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Sample records for catecholaminergic neurons isolated

  1. Acute action of rotenone on excitability of catecholaminergic neurons in rostral ventrolateral medulla.

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    Zhang, Zhaoqiang; Shi, Limin; Du, Xixun; Jiao, Qian; Jiang, Hong

    2017-09-01

    The degeneration of the rostral ventrolateral medulla (RVLM) catecholaminergic neurons was responsible for some cardiovascular symptoms in Parkinson's disease (PD). Our previous study had observed the impairment of these neurons in the early stage of PD in the rotenone-induced PD rat model, but the related mechanisms remain unclear. Rotenone is a mitochondrial inhibitor, influencing the neuronal electrophysiological activity through activation of K-ATP channels that potentially participate in cell death processes. In the present study, effects of rotenone on electrophysiological properties of RVLM catecholaminergic neurons and its underlying mechanisms were investigated. In coronal slices of brain containing the RVLM through patch clamp technique, rotenone (0.5μM) induced gradual postsynaptic inhibition on the spontaneous firing and cell membrane hyperpolarization with outward currents of catecholaminergic neurons. The electrophysiological changes were blocked by glibenclamide (30μM), a blocker of K-ATP channels, and were nearly unchanged by diazoxide (100μM), an opener of K-ATP channels. Our results also showed that effects of rotenone on catecholaminergic neurons including reactive oxygen species (ROS) generation were prevented by pretreatment of coenzyme Q10 (CoQ10, 100μM), a scavenger of ROS. These suggest that rotenone-induced electrophysiological changes of RVLM catecholaminergic neurons are caused by the opening of K-ATP channels, which are partly related to ROS generation. The changes of K-ATP channels might account for the vulnerability of RVLM catecholaminergic neurons. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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

    2017-05-01

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

  3. Impaired mTORC2 signaling in catecholaminergic neurons exaggerates high fat diet-induced hyperphagia

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    Olga I. Dadalko

    2015-09-01

    Conclusions: Our data support a model in which mTORC2 signaling within catecholaminergic neurons constrains consumption of a high-fat diet, while disruption causes high-fat diet-specific exaggerated hyperphagia. In parallel, impaired mTORC2 signaling leads to aberrant striatal DA neurotransmission, which has been associated with obesity in human and animal models, as well as with escalating substance abuse. These data suggest that defects localized to the catecholaminergic pathways are capable of overriding homeostatic circuits, leading to obesity, metabolic impairment, and aberrant DA-dependent behaviors.

  4. Depletion of catecholaminergic neurons of the rostral ventrolateral medulla in multiple systems atrophy with autonomic failure

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    Benarroch, E. E.; Smithson, I. L.; Low, P. A.; Parisi, J. E.

    1998-01-01

    The ventrolateral portion of the intermediate reticular formation of the medulla (ventrolateral medulla, VLM), including the C1/A1 groups of catecholaminergic neurons, is thought to be involved in control of sympathetic cardiovascular outflow, cardiorespiratory interactions, and reflex control of vasopressin release. As all these functions are affected in patients with multiple systems atrophy (MSA) with autonomic failure, we sought to test the hypothesis that catecholaminergic (tyrosine hydroxylase [TH]-positive) neurons of the VLM are depleted in these patients. Medullas were obtained at autopsy from 4 patients with MSA with prominent autonomic failure and 5 patients with no neurological disease. Patients with MSA had laboratory evidence of severe adrenergic sudomotor and cardiovagal failure. Tissue was immersion fixed in 2% paraformaldehyde at 4 degrees C for 24 hours and cut into 1-cm blocks in the coronal plane from throughout the medulla. Serial 50-microm sections were collected and one section every 300 microm was stained for TH. There was a pronounced depletion of TH neurons in the rostral VLM in all cases of MSA. There was also significant reduction of TH neurons in the caudal VLM in 3 MSA patients compared with 3 control subjects. In 2 MSA cases and in 2 control subjects, the thoracic spinal cord was available for study. There was also depletion of TH fibers and sympathetic preganglionic neurons (SPNs) in the 2 MSA cases examined. Thus, depletion of catecholaminergic neurons in the VLM may provide a substrate for some of the autonomic and endocrine manifestations of MSA.

  5. MIDBRAIN CATECHOLAMINERGIC NEURONS CO-EXPRESS α-SYNUCLEIN AND TAU IN PROGRESSIVE SUPRANUCLEAR PALSY

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    María Elena eErro Aguirre

    2015-03-01

    Full Text Available Objective: To analyze the frequency and distribution of α-synuclein deposits in progressive supranuclear palsy (PSP.Methods: The brains of 25 cases of pathologically confirmed PSP were evaluated with immunohistochemistry for α-synuclein and tau. Multiple immunofluorescent stains were applied to analyze the expression of tau and α-synuclein aggregates in catecholaminergic neurons. Patients’ clinical symptoms were retrospectively recorded. Results: Deposits α-synuclein in the form of typical Lewy bodies (LBs were only found in two PSP cases (8% that fulfilled the clinical subtype of PSP known as Richardson’s syndrome (RS. LBs were present in the locus ceruleus, substantia nigra pars compacta, basal forebrain, amygdala and cingulated cortex in a distribution mimicking that of Parkinson’s disease. Triple-immunolabeling revealed co-expression of α-synuclein and tau proteins in some tyrosine hydroxilase-positive neurons of the locus ceruleus and substantia nigra pars compacta.Conclusions: There is no apparent clinical correlation between the presence of LBs in PSP. Tau protein co-aggregate with α-synuclein in catecholaminergic neurons of PSP brains suggesting a synergistic interaction between the two proteins. This is in keeping with the current view of neurodegenerative disorders as ‘misfolded protein diseases’.

  6. Control of sympathetic vasomotor tone by catecholaminergic C1 neurones of the rostral ventrolateral medulla oblongata

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    Marina, Nephtali; Abdala, Ana P.L.; Korsak, Alla; Simms, Annabel E.; Allen, Andrew M.; Paton, Julian F.R.; Gourine, Alexander V.

    2011-01-01

    Aims Increased sympathetic tone in obstructive sleep apnoea results from recurrent episodes of systemic hypoxia and hypercapnia and might be an important contributor to the development of cardiovascular disease. In this study, we re-evaluated the role of a specific population of sympathoexcitatory catecholaminergic C1 neurones of the rostral ventrolateral medulla oblongata in the control of sympathetic vasomotor tone, arterial blood pressure, and hypercapnia-evoked sympathetic and cardiovascular responses. Methods and results In anaesthetized rats in vivo and perfused rat working heart brainstem preparations in situ, C1 neurones were acutely silenced by application of the insect peptide allatostatin following cell-specific targeting with a lentiviral vector to express the inhibitory Drosophila allatostatin receptor. In anaesthetized rats with denervated peripheral chemoreceptors, acute inhibition of 50% of the C1 neuronal population resulted in ∼50% reduction in renal sympathetic nerve activity and a profound fall in arterial blood pressure (by ∼25 mmHg). However, under these conditions systemic hypercapnia still evoked vigorous sympathetic activation and the slopes of the CO2-evoked sympathoexcitatory and cardiovascular responses were not affected by inhibition of C1 neurones. Inhibition of C1 neurones in situ resulted in a reversible fall in perfusion pressure and the amplitude of respiratory-related bursts of thoracic sympathetic nerve activity. Conclusion These data confirm a fundamental physiological role of medullary catecholaminergic C1 neurones in maintaining resting sympathetic vasomotor tone and arterial blood pressure. However, C1 neurones do not appear to mediate sympathoexcitation evoked by central actions of CO2. PMID:21543384

  7. Deletion of Rictor in catecholaminergic neurons alters locomotor activity and ingestive behavior.

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    Kaska, Sophia; Brunk, Rebecca; Bali, Vedrana; Kechner, Megan; Mazei-Robison, Michelle S

    2017-05-01

    While the etiology of depression is not fully understood, increasing evidence from animal models suggests a role for the ventral tegmental area (VTA) in pathogenesis. In this paper, we investigate the potential role of VTA mechanistic target of rapamycin 2 (TORC2) signaling in mediating susceptibility to chronic social defeat stress (CSDS), a well-established mouse model of depression. Utilizing genetic and viral knockout of Rictor (rapamycin-insensitive companion of target of rapamycin), a requisite component of TORC2, we demonstrate that decreasing Rictor-dependent TORC2 signaling in catecholaminergic neurons, or within the VTA specifically, does not alter susceptibility to CSDS. Opiate abuse and mood disorders are often comorbid, and previous data demonstrate a role for VTA TORC2 in mediating opiate reward. Thus, we also investigated its potential role in mediating changes in opiate reward following CSDS. Catecholaminergic deletion of Rictor increases water, sucrose, and morphine intake but not preference in a two-bottle choice assay in stress-naïve mice, and these effects are maintained after stress. VTA-specific knockout of Rictor increases water and sucrose intake after physical CSDS, but does not alter consummatory behavior in the absence of stress. These findings suggest a novel role for TORC2 in mediating stress-induced changes in consummatory behaviors that may contribute to some aspects of mood disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. (-)Deprenyl and (-)1-phenyl-2-propylaminopentane, [(-)PPAP], act primarily as potent stimulants of action potential-transmitter release coupling in the catecholaminergic neurons.

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    Knoll, J; Miklya, I; Knoll, B; Markó, R; Kelemen, K

    1996-01-01

    The activity of the catecholaminergic neurons in the rat brain is enhanced significantly 30 min after the subcutaneous injection of very small doses of (-)deprenyl (threshold doses: 0.01 mg/kg for noradrenergic neurons and 0.025 mg/kg for dopaminergic neurons). As a catecholaminergic activity enhancer (CAE) substance (-)deprenyl is about ten times more potent than its parent compound, (-)methamphetamine. While the (+)methamphetamine is 3-5 times more potent than (-)methamphetammine in releasing catecholamines, the (-)methamphetamine is the more potent CAE substance. The mechanism of the CAE effect of (-)deprenyl and (-)PPAP, a deprenyl-derived substance devoid of MAO inhibitory potency, was studied in rats by measuring: a) the release of catecholamines from striatum, substantia nigra, tuberculum olfactorium and locus coeruleus; b) the stimulation induced release of 3H-noradrenaline from the isolated brain stem; and c) the antagonistic effect against tetrabenazine-induced depression of learning in the shuttle box. The CAE effect was found to be unrelated: a) to the inhibition of MAO activity; b) to the inhibition of presynaptic catecholamine receptors; c) to the inhibition of the uptake of catecholamines; and d) to the release of catecholamines. It was concluded that (-)deprenyl and (-)PPAP act primarily as potent stimulants of action potential-transmitter release coupling in the catecholaminergic neurons of the brain. We show that both (-)deprenyl and (-)PPAP enhance the inward Ca2+ current in sino-auricular fibers of the frog heart. (-)PPAP was much more potent than either (+)PPAP or (-)deprenyl in this test.

  9. Divergent projections of catecholaminergic neurons in the nucleus of the solitary tract to limbic forebrain and medullary autonomic brain regions.

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    Reyes, Beverly A S; Van Bockstaele, Elisabeth J

    2006-10-30

    The nucleus of the solitary tract (NTS) is a critical structure involved in coordinating autonomic and visceral activities. Previous independent studies have demonstrated efferent projections from the NTS to the nucleus paragigantocellularis (PGi) and the central nucleus of the amygdala (CNA) in rat brain. To further characterize the neural circuitry originating from the NTS with postsynaptic targets in the amygdala and medullary autonomic targets, distinct green or red fluorescent latex microspheres were injected into the PGi and the CNA, respectively, of the same rat. Thirty-micron thick tissue sections through the lower brainstem and forebrain were collected. Every fourth section through the NTS region was processed for immunocytochemical detection of tyrosine hydroxylase (TH), a marker of catecholaminergic neurons. Retrogradely labeled neurons from the PGi or CNA were distributed throughout the rostro-caudal segments of the NTS. However, the majority of neurons containing both retrograde tracers were distributed within the caudal third of the NTS. Cell counts revealed that approximately 27% of neurons projecting to the CNA in the NTS sent collateralized projections to the PGi while approximately 16% of neurons projecting to the PGi sent collateralized projections to the CNA. Interestingly, more than half of the PGi and CNA-projecting neurons in the NTS expressed TH immunoreactivity. These data indicate that catecholaminergic neurons in the NTS are poised to simultaneously coordinate activities in limbic and medullary autonomic brain regions.

  10. Distribution of Fos-Like Immunoreactivity, Catecholaminergic and Serotoninergic Neurons Activated by the Laryngeal Chemoreflex in the Medulla Oblongata of Rats.

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    Wang, Xiaolu; Guo, Ruichen; Zhao, Wenjing

    2015-01-01

    The laryngeal chemoreflex (LCR) induces apnea, glottis closure, bradycardia and hypertension in young and maturing mammals. We examined the distribution of medullary nuclei that are activated by the LCR and used immunofluorescent detection of Fos protein as a cellular marker for neuronal activation to establish that the medullary catecholaminergic and serotoninergic neurons participate in the modulation of the LCR. The LCR was elicited by the infusion of KCl-HCl solution into the laryngeal lumen of adult rats in the experimental group, whereas the control group received the same surgery but no infusion. In comparison, the number of regions of Fos-like immunoreactivity (FLI) that were activated by the LCR significantly increased in the nucleus of the solitary tract (NTS), the vestibular nuclear complex (VNC), the loose formation of the nucleus ambiguus (AmbL), the rostral ventral respiratory group (RVRG), the ventrolateral reticular complex (VLR), the pre-Bötzinger complex (PrBöt), the Bötzinger complex (Böt), the spinal trigeminal nucleus (SP5), and the raphe obscurus nucleus (ROb) bilaterally from the medulla oblongata. Furthermore, 12.71% of neurons with FLI in the dorsolateral part of the nucleus of the solitary tract (SolDL) showed tyrosine hydroxylase-immunoreactivity (TH-ir, catecholaminergic), and 70.87% of neurons with FLI in the ROb were serotoninergic. Our data demonstrated the distribution of medullary nuclei that were activated by the LCR, and further demonstrated that catecholaminergic neurons of the SolDL and serotoninergic neurons of the ROb were activated by the LCR, indicating the potential central pathway of the LCR.

  11. Distribution of Fos-Like Immunoreactivity, Catecholaminergic and Serotoninergic Neurons Activated by the Laryngeal Chemoreflex in the Medulla Oblongata of Rats.

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    Xiaolu Wang

    Full Text Available The laryngeal chemoreflex (LCR induces apnea, glottis closure, bradycardia and hypertension in young and maturing mammals. We examined the distribution of medullary nuclei that are activated by the LCR and used immunofluorescent detection of Fos protein as a cellular marker for neuronal activation to establish that the medullary catecholaminergic and serotoninergic neurons participate in the modulation of the LCR. The LCR was elicited by the infusion of KCl-HCl solution into the laryngeal lumen of adult rats in the experimental group, whereas the control group received the same surgery but no infusion. In comparison, the number of regions of Fos-like immunoreactivity (FLI that were activated by the LCR significantly increased in the nucleus of the solitary tract (NTS, the vestibular nuclear complex (VNC, the loose formation of the nucleus ambiguus (AmbL, the rostral ventral respiratory group (RVRG, the ventrolateral reticular complex (VLR, the pre-Bötzinger complex (PrBöt, the Bötzinger complex (Böt, the spinal trigeminal nucleus (SP5, and the raphe obscurus nucleus (ROb bilaterally from the medulla oblongata. Furthermore, 12.71% of neurons with FLI in the dorsolateral part of the nucleus of the solitary tract (SolDL showed tyrosine hydroxylase-immunoreactivity (TH-ir, catecholaminergic, and 70.87% of neurons with FLI in the ROb were serotoninergic. Our data demonstrated the distribution of medullary nuclei that were activated by the LCR, and further demonstrated that catecholaminergic neurons of the SolDL and serotoninergic neurons of the ROb were activated by the LCR, indicating the potential central pathway of the LCR.

  12. Differential radioautographic visualization of central catecholaminergic neurons following intracisternal or intraventricular injection of tritiated norepinephrine

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    Nowaczyk, T.; Pujol, J.F.; Valatx, J.L.; Bobillier, P.

    1978-01-01

    The differential [ 3 H]NE labeling of CA groups following cerebrospinal fluid (CSF) injection procedures seems to be accounted by the dynamics of CSF formation and circulation, which is similar in the rat to that known in man. Following intraventricular injection there was a lack of labeling of CA neurons located at a distance from the cerebrospinal cavities. Labeled neurons were also visualized outside known CA groups, questioning the nature and functional significance of these cells. (C.F.)

  13. Rapid metabolism of exogenous angiotensin II by catecholaminergic neuronal cells in culture media.

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    Basu, Urmi; Seravalli, Javier; Madayiputhiya, Nandakumar; Adamec, Jiri; Case, Adam J; Zimmerman, Matthew C

    2015-02-01

    Angiotensin II (AngII) acts on central neurons to increase neuronal firing and induce sympathoexcitation, which contribute to the pathogenesis of cardiovascular diseases including hypertension and heart failure. Numerous studies have examined the precise AngII-induced intraneuronal signaling mechanism in an attempt to identify new therapeutic targets for these diseases. Considering the technical challenges in studying specific intraneuronal signaling pathways in vivo, especially in the cardiovascular control brain regions, most studies have relied on neuronal cell culture models. However, there are numerous limitations in using cell culture models to study AngII intraneuronal signaling, including the lack of evidence indicating the stability of AngII in culture media. Herein, we tested the hypothesis that exogenous AngII is rapidly metabolized in neuronal cell culture media. Using liquid chromatography-tandem mass spectrometry, we measured levels of AngII and its metabolites, Ang III, Ang IV, and Ang-1-7, in neuronal cell culture media after administration of exogenous AngII (100 nmol/L) to a neuronal cell culture model (CATH.a neurons). AngII levels rapidly declined in the media, returning to near baseline levels within 3 h of administration. Additionally, levels of Ang III and Ang-1-7 acutely increased, while levels of Ang IV remained unchanged. Replenishing the media with exogenous AngII every 3 h for 24 h resulted in a consistent and significant increase in AngII levels for the duration of the treatment period. These data indicate that AngII is rapidly metabolized in neuronal cell culture media, and replenishing the media at least every 3 h is needed to sustain chronically elevated levels. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  14. Exposure to advertisement calls of reproductive competitors activates vocal-acoustic and catecholaminergic neurons in the plainfin midshipman fish, Porichthys notatus.

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    Petersen, Christopher L; Timothy, Miky; Kim, D Spencer; Bhandiwad, Ashwin A; Mohr, Robert A; Sisneros, Joseph A; Forlano, Paul M

    2013-01-01

    While the neural circuitry and physiology of the auditory system is well studied among vertebrates, far less is known about how the auditory system interacts with other neural substrates to mediate behavioral responses to social acoustic signals. One species that has been the subject of intensive neuroethological investigation with regard to the production and perception of social acoustic signals is the plainfin midshipman fish, Porichthys notatus, in part because acoustic communication is essential to their reproductive behavior. Nesting male midshipman vocally court females by producing a long duration advertisement call. Females localize males by their advertisement call, spawn and deposit all their eggs in their mate's nest. As multiple courting males establish nests in close proximity to one another, the perception of another male's call may modulate individual calling behavior in competition for females. We tested the hypothesis that nesting males exposed to advertisement calls of other males would show elevated neural activity in auditory and vocal-acoustic brain centers as well as differential activation of catecholaminergic neurons compared to males exposed only to ambient noise. Experimental brains were then double labeled by immunofluorescence (-ir) for tyrosine hydroxylase (TH), an enzyme necessary for catecholamine synthesis, and cFos, an immediate-early gene product used as a marker for neural activation. Males exposed to other advertisement calls showed a significantly greater percentage of TH-ir cells colocalized with cFos-ir in the noradrenergic locus coeruleus and the dopaminergic periventricular posterior tuberculum, as well as increased numbers of cFos-ir neurons in several levels of the auditory and vocal-acoustic pathway. Increased activation of catecholaminergic neurons may serve to coordinate appropriate behavioral responses to male competitors. Additionally, these results implicate a role for specific catecholaminergic neuronal groups in

  15. Immunotoxic destruction of distinct catecholaminergic neuron populations disrupts the reproductive response to glucoprivation in female rats.

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    I'Anson, Helen; Sundling, Lois A; Roland, Shannon M; Ritter, Sue

    2003-10-01

    We tested the hypothesis that hindbrain catecholamine (norepinephrine or epinephrine) neurons, in addition to their essential role in glucoprivic feeding, are responsible for suppressing estrous cycles during chronic glucoprivation. Normally cycling female rats were given bilateral injections of the retrogradely transported ribosomal toxin, saporin, conjugated to monoclonal dopamine beta-hydroxylase antibody (DSAP) into the paraventricular nucleus (PVN) of the hypothalamus to selectively destroy norepinephrine and epinephrine neurons projecting to the PVN. Controls were injected with unconjugated saporin. After recovery, we assessed the lesion effects on estrous cyclicity under basal conditions and found that DSAP did not alter estrous cycle length. Subsequently, we examined effects of chronic 2-deoxy-d-glucose-induced glucoprivation on cycle length. After two normal 4- to 5-d cycles, rats were injected with 2-deoxy-d-glucose (200 mg/kg every 6 h for 72 h) beginning 24 h after detection of estrus. Chronic glucoprivation increased cycle length in seven of eight unconjugated saporin rats but in only one of eight DSAP rats. Immunohistochemical results confirmed loss of dopamine beta-hydroxylase immunoreactivity in PVN. Thus, hindbrain catecholamine neurons with projections to the PVN are required for inhibition of reproductive function during chronic glucose deficit but are not required for normal estrous cyclicity when metabolic fuels are in abundance.

  16. Catecholaminergic contributions to vocal communication signals.

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    Matheson, Laura E; Sakata, Jon T

    2015-05-01

    Social context affects behavioral displays across a variety of species. For example, social context acutely influences the acoustic and temporal structure of vocal communication signals such as speech and birdsong. Despite the prevalence and importance of such social influences, little is known about the neural mechanisms underlying the social modulation of communication. Catecholamines are implicated in the regulation of social behavior and motor control, but the degree to which catecholamines influence vocal communication signals remains largely unknown. Using a songbird, the Bengalese finch, we examined the extent to which the social context in which song is produced affected immediate early gene expression (EGR-1) in catecholamine-synthesising neurons in the midbrain. Further, we assessed the degree to which administration of amphetamine, which increases catecholamine concentrations in the brain, mimicked the effect of social context on vocal signals. We found that significantly more catecholaminergic neurons in the ventral tegmental area and substantia nigra (but not the central grey, locus coeruleus or subcoeruleus) expressed EGR-1 in birds that were exposed to females and produced courtship song than in birds that produced non-courtship song in isolation. Furthermore, we found that amphetamine administration mimicked the effects of social context and caused many aspects of non-courtship song to resemble courtship song. Specifically, amphetamine increased the stereotypy of syllable structure and sequencing, the repetition of vocal elements and the degree of sequence completions. Taken together, these data highlight the conserved role of catecholamines in vocal communication across species, including songbirds and humans. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  17. Distribution and morphology of cholinergic, putative catecholaminergic and serotonergic neurons in the brain of the Egyptian rousette flying fox, Rousettus aegyptiacus.

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    Maseko, Busisiwe C; Bourne, James A; Manger, Paul R

    2007-11-01

    Over the past decade much controversy has surrounded the hypothesis that the megachiroptera, or megabats, share unique neural characteristics with the primates. These observations, which include similarities in visual pathways, have suggested that the megabats are more closely related to the primates than to the other group of the Chiropteran order, the microbats, and suggests a diphyletic origin of the Chiroptera. To contribute data relevant to this debate, we used immunohistochemical techniques to reveal the architecture of the neuromodulatory systems of the Egyptian rousette (Rousettus aegypticus), an echolocating megabat. Our findings revealed many similarities in the nuclear parcellation of the cholinergic, putative catecholaminergic and serotonergic systems with that seen in other mammals including the microbat. However, there were 11 discrete nuclei forming part of these systems in the brain of the megabat studied that were not evident in an earlier study of a microbat. The occurrence of these nuclei align the megabat studied more closely with primates than any other mammalian group and clearly distinguishes them from the microbat, which aligns with the insectivores. The neural systems investigated are not related to such Chiropteran specializations as echolocation, flight, vision or olfaction. If neural characteristics are considered strong indicators of phylogenetic relationships, then the data of the current study strongly supports the diphyletic origin of Chiroptera and aligns the megabat most closely with primates in agreement with studies of other neural characters.

  18. Dorsal Raphe Dopamine Neurons Represent the Experience of Social Isolation

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    Matthews, Gillian A.; Nieh, Edward H.; Vander Weele, Caitlin M.; Halbert, Sarah A.; Pradhan, Roma V.; Yosafat, Ariella S.; Glober, Gordon F.; Izadmehr, Ehsan M.; Thomas, Rain E.; Lacy, Gabrielle D.; Wildes, Craig P.; Ungless, Mark A.; Tye, Kay M.

