Science.gov (United States)

    Béhuret, Sébastien; Deleuze, Charlotte; Bal, Thierry

    2015-01-01

    A reason why the thalamus is more than a passive gateway for sensory signals is that two-third of the synapses of thalamocortical neurons are directly or indirectly related to the activity of corticothalamic axons. While the responses of thalamocortical neurons evoked by sensory stimuli are well characterized, with ON- and OFF-center receptive field structures, the prevalence of synaptic noise resulting from neocortical feedback in intracellularly recorded thalamocortical neurons in vivo has attracted little attention. However, in vitro and modeling experiments point to its critical role for the integration of sensory signals. Here we combine our recent findings in a unified framework suggesting the hypothesis that corticothalamic synaptic activity is adapted to modulate the transfer efficiency of thalamocortical neurons during selective attention at three different levels: First, on ionic channels by interacting with intrinsic membrane properties, second at the neuron level by impacting on the input-output gain, and third even more effectively at the cell assembly level by boosting the information transfer of sensory features encoded in thalamic subnetworks. This top-down population control is achieved by tuning the correlations in subthreshold membrane potential fluctuations and is adapted to modulate the transfer of sensory features encoded by assemblies of thalamocortical relay neurons. We thus propose that cortically-controlled (de-)correlation of subthreshold noise is an efficient and swift dynamic mechanism for selective attention in the thalamus. PMID:26733818

  15. Corticothalamic Synaptic Noise as a Mechanism for Selective Attention in Thalamic Neurons.

    Science.gov (United States)

    Béhuret, Sébastien; Deleuze, Charlotte; Bal, Thierry

    2015-01-01

    A reason why the thalamus is more than a passive gateway for sensory signals is that two-third of the synapses of thalamocortical neurons are directly or indirectly related to the activity of corticothalamic axons. While the responses of thalamocortical neurons evoked by sensory stimuli are well characterized, with ON- and OFF-center receptive field structures, the prevalence of synaptic noise resulting from neocortical feedback in intracellularly recorded thalamocortical neurons in vivo has attracted little attention. However, in vitro and modeling experiments point to its critical role for the integration of sensory signals. Here we combine our recent findings in a unified framework suggesting the hypothesis that corticothalamic synaptic activity is adapted to modulate the transfer efficiency of thalamocortical neurons during selective attention at three different levels: First, on ionic channels by interacting with intrinsic membrane properties, second at the neuron level by impacting on the input-output gain, and third even more effectively at the cell assembly level by boosting the information transfer of sensory features encoded in thalamic subnetworks. This top-down population control is achieved by tuning the correlations in subthreshold membrane potential fluctuations and is adapted to modulate the transfer of sensory features encoded by assemblies of thalamocortical relay neurons. We thus propose that cortically-controlled (de-)correlation of subthreshold noise is an efficient and swift dynamic mechanism for selective attention in the thalamus.

  16. Corticothalamic Synaptic Noise as a Mechanism for Selective Attention in Thalamic Neurons

    Directory of Open Access Journals (Sweden)

    Sébastien eBéhuret

    2015-12-01

    Full Text Available A reason why the thalamus is more than a passive gateway for sensory signals is that two-third of the synapses of thalamocortical neurons are directly or indirectly related to the activity of corticothalamic axons. While the responses of thalamocortical neurons evoked by sensory stimuli are well characterized, with ON- and OFF-center receptive field structures, the prevalence of synaptic noise resulting from neocortical feedback in intracellularly recorded thalamocortical neurons in vivo has attracted little attention. However, in vitro and modeling experiments point to its critical role for the integration of sensory signals. Here we combine our recent findings in a unified framework suggesting the hypothesis that corticothalamic synaptic activity is adapted to modulate the transfer efficiency of thalamocortical neurons during selective attention at three different levels: First, on ionic channels by interacting with intrinsic membrane properties, second at the neuron level by impacting on the input-output gain, and third even more effectively at the cell assembly level by boosting the information transfer of sensory features encoded in thalamic subnetworks. This top-down population control is achieved by tuning the correlations in subthreshold membrane potential fluctuations and is adapted to modulate the transfer of sensory features encoded by assemblies of thalamocortical relay neurons. We thus propose that cortically-controlled (de-correlation of subthreshold noise is an efficient and swift dynamic mechanism for selective attention in the thalamus.

  17. Sensory Cortical Plasticity Participates in the Epigenetic Regulation of Robust Memory Formation

    Science.gov (United States)

    Phan, Mimi L.; Bieszczad, Kasia M.

    2016-01-01

    Neuroplasticity remodels sensory cortex across the lifespan. A function of adult sensory cortical plasticity may be capturing available information during perception for memory formation. The degree of experience-dependent remodeling in sensory cortex appears to determine memory strength and specificity for important sensory signals. A key open question is how plasticity is engaged to induce different degrees of sensory cortical remodeling. Neural plasticity for long-term memory requires the expression of genes underlying stable changes in neuronal function, structure, connectivity, and, ultimately, behavior. Lasting changes in transcriptional activity may depend on epigenetic mechanisms; some of the best studied in behavioral neuroscience are DNA methylation and histone acetylation and deacetylation, which, respectively, promote and repress gene expression. One purpose of this review is to propose epigenetic regulation of sensory cortical remodeling as a mechanism enabling the transformation of significant information from experiences into content-rich memories of those experiences. Recent evidence suggests how epigenetic mechanisms regulate highly specific reorganization of sensory cortical representations that establish a widespread network for memory. Thus, epigenetic mechanisms could initiate events to establish exceptionally persistent and robust memories at a systems-wide level by engaging sensory cortical plasticity for gating what and how much information becomes encoded. PMID:26881129

  18. Sensory Cortical Plasticity Participates in the Epigenetic Regulation of Robust Memory Formation.

    Science.gov (United States)

    Phan, Mimi L; Bieszczad, Kasia M

    2016-01-01

    Neuroplasticity remodels sensory cortex across the lifespan. A function of adult sensory cortical plasticity may be capturing available information during perception for memory formation. The degree of experience-dependent remodeling in sensory cortex appears to determine memory strength and specificity for important sensory signals. A key open question is how plasticity is engaged to induce different degrees of sensory cortical remodeling. Neural plasticity for long-term memory requires the expression of genes underlying stable changes in neuronal function, structure, connectivity, and, ultimately, behavior. Lasting changes in transcriptional activity may depend on epigenetic mechanisms; some of the best studied in behavioral neuroscience are DNA methylation and histone acetylation and deacetylation, which, respectively, promote and repress gene expression. One purpose of this review is to propose epigenetic regulation of sensory cortical remodeling as a mechanism enabling the transformation of significant information from experiences into content-rich memories of those experiences. Recent evidence suggests how epigenetic mechanisms regulate highly specific reorganization of sensory cortical representations that establish a widespread network for memory. Thus, epigenetic mechanisms could initiate events to establish exceptionally persistent and robust memories at a systems-wide level by engaging sensory cortical plasticity for gating what and how much information becomes encoded.

  19. Sensory Cortical Plasticity Participates in the Epigenetic Regulation of Robust Memory Formation

    Directory of Open Access Journals (Sweden)

    Mimi L. Phan

    2016-01-01

    Full Text Available Neuroplasticity remodels sensory cortex across the lifespan. A function of adult sensory cortical plasticity may be capturing available information during perception for memory formation. The degree of experience-dependent remodeling in sensory cortex appears to determine memory strength and specificity for important sensory signals. A key open question is how plasticity is engaged to induce different degrees of sensory cortical remodeling. Neural plasticity for long-term memory requires the expression of genes underlying stable changes in neuronal function, structure, connectivity, and, ultimately, behavior. Lasting changes in transcriptional activity may depend on epigenetic mechanisms; some of the best studied in behavioral neuroscience are DNA methylation and histone acetylation and deacetylation, which, respectively, promote and repress gene expression. One purpose of this review is to propose epigenetic regulation of sensory cortical remodeling as a mechanism enabling the transformation of significant information from experiences into content-rich memories of those experiences. Recent evidence suggests how epigenetic mechanisms regulate highly specific reorganization of sensory cortical representations that establish a widespread network for memory. Thus, epigenetic mechanisms could initiate events to establish exceptionally persistent and robust memories at a systems-wide level by engaging sensory cortical plasticity for gating what and how much information becomes encoded.

  20. Multiple time scales of adaptation in auditory cortex neurons.

    Science.gov (United States)

    Ulanovsky, Nachum; Las, Liora; Farkas, Dina; Nelken, Israel

    2004-11-17

    Neurons in primary auditory cortex (A1) of cats show strong stimulus-specific adaptation (SSA). In probabilistic settings, in which one stimulus is common and another is rare, responses to common sounds adapt more strongly than responses to rare sounds. This SSA could be a correlate of auditory sensory memory at the level of single A1 neurons. Here we studied adaptation in A1 neurons, using three different probabilistic designs. We showed that SSA has several time scales concurrently, spanning many orders of magnitude, from hundreds of milliseconds to tens of seconds. Similar time scales are known for the auditory memory span of humans, as measured both psychophysically and using evoked potentials. A simple model, with linear dependence on both short-term and long-term stimulus history, provided a good fit to A1 responses. Auditory thalamus neurons did not show SSA, and their responses were poorly fitted by the same model. In addition, SSA increased the proportion of failures in the responses of A1 neurons to the adapting stimulus. Finally, SSA caused a bias in the neuronal responses to unbiased stimuli, enhancing the responses to eccentric stimuli. Therefore, we propose that a major function of SSA in A1 neurons is to encode auditory sensory memory on multiple time scales. This SSA might play a role in stream segregation and in binding of auditory objects over many time scales, a property that is crucial for processing of natural auditory scenes in cats and of speech and music in humans.