    2016-01-01

    Summary The motivation to seek social contact may arise from either positive or negative emotional states, as social interaction can be rewarding and social isolation can be aversive. While ventral tegmental area (VTA) dopamine (DA) neurons may mediate social reward, a cellular substrate for the negative affective state of loneliness has remained elusive. Here, we identify a functional role for DA neurons in the dorsal raphe nucleus (DRN), in which we observe synaptic changes following acute social isolation. DRN DA neurons show increased activity upon social contact following isolation, revealed by in vivo calcium imaging. Optogenetic activation of DRN DA neurons increases social preference but causes place avoidance. Furthermore, these neurons are necessary for promoting rebound sociability following an acute period of isolation. Finally, the degree to which these neurons modulate behavior is predicted by social rank, together supporting a role for DRN dopamine neurons in mediating a loneliness-like state. PaperClip PMID:26871628

  19. Catecholaminergic systems in stress: structural and molecular genetic approaches.

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    Kvetnansky, Richard; Sabban, Esther L; Palkovits, Miklos

    2009-04-01

    Stressful stimuli evoke complex endocrine, autonomic, and behavioral responses that are extremely variable and specific depending on the type and nature of the stressors. We first provide a short overview of physiology, biochemistry, and molecular genetics of sympatho-adrenomedullary, sympatho-neural, and brain catecholaminergic systems. Important processes of catecholamine biosynthesis, storage, release, secretion, uptake, reuptake, degradation, and transporters in acutely or chronically stressed organisms are described. We emphasize the structural variability of catecholamine systems and the molecular genetics of enzymes involved in biosynthesis and degradation of catecholamines and transporters. Characterization of enzyme gene promoters, transcriptional and posttranscriptional mechanisms, transcription factors, gene expression and protein translation, as well as different phases of stress-activated transcription and quantitative determination of mRNA levels in stressed organisms are discussed. Data from catecholamine enzyme gene knockout mice are shown. Interaction of catecholaminergic systems with other neurotransmitter and hormonal systems are discussed. We describe the effects of homotypic and heterotypic stressors, adaptation and maladaptation of the organism, and the specificity of stressors (physical, emotional, metabolic, etc.) on activation of catecholaminergic systems at all levels from plasma catecholamines to gene expression of catecholamine enzymes. We also discuss cross-adaptation and the effect of novel heterotypic stressors on organisms adapted to long-term monotypic stressors. The extra-adrenal nonneuronal adrenergic system is described. Stress-related central neuronal regulatory circuits and central organization of responses to various stressors are presented with selected examples of regulatory molecular mechanisms. Data summarized here indicate that catecholaminergic systems are activated in different ways following exposure to distinct

  20. Isolation and culture of adult mouse vestibular nucleus neurons

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    Him, Aydın; Altuntaş, Serap; Öztürk, Gürkan; Erdoğan, Ender; Cengiz, Nureddin

    2017-12-19

    Background/aim: Isolated cell cultures are widely used to study neuronal properties due to their advantages. Although embryonic animals are preferred for culturing, their morphological or electrophysiological properties may not reflect adult neurons, which may be important in neurodegenerative diseases. This paper aims to develop a method for preparing isolated cell cultures of medial vestibular nucleus (MVN) from adult mice and describe its morphological and electrophysiological properties.Materials and methods: Vestibular nucleus neurons were mechanically and enzymatically isolated and cultured using a defined medium with known growth factors. Cell survival was measured with propidium iodide, and electrophysiological properties were investigated with current-clamp recording.Results: Vestibular neurons grew neurites in cultures, gaining adult-like morphological properties, and stayed viable for 3 days in culture. Adding bovine calf serum, nerve growth factor, or insulin-like growth factor into the culture medium enhanced neuronal viability. Current-clamp recording of the cultured neurons revealed tonic and phasic-type neurons with similar input resistance, resting membrane potential, action potential amplitude, and duration. Conclusion: Vestibular neurons from adult mice can be cultured, and regenerate axons in a medium containing appropriate growth factors. Culturing adult vestibular neurons provides a new method to study age-related pathologies of the vestibular system.

  1. Sexually dimorphic neuronal responses to social isolation

    OpenAIRE

    Senst, Laura; Baimoukhametova, Dinara; Sterley, Toni-Lee; Bains, Jaideep Singh

    2016-01-01

    eLife digest Many species, including humans, use social interaction to reduce the effects of stress. In fact, the lack of a social network may itself be a source of stress. Recent research suggests that young girls are more sensitive to social stress than boys. This could mean that social networks are more important for females in general, and that young females from different species, such as mice, may be more sensitive to social isolation than males. However, few studies have examined how s...

  2. Catecholaminergic polymorphic ventricular tachycardia in 2012

    Directory of Open Access Journals (Sweden)

    Christian van der Werf

    2011-12-01

    Full Text Available Catecholaminergic polymorphic ventricular tachycardia (CPVT is a rare, potentially lethal inherited arrhythmia syndrome characterized by stress or emotion-induced ventricular arrhythmias. CPVT was first described in 1960, while the genetic basis underlying this syndrome was discovered in 2001. The past decade has seen substantial advances in understanding the pathophysiology of CPVT. In addition, significant advances have been made in elucidating clinical characteristics of CPVT patients and new treatment options have become available. Here, we review current literature on CPVT to present state-of-the-art knowledge on the subject of the genetic basis, pathophysiology, clinical presentation, diagnosis, treatment and prognosis.

  3. Neurochemistry of neurons in the ventrolateral medulla activated by hypotension: Are the same neurons activated by glucoprivation?

    Science.gov (United States)

    Parker, Lindsay M; Le, Sheng; Wearne, Travis A; Hardwick, Kate; Kumar, Natasha N; Robinson, Katherine J; McMullan, Simon; Goodchild, Ann K

    2017-06-15

    Previous studies have demonstrated that a range of stimuli activate neurons, including catecholaminergic neurons, in the ventrolateral medulla. Not all catecholaminergic neurons are activated and other neurochemical content is largely unknown hence whether stimulus specific populations exist is unclear. Here we determine the neurochemistry (using in situ hybridization) of catecholaminergic and noncatecholaminergic neurons which express c-Fos immunoreactivity throughout the rostrocaudal extent of the ventrolateral medulla, in Sprague Dawley rats treated with hydralazine or saline. Distinct neuronal populations containing PPCART, PPPACAP, and PPNPY mRNAs, which were largely catecholaminergic, were activated by hydralazine but not saline. Both catecholaminergic and noncatecholaminergic neurons containing preprotachykinin and prepro-enkephalin (PPE) mRNAs were also activated, with the noncatecholaminergic population located in the rostral C1 region. Few GlyT2 neurons were activated. A subset of these data was then used to compare the neuronal populations activated by 2-deoxyglucose evoked glucoprivation (Brain Structure and Function (2015) 220:117). Hydralazine activated more neurons than 2-deoxyglucose but similar numbers of catecholaminergic neurons. Commonly activated populations expressing PPNPY and PPE mRNAs were defined. These likely include PPNPY expressing catecholaminergic neurons projecting to vasopressinergic and corticotrophin releasing factor neurons in the paraventricular nucleus, which when activated result in elevated plasma vasopressin and corticosterone. Stimulus specific neurons included noncatecholaminergic neurons and a few PPE positive catecholaminergic neuron but neurochemical codes were largely unidentified. Reasons for the lack of identification of stimulus specific neurons, readily detectable using electrophysiology in anaesthetized preparations and for which neural circuits can be defined, are discussed. © 2017 Wiley Periodicals, Inc.

  4. Enhanced catecholaminergic and serotoninergic activity in rat brain from weaning to sexual maturity: rationale for prophylactic (-)deprenyl (selegiline) medication.

    Science.gov (United States)

    Knoll, J; Miklya, I

    1995-01-01

    Food deprived rats in the late developmental phase of life (2 months of age) are significantly more active than those in the early postdevelopmental phase (4 months of age), pointing to enhanced catecholaminergic activity during the developmental phase. We therefore measured the resting release of dopamine from the striatum, substantia nigra and tuberculum olfactorium, and of noradrenaline from the locus coeruleus, as an indicator of the basic activity of catecholaminergic neurons in the brain, in 2,4,8,16 and 32 weeks old male and female rats. We also measured the release of serotonin from the raphe. Both in male and female rats, the resting release of transmitters from brain catecholaminergic and serotoninergic neurons between weaning and the end of the 2nd month of age, i.e. during the crucial developmental phase of their life, was significantly higher than either before or after that period, signalling a transition from a developmental to a postdevelopmental (aging) phase of life and indicating that safe and effective measures are needed to maintain the catecholaminergic system at a higher activity level during the postdevelopmental phase. Daily administration of low doses (0.01-0.25 mg/kg) of (-)deprenyl for 21 days significantly enhances the resting release of catecholamines and diminishes that of serotonin, providing a rationale for prophylactic medication with this drug during the postdevelopmental lifespan. We also show that (-)methamphetamine, the parent compound of (-)deprenyl and (-)1-phenyl-2-propylaminopentane (PPAP), a deprenyl analogue free of MAO-B inhibitory potency but otherwise possessing the same pharmacological profile as (-)deprenyl, act similarly, furnishing direct evidence that enhancement of catecholaminergic activity in the brain by multiple, small dose administration of (-)deprenyl is unrelated to MAO-B inhibition.

  5. The Isolation of Pure Populations of Neurons by Laser Capture Microdissection: Methods and Application in Neuroscience.

    Science.gov (United States)

    Morris, Renée; Mehta, Prachi

    2018-01-01

    In mammals, the central nervous system (CNS) is constituted of various cellular elements, posing a challenge to isolating specific cell types to investigate their expression profile. As a result, tissue homogenization is not amenable to analyses of motor neurons profiling as these represent less than 10% of the total spinal cord cell population. One way to tackle the problem of tissue heterogeneity and obtain meaningful genomic, proteomic, and transcriptomic profiling is to use laser capture microdissection technology (LCM). In this chapter, we describe protocols for the capture of isolated populations of motor neurons from spinal cord tissue sections and for downstream transcriptomic analysis of motor neurons with RT-PCR. We have also included a protocol for the immunological confirmation that the captured neurons are indeed motor neurons. Although focused on spinal cord motor neurons, these protocols can be easily optimized for the isolation of any CNS neurons.

  6. Left cardiac sympathetic denervation for catecholaminergic polymorphic ventricular tachycardia

    NARCIS (Netherlands)

    Wilde, Arthur A. M.; Bhuiyan, Zahurul A.; Crotti, Lia; Facchini, Mario; de Ferrari, Gaetano M.; Paul, Thomas; Ferrandi, Chiara; Koolbergen, Dave R.; Odero, Attilio; Schwartz, Peter J.

    2008-01-01

    Catecholaminergic polymorphic ventricular tachycardia is a potentially lethal disease characterized by adrenergically mediated ventricular arrhythmias manifested especially in children and teenagers. Beta-blockers are the cornerstone of therapy, but some patients do not have a complete response to

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

    Science.gov (United States)

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

    1996-03-01

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

  8. [Catecholaminergic polymorphic ventricular tachycardia is a rare inherited heart disease.

    DEFF Research Database (Denmark)

    Holst, Anders Gaarsdal; Tfelt-Hansen, 1jacob; Olesen, Morten S

    2010-01-01

    Catecholaminergic polymorphic ventricular tachycardia is a rare inherited heart disease, which can lead to life-threatening ventricular arrhythmias in patients with a structurally normal heart. The age of onset is usually between two and 12 years and the initial symptom is frequently syncope...

  9. Postexertional Supraventricular Tachycardia in Children with Catecholaminergic Polymorphic Ventricular Tachycardia

    Directory of Open Access Journals (Sweden)

    Scott D. N. Else

    2012-01-01

    Full Text Available Catecholaminergic polymorphic ventricular tachycardia (CPVT is a severe arrhythmia associated with sudden death in the young. It is caused by defective calcium handling in ventricular myocytes. The association of supraventricular tachycardia (SVT with CPVT is described in the literature, occurring in the lead-up to ventricular tachycardia during exercise testing. We describe three cases of SVT that were initiated in the recovery period of exercise testing in children with CPVT.

  10. Early-life Social Isolation Impairs the Gonadotropin-Inhibitory Hormone Neuronal Activity and Serotonergic System in Male Rats

    Directory of Open Access Journals (Sweden)

    Tomoko eSoga

    2015-11-01

    Full Text Available Social isolation in early life deregulates the serotonergic system of the brain, compromising reproductive function. Gonadotropin-inhibitory hormone (GnIH neurons in the dorsomedial hypothalamic nucleus are critical to the inhibitory regulation of gonadotropin-releasing hormone neuronal activity in the brain and release of luteinising hormone by the pituitary gland. Although GnIH responds to stress, the role of GnIH in social isolation-induced deregulation of the serotonin system and reproductive function remains unclear. We investigated the effect of social isolation in early life on the serotonergic–GnIH neuronal system using enhanced green fluorescent protein (EGFP-tagged GnIH-transgenic rats. Socially isolated rats were observed for anxious and depressive behaviours. Using immunohistochemistry, we examined c-Fos protein expression in EGFP–GnIH neurons in 9-week-old adult male rats after 6 weeks post-weaning isolation or group -housing. We also inspected serotonergic fibre juxtapositions in EGFP–GnIH neurons in control and socially isolated male rats. Socially isolated rats exhibited anxious and depressive behaviours. The total number of EGFP–GnIH neurons was the same in control and socially isolated rats, but c-Fos expression in GnIH neurons was significantly reduced in socially isolated rats. Serotonin fibre juxtapositions on EGFP–GnIH neurons was also lower in socially isolated rats. In addition, levels of tryptophan hydroxylase mRNA expression in the dorsal raphe nucleus were significantly attenuated in these rats. These results suggest that social isolation in early life results in lower serotonin levels, which reduce GnIH neuronal activity and may lead to reproductive failure.

  11. Early-Life Social Isolation Impairs the Gonadotropin-Inhibitory Hormone Neuronal Activity and Serotonergic System in Male Rats.

    Science.gov (United States)

    Soga, Tomoko; Teo, Chuin Hau; Cham, Kai Lin; Idris, Marshita Mohd; Parhar, Ishwar S

    2015-01-01

    Social isolation in early life deregulates the serotonergic system of the brain, compromising reproductive function. Gonadotropin-inhibitory hormone (GnIH) neurons in the dorsomedial hypothalamic nucleus are critical to the inhibitory regulation of gonadotropin-releasing hormone neuronal activity in the brain and release of luteinizing hormone by the pituitary gland. Although GnIH responds to stress, the role of GnIH in social isolation-induced deregulation of the serotonin system and reproductive function remains unclear. We investigated the effect of social isolation in early life on the serotonergic-GnIH neuronal system using enhanced green fluorescent protein (EGFP)-tagged GnIH transgenic rats. Socially isolated rats were observed for anxious and depressive behaviors. Using immunohistochemistry, we examined c-Fos protein expression in EGFP-GnIH neurons in 9-week-old adult male rats after 6 weeks post-weaning isolation or group housing. We also inspected serotonergic fiber juxtapositions in EGFP-GnIH neurons in control and socially isolated male rats. Socially isolated rats exhibited anxious and depressive behaviors. The total number of EGFP-GnIH neurons was the same in control and socially isolated rats, but c-Fos expression in GnIH neurons was significantly reduced in socially isolated rats. Serotonin fiber juxtapositions on EGFP-GnIH neurons were also lower in socially isolated rats. In addition, levels of tryptophan hydroxylase mRNA expression in the dorsal raphe nucleus were significantly attenuated in these rats. These results suggest that social isolation in early-life results in lower serotonin levels, which reduce GnIH neuronal activity and may lead to reproductive failure.

  12. In Vivo Observation of Structural Changes in Neocortical Catecholaminergic Projections in Response to Drugs of Abuse.

    Science.gov (United States)

    Morimoto, Mai M; Tanaka, Shinji; Mizutani, Shunsuke; Urata, Shinji; Kobayashi, Kazuto; Okabe, Shigeo

    2018-01-01

    Catecholaminergic (dopamine and norepinephrine) projections to the cortex play an important role in cognitive functions and dysfunctions including learning, addiction, and mental disorders. While dynamics of glutamatergic synapses have been well studied in such contexts, little is known regarding catecholaminergic projections, owing to lack of robust methods. Here we report a system to monitor catecholaminergic projections in vivo over the timeframes that such events occur. Green fluorescent protein (GFP) expression driven by tyrosine hydroxylase promoter in a transgenic mouse line enabled us to perform two-photon imaging of cortical catecholaminergic projections through a cranial window. Repetitive imaging of the same axons over 24 h revealed the highly dynamic nature of catecholaminergic boutons. Surprisingly, administration of single high dose methamphetamine (MAP) induced a transient increase in bouton volumes. This new method opens avenues for longitudinal in vivo evaluation of structural changes at single release sites of catecholamines in association with physiology and pathology of cortical functions.

  13. High performing rats are more sensitive toward catecholaminergic activity enhancer (CAE) compounds than their low performing peers.

    Science.gov (United States)

    Knoll, J; Knoll, B; Miklya, I

    1996-01-01

    Two breeds of rats, Charles River Wistar [Crl(Wi)Br.] and HSD Wistar [Wistar per LATI (Budapest) Br.], with remarkable difference in learning performance were selected. The rats were trained in the shuttle box with 100 trials per day and the number of conditioned avoidance responses (CARs), the escape failures (EFs) to the unconditioned stimulus and the intersignal reactions (IRs) were counted and evaluated by multi-way analysis of variance (ANOVA). Rats of the Crl (Wi) breed proved to be the 'low performing' (LP) animals and rats of the Wistar per LATI (Budapest) breed the 'high performing' (HP) ones. The HP rats produced higher number of CARs (pPPAP], which enhances action potential-transmitter release coupling in the catecholaminergic neurons, fully antagonized in a dose of 1 mg/kg, tetrabenazine-induced learning depression in HP rats and this dose was ineffective in LP rats. The findings were regarded as further support for the view that endogenous CAE substances regulate catecholaminergic activity in the brain and (-)PPAP acts via this regulation.

  14. Opioid tolerance in periaqueductal gray neurons isolated from mice chronically treated with morphine.

    Science.gov (United States)

    Bagley, Elena E; Chieng, Billy C H; Christie, MacDonald J; Connor, Mark

    2005-09-01

    The midbrain periaqueductal gray (PAG) is a major site of opioid analgesic action, and a significant site of cellular adaptations to chronic morphine treatment (CMT). We examined mu-opioid receptor (MOP) regulation of voltage-gated calcium channel currents (I(Ca)) and G-protein-activated K channel currents (GIRK) in PAG neurons from CMT mice. Mice were injected s.c. with 300 mg kg(-1) of morphine base in a slow release emulsion three times over 5 days, or with emulsion alone (vehicles). This protocol produced significant tolerance to the antinociceptive effects of morphine in a test of thermal nociception. Voltage clamp recordings were made of I(Ca) in acutely isolated PAG neurons and GIRK in PAG slices. The MOP agonist DAMGO (Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol enkephalin) inhibited I(Ca) in neurons from CMT mice (230 nM) with a similar potency to vehicle (150 nM), but with a reduced maximal effectiveness (37% inhibition in vehicle neurons, 27% in CMT neurons). Inhibition of I(Ca) by the GABA(B) agonist baclofen was not altered by CMT. Met-enkephalin-activated GIRK currents recorded in PAG slices were significantly smaller in neurons from CMT mice than vehicles, while GIRK currents activated by baclofen were unaltered. These data demonstrate that CMT-induced antinociceptive tolerance is accompanied by homologous reduction in the effectiveness of MOP agonists to inhibit I(Ca) and activate GIRK. Thus, a reduction in MOP number and/or functional coupling to G proteins accompanies the characteristic cellular adaptations to CMT previously described in PAG neurons.

  15. Treadmill exercise ameliorates social isolation-induced depression through neuronal generation in rat pups.

    Science.gov (United States)

    Cho, Jung-Wan; Jung, Sun-Young; Lee, Sang-Won; Lee, Sam-Jun; Seo, Tae-Beom; Kim, Young-Pyo; Kim, Dae-Young

    2017-12-01

    Social isolation is known to induce emotional and behavioral changes in animals and humans. The effect of treadmill exercise on depression was investigated using social isolated rat pups. The rat pups in the social isolation groups were housed individually. The rat pups in the exercise groups were forced to run on treadmill for 30 min once a day from postnatal day 21 to postnatal day 34. In order to evaluate depression state of rat pups, forced swimming test was performed. Newly generated cells in the hippocampal dentate gyrus were determined by 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry. We examined the expression of 5-hydroxytryptamine (5-HT) and tryptophan hydroxylase (TPH) in the dorsal raphe using immunofluorescence. The expression of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) was detected by Western blot analysis. The present results demonstrated that social isolation increased resting time and decreased mobility time. Expression of 5-HT and TPH in the dorsal raphe and expression of BDNF and TrkB in the hippocampus were decreased by social isolation. The number of BrdU-positive cells in the hippocampal dentate gyrus was suppressed by social isolation. Treadmill exercise decreased resting time and increased mobility in the social isolated rat pups. Expression of 5-HT, TPH, BDNF, and TrkB was increased by treadmill exercise. The present results suggested that treadmill exercise may ameliorates social isolation-induced depression through increasing neuronal generation.

  16. The catecholaminergic-cholinergic balance hypothesis of bipolar disorder revisited

    Science.gov (United States)

    van Enkhuizen, Jordy; Janowsky, David S; Olivier, Berend; Minassian, Arpi; Perry, William; Young, Jared W; Geyer, Mark A

    2014-01-01

    Bipolar disorder is a unique illness characterized by fluctuations between mood states of depression and mania. Originally, an adrenergic-cholinergic balance hypothesis was postulated to underlie these different affective states. In this review, we update this hypothesis with recent findings from human and animal studies, suggesting that a catecholaminergic-cholinergic hypothesis may be more relevant. Evidence from neuroimaging studies, neuropharmacological interventions, and genetic associations support the notion that increased cholinergic functioning underlies depression, whereas increased activations of the catecholamines (dopamine and norepinephrine) underlie mania. Elevated functional acetylcholine during depression may affect both muscarinic and nicotinic acetylcholine receptors in a compensatory fashion. Increased functional dopamine and norepinephrine during mania on the other hand may affect receptor expression and functioning of dopamine reuptake transporters. Despite increasing evidence supporting this hypothesis, a relationship between these two neurotransmitter systems that could explain cycling between states of depression and mania is missing. Future studies should focus on the influence of environmental stimuli and genetic susceptibilities that may affect the catecholaminergic-cholinergic balance underlying cycling between the affective states. Overall, observations from recent studies add important data to this revised balance theory of bipolar disorder, renewing interest in this field of research. PMID:25107282

  17. Rapid effects of hearing song on catecholaminergic activity in the songbird auditory pathway.

    Directory of Open Access Journals (Sweden)

    Lisa L Matragrano

    Full Text Available Catecholaminergic (CA neurons innervate sensory areas and affect the processing of sensory signals. For example, in birds, CA fibers innervate the auditory pathway at each level, including the midbrain, thalamus, and forebrain. We have shown previously that in female European starlings, CA activity in the auditory forebrain can be enhanced by exposure to attractive male song for one week. It is not known, however, whether hearing song can initiate that activity more rapidly. Here, we exposed estrogen-primed, female white-throated sparrows to conspecific male song and looked for evidence of rapid synthesis of catecholamines in auditory areas. In one hemisphere of the brain, we used immunohistochemistry to detect the phosphorylation of tyrosine hydroxylase (TH, a rate-limiting enzyme in the CA synthetic pathway. We found that immunoreactivity for TH phosphorylated at serine 40 increased dramatically in the auditory forebrain, but not the auditory thalamus and midbrain, after 15 min of song exposure. In the other hemisphere, we used high pressure liquid chromatography to measure catecholamines and their metabolites. We found that two dopamine metabolites, dihydroxyphenylacetic acid and homovanillic acid, increased in the auditory forebrain but not the auditory midbrain after 30 min of exposure to conspecific song. Our results are consistent with the hypothesis that exposure to a behaviorally relevant auditory stimulus rapidly induces CA activity, which may play a role in auditory responses.

  18. Social Isolation Modulates CLOCK Protein and Beta-Catenin Expression Pattern in Gonadotropin-Inhibitory Hormone Neurons in Male Rats

    Directory of Open Access Journals (Sweden)

    Chuin Hau Teo

    2017-09-01

    Full Text Available Postweaning social isolation reduces the amplitude of the daily variation of CLOCK protein in the brain and induces lower reproductive activity. Gonadotropin-inhibitory hormone (GnIH acts as an inhibitor in the reproductive system and has been linked to stress. Social isolation has been shown to lower neuronal activity of GnIH-expressing neurons in the dorsomedial hypothalamus (DMH. The exact mechanism by which social isolation may affect GnIH is still unclear. We investigated the impact of social isolation on regulatory cellular mechanisms in GnIH neurons. We examined via immunohistochemistry the expression of CLOCK protein at four different times throughout the day in GnIH cells tagged with enhanced fluorescent green protein (EGFP-GnIH in 9-week-old adult male rats that have been raised for 6 weeks under postweaning social isolation and compared them with group-raised control rats of the same age. We also studied the expression of β-catenin—which has been shown to be affected by circadian proteins such as Bmal1—in EGFP-GnIH neurons to determine whether it could play a role in linking CLOCK in GnIH neurons. We found that social isolation modifies the pattern of CLOCK expression in GnIH neurons in the DMH. Socially isolated rats displayed greater CLOCK expression in the dark phase, while control rats displayed increased CLOCK expression in the light phase. Furthermore, β-catenin expression pattern in GnIH cells was disrupted by social isolation. This suggests that social isolation triggers changes in CLOCK and GnIH expression, which may be associated with an increase in nuclear β-catenin during the dark phase.

  19. Social Isolation Modulates CLOCK Protein and Beta-Catenin Expression Pattern in Gonadotropin-Inhibitory Hormone Neurons in Male Rats.

    Science.gov (United States)

    Teo, Chuin Hau; Soga, Tomoko; Parhar, Ishwar S

    2017-01-01

    Postweaning social isolation reduces the amplitude of the daily variation of CLOCK protein in the brain and induces lower reproductive activity. Gonadotropin-inhibitory hormone (GnIH) acts as an inhibitor in the reproductive system and has been linked to stress. Social isolation has been shown to lower neuronal activity of GnIH-expressing neurons in the dorsomedial hypothalamus (DMH). The exact mechanism by which social isolation may affect GnIH is still unclear. We investigated the impact of social isolation on regulatory cellular mechanisms in GnIH neurons. We examined via immunohistochemistry the expression of CLOCK protein at four different times throughout the day in GnIH cells tagged with enhanced fluorescent green protein (EGFP-GnIH) in 9-week-old adult male rats that have been raised for 6 weeks under postweaning social isolation and compared them with group-raised control rats of the same age. We also studied the expression of β-catenin-which has been shown to be affected by circadian proteins such as Bmal1-in EGFP-GnIH neurons to determine whether it could play a role in linking CLOCK in GnIH neurons. We found that social isolation modifies the pattern of CLOCK expression in GnIH neurons in the DMH. Socially isolated rats displayed greater CLOCK expression in the dark phase, while control rats displayed increased CLOCK expression in the light phase. Furthermore, β-catenin expression pattern in GnIH cells was disrupted by social isolation. This suggests that social isolation triggers changes in CLOCK and GnIH expression, which may be associated with an increase in nuclear β-catenin during the dark phase.

  20. Flecainide Therapy Reduces Exercise-Induced Ventricular Arrhythmias in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia

    NARCIS (Netherlands)

    van der Werf, Christian; Kannankeril, Prince J.; Sacher, Frederic; Krahn, Andrew D.; Viskin, Sami; Leenhardt, Antoine; Shimizu, Wataru; Sumitomo, Naokata; Fish, Frank A.; Bhuiyan, Zahurul A.; Willems, Albert R.; van der Veen, Maurits J.; Watanabe, Hiroshi; Laborderie, Julien; Haïssaguerre, Michel; Knollmann, Björn C.; Wilde, Arthur A. M.

    2011-01-01

    Objectives This study evaluated the efficacy and safety of flecainide in addition to conventional drug therapy in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT). Background CPVT is an inherited arrhythmia syndrome caused by gene mutations that destabilize cardiac

  1. Risk of catecholaminergic crisis following glucocorticoid administration in patients with an adrenal mass: a literature review

    NARCIS (Netherlands)

    Barrett, C.; Uum, S.H. van; Lenders, J.W.M.

    2015-01-01

    BACKGROUND: Glucocorticoids as diagnostic or therapeutic agents have been reported to carry an increased risk of catecholaminergic crisis (CC) in patients with pheochromocytoma or paraganglioma (PPGL). METHODS: We searched literature databases using the following terms: pheochromocytoma,

  2. Social Isolation During Postweaning Development Causes Hypoactivity of Neurons in the Medial Nucleus of the Male Rat Amygdala

    Science.gov (United States)

    Adams, Thomas; Rosenkranz, J Amiel

    2016-01-01

    Children exposed to neglect or social deprivation are at heightened risk for psychiatric disorders and abnormal social patterns as adults. There is also evidence that prepubertal neglect in children causes abnormal metabolic activity in several brain regions, including the amygdala area. The medial nucleus of the amygdala (MeA) is a key region for performance of social behaviors and still undergoes maturation during the periadolescent period. As such, the normal development of this region may be disrupted by social deprivation. In rodents, postweaning social isolation causes a range of deficits in sexual and agonistic behaviors that normally rely on the posterior MeA (MeAp). However, little is known about the effects of social isolation on the function of MeA neurons. In this study, we tested whether postweaning social isolation caused abnormal activity of MeA neurons. We found that postweaning social isolation caused a decrease of in vivo firing activity of MeAp neurons, and reduced drive from excitatory afferents. In vitro electrophysiological studies found that postweaning social isolation caused a presynaptic impairment of excitatory input to the dorsal MeAp, but a progressive postsynaptic reduction of membrane excitability in the ventral MeAp. These results demonstrate discrete, subnucleus-specific effects of social deprivation on the physiology of MeAp neurons. This pathophysiology may contribute to the disruption of social behavior after developmental social deprivation, and may be a novel target to facilitate the treatment of social disorders. PMID:26677945

  3. Social Isolation During Postweaning Development Causes Hypoactivity of Neurons in the Medial Nucleus of the Male Rat Amygdala.

    Science.gov (United States)

    Adams, Thomas; Rosenkranz, J Amiel

    2016-06-01

    Children exposed to neglect or social deprivation are at heightened risk for psychiatric disorders and abnormal social patterns as adults. There is also evidence that prepubertal neglect in children causes abnormal metabolic activity in several brain regions, including the amygdala area. The medial nucleus of the amygdala (MeA) is a key region for performance of social behaviors and still undergoes maturation during the periadolescent period. As such, the normal development of this region may be disrupted by social deprivation. In rodents, postweaning social isolation causes a range of deficits in sexual and agonistic behaviors that normally rely on the posterior MeA (MeAp). However, little is known about the effects of social isolation on the function of MeA neurons. In this study, we tested whether postweaning social isolation caused abnormal activity of MeA neurons. We found that postweaning social isolation caused a decrease of in vivo firing activity of MeAp neurons, and reduced drive from excitatory afferents. In vitro electrophysiological studies found that postweaning social isolation caused a presynaptic impairment of excitatory input to the dorsal MeAp, but a progressive postsynaptic reduction of membrane excitability in the ventral MeAp. These results demonstrate discrete, subnucleus-specific effects of social deprivation on the physiology of MeAp neurons. This pathophysiology may contribute to the disruption of social behavior after developmental social deprivation, and may be a novel target to facilitate the treatment of social disorders.

  4. Catecholaminergic consolidation of motor cortical neuroplasticity in humans.

    Science.gov (United States)

    Nitsche, Michael A; Grundey, Jessica; Liebetanz, David; Lang, Nicolas; Tergau, Frithjof; Paulus, Walter

    2004-11-01

    Amphetamine, a catecholaminergic re-uptake-blocker, is able to improve neuroplastic mechanisms in humans. However, so far not much is known about the underlying physiological mechanisms. Here, we study the impact of amphetamine on NMDA receptor-dependent long-lasting excitability modifications in the human motor cortex elicited by weak transcranial direct current stimulation (tDCS). Amphetamine significantly enhanced and prolonged increases in anodal, tDCS-induced, long-lasting excitability. Under amphetamine premedication, anodal tDCS resulted in an enhancement of excitability which lasted until the morning after tDCS, compared to approximately 1 h in the placebo condition. Prolongation of the excitability enhancement was most pronounced for long-term effects; the duration of short-term excitability enhancement was only slightly increased. Since the additional application of the NMDA receptor antagonist dextromethorphane blocked any enhancement of tDCS-driven excitability under amphetamine, we conclude that amphetamine consolidates the tDCS-induced neuroplastic effects, but does not initiate them. The fact that propanolol, a beta-adrenergic antagonist, diminished the duration of the tDCS-generated after-effects suggests that adrenergic receptors play a certain role in the consolidation of NMDA receptor-dependent motor cortical excitability modifications in humans. This result may enable researchers to optimize neuroplastic processes in the human brain on the rational basis of purpose-designed pharmacological interventions.

  5. Clonidine, an α2 receptor agonist, diminishes GABAergic neurotransmission to cardiac vagal neurons in the nucleus ambiguus

    OpenAIRE

    Philbin, Kerry E.; Bateman, Ryan J.; Mendelowitz, David

    2010-01-01

    In hypertension there is an autonomic imbalance in which sympathetic activity dominates over parasympathetic control. Parasympathetic activity to the heart originates from cardiac vagal neurons located in the nucleus ambiguus. Pre-sympathetic neurons that project to sympathetic neurons in the spinal cord are located in the ventral brainstem in close proximity to cardiac vagal neurons, and many of these pre-sympathetic neurons are catecholaminergic. In addition to their projection to the spina...

  6. Environmental Enrichment and Social Isolation Mediate Neuroplasticity of Medium Spiny Neurons through the GSK3 Pathway.

    Science.gov (United States)

    Scala, Federico; Nenov, Miroslav N; Crofton, Elizabeth J; Singh, Aditya K; Folorunso, Oluwarotimi; Zhang, Yafang; Chesson, Brent C; Wildburger, Norelle C; James, Thomas F; Alshammari, Musaad A; Alshammari, Tahani K; Elfrink, Hannah; Grassi, Claudio; Kasper, James M; Smith, Ashley E; Hommel, Jonathan D; Lichti, Cheryl F; Rudra, Jai S; D'Ascenzo, Marcello; Green, Thomas A; Laezza, Fernanda

    2018-04-10

    Resilience and vulnerability to neuropsychiatric disorders are linked to molecular changes underlying excitability that are still poorly understood. Here, we identify glycogen-synthase kinase 3β (GSK3β) and voltage-gated Na + channel Nav1.6 as regulators of neuroplasticity induced by environmentally enriched (EC) or isolated (IC) conditions-models for resilience and vulnerability. Transcriptomic studies in the nucleus accumbens from EC and IC rats predicted low levels of GSK3β and SCN8A mRNA as a protective phenotype associated with reduced excitability in medium spiny neurons (MSNs). In vivo genetic manipulations demonstrate that GSK3β and Nav1.6 are molecular determinants of MSN excitability and that silencing of GSK3β prevents maladaptive plasticity of IC MSNs. In vitro studies reveal direct interaction of GSK3β with Nav1.6 and phosphorylation at Nav1.6 T1936 by GSK3β. A GSK3β-Nav1.6 T1936 competing peptide reduces MSNs excitability in IC, but not EC rats. These results identify GSK3β regulation of Nav1.6 as a biosignature of MSNs maladaptive plasticity. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. Comparative studies on mitochondria isolated from neuron-enriched and glia-enriched fractions of rabbit and beef brain.

    Science.gov (United States)

    Hamberger, A; Blomstrand, C; Lehninger, A L

    1970-05-01

    Fractions enriched in neuronal and glial cells were obtained from dispersions of whole beef brain and rabbit cerebral cortex by large-scale density gradient centrifugation procedures. The fractions were characterized by appropriate microscopic observation. Mitochondria were then isolated from these fractions by differential centrifugation of their homogenates. The two different types of mitochondria were characterized with respect to certain enzyme activities, respiratory rate, rate of protein synthesis, and their buoyant density in sucrose gradients. The mitochondria from the neuron-enriched fraction were distinguished by a higher rate of incorporation of amino acids into protein, higher cytochrome oxidase activity, and a higher buoyant density in sucrose density gradients. Mitochondria from the glia-enriched fraction showed relatively high monoamine oxidase and Na(+)- and K(+)-stimulated ATPase activities. The rates of oxidation of various substrates and the acceptor control ratios did not differ appreciably between the two types of mitochondria. The difference in the buoyant density of mitochondria isolated from the neuron-enriched and glia-enriched cell fractions was utilized in attempts to separate neuronal and glial mitochondria from the mixed mitochondria obtained from whole brain homogenates in shallow sucrose gradients. The appearance of two peaks of cytochrome oxidase, monoamine oxidase, and protein concentration in such gradients shows the potential feasibility of such an approach.

  8. Molecular diagnostics of catecholaminergic polymorphic ventricular tachycardia using denaturing high-performance liquid chromatography and sequencing

    NARCIS (Netherlands)

    Postma, Alex V.; Bhuiyan, Zahurul A.; Bikker, Hennie

    2006-01-01

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease characterized by adrenergic-induced arrhythmias in the form of bidirectional and PVT. CPVT is a distinct clinical entity associated with a high mortality rate of up to 50% by the age of 30 yr. Recently, the

  9. New exome data question the pathogenicity of genetic variants previously associated with catecholaminergic polymorphic ventricular tachycardia

    DEFF Research Database (Denmark)

    Jabbari, Javad; Jabbari, Reza; Nielsen, Morten Wagner

    2013-01-01

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal, rare hereditary disease with an estimated prevalence of 1:10 000. The genetic variants that cause CPVT are usually highly penetrant. To date, about 189 variants in 5 genes (RYR2, CASQ2, CALM1, TRND, and KCNJ2) have been...

  10. Calcium current activation kinetics in isolated pyramidal neurones of the Ca1 region of the mature guinea-pig hippocampus.

    Science.gov (United States)

    Kay, A R; Wong, R K

    1987-11-01

    1. Neurones were isolated from the CA1 region of the guinea-pig hippocampus and subjected to the whole-cell mode of voltage clamping, to determine the kinetics of voltage-gated Ca2+ channel activation. 2. Isolated neurones had an abbreviated morphology, having lost most of the distal dendritic tree during the isolation procedure. The electrical compactness of the cells facilitates voltage clamp analysis. 3. Block of sodium and potassium currents revealed a persistent current activated on depolarization above -40 mV, which inactivated slowly when the intracellular medium contained EGTA. The current was blocked by Co2+ and Cd2+, augmented by increases in Ca2+ and could be carried by Ba2+, suggesting that the current is borne by Ca2+. 4. Steady-state activation of the Ca2+ current was found to be well described by the Boltzman equation raised to the second power. 5. The open channel's current-voltage (I-V) relationship rectified in the inward direction and was consistent with the constant-field equation. 6. The kinetics of Ca2+ current onset followed m2 kinetics throughout the range of its activation. Tail current kinetics were in accord with this model. A detailed Hodgkin-Huxley model was derived, defining the activation of this current. 7. The kinetics of the currents observed in this regionally and morphologically defined class of neurones were consistent with the existence of a single kinetic class of channels.

  11. Segmentation of isolated MR images: development and comparison of neuronal networks

    International Nuclear Information System (INIS)

    Paredes, R.; Robles, M.; Marti-Bonmati, L.; Masia, L.

    1998-01-01

    Segmentation defines the capacity to differentiate among types of tissues. In MR. it is frequently applied to volumetric determinations. Digital images can be segmented in a number of ways; neuronal networks (NN) can be employed for this purpose. Our objective was to develop algorithms for automatic segmentation using NN and apply them to central nervous system MR images. The segmentation obtained with NN was compared with that resulting from other procedures (region-growing and K means). Each NN consisted of two layers: one based on unsupervised training, which was utilized for image segmentation in sets of K, and a second layer associating each set obtained by the preceding layer with the real set corresponding to the previously segmented objective image. This NN was trained with previously segmented images with supervised regions-growing algorithms and automatic K means. Thus, 4 different segmentation were obtained: region-growing, K means, NN with region-growing and NN with K means. The tissue volumes corresponding to cerebrospinal fluid, gray matter and white matter obtained with the 4 techniques were compared and the most representative segmented image was selected qualitatively by averaging the visual perception of 3 radiologists. The segmentation that best corresponded to the visual perception of the radiologists was that consisting of trained NN with region-growing. In comparison, the other 3 algorithms presented low percentage differences (mean, 3.44%). The mean percentage error for the 3 tissues from these algorithms was lower for region-growing segmentation (2.34%) than for trained NN with K means (3.31%) and for automatic K-means segmentation (4.66%). Thus, NN are reliable in the automation of isolated MR image segmentation. (Author) 12 refs

  12. Glucose uptake during contraction in isolated skeletal muscles from neuronal nitric oxide synthase μ knockout mice.

    Science.gov (United States)

    Hong, Yet Hoi; Frugier, Tony; Zhang, Xinmei; Murphy, Robyn M; Lynch, Gordon S; Betik, Andrew C; Rattigan, Stephen; McConell, Glenn K

    2015-05-01

    Inhibition of nitric oxide synthase (NOS) significantly attenuates the increase in skeletal muscle glucose uptake during contraction/exercise, and a greater attenuation is observed in individuals with Type 2 diabetes compared with healthy individuals. Therefore, NO appears to play an important role in mediating muscle glucose uptake during contraction. In this study, we investigated the involvement of neuronal NOSμ (nNOSμ), the main NOS isoform activated during contraction, on skeletal muscle glucose uptake during ex vivo contraction. Extensor digitorum longus muscles were isolated from nNOSμ(-/-) and nNOSμ(+/+) mice. Muscles were contracted ex vivo in a temperature-controlled (30°C) organ bath with or without the presence of the NOS inhibitor N(G)-monomethyl-l-arginine (L-NMMA) and the NOS substrate L-arginine. Glucose uptake was determined by radioactive tracers. Skeletal muscle glucose uptake increased approximately fourfold during contraction in muscles from both nNOSμ(-/-) and nNOSμ(+/+) mice. L-NMMA significantly attenuated the increase in muscle glucose uptake during contraction in both genotypes. This attenuation was reversed by L-arginine, suggesting that L-NMMA attenuated the increase in muscle glucose uptake during contraction by inhibiting NOS and not via a nonspecific effect of the inhibitor. Low levels of NOS activity (~4%) were detected in muscles from nNOSμ(-/-) mice, and there was no evidence of compensation from other NOS isoform or AMP-activated protein kinase which is also involved in mediating muscle glucose uptake during contraction. These results indicate that NO regulates skeletal muscle glucose uptake during ex vivo contraction independently of nNOSμ. Copyright © 2015 the American Physiological Society.

  13. Histofluorescent labelling of catecholaminergic structures in rotifers (Aschelminthes). II. Males of Brachionus plicatilis and structures from sectioned females.

    Science.gov (United States)

    Keshmirian, J; Nogrady, T

    1988-01-01

    1. Catecholaminergic structures in the male Brachionus plicatilis were investigated, using aqueous dansylpropranolol as fluorescent label of neurotransmitter receptors. 2. All major organs of the male are innervated by catecholaminergic systems, that may also be involved in the regulation of copulatory behavior. 3. Cryostat-sectioned preparations of the female B. plicatilis were also investigated. They provided additional information to findings on whole animals reported in our previous paper (Keshmirian and Nogrady 1987 a).

  14. Catecholaminergic polymorphic ventricular tachycardia. An important diagnosis in children with syncope and normal heart

    Directory of Open Access Journals (Sweden)

    Luiz Roberto Leite

    2001-01-01

    Full Text Available Syncope in children is primarily related to vagal hyperreactivity, but ventricular tachycardia (VT way rarely be seen. Catecholaminergic polymorphic VT is a rare entity that can occur in children without heart disease and with a normal QT interval, which may cause syncope and sudden cardiac death. In this report, we describe the clinical features, treatment, and clinical follow-up of three children with syncope associated with physical effort or emotion and cathecolaminergic polymorphic VT. Symptoms were controlled with beta-blockers, but one patient died suddenly in the fourth year of follow-up. Despite the rare occurrence, catecholaminergic polymorphic VT is an important cause of syncope and sudden death in children with no identified heart disease and normal QT interval.

  15. Analysis of the Catecholaminergic Phenotype in Human SH-SY5Y and BE(2-M17 Neuroblastoma Cell Lines upon Differentiation.

    Directory of Open Access Journals (Sweden)

    Roberta Filograna

    Full Text Available Human cell lines are often used to investigate cellular pathways relevant for physiological or pathological processes or to evaluate cell toxicity or protection induced by different compounds, including potential drugs. In this study, we analyzed and compared the differentiating activities of three agents (retinoic acid, staurosporine and 12-O-tetradecanoylphorbol-13-acetate on the human neuroblastoma SH-SY5Y and BE(2-M17 cell lines; the first cell line is largely used in the field of neuroscience, while the second is still poorly characterized. After evaluating their effects in terms of cell proliferation and morphology, we investigated their catecholaminergic properties by assessing the expression profiles of the major genes involved in catecholamine synthesis and storage and the cellular concentrations of the neurotransmitters dopamine and noradrenaline. Our results demonstrate that the two cell lines possess similar abilities to differentiate and acquire a neuron-like morphology. The most evident effects in SH-SY5Y cells were observed in the presence of staurosporine, while in BE(2-M17 cells, retinoic acid induced the strongest effects. Undifferentiated SH-SY5Y and BE(2-M17 cells are characterized by the production of both NA and DA, but their levels are considerably higher in BE(2-M17 cells. Moreover, the NAergic phenotype appears to be more pronounced in SH-SY5Y cells, while BE(2-M17 cells have a more prominent DAergic phenotype. Finally, the catecholamine concentration strongly increases upon differentiation induced by staurosporine in both cell lines. In conclusion, in this work the catecholaminergic phenotype of the human BE(2-M17 cell line upon differentiation was characterized for the first time. Our data suggest that SH-SY5Y and BE(2-M17 represent two alternative cell models for the neuroscience field.

  16. Analysis of the Catecholaminergic Phenotype in Human SH-SY5Y and BE(2)-M17 Neuroblastoma Cell Lines upon Differentiation.

    Science.gov (United States)

    Filograna, Roberta; Civiero, Laura; Ferrari, Vanni; Codolo, Gaia; Greggio, Elisa; Bubacco, Luigi; Beltramini, Mariano; Bisaglia, Marco

    2015-01-01

    Human cell lines are often used to investigate cellular pathways relevant for physiological or pathological processes or to evaluate cell toxicity or protection induced by different compounds, including potential drugs. In this study, we analyzed and compared the differentiating activities of three agents (retinoic acid, staurosporine and 12-O-tetradecanoylphorbol-13-acetate) on the human neuroblastoma SH-SY5Y and BE(2)-M17 cell lines; the first cell line is largely used in the field of neuroscience, while the second is still poorly characterized. After evaluating their effects in terms of cell proliferation and morphology, we investigated their catecholaminergic properties by assessing the expression profiles of the major genes involved in catecholamine synthesis and storage and the cellular concentrations of the neurotransmitters dopamine and noradrenaline. Our results demonstrate that the two cell lines possess similar abilities to differentiate and acquire a neuron-like morphology. The most evident effects in SH-SY5Y cells were observed in the presence of staurosporine, while in BE(2)-M17 cells, retinoic acid induced the strongest effects. Undifferentiated SH-SY5Y and BE(2)-M17 cells are characterized by the production of both NA and DA, but their levels are considerably higher in BE(2)-M17 cells. Moreover, the NAergic phenotype appears to be more pronounced in SH-SY5Y cells, while BE(2)-M17 cells have a more prominent DAergic phenotype. Finally, the catecholamine concentration strongly increases upon differentiation induced by staurosporine in both cell lines. In conclusion, in this work the catecholaminergic phenotype of the human BE(2)-M17 cell line upon differentiation was characterized for the first time. Our data suggest that SH-SY5Y and BE(2)-M17 represent two alternative cell models for the neuroscience field.

  17. Analysis of transcription factor mRNAs in identified oxytocin and vasopressin magnocellular neurons isolated by laser capture microdissection.

    Directory of Open Access Journals (Sweden)

    Madison Humerick

    Full Text Available The oxytocin (Oxt and vasopressin (Avp magnocellular neurons (MCNs in the hypothalamus are the only neuronal phenotypes that are present in the supraoptic nucleus (SON, and are characterized by their robust and selective expression of either the Oxt or Avp genes. In this paper, we take advantage of the differential expression of these neuropeptide genes to identify and isolate these two individual phenotypes from the rat SON by laser capture microdissection (LCM, and to analyze the differential expression of several of their transcription factor mRNAs by qRT-PCR. We identify these neuronal phenotypes by stereotaxically injecting recombinant Adeno-Associated Viral (rAAV vectors which contain cell-type specific Oxt or Avp promoters that drive expression of EGFP selectively in either the Oxt or Avp MCNs into the SON. The fluorescent MCNs are then dissected by LCM using a novel Cap Road Map protocol described in this paper, and the purified MCNs are extracted for their RNAs. qRT-PCR of these RNAs show that some transcription factors (RORA and c-jun are differentially expressed in the Oxt and Avp MCNs.

  18. Oleuropein isolated from Fraxinus rhynchophylla inhibits glutamate-induced neuronal cell death by attenuating mitochondrial dysfunction.

    Science.gov (United States)

    Kim, Mi Hye; Min, Ju-Sik; Lee, Joon Yeop; Chae, Unbin; Yang, Eun-Ju; Song, Kyung-Sik; Lee, Hyun-Shik; Lee, Hong Jun; Lee, Sang-Rae; Lee, Dong-Seok

    2017-04-27

    Glutamate-induced neurotoxicity is related to excessive oxidative stress accumulation and results in the increase of neuronal cell death. In addition, glutamate has been reported to lead to neurodegenerative diseases, including Parkinson's and Alzheimer's diseases.It is well known that Fraxinus rhynchophylla contains a significant level of oleuropein (Ole), which exerts various pharmacological effects. However, the mechanism of neuroprotective effects of Ole is still poorly defined. In this study, we aimed to investigate whether Ole prevents glutamate-induced toxicity in HT-22 hippocampal neuronal cells. The exposure of the glutamate treatment caused neuronal cell death through an alteration of Bax/Bcl-2 expression and translocation of mitochondrial apoptosis-inducing factor (AIF) to the cytoplasm of HT-22 cells. In addition, glutamate induced an increase in dephosphorylation of dynamin-related protein 1 (Drp1), mitochondrial fragmentation, and mitochondrial dysfunction. The pretreatment of Ole decreased Bax expression, increased Bcl-2 expression, and inhibited the translocation of mitochondrial AIF to the cytoplasm. Furthermore, Ole amended a glutamate-induced mitochondrial dynamic imbalance and reduced the number of cells with fragmented mitochondria, regulating the phosphorylation of Drp1 at amino acid residue serine 637. In conclusion, our results show that Ole has a preventive effect against glutamate-induced toxicity in HT-22 hippocampal neuronal cells. Therefore, these data imply that Ole may be an efficient approach for the treatment of neurodegenerative diseases.

  19. Oxidative metabolism and Ca2+ handling in isolated brain mitochondria and striatal neurons from R6/2 mice, a model of Huntington's disease.

    Science.gov (United States)

    Hamilton, James; Pellman, Jessica J; Brustovetsky, Tatiana; Harris, Robert A; Brustovetsky, Nickolay

    2016-07-01

    Alterations in oxidative metabolism and defects in mitochondrial Ca 2+ handling have been implicated in the pathology of Huntington's disease (HD), but existing data are contradictory. We investigated the effect of human mHtt fragments on oxidative metabolism and Ca 2+ handling in isolated brain mitochondria and cultured striatal neurons from the R6/2 mouse model of HD. Non-synaptic and synaptic mitochondria isolated from the brains of R6/2 mice had similar respiratory rates and Ca 2+ uptake capacity compared with mitochondria from wild-type (WT) mice. Respiratory activity of cultured striatal neurons measured with Seahorse XF24 flux analyzer revealed unaltered cellular respiration in neurons derived from R6/2 mice compared with neurons from WT animals. Consistent with the lack of respiratory dysfunction, ATP content of cultured striatal neurons from R6/2 and WT mice was similar. Mitochondrial Ca 2+ accumulation was also evaluated in cultured striatal neurons from R6/2 and WT animals. Our data obtained with striatal neurons derived from R6/2 and WT mice show that both glutamate-induced increases in cytosolic Ca 2+ and subsequent carbonilcyanide p-triflouromethoxyphenylhydrazone-induced increases in cytosolic Ca 2+ were similar between WT and R6/2, suggesting that mitochondria in neurons derived from both types of animals accumulated comparable amounts of Ca 2+ Overall, our data argue against respiratory deficiency and impaired Ca 2+ handling induced by human mHtt fragments in both isolated brain mitochondria and cultured striatal neurons from transgenic R6/2 mice. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Isolation of skin-derived precursors from human foreskin and their differentiation into neurons and glial cells

    Directory of Open Access Journals (Sweden)

    Bakhtiari M

    2010-12-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Skin-derived precursors (SKPs are a type of progenitor cells extracted from mammalian dermal tissue and can be differentiate to neural and mesodermal lineage in vitro. These cells can introduce an accessible autologos source of neural precursor cells for treatment of different neurodegenerative diseases. This research was done in order to set up isolation, culture, proliferation and differentiation of human skin derived precursors (hSKPs."n"nMethods: Human foreskin samples were cut into smaller pieces and cultured in proliferation medium after enzymatic digestion. To induce neural differentiation, cells were cultured in neural differentiation medium after fifth passage. We used immunocytochemistry and RT-PCR for characterization of the cells. Neuron and glial cell differentiation potential was assessed by immunofloresence using specific antibodies. The experiments were carried out in triplicate."n"nResults: After differentiation, βΙΙΙ- tubulin and neurofilament-M positive cells were observed that are specific markers for neurons. Moreover, glial fibrillary acid protein (GFAP and S100 positive cells were identified that are markers specifically express in glial cells. Detected neurons and glials were

  1. Phencyclidine block of calcium current in isolated guinea-pig hippocampal neurones.

    Science.gov (United States)

    Ffrench-Mullen, J M; Rogawski, M A

    1992-10-01

    1. Phencyclidine (PCP) block of Ca2+ channel current in enzymatically dissociated neurones from the CA1 region of the adult guinea-pig hippocampus was studied using whole-cell voltage clamp techniques. Ca2+ channel current was recorded with 3 mM-Ba2+ as the charge carrier. Na+ currents were blocked with tetrodotoxin and K+ currents were eliminated by using tetraethylammonium and N-methyl-D-glucamine as the predominant extracellular and intracellular cations, respectively. 2. Peak Ca2+ channel current evoked by depolarization from -80 to -10 mV was reduced in a use-dependent fashion by PCP. The apparent forward and reverse rate constants for block at the depolarized voltage were 10(6) s-1 M-1 and 11-14 s-1, respectively. These values were at least 60 times faster than the corresponding rates at the resting voltage. The steady-state block produced by PCP increased in a concentration-dependent fashion with an IC50 of 7 microM. Other dissociative anaesthetic drugs were substantially weaker inhibitors of the current (tiletamine > dizocilpine (MK-801) > ketamine). 3. The Ca2+ channel current recorded under identical conditions in rat dorsal root ganglion neurones was less sensitive to blockade by PCP (IC50, 90 microM). 4. PCP block of the hippocampal Ca2+ channel current occurred in a voltage-dependent fashion with the fractional block decreasing at positive membrane potentials. Analysis indicated that the PCP blocking site senses 56% of the transmembrane electric field. 5. Analysis of tail currents recorded at -80 mV demonstrated that PCP does not affect the voltage-dependent or time-dependent activation or deactivation of the Ca2+ channel current. 6. The rate and extent of inactivation of the Ca2+ channel current was maximal at -10 mV and diminished at more positive potentials. Experiments with Ba(2+)-free external solution demonstrated that inactivation of the Ca2+ channels is largely voltage-dependent and is not affected by Ba2+ influx. 7. PCP markedly increased the

  2. Assessing social isolation in motor neurone disease: a Rasch analysis of the MND Social Withdrawal Scale.

    Science.gov (United States)

    Gibbons, Chris J; Thornton, Everard W; Ealing, John; Shaw, Pamela J; Talbot, Kevin; Tennant, Alan; Young, Carolyn A

    2013-11-15

    Social withdrawal is described as the condition in which an individual experiences a desire to make social contact, but is unable to satisfy that desire. It is an important issue for patients with motor neurone disease who are likely to experience severe physical impairment. This study aims to reassess the psychometric and scaling properties of the MND Social Withdrawal Scale (MND-SWS) domains and examine the feasibility of a summary scale, by applying scale data to the Rasch model. The MND Social Withdrawal Scale was administered to 298 patients with a diagnosis of MND, alongside the Hospital Anxiety and Depression Scale. The factor structure of the MND Social Withdrawal Scale was assessed using confirmatory factor analysis. Model fit, category threshold analysis, differential item functioning (DIF), dimensionality and local dependency were evaluated. Factor analysis confirmed the suitability of the four-factor solution suggested by the original authors. Mokken scale analysis suggested the removal of item five. Rasch analysis removed a further three items; from the Community (one item) and Emotional (two items) withdrawal subscales. Following item reduction, each scale exhibited excellent fit to the Rasch model. A 14-item Summary scale was shown to fit the Rasch model after subtesting the items into three subtests corresponding to the Community, Family and Emotional subscales, indicating that items from these three subscales could be summed together to create a total measure for social withdrawal. Removal of four items from the Social Withdrawal Scale led to a four factor solution with a 14-item hierarchical Summary scale that were all unidimensional, free for DIF and well fitted to the Rasch model. The scale is reliable and allows clinicians and researchers to measure social withdrawal in MND along a unidimensional construct. © 2013. Published by Elsevier B.V. All rights reserved.