  1. Development of myenteric cholinergic neurons in ChAT-Cre;R26R-YFP mice.

    Science.gov (United States)

    Hao, Marlene M; Bornstein, Joel C; Young, Heather M

    2013-10-01

    Cholinergic neurons are the major excitatory neurons of the enteric nervous system (ENS), and include intrinsic sensory neurons, interneurons, and excitatory motor neurons. Cholinergic neurons have been detected in the embryonic ENS; however, the development of these neurons has been difficult to study as they are difficult to detect prior to birth using conventional immunohistochemistry. In this study we used ChAT-Cre;R26R-YFP mice to examine the development of cholinergic neurons in the gut of embryonic and postnatal mice. Cholinergic (YFP+) neurons were first detected at embryonic day (E)11.5, and the proportion of cholinergic neurons gradually increased during pre- and postnatal development. At birth, myenteric cholinergic neurons comprised less than half of their adult proportions in the small intestine (25% of myenteric neurons were YFP+ at P0 compared to 62% in adults). The earliest cholinergic neurons appear to mainly project anally. Projections into the presumptive circular muscle were first observed at E14.5. A subpopulation of cholinergic neurons coexpress calbindin through embryonic and postnatal development, but only a small proportion coexpressed neuronal nitric oxide synthase. Our study shows that cholinergic neurons in the ENS develop over a protracted period of time. © 2013 Wiley Periodicals, Inc.

  2. Mirror Neurons Modeled Through Spike-Timing-Dependent Plasticity are Affected by Channelopathies Associated with Autism Spectrum Disorder.

    Science.gov (United States)

    Antunes, Gabriela; Faria da Silva, Samuel F; Simoes de Souza, Fabio M

    2018-06-01

    Mirror neurons fire action potentials both when the agent performs a certain behavior and watches someone performing a similar action. Here, we present an original mirror neuron model based on the spike-timing-dependent plasticity (STDP) between two morpho-electrical models of neocortical pyramidal neurons. Both neurons fired spontaneously with basal firing rate that follows a Poisson distribution, and the STDP between them was modeled by the triplet algorithm. Our simulation results demonstrated that STDP is sufficient for the rise of mirror neuron function between the pairs of neocortical neurons. This is a proof of concept that pairs of neocortical neurons associating sensory inputs to motor outputs could operate like mirror neurons. In addition, we used the mirror neuron model to investigate whether channelopathies associated with autism spectrum disorder could impair the modeled mirror function. Our simulation results showed that impaired hyperpolarization-activated cationic currents (Ih) affected the mirror function between the pairs of neocortical neurons coupled by STDP.

  3. The 'sensory tolerance limit': A hypothetical construct determining exercise performance?

    Science.gov (United States)

    Hureau, Thomas J; Romer, Lee M; Amann, Markus

    2018-02-01

    Neuromuscular fatigue compromises exercise performance and is determined by central and peripheral mechanisms. Interactions between the two components of fatigue can occur via neural pathways, including feedback and feedforward processes. This brief review discusses the influence of feedback and feedforward mechanisms on exercise limitation. In terms of feedback mechanisms, particular attention is given to group III/IV sensory neurons which link limb muscle with the central nervous system. Central corollary discharge, a copy of the neural drive from the brain to the working muscles, provides a signal from the motor system to sensory systems and is considered a feedforward mechanism that might influence fatigue and consequently exercise performance. We highlight findings from studies supporting the existence of a 'critical threshold of peripheral fatigue', a previously proposed hypothesis based on the idea that a negative feedback loop operates to protect the exercising limb muscle from severe threats to homeostasis during whole-body exercise. While the threshold theory remains to be disproven within a given task, it is not generalisable across different exercise modalities. The 'sensory tolerance limit', a more theoretical concept, may address this issue and explain exercise tolerance in more global terms and across exercise modalities. The 'sensory tolerance limit' can be viewed as a negative feedback loop which accounts for the sum of all feedback (locomotor muscles, respiratory muscles, organs, and muscles not directly involved in exercise) and feedforward signals processed within the central nervous system with the purpose of regulating the intensity of exercise to ensure that voluntary activity remains tolerable.

  4. Sensory conflict in motion sickness: An observer theory approach

    Science.gov (United States)

    Oman, Charles M.

    1989-01-01

    Motion sickness is the general term describing a group of common nausea syndromes originally attributed to motion-induced cerebral ischemia, stimulation of abdominal organ afferent, or overstimulation of the vestibular organs of the inner ear. Sea-, car-, and airsicknesses are the most commonly experienced examples. However, the discovery of other variants such as Cinerama-, flight simulator-, spectacle-, and space sickness in which the physical motion of the head and body is normal or absent has led to a succession of sensory conflict theories which offer a more comprehensive etiologic perspective. Implicit in the conflict theory is the hypothesis that neutral and/or humoral signals originate in regions of the brain subversing spatial orientation, and that these signals somehow traverse to other centers mediating sickness symptoms. Unfortunately, the present understanding of the neurophysiological basis of motion sickness is far from complete. No sensory conflict neuron or process has yet been physiologically identified. To what extent can the existing theory be reconciled with current knowledge of the physiology and pharmacology of nausea and vomiting. The stimuli which causes sickness, synthesizes a contemporary Observer Theory view of the Sensory Conflict hypothesis are reviewed, and a revised model for the dynamic coupling between the putative conflict signals and nausea magnitude estimates is presented. The use of quantitative models for sensory conflict offers a possible new approach to improving the design of visual and motion systems for flight simulators and other virtual environment display systems.

  5. Performance limitations of relay neurons.

    Directory of Open Access Journals (Sweden)

    Rahul Agarwal

    Full Text Available Relay cells are prevalent throughout sensory systems and receive two types of inputs: driving and modulating. The driving input contains receptive field properties that must be transmitted while the modulating input alters the specifics of transmission. For example, the visual thalamus contains relay neurons that receive driving inputs from the retina that encode a visual image, and modulating inputs from reticular activating system and layer 6 of visual cortex that control what aspects of the image will be relayed back to visual cortex for perception. What gets relayed depends on several factors such as attentional demands and a subject's goals. In this paper, we analyze a biophysical based model of a relay cell and use systems theoretic tools to construct analytic bounds on how well the cell transmits a driving input as a function of the neuron's electrophysiological properties, the modulating input, and the driving signal parameters. We assume that the modulating input belongs to a class of sinusoidal signals and that the driving input is an irregular train of pulses with inter-pulse intervals obeying an exponential distribution. Our analysis applies to any [Formula: see text] order model as long as the neuron does not spike without a driving input pulse and exhibits a refractory period. Our bounds on relay reliability contain performance obtained through simulation of a second and third order model, and suggest, for instance, that if the frequency of the modulating input increases or the DC offset decreases, then relay increases. Our analysis also shows, for the first time, how the biophysical properties of the neuron (e.g. ion channel dynamics define the oscillatory patterns needed in the modulating input for appropriately timed relay of sensory information. In our discussion, we describe how our bounds predict experimentally observed neural activity in the basal ganglia in (i health, (ii in Parkinson's disease (PD, and (iii in PD during

  6. Noise and neuronal populations conspire to encode simple waveforms reliably

    Science.gov (United States)

    Parnas, B. R.

    1996-01-01

    Sensory systems rely on populations of neurons to encode information transduced at the periphery into meaningful patterns of neuronal population activity. This transduction occurs in the presence of intrinsic neuronal noise. This is fortunate. The presence of noise allows more reliable encoding of the temporal structure present in the stimulus than would be possible in a noise-free environment. Simulations with a parallel model of signal processing at the auditory periphery have been used to explore the effects of noise and a neuronal population on the encoding of signal information. The results show that, for a given set of neuronal modeling parameters and stimulus amplitude, there is an optimal amount of noise for stimulus encoding with maximum fidelity.

  7. Supervised learning with decision margins in pools of spiking neurons.

    Science.gov (United States)

    Le Mouel, Charlotte; Harris, Kenneth D; Yger, Pierre

    2014-10-01

    Learning to categorise sensory inputs by generalising from a few examples whose category is precisely known is a crucial step for the brain to produce appropriate behavioural responses. At the neuronal level, this may be performed by adaptation of synaptic weights under the influence of a training signal, in order to group spiking patterns impinging on the neuron. Here we describe a framework that allows spiking neurons to perform such "supervised learning", using principles similar to the Support Vector Machine, a well-established and robust classifier. Using a hinge-loss error function, we show that requesting a margin similar to that of the SVM improves performance on linearly non-separable problems. Moreover, we show that using pools of neurons to discriminate categories can also increase the performance by sharing the load among neurons.

  8. Prefrontal Neurons Represent Motion Signals from Across the Visual Field But for Memory-Guided Comparisons Depend on Neurons Providing These Signals.

    Science.gov (United States)

    Wimmer, Klaus; Spinelli, Philip; Pasternak, Tatiana

    2016-09-07

    Visual decisions often involve comparisons of sequential stimuli that can appear at any location in the visual field. The lateral prefrontal cortex (LPFC) in nonhuman primates, shown to play an important role in such comparisons, receives information about contralateral stimuli directly from sensory neurons in the same hemisphere, and about ipsilateral stimuli indirectly from neurons in the opposite hemisphere. This asymmetry of sensory inputs into the LPFC poses the question of whether and how its neurons incorporate sensory information arriving from the two hemispheres during memory-guided comparisons of visual motion. We found that, although responses of individual LPFC neurons to contralateral stimuli were stronger and emerged 40 ms earlier, they carried remarkably similar signals about motion direction in the two hemifields, with comparable direction selectivity and similar direction preferences. This similarity was also apparent around the time of the comparison between the current and remembered stimulus because both ipsilateral and contralateral responses showed similar signals reflecting the remembered direction. However, despite availability in the LPFC of motion information from across the visual field, these "comparison effects" required for the comparison stimuli to appear at the same retinal location. This strict dependence on spatial overlap of the comparison stimuli suggests participation of neurons with localized receptive fields in the comparison process. These results suggest that while LPFC incorporates many key aspects of the information arriving from sensory neurons residing in opposite hemispheres, it continues relying on the interactions with these neurons at the time of generating signals leading to successful perceptual decisions. Visual decisions often involve comparisons of sequential visual motion that can appear at any location in the visual field. We show that during such comparisons, the lateral prefrontal cortex (LPFC) contains

  9. Deriving Dorsal Spinal Sensory Interneurons from Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Sandeep Gupta

    2018-02-01

    Full Text Available Summary: Cellular replacement therapies for neurological conditions use human embryonic stem cell (hESC- or induced pluripotent stem cell (hiPSC-derived neurons to replace damaged or diseased populations of neurons. For the spinal cord, significant progress has been made generating the in-vitro-derived motor neurons required to restore coordinated movement. However, there is as yet no protocol to generate in-vitro-derived sensory interneurons (INs, which permit perception of the environment. Here, we report on the development of a directed differentiation protocol to derive sensory INs for both hESCs and hiPSCs. Two developmentally relevant factors, retinoic acid in combination with bone morphogenetic protein 4, can be used to generate three classes of sensory INs: the proprioceptive dI1s, the dI2s, and mechanosensory dI3s. Critical to this protocol is the competence state of the neural progenitors, which changes over time. This protocol will facilitate developing cellular replacement therapies to reestablish sensory connections in injured patients. : In this article, Gupta and colleagues describe a robust protocol to derive spinal dorsal sensory interneurons from human pluripotent stem cells using the sequential addition of RA and BMP4. They find that neural progenitors must be in the correct competence state to respond to RA/BMP4 as dorsalizing signals. This competence state changes over time and determines the efficiency of the protocol. Keywords: spinal cord, neurons, sensory interneurons, proprioception, mechanosensation, human embryonic stem cells, induced pluripotent stem cells, directed differentiation, primate spinal cord, mouse spinal cord

  10. Analyzing sensory data with R

    CERN Document Server

    Le, Sebastien

    2014-01-01

    Quantitative Descriptive Approaches When panelists rate products according to one single list of attributes Data, sensory issues, notations In practice For experienced users: Measuring the impact of the experimental design on the perception of the products? When products are rated according to one single list of attributesData, sensory issues, notations In practice For experienced users: Adding supplementary information to the product space When products are rated according to several lists

  11. Sensory Dissonance Using Memory Model

    DEFF Research Database (Denmark)

    Jensen, Karl Kristoffer

    2015-01-01

    Music may occur concurrently or in temporal sequences. Current machine-based methods for the estimation of qualities of the music are unable to take into account the influence of temporal context. A method for calculating dissonance from audio, called sensory dissonance is improved by the use of ...... of a memory model. This approach is validated here by the comparison of the sensory dissonance using memory model to data obtained using human subjects....

  12. Direct neuronal glucose uptake Heralds activity-dependent increases in cerebral metabolism

    DEFF Research Database (Denmark)

    Lundgaard, Iben; Li, Baoman; Xie, Lulu

    2015-01-01

    Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using two......-photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice. Anaesthesia suppressed neuronal 2DG-IR uptake and sensory stimulation was associated with a sharp increase in neuronal, but not astrocytic, 2DG-IR uptake. Moreover......, hexokinase, which catalyses the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identify the neuron as the principal locus...

  13. Direct neuronal glucose uptake heralds activity-dependent increases in cerebral metabolism.

    Science.gov (United States)

    Lundgaard, Iben; Li, Baoman; Xie, Lulu; Kang, Hongyi; Sanggaard, Simon; Haswell, John D R; Sun, Wei; Goldman, Siri; Blekot, Solomiya; Nielsen, Michael; Takano, Takahiro; Deane, Rashid; Nedergaard, Maiken

    2015-04-23

    Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using two-photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice. Anaesthesia suppressed neuronal 2DG-IR uptake and sensory stimulation was associated with a sharp increase in neuronal, but not astrocytic, 2DG-IR uptake. Moreover, hexokinase, which catalyses the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identify the neuron as the principal locus of glucose uptake as visualized by functional brain imaging.

  14. Direct neuronal glucose uptake heralds activity-dependent increases in cerebral metabolism

    Science.gov (United States)

    Lundgaard, Iben; Li, Baoman; Xie, Lulu; Kang, Hongyi; Sanggaard, Simon; Haswell, John Douglas R; Sun, Wei; Goldman, Siri; Blekot, Solomiya; Nielsen, Michael; Takano, Takahiro; Deane, Rashid; Nedergaard, Maiken

    2015-01-01

    Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using 2-photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice. Anesthesia suppressed neuronal 2DG-IR uptake and sensory stimulation was associated with a sharp increase in neuronal, but not astrocytic, 2DG-IR uptake. Moreover, hexokinase, which catalyze the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identifies the neuron as the principal locus of glucose uptake as visualized by functional brain imaging. PMID:25904018

  15. Central representation of sensory inputs from the cardio-renal system in Aplysia depilans.

    Science.gov (United States)

    Rózsa, K S; Salánki, J; Véró, M; Kovacević, N; Konjevic, D

    1980-01-01

    Studying the central representation of sensory inputs originating from the heart in Aplysia depilans, it was found that: 1. Neurons responding to heart stimulation can be found in the abdominal, pedal and pleural ganglia alike. 2. The representation of heart input signals was more abundant in the left hemisphere of the abdominal ganglion and in the left pedal and pleural ganglia. 3. The giant neurons of Aplysia depilans can be compared to the homologous cells of Aplysia californica. Two motoneurons (RBHE, LDHI) and one interneuron (L10) proved to be identical in the two subspecies. 4. Sensory inputs originating from the heart may modify the pattern of both heart regulatory motoneurons and interneurons. 5. Nine giant and 19 small neurons of the abdominal ganglion, 3--3 neurons of the right and left pleural ganglion, 6 neurons of the left pedal ganglion responded to heart stimulation. 6. The bursting patterns of cells R15 and L4 were modified to tonic discharge in response to heart stimulation. 7. The representation of sensory inputs originating from the heart is scattered throughout the CNS of Aplysia depilans and heart regulation is based on a feedback mechanism similar to that found in other gastropod species.

  16. Somatosensory neuron types identified by high-coverage single-cell RNA-sequencing and functional heterogeneity

    Science.gov (United States)

    Li, Chang-Lin; Li, Kai-Cheng; Wu, Dan; Chen, Yan; Luo, Hao; Zhao, Jing-Rong; Wang, Sa-Shuang; Sun, Ming-Ming; Lu, Ying-Jin; Zhong, Yan-Qing; Hu, Xu-Ye; Hou, Rui; Zhou, Bei-Bei; Bao, Lan; Xiao, Hua-Sheng; Zhang, Xu

    2016-01-01

    Sensory neurons are distinguished by distinct signaling networks and receptive characteristics. Thus, sensory neuron types can be defined by linking transcriptome-based neuron typing with the sensory phenotypes. Here we classify somatosensory neurons of the mouse dorsal root ganglion (DRG) by high-coverage single-cell RNA-sequencing (10 950 ± 1 218 genes per neuron) and neuron size-based hierarchical clustering. Moreover, single DRG neurons responding to cutaneous stimuli are recorded using an in vivo whole-cell patch clamp technique and classified by neuron-type genetic markers. Small diameter DRG neurons are classified into one type of low-threshold mechanoreceptor and five types of mechanoheat nociceptors (MHNs). Each of the MHN types is further categorized into two subtypes. Large DRG neurons are categorized into four types, including neurexophilin 1-expressing MHNs and mechanical nociceptors (MNs) expressing BAI1-associated protein 2-like 1 (Baiap2l1). Mechanoreceptors expressing trafficking protein particle complex 3-like and Baiap2l1-marked MNs are subdivided into two subtypes each. These results provide a new system for cataloging somatosensory neurons and their transcriptome databases. PMID:26691752

  17. The Significance of Memory in Sensory Cortex.

    Science.gov (United States)

    Muckli, Lars; Petro, Lucy S

    2017-05-01

    Early sensory cortex is typically investigated in response to sensory stimulation, masking the contribution of internal signals. Recently, van Kerkoerle and colleagues reported that attention and memory signals segregate from sensory signals within specific layers of primary visual cortex, providing insight into the role of internal signals in sensory processing. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. The significance of memory in sensory cortex

    OpenAIRE

    Muckli, Lars; Petro, Lucy S.