  3. Catecholaminergic activation in acute myocardial infarction: time course and relation to left ventricular performance

    DEFF Research Database (Denmark)

    Petersen, Claus Leth; Nielsen, Jens Rokkedal; Petersen, Bodil Laub

    2003-01-01

    AIM: The study was designed to assess (1) the time course of catecholaminergic activation in acute myocardial infarction (AMI) as estimated by adrenaline (ADR) and noradrenaline (NOR) concentrations, and (2) to relate activation of these hormones to predict the outcome of cardiac performance......-ventricular ejection fraction (LVEF). RESULTS: In the study group as a whole, the concentrations of ADR decreased from (mean +/- SEM) 0.80 +/- 0.12 nmol/l on admission to 0.33 +/- 0.03 nmol/l at discharge (p ... of both ADR and NOR on admission were correlated to LVEF at discharge (r = -0.56, p ADR and NOR after 1 year follow-up was 0...

  4. Catecholaminergic System of Invertebrates: Comparative and Evolutionary Aspects in Comparison With the Octopaminergic System.

    Science.gov (United States)

    Gallo, Valentina P; Accordi, Fiorenza; Chimenti, Claudio; Civinini, Annalena; Crivellato, Enrico

    2016-01-01

    In this review we examined the catecholaminergic system of invertebrates, starting from protists and getting to chordates. Different techniques used by numerous researchers revealed, in most examined phyla, the presence of catecholamines dopamine, noradrenaline, and adrenaline or of the enzymes involved in their synthesis. The catecholamines are generally linked to the nervous system and they can act as neurotransmitters, neuromodulators, and hormones; moreover they play a very important role as regards the response to a large number of stress situations. Nevertheless, in some invertebrate phyla belonging to Protostoma, the monoamine octopamine is the main biogenic amine. The presence of catecholamines in some protists suggests a role as intracellular or interorganismal signaling molecules and an ancient origin of their synthetic pathways. The catecholamines appear also involved in the regulation of bioluminescence and in the control of larval development and metamorphosis in some marine invertebrate phyla. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Catecholaminergic and cholinergic systems of mouse brain are modulated by LMN diet, rich in theobromine, polyphenols and polyunsaturated fatty acids.

    Science.gov (United States)

    Fernández-Fernández, Laura; Esteban, Gerard; Giralt, Mercedes; Valente, Tony; Bolea, Irene; Solé, Montse; Sun, Ping; Benítez, Susana; Morelló, José Ramón; Reguant, Jordi; Ramírez, Bartolomé; Hidalgo, Juan; Unzeta, Mercedes

    2015-04-01

    The possible modulatory effect of the functional LMN diet, rich in theobromine, polyphenols and polyunsaturated fatty acids, on the catecholaminergic and cholinergic neurotransmission, affecting cognition decline during aging has been studied. 129S1/SvlmJ mice were fed for 10, 20, 30 and 40 days with either LMN or control diets. The enzymes involved in catecholaminergic and cholinergic metabolism were determined by both immunohistological and western blot analyses. Noradrenalin, dopamine and other metabolites were quantified by HPLC analysis. Theobromine, present in cocoa, the main LMN diet component, was analysed in parallel using SH-SY5Y and PC12 cell lines. An enhanced modulatory effect on both cholinergic and catecholaminergic transmissions was observed on 20 day fed mice. Similar effect was observed with theobromine, besides its antioxidant capacity inducing SOD-1 and GPx expression. The enhancing effect of the LMN diet and theobromine on the levels of acetylcholine-related enzymes, dopamine and specially noradrenalin confirms the beneficial role of this diet on the "cognitive reserve" and hence a possible reducing effect on cognitive decline underlying aging and Alzheimer's disease.

  6. [Ultrastructural changes in the MP3 neuron of the mollusk Lymnaea stagnalis after cryopreservation of the isolated brain].

    Science.gov (United States)

    Dmitrieva, E V; Moshkov, D A; Gakhova, E N

    2006-01-01

    Investigation of a possibility of long-term storage of frozen (-196 degrees C) viable neurons and nervous tissue is one of the central present day problems. In this study ultrastructural changes in neurons of frozen-thawed snail brain were examined as a function of time. We studied the influence of cryopreservation, cryoprotectant (Me2SO), cooling to 4-6 degrees C, and a prolonged incubation in physiological solution at 4-6 degrees C on dictyosomes of Golgi apparatus, endoplasmic reticulum (ER) cisternae and mitochondria. It has been found that responses of these intracellular structures of cryopreserved neurons to the above influences are similar: dissociation of Golgi dictyosomes, swelling of endoplasmic reticulum cisternae and mitochondrial cristae. Both freezing-thawing and cryoprotectant were seen to cause an increase in the number of lysosomes, liposomes, myelin-like structures, and to form large vacuoles. The structural changes in molluscan neurons caused by cryopreservation with Me2SO (2 M) were reversible.

  7. Loss of catecholaminergic neuromodulation of persistent forms of hippocampal synaptic plasticity with increasing age

    Directory of Open Access Journals (Sweden)

    Hannah Twarkowski

    2016-09-01

    Full Text Available Neuromodulation by means of the catecholaminergic system is a key component of motivation-driven learning and behaviorally modulated hippocampal synaptic plasticity. In particular, dopamine acting on D1/D5 receptors and noradrenaline acting on beta-adrenergic receptors exert a very potent regulation of forms of hippocampal synaptic plasticity that last for very long-periods of time (>24h, and occur in conjunction with novel spatial learning. Antagonism of these receptors not only prevents long-term potentiation (LTP and long-term depression (LTD, but prevents the memory of the spatial event that, under normal circumstances, leads to the perpetuation of these plasticity forms. Spatial learning behavior that normally comes easily to rats, such as object-place learning and spatial reference learning, becomes increasingly impaired with aging. Middle-aged animals display aging-related deficits of specific, but not all, components of spatial learning, and one possibility is that this initial manifestation of decrements in learning ability that become manifest in middle-age relate to changes in motivation, attention and/or the regulation by neuromodulatory systems of these behavioral states.Here, we compared the regulation by dopaminergic D1/D5 and beta-adrenergic receptors of persistent LTP in young (2-4 month old and middle-aged (8-14 month old rats. We observed in young rats, that weak potentiation that typically lasts for ca. 2h could be strengthened into persistent (>24h LTP by pharmacological activation of either D1/D5 or beta-adrenergic receptors. By contrast, no such facilitation occurred in middle-aged rats. This difference was not related to an ostensible learning deficit: a facilitation of weak potentiation into LTP by spatial learning was possible both in young and middle-aged rats. It was also not directly linked to deficits in LTP: strong afferent stimulation resulted in equivalent LTP in both age groups. We postulate that this change in

  8. pKI values of prazosin and idazoxan for receptors stimulated by neuronally released transmitter in the epididymal portion of rat isolated vas deferens.

    OpenAIRE

    Mackay, D.; Kengatharan, M.

    1994-01-01

    1. A new method has been used to measure pKI values of prazosin and idazoxan against neuronally-released transmitter in the epididymal portion of the rat isolated vas deferens. The most reproducible results were obtained with a prolonged antagonist equilibration time (1 h). 2. Under these conditions the pKI of prazosin was practically unaffected by addition of alpha, beta-methylene-adenosine-5'-triphosphate (10 microM) to desensitize purinoceptors. Addition of desmethylimipramine (DMI) (0.3 m...

  9. NKX6.1 induced pluripotent stem cell reporter lines for isolation and analysis of functionally relevant neuronal and pancreas populations

    Directory of Open Access Journals (Sweden)

    Shailesh Kumar Gupta

    2018-05-01

    Full Text Available Recent studies have reported significant advances in the differentiation of human pluripotent stem cells to clinically relevant cell types such as the insulin producing beta-like cells and motor neurons. However, many of the current differentiation protocols lead to heterogeneous cell cultures containing cell types other than the targeted cell fate. Genetically modified human pluripotent stem cells reporting the expression of specific genes are of great value for differentiation protocol optimization and for the purification of relevant cell populations from heterogeneous cell cultures. Here we present the generation of human induced pluripotent stem cell (iPSC lines with a GFP reporter inserted in the endogenous NKX6.1 locus. Characterization of the reporter lines demonstrated faithful GFP labelling of NKX6.1 expression during pancreas and motor neuron differentiation. Cell sorting and gene expression profiling by RNA sequencing revealed that NKX6.1-positive cells from pancreatic differentiations closely resemble human beta cells. Furthermore, functional characterization of the isolated cells demonstrated that glucose-stimulated insulin secretion is mainly confined to the NKX6.1-positive cells. We expect that the NKX6.1-GFP iPSC lines and the results presented here will contribute to the further refinement of differentiation protocols and characterization of hPSC-derived beta cells and motor neurons for disease modelling and cell replacement therapies. Keywords: Human induced pluripotent stem cells, NKX6.1, Reporter cell line, Directed differentiation, hiPSC-derived beta cells

  10. Characterization and Evaluation of Neuronal Trans-Differentiation with Electrophysiological Properties of Mesenchymal Stem Cells Isolated from Porcine Endometrium

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    Raghavendra Baregundi Subbarao

    2015-05-01

    Full Text Available Endometrial stromal cells (EMSCs obtained from porcine uterus (n = 6 were positive for mesenchymal stem cell markers (CD29, CD44 and CD90, and negative for epithelial marker CD9 and hematopoietic markers CD34, CD45 analyzed by flow cytometry. Further the cells were positive for expression of mesenchymal markers, CD105, CD140b, and CD144 by PCR. Pluripotent markers OCT4, SOX2, and NANOG were positively expressed in EMSCs analyzed by Western blotting and PCR. Further, differentiation into adipocytes and osteocytes was confirmed by cytochemical staining and lineage specific gene expression by quantitative realtime-PCR. Adipocyte (FABP, LPL, AP2 and osteocyte specific genes (ON, BG, RUNX2 in differentiated EMSCs showed significant (p < 0.05 increase in expression compared to undifferentiated control cells. Neurogenic transdifferentiation of EMSCs exhibited distinctive dendritic morphology with axon projections and neuronal specific genes, NFM, NGF, MBP, NES, B3T and MAP2 and proteins, B3T, NFM, NGF, and TRKA were positively expressed in neuronal differentiated cells. Functional analysis of neuronal differentiated EMSCs displayed voltage-dependence and kinetics for transient outward K+ currents (Ito, at holding potential of −80 mV, Na+ currents and during current clamp, neuronal differentiated EMSCs was more negative than that of control EMSCs. Porcine EMSCs is a suitable model for studying molecular mechanism of transdifferentiation, assessment of electrophysiological properties and their efficiency during in vivo transplantation.

  11. Neuronal activity in the isolated mouse spinal cord during spontaneous deletions in fictive locomotion: insights into locomotor central pattern generator organization

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    Zhong, Guisheng; Shevtsova, Natalia A; Rybak, Ilya A; Harris-Warrick, Ronald M

    2012-01-01

    We explored the organization of the spinal central pattern generator (CPG) for locomotion by analysing the activity of spinal interneurons and motoneurons during spontaneous deletions occurring during fictive locomotion in the isolated neonatal mouse spinal cord, following earlier work on locomotor deletions in the cat. In the isolated mouse spinal cord, most spontaneous deletions were non-resetting, with rhythmic activity resuming after an integer number of cycles. Flexor and extensor deletions showed marked asymmetry: flexor deletions were accompanied by sustained ipsilateral extensor activity, whereas rhythmic flexor bursting was not perturbed during extensor deletions. Rhythmic activity on one side of the cord was not perturbed during non-resetting spontaneous deletions on the other side, and these deletions could occur with no input from the other side of the cord. These results suggest that the locomotor CPG has a two-level organization with rhythm-generating (RG) and pattern-forming (PF) networks, in which only the flexor RG network is intrinsically rhythmic. To further explore the neuronal organization of the CPG, we monitored activity of motoneurons and selected identified interneurons during spontaneous non-resetting deletions. Motoneurons lost rhythmic synaptic drive during ipsilateral deletions. Flexor-related commissural interneurons continued to fire rhythmically during non-resetting ipsilateral flexor deletions. Deletion analysis revealed two classes of rhythmic V2a interneurons. Type I V2a interneurons retained rhythmic synaptic drive and firing during ipsilateral motor deletions, while type II V2a interneurons lost rhythmic synaptic input and fell silent during deletions. This suggests that the type I neurons are components of the RG, whereas the type II neurons are components of the PF network. We propose a computational model of the spinal locomotor CPG that reproduces our experimental results. The results may provide novel insights into the

  12. The effect of acute moderate psychological stress on working memory-related neural activity is modulated by a genetic variation in catecholaminergic function in humans

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    Shaozheng eQin

    2012-05-01

    Full Text Available Acute stress has an important impact on higher-order cognitive functions supported by the prefrontal cortex (PFC such as working memory (WM. In rodents, such effects are mediated by stress-induced alterations in catecholaminergic signaling, but human data in support of this notion is lacking. A common variation in the gene encoding Catechol-O-methyltransferase (COMT is known to affect basal catecholaminergic availability and PFC functions. Here, we investigated whether this genetic variation (Val158Met modulates effects of stress on WM-related prefrontal activity in humans. In a counterbalanced crossover design, 41 healthy young men underwent functional Magnetic Resonance Imaging (fMRI while performing a numerical N-back WM task embedded in a stressful or neutral context. Moderate psychological stress was induced by a well-controlled procedure involving viewing strongly aversive (versus emotionally neutral movie material in combination with a self-referencing instruction. Acute stress resulted in genotype-dependent effects on WM performance and WM-related activation in the dorsolateral PFC, with a relatively negative impact of stress in COMT Met-homozygotes as opposed to a relatively positive effect in Val-carriers. A parallel interaction was found for WM-related deactivation in the anterior medial temporal lobe. Our findings suggest that individuals with higher baseline catecholaminergic availability (COMT Met-homozygotes appear to reach a supraoptimal state under moderate levels of stress. In contrast, individuals with lower baselines (Val-carriers may reach an optimal state. Thus, our data show that effects of acute stress on higher-order cognitive functions vary depending on catecholaminergic availability at baseline, and thereby corroborate animal models of catecholaminergic signaling that propose a non-linear relationship between catecholaminergic activity and prefrontal functions.

  13. Catecholaminergic and serotoninergic fibres innervate the ventricular system of the hedgehog CNS.

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    Michaloudi, H C; Papadopoulos, G C

    1996-01-01

    Immunocytochemistry with antisera against serotonin (5-HT), dopamine (DA) and noradrenaline (NA) was used to detect monoaminergic (MA) fibres in the ventricular system of the hedgehog Erinaceus europaeus. Light microscopic examination of immunocytochemically stained sections revealed that the ventricular system of the hedgehog is unique among mammals in that the choroid plexuses receive CA axons and that the supraependyma and subependyma of the cerebral ventricles and the spinal central canal are innervated both by serotoninergic and catecholaminergic (CA) fibres. Supraependymal 5-HT axons were generally more abundant and created at places a large number of interconnected basket-like structures, whereas CA fibres were usually directed towards the ventricular lumen. In the lateral ventricles, CA fibres were more numerous in the ependyma lining grey matter, whereas a higher 5-HT innervation density was observed in the area between the corpus callosum and the caudate nucleus or the septum. In the 3rd ventricle, the ependyma of its dorsal part exhibited a higher 5-HT and NA innervation density, whereas DA fibres were preferentially distributed in the ventral half of the basal region. The ependyma lining the cerebral aqueduct displayed a higher MA innervation density in its ventral part. The ependymal wall of the 4th ventricle exhibited an extremely dense 5-HT innervation, mainly in the floor of the ventricle, relatively fewer NA fibres and only sparse DA ones. Few NA and relatively more 5-HT fibres were detected in the ependyma of the central canal. Finally, the circumventricular organs were unevenly innervated by the 3 types of MA fibres. The extensive monoaminergic innervation of the hedgehog ventricular system described here probably reflects a transitory evolutionary stage in the phylogeny of the MA systems with presently unknown functional implications. Images Fig. 1 Fig. 2 Figs 3-8 Figs 9-14 Figs 15-20 PMID:8886949

  14. Risk of catecholaminergic crisis following glucocorticoid administration in patients with an adrenal mass: a literature review.

    Science.gov (United States)

    Barrett, Catherine; van Uum, Stan H M; Lenders, Jacques W M

    2015-11-01

    Glucocorticoids as diagnostic or therapeutic agents have been reported to carry an increased risk of catecholaminergic crisis (CC) in patients with pheochromocytoma or paraganglioma (PPGL). We searched literature databases using the following terms: pheochromocytoma, paraganglioma, adrenal incidentaloma, steroids, glucocorticoids, dexamethasone suppression test (DST), hypertensive crisis, cosyntropin and CRH. From all published case reports (1962-2013), we reviewed medical history, presenting symptoms, dose and route of steroid administration, location and size of adrenal mass, biochemical phenotype and outcome. Twenty-five case reports describing a CC were identified. Three patients with an adrenal incidentaloma suffered a CC following high-dose DST, and in one case, this was fatal. In two of these patients, biochemical testing missed the diagnosis, and in the third, a DST was done despite elevated urinary metanephrines. No CC has been reported for patients undergoing a low-dose DST. Three of 16 patients who received therapeutic glucocorticoids and four of six patients following cosyntropin testing died. No specific biochemical phenotype was related to adverse events. Although a causal relationship cannot be established from this review, it seems prudent to exclude a PPGL in patients with a large incidentaloma or when high-dose DST is considered in a patient with an incidentaloma of any size. Our literature review does not support the need for biochemical testing for PPGL prior to a low-dose (1 mg) DST. Finally, before starting therapeutic glucocorticoids, any clinical signs or symptoms of a potential PPGL should prompt reliable biochemical testing to rule out a PPGL. © 2015 John Wiley & Sons Ltd.

  15. pKI values of prazosin and idazoxan for receptors stimulated by neuronally released transmitter in the epididymal portion of rat isolated vas deferens.

    Science.gov (United States)

    Mackay, D; Kengatharan, M

    1994-01-01

    1. A new method has been used to measure pKI values of prazosin and idazoxan against neuronally-released transmitter in the epididymal portion of the rat isolated vas deferens. The most reproducible results were obtained with a prolonged antagonist equilibration time (1 h). 2. Under these conditions the pKI of prazosin was practically unaffected by addition of alpha, beta-methylene-adenosine-5'-triphosphate (10 microM) to desensitize purinoceptors. Addition of desmethylimipramine (DMI) (0.3 microM) produced a small, but statistically non-significant, reduction. 3. The same method has been used to measure the pKI of prazosin against exogenous noradrenaline. In the latter case addition of DMI (0.3 microM) and corticosterone (30 microM) together produced a statistically significant reduction in the apparent pKI of prazosin. 4. The new method for estimating pKI values shows that DMI itself acts either pseudo-irreversibly or non-competitively and may be reducing the apparent pKI of prazosin. 5. The pKI values obtained for prazosin and idazoxan against neuronally-released transmitter are in good agreement with those obtained by other workers for the actions of these drugs on alpha-adrenoceptors.

  16. Enhanced sensitivity to ethanol-induced inhibition of LTP in CA1 pyramidal neurons of socially isolated C57BL/6J mice: role of neurosteroids

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    Giuseppe eTalani

    2011-10-01

    Full Text Available Ethanol (EtOH–induced impairment of long-term potentiation (LTP in the rat hippocampus is prevented by the 5α-reductase inhibitor finasteride, suggesting that this effect of EtOH is dependent on the increased local release of neurosteroids such as 3α,5α-THP that promote GABA–mediated transmission. Given that social isolation (SI in rodents is associated with altered plasma and brain levels of such neurosteroids as well as with an enhanced neurosteroidogenic action of EtOH, we examined whether the inhibitory effect of EtOH on LTP at CA3-CA1 hippocampal excitatory synapses is altered in C57BL/6J mice subjected to SI for 6 weeks in comparison with group-housed (GH animals. Extracellular recording of fEPSPs as well as patch-clamp analysis were performed in hippocampal slices prepared from both SI and GH mice. Consistent with previous observations, recording of fEPSPs revealed that the extent of LTP induced in the CA1 region of SI mice was significantly reduced compared with that in GH animals. EtOH (40 mM inhibited LTP in slices from SI mice but not in those from GH mice, and this effect of EtOH was abolished by co-application of 1 µM finasteride. Current-clamp analysis of CA1 pyramidal neurons revealed a decrease in action potential frequency and an increase in the intensity of injected current required to evoke the first action potential in SI mice compared with GH mice, indicative of a decrease in neuronal excitability associated with SI. Together, our data suggest that SI results in reduced levels of neuronal excitability and synaptic plasticity in the hippocampus. Furthermore, the increased sensitivity to the neurosteroidogenic effect of EtOH associated with SI likely accounts for the greater inhibitory effect of EtOH on LTP in SI mice. The increase in EtOH sensitivity induced by SI may be important for the changes in the effects of EtOH on anxiety and on learning and memory associated with the prolonged stress attributable to social

  17. Thoracoscopic Left Cardiac Sympathetic Denervation for a Patient with Catecholaminergic Polymorphic Ventricular Tachycardia and Recurrent Implantable Cardioverter-Defibrillator Shocks

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    Woo-Sik Yu

    2015-06-01

    Full Text Available A patient presented with loss of consciousness and conversion. During an exercise test, catecholaminergic polymorphic ventricular tachycardia (CPVT resulted in cardiac arrest. He started taking medication (a beta-blocker and flecainide and an implantable cardioverter defibrillator (ICD was inserted, but the ventricular tachycardia did not resolve. Left cardiac sympathetic denervation (LCSD was then performed under general anesthesia, and the patient was discharged on the second postoperative day without complications. One month after the operation, no shock had been administered by the ICD, and an exercise stress test did not induce ventricular tachycardia. Although beta- blockers are the gold standard of therapy in patients with CPVT, thoracoscopic LCSD is safe and can be an effective alternative treatment option for patients with intractable CPVT.

  18. 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.

  19. Effects of serum immunoglobulins from patients with complex regional pain syndrome (CRPS) on depolarisation-induced calcium transients in isolated dorsal root ganglion (DRG) neurons.

    Science.gov (United States)

    Reilly, Joanne M; Dharmalingam, Backialakshmi; Marsh, Stephen J; Thompson, Victoria; Goebel, Andreas; Brown, David A

    2016-03-01

    Complex regional pain syndrome (CRPS) is thought to have an auto-immune component. One such target recently proposed from the effects of auto-immune IgGs on Ca(2+) transients in cardiac myocytes and cell lines is the α1-adrenoceptor. We have tested whether such IgGs exerted comparable effects on nociceptive sensory neurons isolated from rat dorsal root ganglia. Depolarisation-induced [Ca(2+)]i transients were generated by applying 30 mM KCl for 2 min and monitored by Fura-2 fluorescence imaging. No IgGs tested (including 3 from CRPS patients) had any significant effect on these [Ca(2+)]i transients. However, IgG from one CRPS patient consistently and significantly reduced the K(+)-induced response of cells that had been pre-incubated for 24h with a mixture of inflammatory mediators (1 μM histamine, 5-hydroxytryptamine, bradykinin and PGE2). Since this pre-incubation also appeared to induce a comparable inhibitory response to the α1-agonist phenylephrine, this is compatible with the α1-adrenoceptor as a target for CRPS auto-immunity. A mechanism whereby this might enhance pain is suggested. Copyright © 2015. Published by Elsevier Inc.

  20. Production of high quality brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) RNA from isolated populations of rat spinal cord motor neurons obtained by Laser Capture Microdissection (LCM).