    2017-01-01

    Early sensory cortex is typically investigated in response to sensory stimulation, masking the contribution of internal signals. Recently, van Kerkoerle and colleagues reported that attention and memory signals segregate from sensory signals within specific layers of primary visual cortex, providing insight into the role of internal signals in sensory processing.

  19. Optimized connectome architecture for sensory-motor integration

    Directory of Open Access Journals (Sweden)

    Jacob C. Worrell

    2017-12-01

    Full Text Available The intricate connectivity patterns of neural circuits support a wide repertoire of communication processes and functional interactions. Here we systematically investigate how neural signaling is constrained by anatomical connectivity in the mesoscale Drosophila (fruit fly brain network. We use a spreading model that describes how local perturbations, such as external stimuli, trigger global signaling cascades that spread through the network. Through a series of simple biological scenarios we demonstrate that anatomical embedding potentiates sensory-motor integration. We find that signal spreading is faster from nodes associated with sensory transduction (sensors to nodes associated with motor output (effectors. Signal propagation was accelerated if sensor nodes were activated simultaneously, suggesting a topologically mediated synergy among sensors. In addition, the organization of the network increases the likelihood of convergence of multiple cascades towards effector nodes, thereby facilitating integration prior to motor output. Moreover, effector nodes tend to coactivate more frequently than other pairs of nodes, suggesting an anatomically enhanced coordination of motor output. Altogether, our results show that the organization of the mesoscale Drosophila connectome imparts privileged, behaviorally relevant communication patterns among sensors and effectors, shaping their capacity to collectively integrate information. The complex network spanned by neurons and their axonal projections promotes a diverse set of functions. In the present report, we study how the topological organization of the fruit fly brain supports sensory-motor integration. Using a simple communication model, we demonstrate that the topology of this network allows efficient coordination among sensory and motor neurons. Our results suggest that brain network organization may profoundly shape the functional repertoire of this simple organism.

  20. [Two cases of hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P)].

    Science.gov (United States)

    Mori, Chiaki; Saito, Tomoko; Saito, Toshio; Fujimura, Harutoshi; Sakoda, Saburo

    2015-01-01

    We, herein, report two independent cases with hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) inherited in an autosomal dominant fashion. Their common clinical features are slowly progressive proximal dominant muscular atrophy, fasciculations and mild to moderate distal sensory disturbance with areflexia. Nerve conduction study revealed an absence of sensory nerve action potentials, in contrast to almost normal compound muscle action potentials. Gene analysis in both patients elucidated heterozygous mutation (c.854C>T, p.Pro285Leu) in the TFG, which is an identical mutation, already described by Ishiura et al. Okinawa and Shiga are two foci of HMSN-P in Japan. Eventually, one patient is from Okinawa and the other is from a mountain village in Shiga prefecture. When we see a patient who has symptoms suggestive of motor neuron disease with sensory neuropathy, HMSN-P should be considered as a differential diagnosis despite the patient's actual resident place.

  1. Prenatal VPA exposure and changes in sensory processing by the superior colliculus

    Directory of Open Access Journals (Sweden)

    Georgia eDendrinos

    2011-10-01

    Full Text Available Disorders involving dysfunctional sensory processing are characterized by an inability to filter sensory information, particularly simultaneously arriving multimodal inputs. We examined the effects of prenatal exposure to valproic acid (VPA, a teratogen linked to sensory dysfunction, on the behavior of juvenile and adult rats, and on the anatomy of the superior colliculus, a critical multisensory integration center in the brain. VPA-exposed rats showed deficits in colliculus-dependent behaviors including startle response, prepulse inhibition and nociceptive responses. Some deficits reversed with age. Stereological analyses revealed that colliculi of VPA-treated rats had significantly fewer parvalbumin-positive neurons, a subset of GABAergic cells. These results suggest that prenatal VPA treatment affects the development of the superior colliculus and leads to persistent anatomical changes evidenced by aberrant behavior in tasks that require sensory processing.

  2. Sensory memory for odors is encoded in spontaneous correlated activity between olfactory glomeruli.

    Science.gov (United States)

    Galán, Roberto F; Weidert, Marcel; Menzel, Randolf; Herz, Andreas V M; Galizia, C Giovanni

    2006-01-01

    Sensory memory is a short-lived persistence of a sensory stimulus in the nervous system, such as iconic memory in the visual system. However, little is known about the mechanisms underlying olfactory sensory memory. We have therefore analyzed the effect of odor stimuli on the first odor-processing network in the honeybee brain, the antennal lobe, which corresponds to the vertebrate olfactory bulb. We stained output neurons with a calcium-sensitive dye and measured across-glomerular patterns of spontaneous activity before and after a stimulus. Such a single-odor presentation changed the relative timing of spontaneous activity across glomeruli in accordance with Hebb's theory of learning. Moreover, during the first few minutes after odor presentation, correlations between the spontaneous activity fluctuations suffice to reconstruct the stimulus. As spontaneous activity is ubiquitous in the brain, modifiable fluctuations could provide an ideal substrate for Hebbian reverberations and sensory memory in other neural systems.

  3. Thoracic spinal cord and cervical vagosympathetic neuromodulation obtund nodose sensory transduction of myocardial ischemia.

    Science.gov (United States)

    Salavatian, Siamak; Beaumont, Eric; Gibbons, David; Hammer, Matthew; Hoover, Donald B; Armour, J Andrew; Ardell, Jeffrey L

    2017-12-01

    Autonomic regulation therapy involving either vagus nerve stimulation (VNS) or spinal cord stimulation (SCS) represents emerging bioelectronic therapies for heart disease. The objective of this study was to determine if VNS and/or SCS modulate primary cardiac afferent sensory transduction of the ischemic myocardium. Using extracellular recordings in 19 anesthetized canines, of 88 neurons evaluated, 36 ventricular-related nodose ganglia sensory neurons were identified by their functional activity responses to epicardial touch, chemical activation of their sensory neurites (epicardial veratridine) and great vessel (descending aorta or inferior vena cava) occlusion. Neural responses to 1min left anterior descending (LAD) coronary artery occlusion (CAO) were then evaluated. These interventions were then studied following either: i) SCS [T1-T3 spinal level; 50Hz, 90% motor threshold] or ii) cervical VNS [15-20Hz; 1.2× threshold]. LAD occlusion activated 66% of identified nodose ventricular sensory neurons (0.33±0.08-0.79±0.20Hz; baseline to CAO; p<0.002). Basal activity of cardiac-related nodose neurons was differentially reduced by VNS (0.31±0.11 to 0.05±0.02Hz; p<0.05) as compared to SCS (0.36±0.12 to 0.28±0.14, p=0.59), with their activity response to transient LAD CAO being suppressed by either SCS (0.85±0.39-0.11±0.04Hz; p<0.03) or VNS (0.75±0.27-0.12±0.05Hz; p<0.04). VNS did not alter evoked neural responses of cardiac-related nodose neurons to great vessel occlusion. Both VNS and SCS obtund ventricular ischemia induced enhancement of nodose afferent neuronal inputs to the medulla. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Binding by asynchrony: the neuronal phase code

    Directory of Open Access Journals (Sweden)

    Zoltan Nadasdy

    2010-09-01

    Full Text Available Neurons display continuous subthreshold oscillations and discrete action potentials. When action potentials are phase-locked to the subthreshold oscillation, we hypothesize they represent two types of information: the presence/absence of a sensory feature and the phase of subthreshold oscillation. If subthreshold oscillation phases are neuron-specific, then the sources of action potentials can be recovered based on the action potential times. If the spatial information about the stimulus is converted to action potential phases, then action potentials from multiple neurons can be combined into a single axon and the spatial configuration reconstructed elsewhere. For the reconstruction to be successful, we introduce two assumptions: that a subthreshold oscillation field has a constant phase gradient and that coincidences between action potentials and intracellular subthreshold oscillations are neuron-specific as defined by the "interference principle." Under these assumptions, a phase coding model enables information transfer between structures and reproduces experimental phenomenons such as phase precession, grid cell architecture, and phase modulation of cortical spikes. This article reviews a recently proposed neuronal algorithm for information encoding and decoding from the phase of action potentials (Nadasdy 2009. The focus is given to the principles common across different systems instead of emphasizing system specific differences.

  5. Mechano- and Chemo-Sensory Polycystins

    Science.gov (United States)

    Patel, Amanda; Delmas, Patrick; Honoré, Eric

    Polycystins belong to the superfamily of transient receptor potential (TRP) channels and comprise five PKD1-like and three PKD2-like (TRPP) subunits. In this chapter, we review the general properties of polycystins and discuss their specific role in both mechanotransduction and chemoreception. The heteromer PKD1/PKD2 expressed at the membrane of the primary cilium of kidney epithelial cells is proposed to form a mechano-sensitive calcium channel that is opened by physiological fluid flow. Dysfunction or loss of PKD1 or PKD2 polycystin genes may be responsible for the inability of epithelial cells to sense mechanical cues, thus provoking autosomal dominant polycystic kidney disease (ADPKD), one of the most prevalent genetic kidney disorders. pkd1 and pkd2 knock-out mice recapitulate the human disease. Similarly, PKD2 may function as a mechanosensory calcium channel in the immotile monocilia of the developing node transducing leftward flow into an increase in calcium and specifying the left-right axis. pkd2, unlike pkd1 knock-out embryos are characterized by right lung isomerism (situs inversus). Mechanical stimuli also induce cleavage and nuclear translocation of the PKD1 C-terminal tail, which enters the nucleus and initiates signaling processes involving the AP-1, STAT6 and P100 pathways. This intraproteolytic mechanism is implicated in the transduction of a change in renal fluid flow to a transcriptional long-term response. The heteromer PKD1L3/PKD2L1 is the basis for acid sensing in specialised sensory cells including the taste bud cells responsible for sour taste. Moreover, PKD1L3/PKD2L1 may be implicated in the chemosensitivity of neurons surrounding the spinal cord canal, sensing protons in the cerebrospinal fluid. These recent results demonstrate that polycystins fulfill a major sensory role in a variety of cells including kidney epithelial cells, taste buds cells and spinal cord neurons. Such mechanisms are involved in short- and long-term physiological

  6. Infection and Transport of Herpes Simplex Virus Type 1 in Neurons: Role of the Cytoskeleton

    Science.gov (United States)

    2018-01-01

    Herpes simplex virus type 1 (HSV-1) is a neuroinvasive human pathogen that has the ability to infect and replicate within epithelial cells and neurons and establish a life-long latent infection in sensory neurons. HSV-1 depends on the host cellular cytoskeleton for entry, replication, and exit. Therefore, HSV-1 has adapted mechanisms to promote its survival by exploiting the microtubule and actin cytoskeletons to direct its active transport, infection, and spread between neurons and epithelial cells during primary and recurrent infections. This review will focus on the currently known mechanisms utilized by HSV-1 to harness the neuronal cytoskeleton, molecular motors, and the secretory and exocytic pathways for efficient virus entry, axonal transport, replication, assembly, and exit from the distinct functional compartments (cell body and axon) of the highly polarized sensory neurons. PMID:29473915

  7. Npn-1 contributes to axon-axon interactions that differentially control sensory and motor innervation of the limb.

    Directory of Open Access Journals (Sweden)

    Rosa-Eva Huettl

    2011-02-01

    Full Text Available The initiation, execution, and completion of complex locomotor behaviors are depending on precisely integrated neural circuitries consisting of motor pathways that activate muscles in the extremities and sensory afferents that deliver feedback to motoneurons. These projections form in tight temporal and spatial vicinities during development, yet the molecular mechanisms and cues coordinating these processes are not well understood. Using cell-type specific ablation of the axon guidance receptor Neuropilin-1 (Npn-1 in spinal motoneurons or in sensory neurons in the dorsal root ganglia (DRG, we have explored the contribution of this signaling pathway to correct innervation of the limb. We show that Npn-1 controls the fasciculation of both projections and mediates inter-axonal communication. Removal of Npn-1 from sensory neurons results in defasciculation of sensory axons and, surprisingly, also of motor axons. In addition, the tight coupling between these two heterotypic axonal populations is lifted with sensory fibers now leading the spinal nerve projection. These findings are corroborated by partial genetic elimination of sensory neurons, which causes defasciculation of motor projections to the limb. Deletion of Npn-1 from motoneurons leads to severe defasciculation of motor axons in the distal limb and dorsal-ventral pathfinding errors, while outgrowth and fasciculation of sensory trajectories into the limb remain unaffected. Genetic elimination of motoneurons, however, revealed that sensory axons need only minimal scaffolding by motor axons to establish their projections in the distal limb. Thus, motor and sensory axons are mutually dependent on each other for the generation of their trajectories and interact in part through Npn-1-mediated fasciculation before and within the plexus region of the limbs.

  8. Bayesian Inference and Online Learning in Poisson Neuronal Networks.

    Science.gov (United States)

    Huang, Yanping; Rao, Rajesh P N

    2016-08-01

    Motivated by the growing evidence for Bayesian computation in the brain, we show how a two-layer recurrent network of Poisson neurons can perform both approximate Bayesian inference and learning for any hidden Markov model. The lower-layer sensory neurons receive noisy measurements of hidden world states. The higher-layer neurons infer a posterior distribution over world states via Bayesian inference from inputs generated by sensory neurons. We demonstrate how such a neuronal network with synaptic plasticity can implement a form of Bayesian inference similar to Monte Carlo methods such as particle filtering. Each spike in a higher-layer neuron represents a sample of a particular hidden world state. The spiking activity across the neural population approximates the posterior distribution over hidden states. In this model, variability in spiking is regarded not as a nuisance but as an integral feature that provides the variability necessary for sampling during inference. We demonstrate how the network can learn the likelihood model, as well as the transition probabilities underlying the dynamics, using a Hebbian learning rule. We present results illustrating the ability of the network to perform inference and learning for arbitrary hidden Markov models.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Sensory overload: A concept analysis.

    Science.gov (United States)

    Scheydt, Stefan; Müller Staub, Maria; Frauenfelder, Fritz; Nielsen, Gunnar H; Behrens, Johann; Needham, Ian

    2017-04-01

    In the context of mental disorders sensory overload is a widely described phenomenon used in conjunction with psychiatric interventions such as removal from stimuli. However, the theoretical foundation of sensory overload as addressed in the literature can be described as insufficient and fragmentary. To date, the concept of sensory overload has not yet been sufficiently specified or analyzed. The aim of the study was to analyze the concept of sensory overload in mental health care. A literature search was undertaken using specific electronic databases, specific journals and websites, hand searches, specific library catalogues, and electronic publishing databases. Walker and Avant's method of concept analysis was used to analyze the sources included in the analysis. All aspects of the method of Walker and Avant were covered in this concept analysis. The conceptual understanding has become more focused, the defining attributes, influencing factors and consequences are described and empirical referents identified. The concept analysis is a first step in the development of a middle-range descriptive theory of sensory overload based on social scientific and stress-theoretical approaches. This specification may serve as a fundament for further research, for the development of a nursing diagnosis or for guidelines. © 2017 Australian College of Mental Health Nurses Inc.

  11. Effect of low frequency transcutaneous magnetic stimulation on sensory and motor transmission.

    Science.gov (United States)

    Leung, Albert; Shukla, Shivshil; Lee, Jacquelyn; Metzger-Smith, Valerie; He, Yifan; Chen, Jeffrey; Golshan, Shahrokh

    2015-09-01

    Peripheral nerve injury diminishes fast conducting large myelinated afferent fibers transmission but enhances smaller pain transmitting fibers firing. This aberrant afferent neuronal behavior contributes to development of chronic post-traumatic peripheral neuropathic pain (PTP-NP). Non-invasive dynamic magnetic flux stimulation has been implicated in treating PTP-NP, a condition currently not adequately addressed by other therapies including transcutaneous electrical nerve stimulation (TENS). The current study assessed the effect of low frequency transcutaneous magnetic stimulation (LFTMS) on peripheral sensory thresholds, nerve conduction properties, and TENS induced fast afferent slowing effect as measured by motor and sensory conduction studies in the ulnar nerve. Results indicated sham LFTMS with TENS (Sham + TENS) significantly (P = 0.02 and 0.007, respectively) reduces sensory conduction velocity (CV) and increases sensory onset latency (OL), and motor peak latency (PL) whereas, real LFTMS with TENS (Real + TENS) reverses effects of TENS on sensory CV and OL, and significantly (P = 0.036) increases the sensory PL. LFTMS alone significantly (P sensory PL and onset-to-peak latency. LFTMS appears to reverse TENS slowing effect on fast conducting fibers and casts a selective peripheral modulatory effect on slow conducting pain afferent fibers. © 2015 Wiley Periodicals, Inc.

  12. Channel properties of Nax expressed in neurons.

    Directory of Open Access Journals (Sweden)

    Masahito Matsumoto

    Full Text Available Nax is a sodium-concentration ([Na+]-sensitive Na channel with a gating threshold of ~150 mM for extracellular [Na+] ([Na+]o in vitro. We previously reported that Nax was preferentially expressed in the glial cells of sensory circumventricular organs including the subfornical organ, and was involved in [Na+] sensing for the control of salt-intake behavior. Although Nax was also suggested to be expressed in the neurons of some brain regions including the amygdala and cerebral cortex, the channel properties of Nax have not yet been adequately characterized in neurons. We herein verified that Nax was expressed in neurons in the lateral amygdala of mice using an antibody that was newly generated against mouse Nax. To investigate the channel properties of Nax expressed in neurons, we established an inducible cell line of Nax using the mouse neuroblastoma cell line, Neuro-2a, which is endogenously devoid of the expression of Nax. Functional analyses of this cell line revealed that the [Na+]-sensitivity of Nax in neuronal cells was similar to that expressed in glial cells. The cation selectivity sequence of the Nax channel in cations was revealed to be Na+ ≈ Li+ > Rb+ > Cs+ for the first time. Furthermore, we demonstrated that Nax bound to postsynaptic density protein 95 (PSD95 through its PSD95/Disc-large/ZO-1 (PDZ-binding motif at the C-terminus in neurons. The interaction between Nax and PSD95 may be involved in promoting the surface expression of Nax channels because the depletion of endogenous PSD95 resulted in a decrease in Nax at the plasma membrane. These results indicated, for the first time, that Nax functions as a [Na+]-sensitive Na channel in neurons as well as in glial cells.