    Science.gov (United States)

    Mehta, Prachi; Premkumar, Brian; Morris, Renée

    2016-08-03

    The mammalian central nervous system (CNS) is composed of multiple cellular elements, making it challenging to segregate one particular cell type to study their gene expression profile. For instance, as motor neurons represent only 5-10% of the total cell population of the spinal cord, meaningful transcriptional analysis on these neurons is almost impossible to achieve from homogenized spinal cord tissue. A major challenge faced by scientists is to obtain good quality RNA from small amounts of starting material. In this paper, we used Laser Capture Microdissection (LCM) techniques to identify and isolate spinal cord motor neurons. The present analysis revealed that perfusion with paraformaldehyde (PFA) does not alter RNA quality. RNA integrity numbers (RINs) of tissue samples from rubrospinal tract (RST)-transected, intact spinal cord or from whole spinal cord homogenate were all above 8, which indicates intact, high-quality RNA. Levels of mRNA for brain-derived neurotrophic factor (BDNF) or for its tropomyosin receptor kinase B (TrkB) were not affected by rubrospinal tract (RST) transection, a surgical procedure that deprive motor neurons from one of their main supraspinal input. The isolation of pure populations of neurons with LCM techniques allows for robust transcriptional characterization that cannot be achieved with spinal cord homogenates. Such preparations of pure population of motor neurons will provide valuable tools to advance our understanding of the molecular mechanisms underlying spinal cord injury and neuromuscular diseases. In the near future, LCM techniques might be instrumental to the success of gene therapy for these debilitating conditions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Effects of stress on catecholamine stores in central and peripheral tissues of long-term socially isolated rats.

    Science.gov (United States)

    Dronjak, S; Gavrilovic, L

    2006-06-01

    Both the peripheral sympatho-adrenomedullary and central catecholaminergic systems are activated by various psycho-social and physical stressors. Catecholamine stores in the hypothalamus, hippocampus, adrenal glands, and heart auricles of long-term socially isolated (21 days) and control 3-month-old male Wistar rats, as well as their response to immobilization of all 4 limbs and head fixed for 2 h and cold stress (4 degrees C, 2 h), were studied. A simultaneous single isotope radioenzymatic assay based on the conversion of catecholamines to the corresponding O-methylated derivatives by catechol-O-methyl-transferase in the presence of S-adenosyl-l-(3H-methyl)-methionine was used. The O-methylated derivatives were oxidized to 3H-vanilline and the radioactivity measured. Social isolation produced depletion of hypothalamic norepinephrine (about 18%) and hippocampal dopamine (about 20%) stores and no changes in peripheral tissues. Immobilization decreased catecholamine stores (approximately 39%) in central and peripheral tissues of control animals. However, in socially isolated rats, these reductions were observed only in the hippocampus and peripheral tissues. Cold did not affect hypothalamic catecholamine stores but reduced hippocampal dopamine (about 20%) as well as norepinephrine stores in peripheral tissues both in control and socially isolated rats, while epinephrine levels were unchanged. Thus, immobilization was more efficient in reducing catecholamine stores in control and chronically isolated rats compared to cold stress. The differences in rearing conditions appear to influence the response of adult animals to additional stress. In addition, the influence of previous exposure to a stressor on catecholaminergic activity in the brainstem depends on both the particular catecholaminergic area studied and the properties of additional acute stress. Therefore, the sensitivity of the catecholaminergic system to habituation appears to be tissue-specific.

  2. Effects of stress on catecholamine stores in central and peripheral tissues of long-term socially isolated rats

    Directory of Open Access Journals (Sweden)

    Dronjak S.

    2006-01-01

    Full Text Available Both the peripheral sympatho-adrenomedullary and central catecholaminergic systems are activated by various psycho-social and physical stressors. Catecholamine stores in the hypothalamus, hippocampus, adrenal glands, and heart auricles of long-term socially isolated (21 days and control 3-month-old male Wistar rats, as well as their response to immobilization of all 4 limbs and head fixed for 2 h and cold stress (4ºC, 2 h, were studied. A simultaneous single isotope radioenzymatic assay based on the conversion of catecholamines to the corresponding O-methylated derivatives by catechol-O-methyl-transferase in the presence of S-adenosyl-l-(³H-methyl-methionine was used. The O-methylated derivatives were oxidized to ³H-vanilline and the radioactivity measured. Social isolation produced depletion of hypothalamic norepinephrine (about 18% and hippocampal dopamine (about 20% stores and no changes in peripheral tissues. Immobilization decreased catecholamine stores (approximately 39% in central and peripheral tissues of control animals. However, in socially isolated rats, these reductions were observed only in the hippocampus and peripheral tissues. Cold did not affect hypothalamic catecholamine stores but reduced hippocampal dopamine (about 20% as well as norepinephrine stores in peripheral tissues both in control and socially isolated rats, while epinephrine levels were unchanged. Thus, immobilization was more efficient in reducing catecholamine stores in control and chronically isolated rats compared to cold stress. The differences in rearing conditions appear to influence the response of adult animals to additional stress. In addition, the influence of previous exposure to a stressor on catecholaminergic activity in the brainstem depends on both the particular catecholaminergic area studied and the properties of additional acute stress. Therefore, the sensitivity of the catecholaminergic system to habituation appears to be tissue-specific.

  3. The Brain of the Archerfish Toxotes chatareus: A Nissl-Based Neuroanatomical Atlas and Catecholaminergic/Cholinergic Systems

    Science.gov (United States)

    Karoubi, Naomi; Segev, Ronen; Wullimann, Mario F.

    2016-01-01

    Over recent years, the seven-spot archerfish (Toxotes chatareus) has emerged as a new model for studies in visual and behavioral neuroscience thanks to its unique hunting strategy. Its natural ability to spit at insects outside of water can be used in the laboratory for well controlled behavioral experiments where the fish is trained to aim at targets on a screen. The need for a documentation of the neuroanatomy of this animal became critical as more research groups use it as a model. Here we present an atlas of adult T. chatareus specimens caught in the wild in South East Asia. The atlas shows representative sections of the brain and specific structures revealed by a classic Nissl staining as well as corresponding schematic drawings. Additional immunostainings for catecholaminergic and cholinergic systems were conducted to corroborate the identification of certain nuclei and the data of a whole brain scanner is available online. We describe the general features of the archerfish brain as well as its specificities, especially for the visual system and compare the neuroanatomy of the archerfish with other teleosts. This atlas of the archerfish brain shows all levels of the neuraxis and intends to provide a solid basis for further neuroscientific research on T. chatareus, in particular electrophysiological studies. PMID:27891081

  4. Effects of piracetam on the incorporation of 32P into the phospholipids of neurons and glial cells isolated from rabbit cerebral cortex

    International Nuclear Information System (INIS)

    Woelk, H.

    1979-01-01

    In the search for the biochemical basis of the action of Piracetam, the effects of this encephalotropic substance on the neuronal and glial phospholipid metabolism was investigated. Piracetam increases the incorporation of 32 P into phosphatidylinositol and phosphatidyl choline of both glia and neuronal cell bodies. When taking the important role of phosphatidylinoitol in the processes of synaptic transmission and axonal conduction into consideration, the data obtained in the present work suggest that piracetam may stimulate excitatory neurons and may be involved in the process of synaptic transmission. The stimulatory effect of piracetam on the incorporation of 32 P into phosphatidylinositol and phosphatidyl choline appears to be mediated by norepinephrine or another neurotransmitter. (orig.) [de

  5. Is activation of the Na+K+ pump necessary for NGF-mediated neuronal survival

    International Nuclear Information System (INIS)

    Sendtner, M.; Gnahn, H.; Wakade, A.; Thoenen, H.

    1988-01-01

    The ability of nerve growth factor to cause rapid activation of the Na+K+ pump of its responsive cells was examined by measuring the uptake of 86 Rb+. A significant increase in 86 Rb+ uptake in E8 chick dorsal root ganglion sensory neurons after NGF treatment was seen only if the cells had been damaged during the preparation procedure. Such damaged cells could not survive in culture in the presence of NGF, and undamaged cells that did survive in response to NGF exhibited no increased 86 Rb+ uptake rate. Furthermore, cultured calf adrenal medullary cells did not show an increase in 86 Rb+ uptake after treatment with NGF, although these cells respond to NGF with an increased synthesis of catecholaminergic enzymes. These results are incompatible with the hypothesis that the mechanism of action of NGF that promotes neuronal survival and enzyme induction results from an initial stimulation of the Na+K+ pump

  6. Neural control of left ventricular contractility in the dog heart: synaptic interactions of negative inotropic vagal preganglionic neurons in the nucleus ambiguus with tyrosine hydroxylase immunoreactive terminals.

    Science.gov (United States)

    Massari, V J; Dickerson, L W; Gray, A L; Lauenstein, J M; Blinder, K J; Newsome, J T; Rodak, D J; Fleming, T J; Gatti, P J; Gillis, R A

    1998-08-17

    Recent physiological evidence indicates that vagal postganglionic control of left ventricular contractility is mediated by neurons found in a ventricular epicardial fat pad ganglion. In the dog this region has been referred to as the cranial medial ventricular (CMV) ganglion [J.L. Ardell, Structure and function of mammalian intrinsic cardiac neurons, in: J.A. Armour, J.L. Ardell (Eds.). Neurocardiology, Oxford Univ. Press, New York, 1994, pp. 95-114; B.X. Yuan, J.L. Ardell, D.A. Hopkins, A.M. Losier, J.A. Armour, Gross and microscopic anatomy of the canine intrinsic cardiac nervous system, Anat. Rec., 239 (1994) 75-87]. Since activation of the vagal neuronal input to the CMV ganglion reduces left ventricular contractility without influencing cardiac rate or AV conduction, this ganglion contains a functionally selective pool of negative inotropic parasympathetic postganglionic neurons. In the present report we have defined the light microscopic distribution of preganglionic negative inotropic neurons in the CNS which are retrogradely labeled from the CMV ganglion. Some tissues were also processed for the simultaneous immunocytochemical visualization of tyrosine hydroxylase (TH: a marker for catecholaminergic neurons) and examined with both light microscopic and electron microscopic methods. Histochemically visualized neurons were observed in a long slender column in the ventrolateral nucleus ambiguus (NA-VL). The greatest number of retrogradely labeled neurons were observed just rostral to the level of the area postrema. TH perikarya and dendrites were commonly observed interspersed with vagal motoneurons in the NA-VL. TH nerve terminals formed axo-dendritic synapses upon negative inotropic vagal motoneurons, however the origin of these terminals remains to be determined. We conclude that synaptic interactions exist which would permit the parasympathetic preganglionic vagal control of left ventricular contractility to be modulated monosynaptically by

  7. Neuroprotective effects of a novel single compound 1-methoxyoctadecan-1-ol isolated from Uncaria sinensis in primary cortical neurons and a photothrombotic ischemia model.

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    Ji Yeon Jang

    Full Text Available We identified a novel neuroprotective compound, 1-methoxyoctadecan-1-ol, from Uncaria sinensis (Oliv. Havil and investigated its effects and mechanisms in primary cortical neurons and in a photothrombotic ischemic model. In primary rat cortical neurons against glutamate-induced neurotoxicity, pretreatment with 1-methoxyoctadecan-1-ol resulted in significantly reduced neuronal death in a dose-dependent manner. In addition, treatment with 1-methoxyoctadecan-1-ol resulted in decreased neuronal apoptotic death, as assessed by nuclear morphological approaches. To clarify the neuroprotective mechanism of 1-methoxyoctadecan-1-ol, we explored the downstream signaling pathways of N-methyl-D-aspartate receptor (NMDAR with calpain activation. Treatment with glutamate leads to early activation of NMDAR, which in turn leads to calpain-mediated cleavage of striatal-enriched protein tyrosine phosphatase (STEP and subsequent activation of p38 mitogen activated protein kinase (MAPK. However, pretreatment with 1-methoxyoctadecan-1-ol resulted in significantly attenuated activation of GluN2B-NMDAR and a decrease in calpain-mediated STEP cleavage, leading to subsequent attenuation of p38 MAPK activation. We confirmed the critical role of p38 MAPK in neuroprotective effects of 1-methoxyoctadecan-1-ol using specific inhibitor SB203580. In the photothrombotic ischemic injury in mice, treatment with 1-methoxyoctadecan-1-ol resulted in significantly reduced infarct volume, edema size, and improved neurological function. 1-methoxyoctadecan-1-ol effectively prevents cerebral ischemic damage through down-regulation of calpain-mediated STEP cleavage and activation of p38 MAPK. These results suggest that 1-methoxyoctadecan-1-ol showed neuroprotective effects through down-regulation of calpain-mediated STEP cleavage with activation of GluN2B-NMDAR, and subsequent alleviation of p38 MAPK activation. In addition, 1-methoxyoctadecan-1-ol might be a useful therapeutic agent for

  8. Genetically-directed, cell type-specific sparse labeling for the analysis of neuronal morphology.

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    Thomas Rotolo

    Full Text Available In mammals, genetically-directed cell labeling technologies have not yet been applied to the morphologic analysis of neurons with very large and complex arbors, an application that requires extremely sparse labeling and that is only rendered practical by limiting the labeled population to one or a few predetermined neuronal subtypes.In the present study we have addressed this application by using CreER technology to non-invasively label very small numbers of neurons so that their morphologies can be fully visualized. Four lines of IRES-CreER knock-in mice were constructed to permit labeling selectively in cholinergic or catecholaminergic neurons [choline acetyltransferase (ChAT-IRES-CreER or tyrosine hydroxylase (TH-IRES-CreER], predominantly in projection neurons [neurofilament light chain (NFL-IRES-CreER], or broadly in neurons and some glia [vesicle-associated membrane protein2 (VAMP2-IRES-CreER]. When crossed to the Z/AP reporter and exposed to 4-hydroxytamoxifen in the early postnatal period, the number of neurons expressing the human placental alkaline phosphatase reporter can be reproducibly lowered to fewer than 50 per brain. Sparse Cre-mediated recombination in ChAT-IRES-CreER;Z/AP mice shows the full axonal and dendritic arbors of individual forebrain cholinergic neurons, the first time that the complete morphologies of these very large neurons have been revealed in any species.Sparse genetically-directed, cell type-specific neuronal labeling with IRES-creER lines should prove useful for studying a wide variety of questions in neuronal development and disease.

  9. Complementary neural correlates of motivation in dopaminergic and noradrenergic neurons of monkeys.

    Directory of Open Access Journals (Sweden)

    Sebastien eBouret

    2012-07-01

    Full Text Available Rewards have many influences on learning, decision-making and performance. All seem to rely on complementary actions of two closely related catecholaminergic neuromodulators, dopamine and noradrenaline. We compared single unit activity of dopaminergic neurons of the substantia nigra pars compacta and noradrenergic neurons of the locus coeruleus in monkeys performing a reward schedule task. Their motivation, indexed using operant performance, increased as they progressed through schedules ending in reward delivery. The responses of dopaminergic and noradrenergic neurons around the time of major task events, visual cues predicting trial outcome and operant action to complete a trial, were similar, in that they occurred at the same time. They were also similar in that they both responded most strongly to the first cues in schedules, which are the most informative cues. The neuronal responses around the time of the monkeys’ actions were different, in that the response intensity profiles changed in opposite directions. Dopaminergic responses were stronger around predictably rewarded correct actions whereas noradrenergic responses were greater around predictably unrewarded correct actions. The complementary response profiles related to the monkeys operant actions suggest that dopamine neurons might relate to the value of the current action whereas the noradrenergic neurons relate to the psychological cost of that action.

  10. Molecular phenotyping of transient postnatal tyrosine hydroxylase neurons in the rat bed nucleus of the stria terminalis.

    Science.gov (United States)

    Carter, David A

    2017-07-01

    The bed nucleus of the stria terminalis (BNST) is a complex integrative centre in the forebrain, composed of multiple sub-nuclei, each with discrete populations of neurons. Progress in understanding BNST function, both in the adult and during postnatal maturation, is dependent upon a more complete characterization of neuronal phenotypes in the BNST. The aim of the current study was to define the molecular phenotype of one postnatal BNST neuronal population, in order to identify molecular factors that may underlie both (protein marker-related) immaturity, and secondly, the transience of this phenotype. This BNST population was originally identified by high, but transient expression of the EGR1 transcription factor (TF) in postnatal rat lateral intermediate BNST (BNSTLI). The current results confirm a high level of Egr1 activation in postnatal day 10 (PN10) male BNSTLI that is lost at PN40, and now demonstrate a similar pattern of transient activation in female brains. Apparent cellular immaturity in this population, as indicated by low levels of the adult neuronal marker NeuN/RBFOX3, was found to be uncorrelated with both key neuronal regulator protein expression (SOX2 and REST), and also RBFOX2 protein levels. The BNSTLI neurons have a partial catecholaminergic phenotype (tyrosine hydroxylase-positive/dopa decarboxylase-negative; TH+ve/DDC-ve) that is lost at PN40. In contrast, the co-expressed neuropeptide, somatostatin, is maintained, albeit at lower levels, at PN40. The transcriptional basis of the transient and partial catecholaminergic phenotype was investigated by analysing TFs known to maintain adult dopaminergic (TH+ve/DDC+ve) neuronal phenotypes. The BNSTLI neurons were shown to lack forkhead TFs including FOXA1, FOXA2 and FOXO1. In addition, the BNSTLI neurons had low, primarily cytoplasmic, expression of NR4A2/NURR1, an orphan nuclear receptor that is critical for adult maintenance of midbrain dopamine neurons. These results detail the molecular features

  11. Chronic Blockade of Brain Endothelin Receptor Type-A (ETA Reduces Blood Pressure and Prevents Catecholaminergic Overactivity in the Right Olfactory Bulb of DOCA-Salt Hypertensive Rats

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    Luis R. Cassinotti

    2018-02-01

    Full Text Available Overactivity of the sympathetic nervous system and central endothelins (ETs are involved in the development of hypertension. Besides the well-known brain structures involved in the regulation of blood pressure like the hypothalamus or locus coeruleus, evidence suggests that the olfactory bulb (OB also modulates cardiovascular function. In the present study, we evaluated the interaction between the endothelinergic and catecholaminergic systems in the OB of deoxycorticosterone acetate (DOCA-salt hypertensive rats. Following brain ET receptor type A (ETA blockade by BQ610 (selective antagonist, transcriptional, traductional, and post-traductional changes in tyrosine hydroxylase (TH were assessed in the OB of normotensive and DOCA-salt hypertensive rats. Time course variations in systolic blood pressure and heart rate were also registered. Results showed that ETA blockade dose dependently reduced blood pressure in hypertensive rats, but it did not change heart rate. It also prevented the increase in TH activity and expression (mRNA and protein in the right OB of hypertensive animals. However, ETA blockade did not affect hemodynamics or TH in normotensive animals. Present results support that brain ETA are not involved in blood pressure regulation in normal rats, but they significantly contribute to chronic blood pressure elevation in hypertensive animals. Changes in TH activity and expression were observed in the right but not in the left OB, supporting functional asymmetry, in line with previous studies regarding cardiovascular regulation. Present findings provide further evidence on the role of ETs in the regulation of catecholaminergic activity and the contribution of the right OB to DOCA-salt hypertension.

  12. Chronic Blockade of Brain Endothelin Receptor Type-A (ETA) Reduces Blood Pressure and Prevents Catecholaminergic Overactivity in the Right Olfactory Bulb of DOCA-Salt Hypertensive Rats.

    Science.gov (United States)

    Cassinotti, Luis R; Guil, María J; Schöller, Mercedes I; Navarro, Mónica P; Bianciotti, Liliana G; Vatta, Marcelo S

    2018-02-27

    Overactivity of the sympathetic nervous system and central endothelins (ETs) are involved in the development of hypertension. Besides the well-known brain structures involved in the regulation of blood pressure like the hypothalamus or locus coeruleus, evidence suggests that the olfactory bulb (OB) also modulates cardiovascular function. In the present study, we evaluated the interaction between the endothelinergic and catecholaminergic systems in the OB of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Following brain ET receptor type A (ET A ) blockade by BQ610 (selective antagonist), transcriptional, traductional, and post-traductional changes in tyrosine hydroxylase (TH) were assessed in the OB of normotensive and DOCA-salt hypertensive rats. Time course variations in systolic blood pressure and heart rate were also registered. Results showed that ET A blockade dose dependently reduced blood pressure in hypertensive rats, but it did not change heart rate. It also prevented the increase in TH activity and expression (mRNA and protein) in the right OB of hypertensive animals. However, ET A blockade did not affect hemodynamics or TH in normotensive animals. Present results support that brain ET A are not involved in blood pressure regulation in normal rats, but they significantly contribute to chronic blood pressure elevation in hypertensive animals. Changes in TH activity and expression were observed in the right but not in the left OB, supporting functional asymmetry, in line with previous studies regarding cardiovascular regulation. Present findings provide further evidence on the role of ETs in the regulation of catecholaminergic activity and the contribution of the right OB to DOCA-salt hypertension.

  13. 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....

  14. Neurons of the A5 region are required for the tachycardia evoked by electrical stimulation of the hypothalamic defence area in anaesthetized rats.

    Science.gov (United States)

    López-González, M V; Díaz-Casares, A; Peinado-Aragonés, C A; Lara, J P; Barbancho, M A; Dawid-Milner, M S

    2013-08-01

    In order to assess the possible interactions between the pontine A5 region and the hypothalamic defence area (HDA), we have examined the pattern of double staining for c-Fos protein immunoreactivity (c-Fos-ir) and tyrosine hydroxylase, throughout the rostrocaudal extent of the A5 region in spontaneously breathing anaesthetized male Sprague-Dawley rats during electrical stimulation of the HDA. Activation of the HDA elicited a selective increase in c-Fos-ir with an ipsilateral predominance in catecholaminergic and non-catecholaminergic A5 somata (P HDA. Cardiorespiratory changes were analysed in response to electrical stimulation of the HDA before and after ipsilateral microinjection of muscimol within the A5 region. Stimulation of the HDA evoked an inspiratory facilitatory response, consisting of an increase in respiratory rate (P HDA stimulation were reduced (P HDA and the A5 region, extracellular recordings of putative A5 neurones were obtained during HDA stimulation. Seventy-five A5 cells were recorded, 35 of which were affected by the HDA (47%). These results indicate that neurones of the A5 region participate in the cardiovascular response evoked from the HDA. The possible mechanisms involved in these interactions are discussed.

  15. Clonidine, an alpha2-receptor agonist, diminishes GABAergic neurotransmission to cardiac vagal neurons in the nucleus ambiguus.

    Science.gov (United States)

    Philbin, Kerry E; Bateman, Ryan J; Mendelowitz, David

    2010-08-06

    In hypertension, there is an autonomic imbalance in which sympathetic activity dominates over parasympathetic control. Parasympathetic activity to the heart originates from cardiac vagal neurons located in the nucleus ambiguus. Presympathetic neurons that project to sympathetic neurons in the spinal cord are located in the ventral brainstem in close proximity to cardiac vagal neurons, and many of these presympathetic neurons are catecholaminergic. In addition to their projection to the spinal cord, many of these presympathetic neurons have axon collaterals that arborize into neighboring cardiorespiratory locations and likely release norepinephrine onto nearby neurons. Activation of alpha(2)-adrenergic receptors in the central nervous system evokes a diverse range of physiological effects, including reducing blood pressure. This study tests whether clonidine, an alpha(2)-adrenergic receptor agonist, alters excitatory glutamatergic, and/or inhibitory GABAergic or glycinergic synaptic neurotransmission to cardiac vagal neurons in the nucleus ambiguus. Cardiac vagal neurons were identified in an in vitro brainstem slice preparation, and synaptic events were recording using whole cell voltage clamp methodologies. Clonidine significantly inhibited GABAergic neurotransmission but had no effect on glycinergic or glutamatergic pathways to cardiac vagal neurons. This diminished inhibitory GABAergic neurotransmission to cardiac vagal neurons would increase parasympathetic activity to the heart, decreasing heart rate and blood pressure. The results presented here provide a cellular substrate for the clinical use of clonidine as a treatment for hypertension as well as a role in alleviating posttraumatic stress disorder by evoking an increase in parasympathetic cardiac vagal activity, and a decrease in heart rate and blood pressure. Copyright 2010 Elsevier B.V. All rights reserved.

  16. [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.

  17. 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.

  18. Electrophysiological effects of trace amines on mesencephalic dopaminergic neurons

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    Ada eLedonne

    2011-07-01

    Full Text Available Trace amines (TAs are a class of endogenous compounds strictly related to classic monoamine neurotransmitters with regard to their structure, metabolism and tissue distribution. Although the presence of TAs in mammalian brain has been recognized for decades, until recently they were considered to be by-products of amino acid metabolism or as ‘false’ neurotransmitters. The discovery in 2001 of a new family of G protein-coupled receptors (GPCRs, namely trace amines receptors, has re-ignited interest in TAs. In particular, two members of the family, trace amine receptor 1 (TA1 and trace amine receptor 2 (TA2, were shown to be highly sensitive to these endogenous compounds. Experimental evidence suggests that TAs modulate the activity of catecholaminergic neurons and that TA dysregulation may contribute to neuropsychiatric disorders, including schizophrenia, attention deficit hyperactivity disorder, depression and Parkinson’s disease, all of which are characterised by altered monoaminergic networks. Here we review recent data concerning the electrophysiological effects of TAs on the activity of mesencephalic dopaminergic neurons. In the context of recent data obtained with TA1 receptor knockout mice, we also discuss the mechanisms by which the activation of these receptors modulates the activity of these neurons. Three important new aspects of TAs action have recently emerged: (a inhibition of firing due to increased release of dopamine; (b reduction of D2 and GABAB receptor-mediated inhibitory responses (excitatory effects due to dysinhibition; and (c a direct TA1 receptor-mediated activation of GIRK channels which produce cell membrane hyperpolarization. While the first two effects have been well documented in our laboratory, the direct activation of GIRK channels by TA1 receptors has been reported by others, but has not been seen in our laboratory (Geracitano et al., 2004. Further research is needed to address this point, and to further

  19. Calcium signals in olfactory neurons.

    Science.gov (United States)

    Tareilus, E; Noé, J; Breer, H

    1995-11-09

    Laser scanning confocal microscopy in combination with the fluorescent calcium indicators Fluo-3 and Fura-Red was employed to estimate the intracellular concentration of free calcium ions in individual olfactory receptor neurons and to monitor temporal and spatial changes in the Ca(2+)-level upon stimulation. The chemosensory cells responded to odorants with a significant increase in the calcium concentration, preferentially in the dendritic knob. Applying various stimulation paradigma, it was found that in a population of isolated cells, subsets of receptor neurons display distinct patterns of responsiveness.

  20. Role of nucleus of the solitary tract noradrenergic neurons in post-stress cardiovascular and hormonal control in male rats.