  13. Short-term depression and transient memory in sensory cortex.

    Science.gov (United States)

    Gillary, Grant; Heydt, Rüdiger von der; Niebur, Ernst

    2017-12-01

    Persistent neuronal activity is usually studied in the context of short-term memory localized in central cortical areas. Recent studies show that early sensory areas also can have persistent representations of stimuli which emerge quickly (over tens of milliseconds) and decay slowly (over seconds). Traditional positive feedback models cannot explain sensory persistence for at least two reasons: (i) They show attractor dynamics, with transient perturbations resulting in a quasi-permanent change of system state, whereas sensory systems return to the original state after a transient. (ii) As we show, those positive feedback models which decay to baseline lose their persistence when their recurrent connections are subject to short-term depression, a common property of excitatory connections in early sensory areas. Dual time constant network behavior has also been implemented by nonlinear afferents producing a large transient input followed by much smaller steady state input. We show that such networks require unphysiologically large onset transients to produce the rise and decay observed in sensory areas. Our study explores how memory and persistence can be implemented in another model class, derivative feedback networks. We show that these networks can operate with two vastly different time courses, changing their state quickly when new information is coming in but retaining it for a long time, and that these capabilities are robust to short-term depression. Specifically, derivative feedback networks with short-term depression that acts differentially on positive and negative feedback projections are capable of dynamically changing their time constant, thus allowing fast onset and slow decay of responses without requiring unrealistically large input transients.

  14. Contribution of sensory feedback to plantar flexor muscle activation during push-off in adults with cerebral palsy

    DEFF Research Database (Denmark)

    Frisk, Rasmus F.; Jensen, Peter; Kirk, Henrik

    2017-01-01

    applied unload perturbations at the ankle, thereby removing sensory feedback naturally activated during push-off. Reduction of electromyographic (EMG) activity in the soleus muscle caused by unloads was compared and related to kinematics and ankle joint stiffness measurements. Similar measures were...... feedback to ongoing soleus muscle activation during push-off than uninjured individuals. Increased passive stiffness around the ankle joint is likely to diminishn sensory feedback during gait, and/or sensory feedback is less integrated with central motor commands in the activation of spinal motor neurons...

  15. Differences in peripheral sensory input to the olfactory bulb between male and female mice

    Science.gov (United States)

    Kass, Marley D.; Czarnecki, Lindsey A.; Moberly, Andrew H.; McGann, John P.

    2017-04-01

    Female mammals generally have a superior sense of smell than males, but the biological basis of this difference is unknown. Here, we demonstrate sexually dimorphic neural coding of odorants by olfactory sensory neurons (OSNs), primary sensory neurons that physically contact odor molecules in the nose and provide the initial sensory input to the brain’s olfactory bulb. We performed in vivo optical neurophysiology to visualize odorant-evoked OSN synaptic output into olfactory bub glomeruli in unmanipulated (gonad-intact) adult mice from both sexes, and found that in females odorant presentation evoked more rapid OSN signaling over a broader range of OSNs than in males. These spatiotemporal differences enhanced the contrast between the neural representations of chemically related odorants in females compared to males during stimulus presentation. Removing circulating sex hormones makes these signals slower and less discriminable in females, while in males they become faster and more discriminable, suggesting opposite roles for gonadal hormones in influencing male and female olfactory function. These results demonstrate that the famous sex difference in olfactory abilities likely originates in the primary sensory neurons, and suggest that hormonal modulation of the peripheral olfactory system could underlie differences in how males and females experience the olfactory world.

  16. The beauty of sensory ecology.

    Science.gov (United States)

    Otálora-Luna, Fernando; Aldana, Elis

    2017-08-10

    Sensory ecology is a discipline that focuses on how living creatures use information to survive, but not to live. By trans-defining the orthodox concept of sensory ecology, a serious heterodox question arises: how do organisms use their senses to live, i.e. to enjoy or suffer life? To respond to such a query the objective (time-independent) and emotional (non-rational) meaning of symbols must be revealed. Our program is distinct from both the neo-Darwinian and the classical ecological perspective because it does not focus on survival values of phenotypes and their functions, but asks for the aesthetic effect of biological structures and their symbolism. Our message recognizes that sensing apart from having a survival value also has a beauty value. Thus, we offer a provoking and inspiring new view on the sensory relations of 'living things' and their surroundings, where the innovating power of feelings have more weight than the privative power of reason.

  17. Sensory analysis in grapes benitaka

    Energy Technology Data Exchange (ETDEWEB)

    Santillo, Amanda G.; Rodrigues, Flavio T.; Arthur, Paula B.; Villavicencio, Ana Lucia C.H. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    Abstract Sensory analysis is considered one of the main techniques when you want to know the organoleptic qualities of foods. Marketing strategies, showing that some foods produced organically is more nutritious, flavorful than conventional ones are affecting some consumers. The advantages of using radiation in sensory analysis are not the formation of waste, the less nutritional loss and little change in taste of food. The possibility that the fruit is harvested at more advanced maturity, when all characteristics of flavor and external appearance are fully developed is another advantage. The possibility of fruits being packed irradiated prevents contamination after processing. This type of study, ionizing radiation associated with sensory evaluation scarce, making it necessary for future discoveries. The objective this paper was to evaluate the quality of grapes Benitaka after the irradiation process with doses 0,5; 1; 1,5 e 2 kGy. (author)

  18. Sensory analysis in grapes benitaka

    International Nuclear Information System (INIS)

    Santillo, Amanda G.; Rodrigues, Flavio T.; Arthur, Paula B.; Villavicencio, Ana Lucia C.H.

    2011-01-01

    Abstract Sensory analysis is considered one of the main techniques when you want to know the organoleptic qualities of foods. Marketing strategies, showing that some foods produced organically is more nutritious, flavorful than conventional ones are affecting some consumers. The advantages of using radiation in sensory analysis are not the formation of waste, the less nutritional loss and little change in taste of food. The possibility that the fruit is harvested at more advanced maturity, when all characteristics of flavor and external appearance are fully developed is another advantage. The possibility of fruits being packed irradiated prevents contamination after processing. This type of study, ionizing radiation associated with sensory evaluation scarce, making it necessary for future discoveries. The objective this paper was to evaluate the quality of grapes Benitaka after the irradiation process with doses 0,5; 1; 1,5 e 2 kGy. (author)

  19. Sensory feedback plays a significant role in generating walking gait and in gait transition in salamanders: A simulation study

    Directory of Open Access Journals (Sweden)

    Nalin eHarischandra

    2011-11-01

    Full Text Available Here, we use a three-dimensional, neuro-musculo-mechanical model of a salamander with realistic physical parameters in order to investigate the role of sensory feedback in gait generation and transition. Activation of limb and axial muscles were driven by neural output patterns obtained from a central pattern generator (CPG which is composed of simulated spiking neurons with adaptation. The CPG consists of a body CPG and four limb CPGs that are interconnected via synapses both ipsilateraly and contralaterally. We use the model both with and without sensory modulation and for different combinations of ipsilateral and contralateral coupling between the limb CPGs. We found that the proprioceptive sensory inputs are essential in obtaining a coordinated walking gait. The sensory feedback includes the signals coming from the stretch receptor like intraspinal neurons located in the girdle regions and the limb stretch receptors residing in the hip and scapula regions of the salamander. On the other hand, coordinated motor output patterns for the trotting gait were obtainable without the sensory inputs. We found that the gait transition from walking to trotting can be induced by increased activity of the descending drive coming from the mesencephalic locomotor region (MLR and is helped by the sensory inputs at the hip and scapula regions detecting the late stance phase. More neurophysiological experiments are required to identify the precise type of mechanoreceptors in the salamander and the neural mechanisms mediating the sensory modulation.

  20. Neuronal Migration Disorders

    Science.gov (United States)

    ... Understanding Sleep The Life and Death of a Neuron Genes At Work In The Brain Order Publications ... birth defects caused by the abnormal migration of neurons in the developing brain and nervous system. In ...

  1. Motor Neuron Diseases

    Science.gov (United States)

    ... and other neurodegenerative diseases to better understand the function of neurons and other support cells and identify candidate therapeutic ... and other neurodegenerative diseases to better understand the function of neurons and other support cells and identify candidate therapeutic ...

  2. Mutations in the Heme Exporter FLVCR1 Cause Sensory Neurodegeneration with Loss of Pain Perception.

    Science.gov (United States)

    Chiabrando, Deborah; Castori, Marco; di Rocco, Maja; Ungelenk, Martin; Gießelmann, Sebastian; Di Capua, Matteo; Madeo, Annalisa; Grammatico, Paola; Bartsch, Sophie; Hübner, Christian A; Altruda, Fiorella; Silengo, Lorenzo; Tolosano, Emanuela; Kurth, Ingo

    2016-12-01

    Pain is necessary to alert us to actual or potential tissue damage. Specialized nerve cells in the body periphery, so called nociceptors, are fundamental to mediate pain perception and humans without pain perception are at permanent risk for injuries, burns and mutilations. Pain insensitivity can be caused by sensory neurodegeneration which is a hallmark of hereditary sensory and autonomic neuropathies (HSANs). Although mutations in several genes were previously associated with sensory neurodegeneration, the etiology of many cases remains unknown. Using next generation sequencing in patients with congenital loss of pain perception, we here identify bi-allelic mutations in the FLVCR1 (Feline Leukemia Virus subgroup C Receptor 1) gene, which encodes a broadly expressed heme exporter. Different FLVCR1 isoforms control the size of the cytosolic heme pool required to sustain metabolic activity of different cell types. Mutations in FLVCR1 have previously been linked to vision impairment and posterior column ataxia in humans, but not to HSAN. Using fibroblasts and lymphoblastoid cell lines from patients with sensory neurodegeneration, we here show that the FLVCR1-mutations reduce heme export activity, enhance oxidative stress and increase sensitivity to programmed cell death. Our data link heme metabolism to sensory neuron maintenance and suggest that intracellular heme overload causes early-onset degeneration of pain-sensing neurons in humans.

  3. Anatomical Inputs From the Sensory and Value Structures to the Tail of the Rat Striatum

    Directory of Open Access Journals (Sweden)

    Haiyan Jiang

    2018-05-01

    Full Text Available The caudal region of the rodent striatum, called the tail of the striatum (TS, is a relatively small area but might have a distinct function from other striatal subregions. Recent primate studies showed that this part of the striatum has a unique function in encoding long-term value memory of visual objects for habitual behavior. This function might be due to its specific connectivity. We identified inputs to the rat TS and compared those with inputs to the dorsomedial striatum (DMS in the same animals. The TS directly received anatomical inputs from both sensory structures and value-coding regions, but the DMS did not. First, inputs from the sensory cortex and sensory thalamus to the TS were found; visual, auditory, somatosensory and gustatory cortex and thalamus projected to the TS but not to the DMS. Second, two value systems innervated the TS; dopamine and serotonin neurons in the lateral part of the substantia nigra pars compacta (SNc and dorsal raphe nucleus projected to the TS, respectively. The DMS received inputs from the separate group of dopamine neurons in the medial part of the SNc. In addition, learning-related regions of the limbic system innervated the TS; the temporal areas and the basolateral amygdala selectively innervated the TS, but not the DMS. Our data showed that both sensory and value-processing structures innervated the TS, suggesting its plausible role in value-guided sensory-motor association for habitual behavior.

  4. Mutations in the Heme Exporter FLVCR1 Cause Sensory Neurodegeneration with Loss of Pain Perception.

    Directory of Open Access Journals (Sweden)

    Deborah Chiabrando

    2016-12-01

    Full Text Available Pain is necessary to alert us to actual or potential tissue damage. Specialized nerve cells in the body periphery, so called nociceptors, are fundamental to mediate pain perception and humans without pain perception are at permanent risk for injuries, burns and mutilations. Pain insensitivity can be caused by sensory neurodegeneration which is a hallmark of hereditary sensory and autonomic neuropathies (HSANs. Although mutations in several genes were previously associated with sensory neurodegeneration, the etiology of many cases remains unknown. Using next generation sequencing in patients with congenital loss of pain perception, we here identify bi-allelic mutations in the FLVCR1 (Feline Leukemia Virus subgroup C Receptor 1 gene, which encodes a broadly expressed heme exporter. Different FLVCR1 isoforms control the size of the cytosolic heme pool required to sustain metabolic activity of different cell types. Mutations in FLVCR1 have previously been linked to vision impairment and posterior column ataxia in humans, but not to HSAN. Using fibroblasts and lymphoblastoid cell lines from patients with sensory neurodegeneration, we here show that the FLVCR1-mutations reduce heme export activity, enhance oxidative stress and increase sensitivity to programmed cell death. Our data link heme metabolism to sensory neuron maintenance and suggest that intracellular heme overload causes early-onset degeneration of pain-sensing neurons in humans.

  5. Heterogeneous sensory innervation and extensive intrabulbar connections of olfactory necklace glomeruli.

    Directory of Open Access Journals (Sweden)

    Renee E Cockerham

    Full Text Available The mammalian nose employs several olfactory subsystems to recognize and transduce diverse chemosensory stimuli. These subsystems differ in their anatomical position within the nasal cavity, their targets in the olfactory forebrain, and the transduction mechanisms they employ. Here we report that they can also differ in the strategies they use for stimulus coding. Necklace glomeruli are the sole main olfactory bulb (MOB targets of an olfactory sensory neuron (OSN subpopulation distinguished by its expression of the receptor guanylyl cyclase GC-D and the phosphodiesterase PDE2, and by its chemosensitivity to the natriuretic peptides uroguanylin and guanylin and the gas CO(2. In stark contrast to the homogeneous sensory innervation of canonical MOB glomeruli from OSNs expressing the same odorant receptor (OR, we find that each necklace glomerulus of the mouse receives heterogeneous innervation from at least two distinct sensory neuron populations: one expressing GC-D and PDE2, the other expressing olfactory marker protein. In the main olfactory system it is thought that odor identity is encoded by a combinatorial strategy and represented in the MOB by a pattern of glomerular activation. This combinatorial coding scheme requires functionally homogeneous sensory inputs to individual glomeruli by OSNs expressing the same OR and displaying uniform stimulus selectivity; thus, activity in each glomerulus reflects the stimulation of a single OSN type. The heterogeneous sensory innervation of individual necklace glomeruli by multiple, functionally distinct, OSN subtypes precludes a similar combinatorial coding strategy in this olfactory subsystem.

  6. Sensory coding by cerebellar mossy fibres through inhibition-driven phase resetting and synchronisation.

    Directory of Open Access Journals (Sweden)

    Tahl Holtzman

    Full Text Available Temporal coding of spike-times using oscillatory mechanisms allied to spike-time dependent plasticity could represent a powerful mechanism for neuronal communication. However, it is unclear how temporal coding is constructed at the single neuronal level. Here we investigate a novel class of highly regular, metronome-like neurones in the rat brainstem which form a major source of cerebellar afferents. Stimulation of sensory inputs evoked brief periods of inhibition that interrupted the regular firing of these cells leading to phase-shifted spike-time advancements and delays. Alongside phase-shifting, metronome cells also behaved as band-pass filters during rhythmic sensory stimulation, with maximal spike-stimulus synchronisation at frequencies close to the idiosyncratic firing frequency of each neurone. Phase-shifting and band-pass filtering serve to temporally align ensembles of metronome cells, leading to sustained volleys of near-coincident spike-times, thereby transmitting synchronised sensory information to downstream targets in the cerebellar cortex.

  7. Sensory Coding by Cerebellar Mossy Fibres through Inhibition-Driven Phase Resetting and Synchronisation

    Science.gov (United States)

    Holtzman, Tahl; Jörntell, Henrik

    2011-01-01

    Temporal coding of spike-times using oscillatory mechanisms allied to spike-time dependent plasticity could represent a powerful mechanism for neuronal communication. However, it is unclear how temporal coding is constructed at the single neuronal level. Here we investigate a novel class of highly regular, metronome-like neurones in the rat brainstem which form a major source of cerebellar afferents. Stimulation of sensory inputs evoked brief periods of inhibition that interrupted the regular firing of these cells leading to phase-shifted spike-time advancements and delays. Alongside phase-shifting, metronome cells also behaved as band-pass filters during rhythmic sensory stimulation, with maximal spike-stimulus synchronisation at frequencies close to the idiosyncratic firing frequency of each neurone. Phase-shifting and band-pass filtering serve to temporally align ensembles of metronome cells, leading to sustained volleys of near-coincident spike-times, thereby transmitting synchronised sensory information to downstream targets in the cerebellar cortex. PMID:22046297

  8. Relationships among Sensory Responsiveness, Anxiety, and Ritual Behaviors in Children with and without Atypical Sensory Responsiveness.

    Science.gov (United States)

    Bart, Orit; Bar-Shalita, Tami; Mansour, Hanin; Dar, Reuven

    2017-08-01

    To explore relationships between sensory responsiveness, anxiety, and ritual behaviors in boys with typical and atypical sensory responsiveness. Forty-eight boys, ages 5-9 participated in the study (28 boys with atypical sensory responsiveness and 20 controls). Atypical sensory responsiveness was defined as a score of ≤154 on the Short Sensory Profile. Parents completed the Sensory Profile, the Screen for Child Anxiety Related Emotional Disorders, and the Childhood Routines Inventory. Children with atypical sensory responsiveness had significantly higher levels of anxiety and a higher frequency of ritual behaviors than controls. Atypical sensory responsiveness was significantly related to both anxiety and ritual behaviors, with anxiety mediating the relationship between sensory modulation and ritual behaviors. The findings elucidate the potential consequences of atypical sensory responsiveness and could support the notion that ritual behaviors develop as a coping mechanism in response to anxiety stemming from primary difficulty in modulating sensory input.