    Science.gov (United States)

    Bundzikova-Osacka, Jana; Ghosal, Sriparna; Packard, Benjamin A; Ulrich-Lai, Yvonne M; Herman, James P

    2015-01-01

    Chronic stress causes hypothalamo-pituitary-adrenal (HPA) axis hyperactivity and cardiovascular dyshomeostasis. Noradrenergic (NA) neurons in the nucleus of the solitary tract (NTS) are considered to play a role in these changes. In this study, we tested the hypothesis that NTS NA A2 neurons are required for cardiovascular and HPA axis responses to both acute and chronic stress. Adult male rats received bilateral microinjection into the NTS of 6-hydroxydopamine (6-OHDA) to lesion A2 neurons [cardiovascular study, n = 5; HPA study, n = 5] or vehicle [cardiovascular study, n = 6; HPA study, n = 4]. Rats were exposed to acute restraint stress followed by 14 d of chronic variable stress (CVS). On the last day of testing, rats were placed in a novel elevated plus maze (EPM) to test post-CVS stress responses. Lesions of NTS A2 neurons reduced the tachycardic response to acute restraint, confirming that A2 neurons promote sympathetic activation following acute stress. In addition, CVS increased the ratio of low-frequency to high-frequency power for heart rate variability, indicative of sympathovagal imbalance, and this effect was significantly attenuated by 6-OHDA lesion. Lesions of NTS A2 neurons reduced acute restraint-induced corticosterone secretion, but did not affect the corticosterone response to the EPM, indicating that A2 neurons promote acute HPA axis responses, but are not involved in CVS-mediated HPA axis sensitization. Collectively, these data indicate that A2 neurons promote both cardiovascular and HPA axis responses to acute stress. Moreover, A2 catecholaminergic neurons may contribute to the potentially deleterious enhancement of sympathetic drive following chronic stress.

  1. Protective effects of Hericium erinaceus mycelium and its isolated erinacine A against ischemia-injury-induced neuronal cell death via the inhibition of iNOS/p38 MAPK and nitrotyrosine.

    Science.gov (United States)

    Lee, Kam-Fai; Chen, Jiann-Hwa; Teng, Chih-Chuan; Shen, Chien-Heng; Hsieh, Meng-Chiao; Lu, Chien-Chang; Lee, Ko-Chao; Lee, Li-Ya; Chen, Wan-Ping; Chen, Chin-Chu; Huang, Wen-Shih; Kuo, Hsing-Chun

    2014-08-27

    Hericium erinaceus, an edible mushroom, has been demonstrated to potentiate the effects of numerous biological activities. The aim of this study was to investigate whether H. erinaceus mycelium could act as an anti-inflammatory agent to bring about neuroprotection using a model of global ischemic stroke and the mechanisms involved. Rats were treated with H. erinaceus mycelium and its isolated diterpenoid derivative, erinacine A, after ischemia reperfusion brain injuries caused by the occlusion of the two common carotid arteries. The production of inflammatory cytokines in serum and the infracted volume of the brain were measured. The proteins from the stroke animal model (SAM) were evaluated to determine the effect of H. erinaceus mycelium. H. erinaceus mycelium reduced the total infarcted volumes by 22% and 44% at a concentration of 50 and 300 mg/kg, respectively, compared to the SAM group. The levels of acute inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor á, were all reduced by erinacine A. Levels of nitrotyrosine-containing proteins, phosphorylation of p38 MAPK and CCAAT enhancer-binding protein (C/EBP) and homologous protein (CHOP) expression were attenuated by erinacine A. Moreover, the modulation of ischemia injury factors present in the SAM model by erinacine A seemed to result in the suppression of reactive nitrogen species and the downregulation of inducible NO synthase (iNOS), p38 MAPK and CHOP. These findings confirm the nerve-growth properties of Hericium erinaceus mycelium, which include the prevention of ischemic injury to neurons; this protective effect seems to be involved in the in vivo activity of iNOS, p38 MAPK and CHOP.

  2. Protective Effects of Hericium erinaceus Mycelium and Its Isolated Erinacine A against Ischemia-Injury-Induced Neuronal Cell Death via the Inhibition of iNOS/p38 MAPK and Nitrotyrosine

    Directory of Open Access Journals (Sweden)

    Kam-Fai Lee

    2014-08-01

    Full Text Available Hericium erinaceus, an edible mushroom, has been demonstrated to potentiate the effects of numerous biological activities. The aim of this study was to investigate whether H. erinaceus mycelium could act as an anti-inflammatory agent to bring about neuroprotection using a model of global ischemic stroke and the mechanisms involved. Rats were treated with H. erinaceus mycelium and its isolated diterpenoid derivative, erinacine A, after ischemia reperfusion brain injuries caused by the occlusion of the two common carotid arteries. The production of inflammatory cytokines in serum and the infracted volume of the brain were measured. The proteins from the stroke animal model (SAM were evaluated to determine the effect of H. erinaceus mycelium. H. erinaceus mycelium reduced the total infarcted volumes by 22% and 44% at a concentration of 50 and 300 mg/kg, respectively, compared to the SAM group. The levels of acute inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor á, were all reduced by erinacine A. Levels of nitrotyrosine-containing proteins, phosphorylation of p38 MAPK and CCAAT enhancer-binding protein (C/EBP and homologous protein (CHOP expression were attenuated by erinacine A. Moreover, the modulation of ischemia injury factors present in the SAM model by erinacine A seemed to result in the suppression of reactive nitrogen species and the downregulation of inducible NO synthase (iNOS, p38 MAPK and CHOP. These findings confirm the nerve-growth properties of Hericium erinaceus mycelium, which include the prevention of ischemic injury to neurons; this protective effect seems to be involved in the in vivo activity of iNOS, p38 MAPK and CHOP.

  3. Effects of pre-experience of social exclusion on hypothalamus-pituitary-adrenal axis and catecholaminergic responsiveness to public speaking stress.

    Science.gov (United States)

    Weik, Ulrike; Kuepper, Yvonne; Hennig, Juergen; Deinzer, Renate

    2013-01-01

    Being socially excluded is associated with a variety of psychological changes and with an increased risk of disease. Today, the immediate physiological consequences of being socially excluded are not well understood. In two recent studies employing a standardized exclusion paradigm (Cyberball) we found social exclusion in this virtual game did not alter cortisol secretion directly. However, exclusion pre-experience suppresses the normal cortisol response to public speaking stress in women. The present study aims to replicate our previous finding and further elucidate it by analyzing for the first time whether this alteration of cortisol-responsiveness is associated to ACTH and whether the catecholaminergic system is affected as well. Women were randomly assigned to Cyberball-induced exclusion (SE, n = 22) or inclusion (SI, n = 21), respectively. Immediately afterwards they were subjected to public speaking stress. Salivary cortisol, plasma ACTH, catecholamines and estradiol were assessed as were psychological distress and mood. Cyberball exclusion led to a highly significant immediate increase in negative affect in excluded women. After public speaking negative affect in included women increased as well and groups no longer differed. We replicate our previous finding of cortisol non-responsiveness to public speaking stress after exclusion pre-experience and find this effect to be significantly correlated with ACTH alterations. No such effects are observed for catecholamines. We replicated our previous study result of a suppressed cortisol stress response after a short exclusion experience via Cyberball, thereby underlining the profound effects of social exclusion on a subsequent cortisol stress response. This further demonstrates that these alterations are associated with ACTH. Lack of effects on catecholamines is discussed in view of the tend-and-befriend hypothesis but also from a methodological perspective.

  4. Patient-Specific Human Induced Pluripotent Stem Cell Model Assessed with Electrical Pacing Validates S107 as a Potential Therapeutic Agent for Catecholaminergic Polymorphic Ventricular Tachycardia.

    Directory of Open Access Journals (Sweden)

    Kenichi Sasaki

    Full Text Available Human induced pluripotent stem cells (hiPSCs offer a unique opportunity for disease modeling. However, it is not invariably successful to recapitulate the disease phenotype because of the immaturity of hiPSC-derived cardiomyocytes (hiPSC-CMs. The purpose of this study was to establish and analyze iPSC-based model of catecholaminergic polymorphic ventricular tachycardia (CPVT, which is characterized by adrenergically mediated lethal arrhythmias, more precisely using electrical pacing that could promote the development of new pharmacotherapies.We generated hiPSCs from a 37-year-old CPVT patient and differentiated them into cardiomyocytes. Under spontaneous beating conditions, no significant difference was found in the timing irregularity of spontaneous Ca2+ transients between control- and CPVT-hiPSC-CMs. Using Ca2+ imaging at 1 Hz electrical field stimulation, isoproterenol induced an abnormal diastolic Ca2+ increase more frequently in CPVT- than in control-hiPSC-CMs (control 12% vs. CPVT 43%, p<0.05. Action potential recordings of spontaneous beating hiPSC-CMs revealed no significant difference in the frequency of delayed afterdepolarizations (DADs between control and CPVT cells. After isoproterenol application with pacing at 1 Hz, 87.5% of CPVT-hiPSC-CMs developed DADs, compared to 30% of control-hiPSC-CMs (p<0.05. Pre-incubation with 10 μM S107, which stabilizes the closed state of the ryanodine receptor 2, significantly decreased the percentage of CPVT-hiPSC-CMs presenting DADs to 25% (p<0.05.We recapitulated the electrophysiological features of CPVT-derived hiPSC-CMs using electrical pacing. The development of DADs in the presence of isoproterenol was significantly suppressed by S107. Our model provides a promising platform to study disease mechanisms and screen drugs.

  5. Effects of pre-experience of social exclusion on hypothalamus-pituitary-adrenal axis and catecholaminergic responsiveness to public speaking stress.

    Directory of Open Access Journals (Sweden)

    Ulrike Weik

    Full Text Available BACKGROUND: Being socially excluded is associated with a variety of psychological changes and with an increased risk of disease. Today, the immediate physiological consequences of being socially excluded are not well understood. In two recent studies employing a standardized exclusion paradigm (Cyberball we found social exclusion in this virtual game did not alter cortisol secretion directly. However, exclusion pre-experience suppresses the normal cortisol response to public speaking stress in women. The present study aims to replicate our previous finding and further elucidate it by analyzing for the first time whether this alteration of cortisol-responsiveness is associated to ACTH and whether the catecholaminergic system is affected as well. METHODS: Women were randomly assigned to Cyberball-induced exclusion (SE, n = 22 or inclusion (SI, n = 21, respectively. Immediately afterwards they were subjected to public speaking stress. Salivary cortisol, plasma ACTH, catecholamines and estradiol were assessed as were psychological distress and mood. RESULTS: Cyberball exclusion led to a highly significant immediate increase in negative affect in excluded women. After public speaking negative affect in included women increased as well and groups no longer differed. We replicate our previous finding of cortisol non-responsiveness to public speaking stress after exclusion pre-experience and find this effect to be significantly correlated with ACTH alterations. No such effects are observed for catecholamines. CONCLUSIONS: We replicated our previous study result of a suppressed cortisol stress response after a short exclusion experience via Cyberball, thereby underlining the profound effects of social exclusion on a subsequent cortisol stress response. This further demonstrates that these alterations are associated with ACTH. Lack of effects on catecholamines is discussed in view of the tend-and-befriend hypothesis but also from a methodological

  6. Nervus terminalis ganglion of the bonnethead shark (Sphyrna tiburo): evidence for cholinergic and catecholaminergic influence on two cell types distinguished by peptide immunocytochemistry.

    Science.gov (United States)

    White, J; Meredith, M

    1995-01-16

    The nervus terminalis is a ganglionated vertebrate cranial nerve of unknown function that connects the brain and the peripheral nasal structures. To investigate its function, we have studied nervus terminalis ganglion morphology and physiology in the bonnethead shark (Sphyrna tiburo), where the nerve is particularly prominent. Immunocytochemistry for gonadotropin-releasing hormone (GnRH) and Leu-Pro-Leu-Arg-Phe-NH2 (LPLRFamide) revealed two distinct populations of cells. Both were acetylcholinesterase positive, but LPLR-Famide-immunoreactive cells consistently stained more darkly for acetylcholinesterase activity. Tyrosine hydroxylase immunocytochemistry revealed fibers and terminal-like puncta in the ganglion, primarily in areas containing GnRH-immunoreactive cells. Consistent with the anatomy, in vitro electrophysiological recordings provided evidence for cholinergic and catecholaminergic actions. In extracellular recordings, acetylcholine had a variable effect on baseline ganglion cell activity, whereas norepinephrine consistently reduced activity. Electrical stimulation of the nerve trunks suppressed ganglion activity, as did impulses from the brain in vivo. During electrical suppression, acetylcholine consistently increased activity, and norepinephrine decreased activity. Muscarinic and, to a lesser extent, alpha-adrenergic antagonists both increased activity during the electrical suppression, suggesting involvement of both systems. Intracellular recordings revealed two types of ganglion cells that were distinguishable pharmacologically and physiologically. Some cells were hyperpolarized by cholinergic agonists and unaffected by norepinephrine; these cells did not depolarize with peripheral nerve trunk stimulation. Another group of cells did depolarize with peripheral trunk stimulation; a representative of this group was depolarized by carbachol and hyperpolarized by norepinephrine. These and other data suggest that the bonnethead nervus terminalis ganglion

  7. Antiarrhythmic Effects of Dantrolene in Patients with Catecholaminergic Polymorphic Ventricular Tachycardia and Replication of the Responses Using iPSC Models.

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    Kirsi Penttinen

    Full Text Available Catecholaminergic polymorphic ventricular tachycardia (CPVT is a highly malignant inherited arrhythmogenic disorder. Type 1 CPVT (CPVT1 is caused by cardiac ryanodine receptor (RyR2 gene mutations resulting in abnormal calcium release from sarcoplasmic reticulum. Dantrolene, an inhibitor of sarcoplasmic Ca(2+ release, has been shown to rescue this abnormal Ca(2+ release in vitro. We assessed the antiarrhythmic efficacy of dantrolene in six patients carrying various RyR2 mutations causing CPVT. The patients underwent exercise stress test before and after dantrolene infusion. Dantrolene reduced the number of premature ventricular complexes (PVCs on average by 74% (range 33-97 in four patients with N-terminal or central mutations in the cytosolic region of the RyR2 protein, while dantrolene had no effect in two patients with mutations in or near the transmembrane domain. Induced pluripotent stem cells (iPSCs were generated from all the patients and differentiated into spontaneously beating cardiomyocytes (CMs. The antiarrhythmic effect of dantrolene was studied in CMs after adrenaline stimulation by Ca(2+ imaging. In iPSC derived CMs with RyR2 mutations in the N-terminal or central region, dantrolene suppressed the Ca(2+ cycling abnormalities in 80% (range 65-97 of cells while with mutations in or near the transmembrane domain only in 23 or 32% of cells. In conclusion, we demonstrate that dantrolene given intravenously shows antiarrhythmic effects in a portion of CPVT1 patients and that iPSC derived CM models replicate these individual drug responses. These findings illustrate the potential of iPSC models to individualize drug therapy of inherited diseases.Trial Registration: EudraCT Clinical Trial Registry 2012-005292-14.

  8. Identification of neural transcription factors required for the differentiation of three neuronal subtypes in the sea urchin embryo.

    Science.gov (United States)

    Slota, Leslie A; McClay, David R

    2018-03-15

    Correct patterning of the nervous system is essential for an organism's survival and complex behavior. Embryologists have used the sea urchin as a model for decades, but our understanding of sea urchin nervous system patterning is incomplete. Previous histochemical studies identified multiple neurotransmitters in the pluteus larvae of several sea urchin species. However, little is known about how, where and when neural subtypes are differentially specified during development. Here, we examine the molecular mechanisms of neuronal subtype specification in 3 distinct neural subtypes in the Lytechinus variegatus larva. We show that these subtypes are specified through Delta/Notch signaling and identify a different transcription factor required for the development of each neural subtype. Our results show achaete-scute and neurogenin are proneural for the serotonergic neurons of the apical organ and cholinergic neurons of the ciliary band, respectively. We also show that orthopedia is not proneural but is necessary for the differentiation of the cholinergic/catecholaminergic postoral neurons. Interestingly, these transcription factors are used similarly during vertebrate neurogenesis. We believe this study is a starting point for building a neural gene regulatory network in the sea urchin and for finding conserved deuterostome neurogenic mechanisms. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Mirror neuron system: basic findings and clinical applications.

    Science.gov (United States)

    Iacoboni, Marco; Mazziotta, John C

    2007-09-01

    In primates, ventral premotor and rostral inferior parietal neurons fire during the execution of hand and mouth actions. Some cells (called mirror neurons) also fire when hand and mouth actions are just observed. Mirror neurons provide a simple neural mechanism for understanding the actions of others. In humans, posterior inferior frontal and rostral inferior parietal areas have mirror properties. These human areas are relevant to imitative learning and social behavior. Indeed, the socially isolating condition of autism is associated with a deficit in mirror neuron areas. Strategies inspired by mirror neuron research recently have been used in the treatment of autism and in motor rehabilitation after stroke.

  10. Neuron Morphology Influences Axon Initial Segment Plasticity.

    Science.gov (United States)

    Gulledge, Allan T; Bravo, Jaime J

    2016-01-01

    In most vertebrate neurons, action potentials are initiated in the axon initial segment (AIS), a specialized region of the axon containing a high density of voltage-gated sodium and potassium channels. It has recently been proposed that neurons use plasticity of AIS length and/or location to regulate their intrinsic excitability. Here we quantify the impact of neuron morphology on AIS plasticity using computational models of simplified and realistic somatodendritic morphologies. In small neurons (e.g., dentate granule neurons), excitability was highest when the AIS was of intermediate length and located adjacent to the soma. Conversely, neurons having larger dendritic trees (e.g., pyramidal neurons) were most excitable when the AIS was longer and/or located away from the soma. For any given somatodendritic morphology, increasing dendritic membrane capacitance and/or conductance favored a longer and more distally located AIS. Overall, changes to AIS length, with corresponding changes in total sodium conductance, were far more effective in regulating neuron excitability than were changes in AIS location, while dendritic capacitance had a larger impact on AIS performance than did dendritic conductance. The somatodendritic influence on AIS performance reflects modest soma-to-AIS voltage attenuation combined with neuron size-dependent changes in AIS input resistance, effective membrane time constant, and isolation from somatodendritic capacitance. We conclude that the impact of AIS plasticity on neuron excitability will depend largely on somatodendritic morphology, and that, in some neurons, a shorter or more distally located AIS may promote, rather than limit, action potential generation.

  11. Context-aware modeling of neuronal morphologies

    Directory of Open Access Journals (Sweden)

    Benjamin eTorben-Nielsen

    2014-09-01

    Full Text Available Neuronal morphologies are pivotal for brain functioning: physical overlap between dendrites and axons constrain the circuit topology, and the precise shape and composition of dendrites determine the integration of inputs to produce an output signal. At the same time, morphologies are highly diverse and variant. The variance, presumably, originates from neurons developing in a densely packed brain substrate where they interact (e.g., repulsion or attraction with other actors in this substrate. However, when studying neurons their context is never part of the analysis and they are treated as if they existed in isolation.Here we argue that to fully understand neuronal morphology and its variance it is important to consider neurons in relation to each other and to other actors in the surrounding brain substrate, i.e., their context. We propose a context-aware computational framework, NeuroMaC, in which large numbers of neurons can be grown simultaneously according to growth rules expressed in terms of interactions between the developing neuron and the surrounding brain substrate.As a proof of principle, we demonstrate that by using NeuroMaC we can generate accurate virtual morphologies of distinct classes both in isolation and as part of neuronal forests. Accuracy is validated against population statistics of experimentally reconstructed morphologies. We show that context-aware generation of neurons can explain characteristics of variation. Indeed, plausible variation is an inherent property of the morphologies generated by context-aware rules. We speculate about the applicability of this framework to investigate morphologies and circuits, to classify healthy and pathological morphologies, and to generate large quantities of morphologies for large-scale modeling.

  12. Achalasia: virus-induced euthanasia of neurons?

    NARCIS (Netherlands)

    Boeckxstaens, Guy E.

    2008-01-01

    Achalasia, a motor disorder of the esophagus, is characterized by myenteric plexitis leading to neuronal loss. Cytotoxic T cells, isolated from the lower esophageal sphincter of achalasia patients, respond to human herpes virus-1 (HSV-1) with gamma-IFN (and to a lesser extent IL-2) production and

  13. 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 ...

  14. 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 ...

  15. A low-density culture method of cerebellar granule neurons with paracrine support applicable for the study of neuronal morphogenesis.

    Science.gov (United States)

    Kubota, Kenta; Seno, Takeshi; Konishi, Yoshiyuki

    2013-11-20

    Cerebellar granule neuronal cultures have been used to study the molecular mechanisms underlying neuronal functions, including neuronal morphogenesis. However, a limitation of this system is the difficulty to analyze isolated neurons because these are required to be maintained at a high density. Therefore, in the present study, we aimed to develop a simple and cost-effective method for culturing low-density cerebellar granule neurons. Cerebellar granule cells at two different densities (low- and high-density) were co-cultivated in order for the low-density culture to be supported by the paracrine signals from the high-density culture. This method enabled morphology analysis of isolated cerebellar granule neurons without astrocytic feeder cultures or supplements such as B27. Using this method, we investigated the function of a polarity factor. Studies using hippocampal neurons suggested that glycogen synthase kinase-3 (GSK-3) is an essential regulator of neuronal polarity, and inhibition of GSK-3 results in the formation of multiple axons. Pharmacological inhibitors for GSK-3 (6-bromoindirubin-3'-oxime and lithium chloride) did not cause the formation of multiple axons of cerebellar granule neurons but significantly reduced their length. Consistent results were obtained by introducing kinase-dead form of GSK-3 beta (K85A). These results indicated that GSK-3 is not directly involved in the control of neuronal polarity in cerebellar granule neurons. Overall, this study provides a simple method for culturing low-density cerebellar granule neurons and insights in to the neuronal-type dependent function of GSK-3 in neuronal morphogenesis. © 2013 Elsevier B.V. All rights reserved.

  16. Stress, catecholaminergic system and cancer.

    Science.gov (United States)

    Krizanova, O; Babula, P; Pacak, K

    2016-07-01

    Stress as a modern civilization factor significantly affects our lives. While acute stress might have a positive effect on the organism, chronic stress is usually detrimental and might lead to serious health complications. It is known that stress induced by the physical environment (temperature-induced cold stress) can significantly impair the efficacy of cytotoxic chemotherapies and the anti-tumor immune response. On the other hand, epidemiological evidence has shown that patients taking drugs known as β-adrenergic antagonists ("β-blockers"), which are commonly prescribed to treat arrhythmia, hypertension, and anxiety, have significantly lower rates of several cancers. In this review, we summarize the current knowledge about catecholamines as important stress hormones in tumorigenesis and discuss the use of β-blockers as the potential therapeutic agents.

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

    Science.gov (United States)

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

    2014-02-01

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

  18. The mirror neuron system and the consequences of its dysfunction.

    Science.gov (United States)

    Iacoboni, Marco; Dapretto, Mirella

    2006-12-01

    The discovery of premotor and parietal cells known as mirror neurons in the macaque brain that fire not only when the animal is in action, but also when it observes others carrying out the same actions provides a plausible neurophysiological mechanism for a variety of important social behaviours, from imitation to empathy. Recent data also show that dysfunction of the mirror neuron system in humans might be a core deficit in autism, a socially isolating condition. Here, we review the neurophysiology of the mirror neuron system and its role in social cognition and discuss the clinical implications of mirror neuron dysfunction.

  19. NeuronMetrics: software for semi-automated processing of cultured neuron images.

    Science.gov (United States)

    Narro, Martha L; Yang, Fan; Kraft, Robert; Wenk, Carola; Efrat, Alon; Restifo, Linda L

    2007-03-23

    Using primary cell culture to screen for changes in neuronal morphology requires specialized analysis software. We developed NeuronMetrics for semi-automated, quantitative analysis of two-dimensional (2D) images of fluorescently labeled cultured neurons. It skeletonizes the neuron image using two complementary image-processing techniques, capturing fine terminal neurites with high fidelity. An algorithm was devised to span wide gaps in the skeleton. NeuronMetrics uses a novel strategy based on geometric features called faces to extract a branch number estimate from complex arbors with numerous neurite-to-neurite contacts, without creating a precise, contact-free representation of the neurite arbor. It estimates total neurite length, branch number, primary neurite number, territory (the area of the convex polygon bounding the skeleton and cell body), and Polarity Index (a measure of neuronal polarity). These parameters provide fundamental information about the size and shape of neurite arbors, which are critical factors for neuronal function. NeuronMetrics streamlines optional manual tasks such as removing noise, isolating the largest primary neurite, and correcting length for self-fasciculating neurites. Numeric data are output in a single text file, readily imported into other applications for further analysis. Written as modules for ImageJ, NeuronMetrics provides practical analysis tools that are easy to use and support batch processing. Depending on the need for manual intervention, processing time for a batch of approximately 60 2D images is 1.0-2.5 h, from a folder of images to a table of numeric data. NeuronMetrics' output accelerates the quantitative detection of mutations and chemical compounds that alter neurite morphology in vitro, and will contribute to the use of cultured neurons for drug discovery.

  20. Cerebral CBM1 neuron contributes to synaptic modulation appearing during rejection of seaweed in Aplysia kurodai.

    Science.gov (United States)

    Narusuye, Kenji; Nagahama, Tatsumi

    2002-11-01

    The Japanese species Aplysia kurodai feeds well on Ulva but rejects Gelidium with distinctive rhythmic patterned movements of the jaws and radula. We have previously shown that the patterned jaw movements during the rejection of Gelidium might be caused by long-lasting suppression of the monosynaptic transmission from the multiaction MA neurons to the jaw-closing (JC) motor neurons in the buccal ganglia and that the modulation might be directly produced by some cerebral neurons. In the present paper, we have identified a pair of catecholaminergic neurons (CBM1) in bilateral cerebral M clusters. The CBM1, probably equivalent to CBI-1 in A. californica, simultaneously produced monosynaptic excitatory postsynaptic potentials (EPSPs) in the MA and JC neurons. Firing of the CBM1 reduced the size of the inhibitory postsynaptic currents (IPSCs) in the JC neuron, evoked by the MA spikes, for >100 s. Moreover, the application of dopamine mimicked the CBM1 modulatory effects and pretreatment with a D1 antagonist, SCH23390, blocked the modulatory effects induced by dopamine. It could also largely block the modulatory effects induced by the CBM1 firing. These results suggest that the CBM1 may directly modulate the synaptic transmission by releasing dopamine. Moreover, we explored the CBM1 spike activity induced by taste stimulation of the animal lips with seaweed extracts by the use of calcium imaging. The calcium-sensitive dye, Calcium Green-1, was iontophoretically loaded into a cell body of the CBM1 using a microelectrode. Application of either Ulva or Gelidium extract to the lips increased the fluorescence intensity, but the Gelidium extract always induced a larger change in fluorescence compared with the Ulva extract, although the solution used induced the maximum spike responses of the CBM1 for each of the seaweed extracts. When the firing frequency of the CBM1 activity after taste stimulation was estimated, the Gelidium extract induced a spike activity of ~30 spikes

  1. Efficient and Cost-Effective Generation of Mature Neurons From Human Induced Pluripotent Stem Cells

    OpenAIRE

    Badja , Cherif; Maleeva , Galyna; El-Yazidi , Claire; Barruet , Emilie; Lasserre , Manon; Tropel , Philippe; Binetruy , Bernard; Bregestovski , Piotr; Magdinier , Frédérique

    2014-01-01

    The authors describe a feeder-free method of generating induced pluripotent stem cells by relying on the use of a chemically defined medium that overcomes the need for embryoid body formation and neuronal rosette isolation for neuronal precursors and terminally differentiated neuron production. This specific and efficient single-step strategy allows the production of mature neurons in 20–40 days with multiple applications, especially for modeling human pathologies.

  2. Mechanical Dissociation of Retinal Neurons with Vibration

    Science.gov (United States)

    Motomura, Tamami; Hayashida, Yuki; Murayama, Nobuki

    The neuromorphic device, which implements the functions of biological neural circuits by means of VLSI technology, has been collecting much attention in the engineering fields in the last decade. Concurrently, progress in neuroscience research has revealed the nonlinear computation in single neuron levels, suggesting that individual neurons are not merely the circuit elements but computational units. Thus, elucidating the properties of neuronal signal processing is thought to be an essential step for developing the next generation of neuromorphic devices. In the present study, we developed a method for dissociating single neurons from specific sublayers of mammalian retinas with using no proteolytic enzymes but rather combining tissue incubation in a low-Ca2+ medium and the vibro-dissociation technique developed for the slices of brains and spinal cords previously. Our method took shorter time of the procedure, and required less elaborated skill, than the conventional enzymatic method did; nevertheless it yielded enough number of the cells available for acute electrophysiological experiments. The isolated retinal neurons were useful for measuring the nonlinear membrane conductances as well as the spike firing properties under the perforated-patch whole-cell configuration. These neurons also enabled us to examine the effects of proteolytic enzymes on the membrane excitability in those cells.

  3. Estrogens modulate ventrolateral ventromedial hypothalamic glucose-inhibited neurons

    Directory of Open Access Journals (Sweden)

    Ammy M. Santiago

    2016-10-01

    Full Text Available Objective: Brain regulation of glucose homeostasis is sexually dimorphic; however, the impact sex hormones have on specific neuronal populations within the ventromedial hypothalamic nucleus (VMN, a metabolically sensitive brain region, has yet to be fully characterized. Glucose-excited (GE and -inhibited (GI neurons are located throughout the VMN and may play a critical role in glucose and energy homeostasis. Within the ventrolateral portion of the VMN (VL-VMN, glucose sensing neurons and estrogen receptor (ER distributions overlap. We therefore tested the hypothesis that VL-VMN glucose sensing neurons were sexually dimorphic and regulated by 17β-estradiol (17βE. Methods: Electrophysiological recordings of VL-VMN glucose sensing neurons in brain slices isolated from age- and weight-matched female and male mice were performed in the presence and absence of 17βE. Results: We found a new class of VL-VMN GI neurons whose response to low glucose was transient despite continued exposure to low glucose. Heretofore, we refer to these newly identified VL-VMN GI neurons as ‘adapting’ or AdGI neurons. We found a sexual dimorphic response to low glucose, with male nonadapting GI neurons, but not AdGI neurons, responding more robustly to low glucose than those from females. 17βE blunted the response of both nonadapting GI and AdGI neurons to low glucose in both males and females, which was mediated by activation of estrogen receptor β and inhibition of AMP-activated kinase. In contrast, 17βE had no impact on GE or non-glucose sensing neurons in either sex. Conclusion: These data suggest sex differences and estrogenic regulation of VMN hypothalamic glucose sensing may contribute to the sexual dimorphism in glucose homeostasis. Author Video: Author Video Watch what authors say about their articles Keywords: 17β-estradiol, AMP-activated kinase, Glucose excited neurons, Glucose inhibited neurons, Ventromedial hypothalamic nucleus, Sexual dimorphism

  4. Individual sympathetic postganglionic neurons coinnervate myenteric ganglia and smooth muscle layers in the gastrointestinal tract of the rat.

    Science.gov (United States)

    Walter, Gary C; Phillips, Robert J; McAdams, Jennifer L; Powley, Terry L

    2016-09-01

    A full description of the terminal architecture of sympathetic axons innervating the gastrointestinal (GI) tract has not been available. To label sympathetic fibers projecting to the gut muscle wall, dextran biotin was injected into the celiac and superior mesenteric ganglia (CSMG) of rats. Nine days postinjection, animals were euthanized and stomachs and small intestines were processed as whole mounts (submucosa and mucosa removed) to examine CSMG efferent terminals. Myenteric neurons were counterstained with Cuprolinic Blue; catecholaminergic axons were stained immunohistochemically for tyrosine hydroxylase. Essentially all dextran-labeled axons (135 of 136 sampled) were tyrosine hydroxylase-positive. Complete postganglionic arbors (n = 154) in the muscle wall were digitized and analyzed morphometrically. Individual sympathetic axons formed complex arbors of varicose neurites within myenteric ganglia/primary plexus and, concomitantly, long rectilinear arrays of neurites within circular muscle/secondary plexus or longitudinal muscle/tertiary plexus. Very few CSMG neurons projected exclusively (i.e., ∼100% of an arbor's varicose branches) to myenteric plexus (∼2%) or smooth muscle (∼14%). With less stringent inclusion criteria (i.e., ≥85% of an axon's varicose branches), larger minorities of neurons projected predominantly to either myenteric plexus (∼13%) or smooth muscle (∼27%). The majority (i.e., ∼60%) of all individual CSMG postganglionics formed mixed, heterotypic arbors that coinnervated extensively (>15% of their varicose branches per target) both myenteric ganglia and smooth muscle. The fact that ∼87% of all sympathetics projected either extensively or even predominantly to smooth muscle, while simultaneously contacting myenteric plexus, is consistent with the view that these neurons control GI muscle directly, if not exclusively. J. Comp. Neurol. 524:2577-2603, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Neuronal uptake and intracellular superoxide scavenging of a fullerene (C60)-poly(2-oxazoline)s nanoformulation

    KAUST Repository

    Tong, Jing

    2011-05-01

    Fullerene, the third allotrope of carbon, has been referred to as a "radical sponge" because of its powerful radical scavenging activities. However, the hydrophobicity and toxicity associated with fullerene limits its application as a therapeutic antioxidant. In the present study, we sought to overcome these limitations by generating water-soluble nanoformulations of fullerene (C(60)). Fullerene (C(60)) was formulated with poly(N-vinyl pyrrolidine) (PVP) or poly(2-alkyl-2-oxazoline)s (POx) homopolymer and random copolymer to form nano-complexes. These C(60)-polymer complexes were characterized by UV-vis spectroscopy, infrared spectroscopy (IR), dynamic light scattering (DLS), atomic force microscopy (AFM) and transmission electron microscopy (TEM). Cellular uptake and intracellular distribution of the selected formulations in catecholaminergic (CATH.a) neurons were examined by UV-vis spectroscopy, immunofluorescence and immunogold labeling. Electron paramagnetic resonance (EPR) spectroscopy was used to determine the ability of these C(60)-polymer complexes to scavenge superoxide. Their cytotoxicity was evaluated in three different cell lines. C(60)-POx and C(60)-PVP complexes exhibited similar physicochemical properties and antioxidant activities. C(60)-poly(2-ethyl-2-oxazoline) (PEtOx) complex, but not C(60)-PVP complex, were efficiently taken up by CATH.a neurons and attenuated the increase in intra-neuronal superoxide induced by angiotensin II (Ang II) stimulation. These results show that C(60)-POx complexes are non-toxic, neuronal cell permeable, superoxide scavenging antioxidants that might be promising candidates for the treatment of brain-related diseases associated with increased levels of superoxide.

  6. 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...

  7. Neuron-to-neuron transmission of α-synuclein fibrils through axonal transport

    Science.gov (United States)

    Freundt, Eric C.; Maynard, Nate; Clancy, Eileen K.; Roy, Shyamali; Bousset, Luc; Sourigues, Yannick; Covert, Markus; Melki, Ronald; Kirkegaard, Karla; Brahic, Michel

    2012-01-01

    Objective The lesions of Parkinson's disease spread through the brain in a characteristic pattern that corresponds to axonal projections. Previous observations suggest that misfolded α-synuclein could behave as a prion, moving from neuron to neuron and causing endogenous α-synuclein to misfold. Here, we characterized and quantified the axonal transport of α-synuclein fibrils and showed that fibrils could be transferred from axons to second-order neurons following anterograde transport. Methods We grew primary cortical mouse neurons in microfluidic devices to separate soma from axonal projections in fluidically isolated microenvironments. We used live-cell imaging and immunofluorescence to characterize the transport of fluorescent α-synuclein fibrils and their transfer to second-order neurons. Results Fibrillar α-synuclein was internalized by primary neurons and transported in axons with kinetics consistent with slow component-b of axonal transport (fast axonal transport with saltatory movement). Fibrillar α-synuclein was readily observed in the cell bodies of second-order neurons following anterograde axonal transport. Axon-to-soma transfer appeared not to require synaptic contacts. Interpretation These results support the hypothesis that the progression of Parkinson's disease can be caused by neuron-to-neuron spread of α-synuclein aggregates and that the anatomical pattern of progression of lesions between axonally connected areas results from the axonal transport of such aggregates. That the transfer did not appear to be transsynaptic gives hope that α-synuclein fibrils could be intercepted by drugs during the extra-cellular phase of their journey. PMID:23109146

  8. NEURON and Python.

    Science.gov (United States)

    Hines, Michael L; Davison, Andrew P; Muller, Eilif

    2009-01-01

    The NEURON simulation program now allows Python to be used, alone or in combination with NEURON's traditional Hoc interpreter. Adding Python to NEURON has the immediate benefit of making available a very extensive suite of analysis tools written for engineering and science. It also catalyzes NEURON software development by offering users a modern programming tool that is recognized for its flexibility and power to create and maintain complex programs. At the same time, nothing is lost because all existing models written in Hoc, including graphical user interface tools, continue to work without change and are also available within the Python context. An example of the benefits of Python availability is the use of the xml module in implementing NEURON's Import3D and CellBuild tools to read MorphML and NeuroML model specifications.

  9. Spinal cord: motor neuron diseases.

    Science.gov (United States)

    Rezania, Kourosh; Roos, Raymond P

    2013-02-01

    Spinal cord motor neuron diseases affect lower motor neurons in the ventral horn. This article focuses on the most common spinal cord motor neuron disease, amyotrophic lateral sclerosis, which also affects upper motor neurons. Also discussed are other motor neuron diseases that only affect the lower motor neurons. Despite the identification of several genes associated with familial amyotrophic lateral sclerosis, the pathogenesis of this complex disease remains elusive. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Direct versus indirect actions of ghrelin on hypothalamic NPY neurons.

    Science.gov (United States)

    Hashiguchi, Hiroshi; Sheng, Zhenyu; Routh, Vanessa; Gerzanich, Volodymyr; Simard, J Marc; Bryan, Joseph

    2017-01-01

    Assess direct versus indirect action(s) of ghrelin on hypothalamic NPY neurons. Electrophysiology was used to measure ion channel activity in NPY-GFP neurons in slice preparations. Ca2+ imaging was used to monitor ghrelin activation of isolated NPY GFP-labeled neurons. Immunohistochemistry was used to localize Trpm4, SUR1 and Kir6.2 in the hypothalamus. Acylated ghrelin depolarized the membrane potential (MP) of NPY-GFP neurons in brain slices. Depolarization resulted from a decreased input resistance (IR) in ~70% of neurons (15/22) or an increased IR in the remainder (7/22), consistent with the opening or closing of ion channels, respectively. Although tetrodotoxin (TTX) blockade of presynaptic action potentials reduced ghrelin-induced changes in MP and IR, ghrelin still significantly depolarized the MP and decreased IR in TTX-treated neurons, suggesting that ghrelin directly opens cation channel(s) in NPY neurons. In isolated NPY-GFP neurons, ghrelin produced a sustained rise of [Ca2+]c, with an EC50 ~110 pM. Pharmacologic studies confirmed that the direct action of ghrelin was through occupation of the growth hormone secretagogue receptor, GHS-R, and demonstrated the importance of the adenylate cyclase/cAMP/protein kinase A (PKA) and phospholipase C/inositol triphosphate (PLC/IP3) pathways as activators of 5' AMP-activated protein kinase (AMPK). Activation of isolated neurons was not affected by CNQX or TTX, but reducing [Na+]o suppressed activation, suggesting a role for Na+-permeable cation channels. SUR1 and two channel partners, Kir6.2 and Trpm4, were identified immunologically in NPY-GFP neurons in situ. The actions of SUR1 and Trpm4 modulators were informative: like ghrelin, diazoxide, a SUR1 agonist, elevated [Ca2+]c and glibenclamide, a SUR1 antagonist, partially suppressed ghrelin action, while 9-phenanthrol and flufenamic acid, selective Trpm4 antagonists, blocked ghrelin actions on isolated neurons. Ghrelin activation was unaffected by nifedipine and

  11. Synchronous behavior of two coupled electronic neurons

    International Nuclear Information System (INIS)

    Pinto, R. D.; Varona, P.; Volkovskii, A. R.; Szuecs, A.; Abarbanel, Henry D. I.; Rabinovich, M. I.

    2000-01-01

    We report on experimental studies of synchronization phenomena in a pair of analog electronic neurons (ENs). The ENs were designed to reproduce the observed membrane voltage oscillations of isolated biological neurons from the stomatogastric ganglion of the California spiny lobster Panulirus interruptus. The ENs are simple analog circuits which integrate four-dimensional differential equations representing fast and slow subcellular mechanisms that produce the characteristic regular/chaotic spiking-bursting behavior of these cells. In this paper we study their dynamical behavior as we couple them in the same configurations as we have done for their counterpart biological neurons. The interconnections we use for these neural oscillators are both direct electrical connections and excitatory and inhibitory chemical connections: each realized by analog circuitry and suggested by biological examples. We provide here quantitative evidence that the ENs and the biological neurons behave similarly when coupled in the same manner. They each display well defined bifurcations in their mutual synchronization and regularization. We report briefly on an experiment on coupled biological neurons and four-dimensional ENs, which provides further ground for testing the validity of our numerical and electronic models of individual neural behavior. Our experiments as a whole present interesting new examples of regularization and synchronization in coupled nonlinear oscillators. (c) 2000 The American Physical Society

  12. Signals and Circuits in the Purkinje Neuron

    Directory of Open Access Journals (Sweden)

    Ze'ev R Abrams

    2011-09-01

    Full Text Available Purkinje neurons in the cerebellum have over 100,000 inputs organized in an orthogonal geometry, and a single output channel. As the sole output of the cerebellar cortex layer, their complex firing pattern has been associated with motor control and learning. As such they have been extensively modeled and measured using tools ranging from electrophysiology and neuroanatomy, to dynamic systems and artificial intelligence methods. However, there is an alternative approach to analyze and describe the neuronal output of these cells using concepts from Electrical Engineering, particularly signal processing and digital/analog circuits. By viewing the Purkinje neuron as an unknown circuit to be reverse-engineered, we can use the tools that provide the foundations of today’s integrated circuits and communication systems to analyze the Purkinje system at the circuit level. We use Fourier transforms to analyze and isolate the inherent frequency modes in the Purkinje neuron and define 3 unique frequency ranges associated with the cells’ output. Comparing the Purkinje neuron to a signal generator that can be externally modulated adds an entire level of complexity to the functional role of these neurons both in terms of data analysis and information processing, relying on Fourier analysis methods in place of statistical ones. We also re-describe some of the recent literature in the field, using the nomenclature of signal processing. Furthermore, by comparing the experimental data of the past decade with basic electronic circuitry, we can resolve the outstanding controversy in the field, by recognizing that the Purkinje neuron can act as a multivibrator circuit.

  13. Bax regulates neuronal Ca2+ homeostasis.

    Science.gov (United States)

    D'Orsi, Beatrice; Kilbride, Seán M; Chen, Gang; Perez Alvarez, Sergio; Bonner, Helena P; Pfeiffer, Shona; Plesnila, Nikolaus; Engel, Tobias; Henshall, David C; Düssmann, Heiko; Prehn, Jochen H M

    2015-01-28

    Excessive Ca(2+) entry during glutamate receptor overactivation ("excitotoxicity") induces acute or delayed neuronal death. We report here that deficiency in bax exerted broad neuroprotection against excitotoxic injury and oxygen/glucose deprivation in mouse neocortical neuron cultures and reduced infarct size, necrotic injury, and cerebral edema formation after middle cerebral artery occlusion in mice. Neuronal Ca(2+) and mitochondrial membrane potential (Δψm) analysis during excitotoxic injury revealed that bax-deficient neurons showed significantly reduced Ca(2+) transients during the NMDA excitation period and did not exhibit the deregulation of Δψm that was observed in their wild-type (WT) counterparts. Reintroduction of bax or a bax mutant incapable of proapoptotic oligomerization equally restored neuronal Ca(2+) dynamics during NMDA excitation, suggesting that Bax controlled Ca(2+) signaling independently of its role in apoptosis execution. Quantitative confocal imaging of intracellular ATP or mitochondrial Ca(2+) levels using FRET-based sensors indicated that the effects of bax deficiency on Ca(2+) handling were not due to enhanced cellular bioenergetics or increased Ca(2+) uptake into mitochondria. We also observed that mitochondria isolated from WT or bax-deficient cells similarly underwent Ca(2+)-induced permeability transition. However, when Ca(2+) uptake into the sarco/endoplasmic reticulum was blocked with the Ca(2+)-ATPase inhibitor thapsigargin, bax-deficient neurons showed strongly elevated cytosolic Ca(2+) levels during NMDA excitation, suggesting that the ability of Bax to support dynamic ER Ca(2+) handling is critical for cell death signaling during periods of neuronal overexcitation. Copyright © 2015 the authors 0270-6474/15/351706-17$15.00/0.

  14. Neuronal-glial trafficking

    International Nuclear Information System (INIS)

    Bachelard, H.S.

    2001-01-01

    Full text: The name 'glia' originates from the Greek word for glue, because astro glia (or astrocytes) were thought only to provide an anatomical framework for the electrically-excitable neurones. However, awareness that astrocytes perform vital roles in protecting the neurones, which they surround, emerged from evidence that they act as neuroprotective K + -sinks, and that they remove potentially toxic extracellular glutamate from the vicinity of the neurones. The astrocytes convert the glutamate to non-toxic glutamine which is returned to the neurones and used to replenish transmitter glutamate. This 'glutamate-glutamine cycle' (established in the 1960s by Berl and his colleagues) also contributes to protecting the neurones against a build-up of toxic ammonia. Glial cells also supply the neurones with components for free-radical scavenging glutathione. Recent studies have revealed that glial cells play a more positive interactive role in furnishing the neurones with fuels. Studies using radioactive 14 C, 13 C-MRS and 15 N-GCMS have revealed that glia produce alanine, lactate and proline for consumption by neurones, with increased formation of neurotransmitter glutamate. On neuronal activation the release of NH 4 + and glutamate from the neurones stimulates glucose uptake and glycolysis in the glia to produce more alanine, which can be regarded as an 'alanine-glutamate cycle' Use of 14 C-labelled precursors provided early evidence that neurotransmitter GABA may be partly derived from glial glutamine, and this has been confirmed recently in vivo by MRS isotopomer analysis of the GABA and glutamine labelled from 13 C-acetate. Relative rates of intermediary metabolism in glia and neurones can be calculated using a combination of [1- 13 C] glucose and [1,2- 13 C] acetate. When glutamate is released by neurones there is a net neuronal loss of TCA intermediates which have to be replenished. Part of this is derived from carboxylation of pyruvate, (pyruvate carboxylase

  15. The Limited Utility of Multiunit Data in Differentiating Neuronal Population Activity.

    Directory of Open Access Journals (Sweden)

    Corey J Keller

    Full Text Available To date, single neuron recordings remain the gold standard for monitoring the activity of neuronal populations. Since obtaining single neuron recordings is not always possible, high frequency or 'multiunit activity' (MUA is often used as a surrogate. Although MUA recordings allow one to monitor the activity of a large number of neurons, they do not allow identification of specific neuronal subtypes, the knowledge of which is often critical for understanding electrophysiological processes. Here, we explored whether prior knowledge of the single unit waveform of specific neuron types is sufficient to permit the use of MUA to monitor and distinguish differential activity of individual neuron types. We used an experimental and modeling approach to determine if components of the MUA can monitor medium spiny neurons (MSNs and fast-spiking interneurons (FSIs in the mouse dorsal striatum. We demonstrate that when well-isolated spikes are recorded, the MUA at frequencies greater than 100Hz is correlated with single unit spiking, highly dependent on the waveform of each neuron type, and accurately reflects the timing and spectral signature of each neuron. However, in the absence of well-isolated spikes (the norm in most MUA recordings, the MUA did not typically contain sufficient information to permit accurate prediction of the respective population activity of MSNs and FSIs. Thus, even under ideal conditions for the MUA to reliably predict the moment-to-moment activity of specific local neuronal ensembles, knowledge of the spike waveform of the underlying neuronal populations is necessary, but not sufficient.

  16. Direct evidence for activity-dependent glucose phosphorylation in neurons with implications for the astrocyte-to-neuron lactate shuttle.

    Science.gov (United States)

    Patel, Anant B; Lai, James C K; Chowdhury, Golam M I; Hyder, Fahmeed; Rothman, Douglas L; Shulman, Robert G; Behar, Kevin L

    2014-04-08

    Previous (13)C magnetic resonance spectroscopy experiments have shown that over a wide range of neuronal activity, approximately one molecule of glucose is oxidized for every molecule of glutamate released by neurons and recycled through astrocytic glutamine. The measured kinetics were shown to agree with the stoichiometry of a hypothetical astrocyte-to-neuron lactate shuttle model, which predicted negligible functional neuronal uptake of glucose. To test this model, we measured the uptake and phosphorylation of glucose in nerve terminals isolated from rats infused with the glucose analog, 2-fluoro-2-deoxy-D-glucose (FDG) in vivo. The concentrations of phosphorylated FDG (FDG6P), normalized with respect to known neuronal metabolites, were compared in nerve terminals, homogenate, and cortex of anesthetized rats with and without bicuculline-induced seizures. The increase in FDG6P in nerve terminals agreed well with the increase in cortical neuronal glucose oxidation measured previously under the same conditions in vivo, indicating that direct uptake and oxidation of glucose in nerve terminals is substantial under resting and activated conditions. These results suggest that neuronal glucose-derived pyruvate is the major oxidative fuel for activated neurons, not lactate-derived from astrocytes, contradicting predictions of the original astrocyte-to-neuron lactate shuttle model under the range of study conditions.

  17. Optogenetic release of norepinephrine from cardiac sympathetic neurons alters mechanical and electrical function.

    Science.gov (United States)

    Wengrowski, Anastasia M; Wang, Xin; Tapa, Srinivas; Posnack, Nikki Gillum; Mendelowitz, David; Kay, Matthew W

    2015-02-01

    Release of norepinephrine (NE) from sympathetic neurons enhances heart rate (HR) and developed force through activation of β-adrenergic receptors, and this sympathoexcitation is a key risk for the generation of cardiac arrhythmias. Studies of β-adrenergic modulation of cardiac function typically involve the administration of exogenous β-adrenergic receptor agonists to directly elicit global β-adrenergic receptor activation by bypassing the involvement of sympathetic nerve terminals. In this work, we use a novel method to activate sympathetic fibres within the myocardium of Langendorff-perfused hearts while measuring changes in electrical and mechanical function. The light-activated optogenetic protein channelrhodopsin-2 (ChR2) was expressed in murine catecholaminergic sympathetic neurons. Sympathetic fibres were then photoactivated to examine changes in contractile force, HR, and cardiac electrical activity. Incidence of arrhythmia was measured with and without exposure to photoactivation of sympathetic fibres, and hearts were optically mapped to detect changes in action potential durations and conduction velocities. Results demonstrate facilitation of both developed force and HR after photostimulated release of NE, with increases in contractile force and HR of 34.5 ± 5.5 and 25.0 ± 9.3%, respectively. Photostimulation of sympathetic fibres also made hearts more susceptible to arrhythmia, with greater incidence and severity. In addition, optically mapped action potentials displayed a small but significant shortening of the plateau phase (-5.5 ± 1.0 ms) after photostimulation. This study characterizes a powerful and clinically relevant new model for studies of cardiac arrhythmias generated by increasing the activity of sympathetic nerve terminals and the resulting activation of myocyte β-adrenergic receptors. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  18. Single neuron computation

    CERN Document Server

    McKenna, Thomas M; Zornetzer, Steven F

    1992-01-01

    This book contains twenty-two original contributions that provide a comprehensive overview of computational approaches to understanding a single neuron structure. The focus on cellular-level processes is twofold. From a computational neuroscience perspective, a thorough understanding of the information processing performed by single neurons leads to an understanding of circuit- and systems-level activity. From the standpoint of artificial neural networks (ANNs), a single real neuron is as complex an operational unit as an entire ANN, and formalizing the complex computations performed by real n

  19. Mesmerising mirror neurons.

    Science.gov (United States)

    Heyes, Cecilia

    2010-06-01

    Mirror neurons have been hailed as the key to understanding social cognition. I argue that three currents of thought-relating to evolution, atomism and telepathy-have magnified the perceived importance of mirror neurons. When they are understood to be a product of associative learning, rather than an adaptation for social cognition, mirror neurons are no longer mesmerising, but they continue to raise important questions about both the psychology of science and the neural bases of social cognition. Copyright 2010 Elsevier Inc. All rights reserved.

  20. The mirror neuron system.

    Science.gov (United States)

    Cattaneo, Luigi; Rizzolatti, Giacomo

    2009-05-01

    Mirror neurons are a class of neurons, originally discovered in the premotor cortex of monkeys, that discharge both when individuals perform a given motor act and when they observe others perform that same motor act. Ample evidence demonstrates the existence of a cortical network with the properties of mirror neurons (mirror system) in humans. The human mirror system is involved in understanding others' actions and their intentions behind them, and it underlies mechanisms of observational learning. Herein, we will discuss the clinical implications of the mirror system.

  1. Direct evidence for activity-dependent glucose phosphorylation in neurons with implications for the astrocyte-to-neuron lactate shuttle

    OpenAIRE

    Patel, Anant B.; Lai, James C. K.; Chowdhury, Golam M. I.; Hyder, Fahmeed; Rothman, Douglas L.; Shulman, Robert G.; Behar, Kevin L.

    2014-01-01

    A near one-to-one relationship had previously been observed between increments in the fluxes of the glutamate−glutamine neurotransmitter cycle and neuronal glucose oxidation in the tricarboxylic acid (TCA) cycle. This flux relationship was consistent with a hypothesized mechanism involving glycolytic ATP in astrocytes and astrocyte-to-neuron lactate shuttling. Here, 2-fluoro-2-deoxy-d-glucose was used to evaluate the glucose flux through glycolysis and the TCA cycle in nerve terminals isolate...