  9. Peripheral injury of pelvic visceral sensory nerves alters GFRa (GDNF family receptor alpha localization in sensory and autonomic pathways of the sacral spinal cord

    Directory of Open Access Journals (Sweden)

    Shelley Lynne Forrest

    2015-04-01

    Full Text Available GDNF (glial cell line-derived neurotrophic factor, neurturin and artemin use their co-receptors (GFRα1, GFRα2 and GFRα3, respectively and the tyrosine kinase Ret for downstream signalling. In rodent dorsal root ganglia (DRG most of the unmyelinated and some myelinated sensory afferents express at least one GFRα. The adult function of these receptors is not completely elucidated but their activity after peripheral nerve injury can facilitate peripheral and central axonal regeneration, recovery of sensation, and sensory hypersensitivity that contributes to pain. Our previous immunohistochemical studies of spinal cord and sciatic nerve injuries in adult rodents have identified characteristic changes in GFRα1, GFRα2 or GFRα3 in central spinal cord axons of sensory neurons located in dorsal root ganglia. Here we extend and contrast this analysis by studying injuries of the pelvic and hypogastric nerves that contain the majority of sensory axons projecting to the pelvic viscera (e.g., bladder and lower bowel. At 7 d, we detected some effects of pelvic but not hypogastric nerve transection on the ipsilateral spinal cord. In sacral (L6-S1 cord ipsilateral to nerve injury, GFRα1-immunoreactivity (IR was increased in medial dorsal horn and CGRP-IR was decreased in lateral dorsal horn. Pelvic nerve injury also upregulated GFRα1- and GFRα3-IR terminals and GFRα1-IR neuronal cell bodies in the sacral parasympathetic nucleus that provides the spinal parasympathetic preganglionic output to the pelvic nerve. This evidence suggests peripheral axotomy has different effects on somatic and visceral sensory input to the spinal cord, and identifies sensory-autonomic interactions as a possible site of post-injury regulation.

  10. Multi-sensory Sculpting (MSS)

    DEFF Research Database (Denmark)

    von Wallpach, Sylvia; Kreuzer, Maria

    2013-01-01

    -conscious and modality-specific level and use multi-sensory metaphors to express embodied knowledge. Retrieving embodied brand knowledge requires methods that (a) stimulate various senses that have been involved in brand knowledge formation and (b) give consumers the opportunity to express themselves metaphorically...

  11. Subtype-Specific Corticostriatal Projection Neuron Developmental Gene Expression and Corticospinal Expression of the Paroxysmal Nonkinesigenic Dyskinesia Gene

    OpenAIRE

    Xu, Zhaoying

    2016-01-01

    The mammalian neocortex is responsible for motor control, integration of sensory information, perception, cognitive function, and consciousness. It is complex, yet highly organized, with six layers containing broad classes of excitatory projection neurons (along with interneurons) with diverse subtype and area identities. Corticostriatal projection neurons (CStrPN) are the major cortical efferent neurons connecting the cerebral cortex to the striatum of the basal ganglia, and are critically i...

  12. A Hebbian learning rule gives rise to mirror neurons and links them to control theoretic inverse models

    OpenAIRE

    Hanuschkin, A.; Ganguli, S.; Hahnloser, R. H. R.

    2013-01-01

    Mirror neurons are neurons whose responses to the observation of a motor act resemble responses measured during production of that act. Computationally, mirror neurons have been viewed as evidence for the existence of internal inverse models. Such models, rooted within control theory, map-desired sensory targets onto the motor commands required to generate those targets. To jointly explore both the formation of mirrored responses and their functional contribution to inverse models, we develop...

  13. Cortical plasticity as a mechanism for storing Bayesian priors in sensory perception.

    Science.gov (United States)

    Köver, Hania; Bao, Shaowen

    2010-05-05

    Human perception of ambiguous sensory signals is biased by prior experiences. It is not known how such prior information is encoded, retrieved and combined with sensory information by neurons. Previous authors have suggested dynamic encoding mechanisms for prior information, whereby top-down modulation of firing patterns on a trial-by-trial basis creates short-term representations of priors. Although such a mechanism may well account for perceptual bias arising in the short-term, it does not account for the often irreversible and robust changes in perception that result from long-term, developmental experience. Based on the finding that more frequently experienced stimuli gain greater representations in sensory cortices during development, we reasoned that prior information could be stored in the size of cortical sensory representations. For the case of auditory perception, we use a computational model to show that prior information about sound frequency distributions may be stored in the size of primary auditory cortex frequency representations, read-out by elevated baseline activity in all neurons and combined with sensory-evoked activity to generate a perception that conforms to Bayesian integration theory. Our results suggest an alternative neural mechanism for experience-induced long-term perceptual bias in the context of auditory perception. They make the testable prediction that the extent of such perceptual prior bias is modulated by both the degree of cortical reorganization and the magnitude of spontaneous activity in primary auditory cortex. Given that cortical over-representation of frequently experienced stimuli, as well as perceptual bias towards such stimuli is a common phenomenon across sensory modalities, our model may generalize to sensory perception, rather than being specific to auditory perception.

  14. Unimodal primary sensory cortices are directly connected by long-range horizontal projections in the rat sensory cortex

    Directory of Open Access Journals (Sweden)

    Jimmy eStehberg

    2014-09-01

    Full Text Available Research based on functional imaging and neuronal recordings in the barrel cortex subdivision of primary somatosensory cortex (SI of the adult rat has revealed novel aspects of structure-function relationships in this cortex. Specifically, it has demonstrated that single whisker stimulation evokes subthreshold neuronal activity that spreads symmetrically within gray matter from the appropriate barrel area, crosses cytoarchitectural borders of SI and reaches deeply into other unimodal primary cortices such as primary auditory (AI and primary visual (VI. It was further demonstrated that this spread is supported by a spatially matching underlying diffuse network of border-crossing, long-range projections that could also reach deeply into AI and VI. Here we seek to determine whether such a network of border-crossing, long-range projections is unique to barrel cortex or characterizes also other primary, unimodal sensory cortices and therefore could directly connect them. Using anterograde (BDA and retrograde (CTb tract-tracing techniques, we demonstrate that such diffuse horizontal networks directly and mutually connect VI, AI and SI. These findings suggest that diffuse, border-crossing axonal projections connecting directly primary cortices are an important organizational motif common to all major primary sensory cortices in the rat. Potential implications of these findings for topics including cortical structure-function relationships, multisensory integration, functional imaging and cortical parcellation are discussed.

  15. Validity of Sensory Systems as Distinct Constructs

    OpenAIRE

    Su, Chia-Ting; Parham, L. Diane

    2014-01-01

    Confirmatory factor analysis testing whether sensory questionnaire items represented distinct sensory system constructs found, using data from two age groups, that such constructs can be measured validly using questionnaire data.

  16. Nutritive, Post-ingestive Signals Are the Primary Regulators of AgRP Neuron Activity

    Directory of Open Access Journals (Sweden)

    Zhenwei Su

    2017-12-01

    Full Text Available Summary: The brain regulates food intake by processing sensory cues and peripheral physiological signals, but the neural basis of this integration remains unclear. Hypothalamic, agouti-related protein (AgRP-expressing neurons are critical regulators of food intake. AgRP neuron activity is high during hunger and is rapidly reduced by the sight and smell of food. Here, we reveal two distinct components of AgRP neuron activity regulation: a rapid but transient sensory-driven signal and a slower, sustained calorie-dependent signal. We discovered that nutrients are necessary and sufficient for sustained reductions in AgRP neuron activity and that activity reductions are proportional to the calories obtained. This change in activity is recapitulated by exogenous administration of gut-derived satiation signals. Furthermore, we showed that the nutritive value of food trains sensory systems—in a single trial—to drive rapid, anticipatory AgRP neuron activity inhibition. Together, these data demonstrate that nutrients are the primary regulators of AgRP neuron activity. : Su et al. demonstrate that nutrient content in the GI tract is rapidly signaled to hypothalamic neurons activated by hunger. This rapid effect is mediated by three satiation signals that synergistically reduce the activity of AgRP neurons. These findings uncover how hunger circuits in the brain are regulated and raise the possibility that hunger can be pharmacologically controlled. Keywords: calcium imaging, AgRP neurons, calories, satiation signals, sensory regulation, single trial learning, cholecystokinin, CCK, peptide tyrosine tyrosine, PYY, amylin, homeostasis

  17. Microtubules are organized independently of the centrosome in Drosophila neurons

    Directory of Open Access Journals (Sweden)

    Nguyen Michelle M

    2011-12-01

    Full Text Available Abstract Background The best-studied arrangement of microtubules is that organized by the centrosome, a cloud of microtubule nucleating and anchoring proteins is clustered around centrioles. However, noncentrosomal microtubule arrays are common in many differentiated cells, including neurons. Although microtubules are not anchored at neuronal centrosomes, it remains unclear whether the centrosome plays a role in organizing neuronal microtubules. We use Drosophila as a model system to determine whether centrosomal microtubule nucleation is important in mature neurons. Results In developing and mature neurons, centrioles were not surrounded by the core nucleation protein γ-tubulin. This suggests that the centrioles do not organize functional centrosomes in Drosophila neurons in vivo. Consistent with this idea, centriole position was not correlated with a specific region of the cell body in neurons, and growing microtubules did not cluster around the centriole, even after axon severing when the number of growing plus ends is dramatically increased. To determine whether the centrosome was required for microtubule organization in mature neurons, we used two approaches. First, we used DSas-4 centriole duplication mutants. In these mutants, centrioles were present in many larval sensory neurons, but they were not fully functional. Despite reduced centriole function, microtubule orientation was normal in axons and dendrites. Second, we used laser ablation to eliminate the centriole, and again found that microtubule polarity in axons and dendrites was normal, even 3 days after treatment. Conclusion We conclude that the centrosome is not a major site of microtubule nucleation in Drosophila neurons, and is not required for maintenance of neuronal microtubule organization in these cells.

  18. 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