  2. Tg(Th-Cre)FI172Gsat (Th-Cre) defines neurons that are required for full hypercapnic and hypoxic reflexes.

    Science.gov (United States)

    Sun, Jenny J; Ray, Russell S

    2017-08-15

    The catecholaminergic (CA) system has been implicated in many facets of breathing control and offers an important target to better comprehend the underlying etiologies of both developmental and adult respiratory pathophysiologies. Here, we used a noninvasive DREADD-based pharmacogenetic approach to acutely perturb Tg(Th-Cre)FI172Gsat ( Th-Cre )-defined neurons in awake and unrestrained mice in an attempt to characterize CA function in breathing. We report that clozapine-N-oxide (CNO)-DREADD-mediated inhibition of Th-Cre -defined neurons results in blunted ventilatory responses under respiratory challenge. Under a hypercapnic challenge (5% CO 2 /21% O 2 /74% N 2 ), perturbation of Th-Cre neurons results in reduced f R , [Formula: see text] and [Formula: see text] Under a hypoxic challenge (10% O 2 /90% N 2 ), we saw reduced f R , [Formula: see text] and [Formula: see text], in addition to instability in both interbreath interval and tidal volume, resulting in a Cheyne-Stokes-like respiratory pattern. These findings demonstrate the necessity of Th-Cre -defined neurons for the hypercapnic and hypoxic ventilatory responses and breathing stability during hypoxia. However, given the expanded non-CA expression domains of the Tg(Th-Cre)FI172Gsat mouse line found in the brainstem, full phenotypic effect cannot be assigned solely to CA neurons. Nonetheless, this work identifies a key respiratory population that may lead to further insights into the circuitry that maintains respiratory stability in the face of homeostatic challenges. © 2017. Published by The Company of Biologists Ltd.

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

    Science.gov (United States)

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

    2017-09-01

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

  4. Expression of polysialylated neural cell adhesion molecules on adult stem cells after neuronal differentiation of inner ear spiral ganglion neurons

    Energy Technology Data Exchange (ETDEWEB)

    Park, Kyoung Ho [Department of Otolaryngology Head and Neck Surgery, College of Medicine, Catholic University, Seoul (Korea, Republic of); Yeo, Sang Won, E-mail: swyeo@catholic.ac.kr [Department of Otolaryngology Head and Neck Surgery, College of Medicine, Catholic University, Seoul (Korea, Republic of); Troy, Frederic A., E-mail: fatroy@ucdavis.edu [Department of Biochemistry and Molecular Medicine, University of California, School of Medicine, Davis, CA 95616 (United States); Xiamen University, School of Medicine, Xiamen City (China)

    2014-10-17

    Highlights: • PolySia expressed on neurons primarily during early stages of neuronal development. • PolySia–NCAM is expressed on neural stem cells from adult guinea pig spiral ganglion. • PolySia is a biomarker that modulates neuronal differentiation in inner ear stem cells. - Abstract: During brain development, polysialylated (polySia) neural cell adhesion molecules (polySia–NCAMs) modulate cell–cell adhesive interactions involved in synaptogenesis, neural plasticity, myelination, and neural stem cell (NSC) proliferation and differentiation. Our findings show that polySia–NCAM is expressed on NSC isolated from adult guinea pig spiral ganglion (GPSG), and in neurons and Schwann cells after differentiation of the NSC with epidermal, glia, fibroblast growth factors (GFs) and neurotrophins. These differentiated cells were immunoreactive with mAb’s to polySia, NCAM, β-III tubulin, nestin, S-100 and stained with BrdU. NSC could regenerate and be differentiated into neurons and Schwann cells. We conclude: (1) polySia is expressed on NSC isolated from adult GPSG and on neurons and Schwann cells differentiated from these NSC; (2) polySia is expressed on neurons primarily during the early stage of neuronal development and is expressed on Schwann cells at points of cell–cell contact; (3) polySia is a functional biomarker that modulates neuronal differentiation in inner ear stem cells. These new findings suggest that replacement of defective cells in the inner ear of hearing impaired patients using adult spiral ganglion neurons may offer potential hope to improve the quality of life for patients with auditory dysfunction and impaired hearing disorders.

  5. Expression of polysialylated neural cell adhesion molecules on adult stem cells after neuronal differentiation of inner ear spiral ganglion neurons

    International Nuclear Information System (INIS)

    Park, Kyoung Ho; Yeo, Sang Won; Troy, Frederic A.

    2014-01-01

    Highlights: • PolySia expressed on neurons primarily during early stages of neuronal development. • PolySia–NCAM is expressed on neural stem cells from adult guinea pig spiral ganglion. • PolySia is a biomarker that modulates neuronal differentiation in inner ear stem cells. - Abstract: During brain development, polysialylated (polySia) neural cell adhesion molecules (polySia–NCAMs) modulate cell–cell adhesive interactions involved in synaptogenesis, neural plasticity, myelination, and neural stem cell (NSC) proliferation and differentiation. Our findings show that polySia–NCAM is expressed on NSC isolated from adult guinea pig spiral ganglion (GPSG), and in neurons and Schwann cells after differentiation of the NSC with epidermal, glia, fibroblast growth factors (GFs) and neurotrophins. These differentiated cells were immunoreactive with mAb’s to polySia, NCAM, β-III tubulin, nestin, S-100 and stained with BrdU. NSC could regenerate and be differentiated into neurons and Schwann cells. We conclude: (1) polySia is expressed on NSC isolated from adult GPSG and on neurons and Schwann cells differentiated from these NSC; (2) polySia is expressed on neurons primarily during the early stage of neuronal development and is expressed on Schwann cells at points of cell–cell contact; (3) polySia is a functional biomarker that modulates neuronal differentiation in inner ear stem cells. These new findings suggest that replacement of defective cells in the inner ear of hearing impaired patients using adult spiral ganglion neurons may offer potential hope to improve the quality of life for patients with auditory dysfunction and impaired hearing disorders

  6. Neuromorphic Silicon Neuron Circuits

    Science.gov (United States)

    Indiveri, Giacomo; Linares-Barranco, Bernabé; Hamilton, Tara Julia; van Schaik, André; Etienne-Cummings, Ralph; Delbruck, Tobi; Liu, Shih-Chii; Dudek, Piotr; Häfliger, Philipp; Renaud, Sylvie; Schemmel, Johannes; Cauwenberghs, Gert; Arthur, John; Hynna, Kai; Folowosele, Fopefolu; Saighi, Sylvain; Serrano-Gotarredona, Teresa; Wijekoon, Jayawan; Wang, Yingxue; Boahen, Kwabena

    2011-01-01

    Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain–machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance-based Hodgkin–Huxley models to bi-dimensional generalized adaptive integrate and fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips. PMID:21747754

  7. Neuromorphic silicon neuron circuits

    Directory of Open Access Journals (Sweden)

    Giacomo eIndiveri

    2011-05-01

    Full Text Available Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain-machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance based Hodgkin-Huxley models to bi-dimensional generalized adaptive Integrate and Fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips.

  8. NeuronBank: a tool for cataloging neuronal circuitry

    Directory of Open Access Journals (Sweden)

    Paul S Katz

    2010-04-01

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

  9. Why our brains cherish humanity: Mirror neurons and colamus humanitatem

    OpenAIRE

    Skoyles, John R.

    2008-01-01

    Commonsense says we are isolated. After all, our bodies are physically separate. But Seneca’s colamus humanitatem, and John Donne’s observation that “no man is an island” suggests we are neither entirely isolated nor separate. A recent discovery in neuroscience-that of mirror neurons-argues that the brain and the mind is neither built nor functions remote from what happens in other individuals. What are mirror neurons? They are brain cells that process both what happens to or is done by an in...

  10. Forced swimming test and fluoxetine treatment: in vivo evidence that peripheral 5-HT in rat platelet-rich plasma mirrors cerebral extracellular 5-HT levels, whilst 5-HT in isolated platelets mirrors neuronal 5-HT changes.

    Science.gov (United States)

    Bianchi, M; Moser, C; Lazzarini, C; Vecchiato, E; Crespi, F

    2002-03-01

    Low levels of central serotonin (5-HT) have been related to the state of depression, and 5-HT is the major target of the newer antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs). Neurons and platelets display structural and functional similarities, so that the latter have been proposed as a peripheral model of central functions. In particular, in blood more than 99% of 5-HT is contained in platelets, so that one could consider changes in 5-HT levels in platelets as a mirror of changes in central 5-HT. Here, this hypothesis has been studied via the analysis of the influence of: (1) the forced swimming test (FST, which has been proved to be of utility to predict the clinical efficacy of antidepressants in rodents) and (2) treatment with the SSRI fluoxetine upon 5-HT levels monitored in brain regions and in peripheral platelets by means of electrochemical in vivo and ex vivo measurements. The results obtained confirm that the FST increases immobility; furthermore they show a parallel and significant decrease in cerebral (brain homogenate) and peripheral (in platelet-rich plasma, PRP) voltammetric 5-HT levels following the FST in naive rats. In addition, subchronic treatment with fluoxetine was followed by a significant increase in 5-HT levels in PRP, while the same SSRI treatment performed within the FST resulted in a decrease in the 5-HT levels in PRP. However, this decrease was inferior to that observed without SSRI treatment. These data suggest that there is an inverse relationship between immobility and the levels of 5-HT in PRP and that these peripheral 5-HT levels are sensitive to: (1) the FST, (2) the treatment with fluoxetine and (3) the combination of both treatments, i.e. SSRI + FST. It has been reported that SSRI treatment at first inhibits the 5-HT transporter in brain, resulting in increased extracellular 5-HT, while following sustained SSRI treatments decreased intracellular levels of central 5-HT were observed. Accordingly, the

  11. Spatially tuned normalization explains attention modulation variance within neurons.

    Science.gov (United States)

    Ni, Amy M; Maunsell, John H R

    2017-09-01

    Spatial attention improves perception of attended parts of a scene, a behavioral enhancement accompanied by modulations of neuronal firing rates. These modulations vary in size across neurons in the same brain area. Models of normalization explain much of this variance in attention modulation with differences in tuned normalization across neurons (Lee J, Maunsell JHR. PLoS One 4: e4651, 2009; Ni AM, Ray S, Maunsell JHR. Neuron 73: 803-813, 2012). However, recent studies suggest that normalization tuning varies with spatial location both across and within neurons (Ruff DA, Alberts JJ, Cohen MR. J Neurophysiol 116: 1375-1386, 2016; Verhoef BE, Maunsell JHR. eLife 5: e17256, 2016). Here we show directly that attention modulation and normalization tuning do in fact covary within individual neurons, in addition to across neurons as previously demonstrated. We recorded the activity of isolated neurons in the middle temporal area of two rhesus monkeys as they performed a change-detection task that controlled the focus of spatial attention. Using the same two drifting Gabor stimuli and the same two receptive field locations for each neuron, we found that switching which stimulus was presented at which location affected both attention modulation and normalization in a correlated way within neurons. We present an equal-maximum-suppression spatially tuned normalization model that explains this covariance both across and within neurons: each stimulus generates equally strong suppression of its own excitatory drive, but its suppression of distant stimuli is typically less. This new model specifies how the tuned normalization associated with each stimulus location varies across space both within and across neurons, changing our understanding of the normalization mechanism and how attention modulations depend on this mechanism. NEW & NOTEWORTHY Tuned normalization studies have demonstrated that the variance in attention modulation size seen across neurons from the same cortical

  12. Evaluation of mRNA expression levels and electrophysiological function of neuron-like cells derived from canine bone marrow stromal cells.

    Science.gov (United States)

    Nakano, Rei; Edamura, Kazuya; Sugiya, Hiroshi; Narita, Takanori; Okabayashi, Ken; Moritomo, Tadaaki; Teshima, Kenji; Asano, Kazushi; Nakayama, Tomohiro

    2013-10-01

    To investigate the in vitro differentiation of canine bone marrow stromal cells (BMSCs) into functional, mature neurons. Bone marrow from 6 adult dogs. BMSCs were isolated from bone marrow and chemically induced to develop into neurons. The morphology of the BMSCs during neuronal induction was monitored, and immunocytochemical analyses for neuron markers were performed after the induction. Real-time PCR methods were used to evaluate the mRNA expression levels of markers for neural stem or progenitor cells, neurons, and ion channels, and western blotting was used to assess the expression of neuronal proteins before and after neuronal induction. The electrophysiological properties of the neuron-like cells induced from canine BMSCs were evaluated with fluorescent dye to monitor Ca(2)+ influx. Canine BMSCs developed a neuron-like morphology after neuronal induction. Immunocytochemical analysis revealed that these neuron-like cells were positive for neuron markers. After induction, the cells' mRNA expression levels of almost all neuron and ion channel markers increased, and the protein expression levels of nestin and neurofilament-L increased significantly. However, the neuron-like cells derived from canine BMSCs did not have the Ca(2)+ influx characteristic of spiking neurons. Although canine BMSCs had neuron-like morphological and biochemical properties after induction, they did not develop the electrophysiological characteristics of neurons. Thus, these results have suggested that canine BMSCs could have the capacity to differentiate into a neuronal lineage, but the differentiation protocol used may have been insufficient to induce development into functional neurons.

  13. Neuron Morphology Influences Axon Initial Segment Plasticity123

    Science.gov (United States)

    2016-01-01

    In most vertebrate neurons, action potentials are initiated in the axon initial segment (AIS), a specialized region of the axon containing a high density of voltage-gated sodium and potassium channels. It has recently been proposed that neurons use plasticity of AIS length and/or location to regulate their intrinsic excitability. Here we quantify the impact of neuron morphology on AIS plasticity using computational models of simplified and realistic somatodendritic morphologies. In small neurons (e.g., dentate granule neurons), excitability was highest when the AIS was of intermediate length and located adjacent to the soma. Conversely, neurons having larger dendritic trees (e.g., pyramidal neurons) were most excitable when the AIS was longer and/or located away from the soma. For any given somatodendritic morphology, increasing dendritic membrane capacitance and/or conductance favored a longer and more distally located AIS. Overall, changes to AIS length, with corresponding changes in total sodium conductance, were far more effective in regulating neuron excitability than were changes in AIS location, while dendritic capacitance had a larger impact on AIS performance than did dendritic conductance. The somatodendritic influence on AIS performance reflects modest soma-to-AIS voltage attenuation combined with neuron size-dependent changes in AIS input resistance, effective membrane time constant, and isolation from somatodendritic capacitance. We conclude that the impact of AIS plasticity on neuron excitability will depend largely on somatodendritic morphology, and that, in some neurons, a shorter or more distally located AIS may promote, rather than limit, action potential generation. PMID:27022619

  14. Neuronal avalanches and learning

    Energy Technology Data Exchange (ETDEWEB)

    Arcangelis, Lucilla de, E-mail: dearcangelis@na.infn.it [Department of Information Engineering and CNISM, Second University of Naples, 81031 Aversa (Italy)

    2011-05-01

    Networks of living neurons represent one of the most fascinating systems of biology. If the physical and chemical mechanisms at the basis of the functioning of a single neuron are quite well understood, the collective behaviour of a system of many neurons is an extremely intriguing subject. Crucial ingredient of this complex behaviour is the plasticity property of the network, namely the capacity to adapt and evolve depending on the level of activity. This plastic ability is believed, nowadays, to be at the basis of learning and memory in real brains. Spontaneous neuronal activity has recently shown features in common to other complex systems. Experimental data have, in fact, shown that electrical information propagates in a cortex slice via an avalanche mode. These avalanches are characterized by a power law distribution for the size and duration, features found in other problems in the context of the physics of complex systems and successful models have been developed to describe their behaviour. In this contribution we discuss a statistical mechanical model for the complex activity in a neuronal network. The model implements the main physiological properties of living neurons and is able to reproduce recent experimental results. Then, we discuss the learning abilities of this neuronal network. Learning occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. The system is able to learn all the tested rules, in particular the exclusive OR (XOR) and a random rule with three inputs. The learning dynamics exhibits universal features as function of the strength of plastic adaptation. Any rule could be learned provided that the plastic adaptation is sufficiently slow.

  15. Neuronal avalanches and learning

    International Nuclear Information System (INIS)

    Arcangelis, Lucilla de

    2011-01-01

    Networks of living neurons represent one of the most fascinating systems of biology. If the physical and chemical mechanisms at the basis of the functioning of a single neuron are quite well understood, the collective behaviour of a system of many neurons is an extremely intriguing subject. Crucial ingredient of this complex behaviour is the plasticity property of the network, namely the capacity to adapt and evolve depending on the level of activity. This plastic ability is believed, nowadays, to be at the basis of learning and memory in real brains. Spontaneous neuronal activity has recently shown features in common to other complex systems. Experimental data have, in fact, shown that electrical information propagates in a cortex slice via an avalanche mode. These avalanches are characterized by a power law distribution for the size and duration, features found in other problems in the context of the physics of complex systems and successful models have been developed to describe their behaviour. In this contribution we discuss a statistical mechanical model for the complex activity in a neuronal network. The model implements the main physiological properties of living neurons and is able to reproduce recent experimental results. Then, we discuss the learning abilities of this neuronal network. Learning occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. The system is able to learn all the tested rules, in particular the exclusive OR (XOR) and a random rule with three inputs. The learning dynamics exhibits universal features as function of the strength of plastic adaptation. Any rule could be learned provided that the plastic adaptation is sufficiently slow.

  16. Isolated galaxies

    International Nuclear Information System (INIS)

    Einasto, Maret

    1990-01-01

    To test for the possible presence of really isolated galaxies, which form a randomly distributed population in voids, we compare the distribution of most isolated galaxies in an observed sample with distributions of the same number of random points using the nearest neighbour test. The results show that the random population of really isolated galaxies does not exist - even the most isolated galaxies are connected with systems of galaxies, forming their outlying parts. (author)

  17. 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.

  18. Stochastic neuron models

    CERN Document Server

    Greenwood, Priscilla E

    2016-01-01

    This book describes a large number of open problems in the theory of stochastic neural systems, with the aim of enticing probabilists to work on them. This includes problems arising from stochastic models of individual neurons as well as those arising from stochastic models of the activities of small and large networks of interconnected neurons. The necessary neuroscience background to these problems is outlined within the text, so readers can grasp the context in which they arise. This book will be useful for graduate students and instructors providing material and references for applying probability to stochastic neuron modeling. Methods and results are presented, but the emphasis is on questions where additional stochastic analysis may contribute neuroscience insight. An extensive bibliography is included. Dr. Priscilla E. Greenwood is a Professor Emerita in the Department of Mathematics at the University of British Columbia. Dr. Lawrence M. Ward is a Professor in the Department of Psychology and the Brain...

  19. Enteric bacterial metabolites propionic and butyric acid modulate gene expression, including CREB-dependent catecholaminergic neurotransmission, in PC12 cells--possible relevance to autism spectrum disorders.

    Directory of Open Access Journals (Sweden)

    Bistra B Nankova

    Full Text Available Alterations in gut microbiome composition have an emerging role in health and disease including brain function and behavior. Short chain fatty acids (SCFA like propionic (PPA, and butyric acid (BA, which are present in diet and are fermentation products of many gastrointestinal bacteria, are showing increasing importance in host health, but also may be environmental contributors in neurodevelopmental disorders including autism spectrum disorders (ASD. Further to this we have shown SCFA administration to rodents over a variety of routes (intracerebroventricular, subcutaneous, intraperitoneal or developmental time periods can elicit behavioral, electrophysiological, neuropathological and biochemical effects consistent with findings in ASD patients. SCFA are capable of altering host gene expression, partly due to their histone deacetylase inhibitor activity. We have previously shown BA can regulate tyrosine hydroxylase (TH mRNA levels in a PC12 cell model. Since monoamine concentration is known to be elevated in the brain and blood of ASD patients and in many ASD animal models, we hypothesized that SCFA may directly influence brain monoaminergic pathways. When PC12 cells were transiently transfected with plasmids having a luciferase reporter gene under the control of the TH promoter, PPA was found to induce reporter gene activity over a wide concentration range. CREB transcription factor(s was necessary for the transcriptional activation of TH gene by PPA. At lower concentrations PPA also caused accumulation of TH mRNA and protein, indicative of increased cell capacity to produce catecholamines. PPA and BA induced broad alterations in gene expression including neurotransmitter systems, neuronal cell adhesion molecules, inflammation, oxidative stress, lipid metabolism and mitochondrial function, all of which have been implicated in ASD. In conclusion, our data are consistent with a molecular mechanism through which gut related environmental signals

  20. Neuronal Migration and Neuronal Migration Disorder in Cerebral Cortex

    OpenAIRE

    SUN, Xue-Zhi; TAKAHASHI, Sentaro; GUI, Chun; ZHANG, Rui; KOGA, Kazuo; NOUYE, Minoru; MURATA, Yoshiharu

    2002-01-01

    Neuronal cell migration is one of the most significant features during cortical development. After final mitosis, neurons migrate from the ventricular zone into the cortical plate, and then establish neuronal lamina and settle onto the outermost layer, forming an "inside-out" gradient of maturation. Neuronal migration is guided by radial glial fibers and also needs proper receptors, ligands, and other unknown extracellular factors, requests local signaling (e.g. some emitted by the Cajal-Retz...

  1. A comparison of neuronal growth cone and cell body membrane: electrophysiological and ultrastructural properties.

    Science.gov (United States)

    Guthrie, P B; Lee, R E; Kater, S B

    1989-10-01

    This study investigated a broad set of general electrophysiological and ultrastructural features of growth cone and cell body membrane of individual neurons where membrane from different regions of the same neuron can be directly compared. Growth cones were surgically isolated from identified adult Helisoma neurons in culture and compared with the cell body using whole-cell patch-clamp recording techniques. All isolated growth cones generated overshooting regenerative action potentials. Five neurons (buccal neurons B4, B5, and B19; pedal neurons P1 and P5) were selected that displayed distinctive action potential waveforms. In all cases, the growth cone action potential was indistinguishable from the cell body action potential and different from growth cones from other identified neurons. Two of these neurons (B5 and B19) were studied further using voltage-clamp procedures; growth cones and cell bodies again revealed major similarities within one neuron type and differences between neuron types. The only suggested difference between the growth cone and cell body was an apparent reduction in the magnitude of the A-current in the growth cone. Peak inward and outward current densities, as with other electrophysiological features, were different between neuron types, but were, again, similar between the growth cone and the cell body of the same neuron. Freeze-fracture analysis of intramembraneous particles (IMPs) was also performed on identified regions of the same neuron in culture. Both the density and the size distribution of IMPs were the same in growth cone, cell body, and neurite membranes. In these general electrophysiological and ultrastructural characteristics, therefore, growth cone membranes appear to retain the identity of the parent neuron cell body membrane.

  2. Patterning human neuronal networks on photolithographically engineered silicon dioxide substrates functionalized with glial analogues.

    Science.gov (United States)

    Hughes, Mark A; Brennan, Paul M; Bunting, Andrew S; Cameron, Katherine; Murray, Alan F; Shipston, Mike J

    2014-05-01

    Interfacing neurons with silicon semiconductors is a challenge being tackled through various bioengineering approaches. Such constructs inform our understanding of neuronal coding and learning and ultimately guide us toward creating intelligent neuroprostheses. A fundamental prerequisite is to dictate the spatial organization of neuronal cells. We sought to pattern neurons using photolithographically defined arrays of polymer parylene-C, activated with fetal calf serum. We used a purified human neuronal cell line [Lund human mesencephalic (LUHMES)] to establish whether neurons remain viable when isolated on-chip or whether they require a supporting cell substrate. When cultured in isolation, LUHMES neurons failed to pattern and did not show any morphological signs of differentiation. We therefore sought a cell type with which to prepattern parylene regions, hypothesizing that this cellular template would enable secondary neuronal adhesion and network formation. From a range of cell lines tested, human embryonal kidney (HEK) 293 cells patterned with highest accuracy. LUHMES neurons adhered to pre-established HEK 293 cell clusters and this coculture environment promoted morphological differentiation of neurons. Neurites extended between islands of adherent cell somata, creating an orthogonally arranged neuronal network. HEK 293 cells appear to fulfill a role analogous to glia, dictating cell adhesion, and generating an environment conducive to neuronal survival. We next replaced HEK 293 cells with slower growing glioma-derived precursors. These primary human cells patterned accurately on parylene and provided a similarly effective scaffold for neuronal adhesion. These findings advance the use of this microfabrication-compatible platform for neuronal patterning. Copyright © 2013 Wiley Periodicals, Inc.

  3. Myostatin-like proteins regulate synaptic function and neuronal morphology.

    Science.gov (United States)

    Augustin, Hrvoje; McGourty, Kieran; Steinert, Joern R; Cochemé, Helena M; Adcott, Jennifer; Cabecinha, Melissa; Vincent, Alec; Halff, Els F; Kittler, Josef T; Boucrot, Emmanuel; Partridge, Linda

    2017-07-01

    Growth factors of the TGFβ superfamily play key roles in regulating neuronal and muscle function. Myostatin (or GDF8) and GDF11 are potent negative regulators of skeletal muscle mass. However, expression of myostatin and its cognate receptors in other tissues, including brain and peripheral nerves, suggests a potential wider biological role. Here, we show that Myoglianin (MYO), the Drosophila homolog of myostatin and GDF11, regulates not only body weight and muscle size, but also inhibits neuromuscular synapse strength and composition in a Smad2-dependent manner. Both myostatin and GDF11 affected synapse formation in isolated rat cortical neuron cultures, suggesting an effect on synaptogenesis beyond neuromuscular junctions. We also show that MYO acts in vivo to inhibit synaptic transmission between neurons in the escape response neural circuit of adult flies. Thus, these anti-myogenic proteins act as important inhibitors of synapse function and neuronal growth. © 2017. Published by The Company of Biologists Ltd.

  4. Differential labelling of retinal neurones by 3H-2-deoxyglucose

    International Nuclear Information System (INIS)

    Basinger, S.F.; Gordon, W.C.; Lam, D.M.K.

    1979-01-01

    The use of tritium-labelled 2-deoxyglucose in combination with plastic embedding is reported to produce stimulus dependent labelling at cellular level in the isolated goldfish retina. The results suggest that the use of tritium in place of the more usual 14 C labelled tracer is advantageous in studying the physiology and functional connections of retinal neurones. (U.K.)

  5. Neuronal nets in robotics

    International Nuclear Information System (INIS)

    Jimenez Sanchez, Raul

    1999-01-01

    The paper gives a generic idea of the solutions that the neuronal nets contribute to the robotics. The advantages and the inconveniences are exposed that have regarding the conventional techniques. It also describe the more excellent applications as the pursuit of trajectories, the positioning based on images, the force control or of the mobile robots management, among others

  6. Electrophysiological properties of neurons derived from human stem cells and iNeurons in vitro.

    Science.gov (United States)

    Halliwell, Robert F

    2017-06-01

    Functional studies of neurons have traditionally used nervous system tissues from a variety of non-human vertebrate and invertebrate species, even when the focus of much of this research has been directed at understanding human brain function. Over the last decade, the identification and isolation of human stem cells from embryonic, tissue (or adult) and induced pluripotent stem cells (iPSCs) has revolutionized the availability of human neurons for experimental studies in vitro. In addition, the direct conversion of terminally differentiated fibroblasts into Induced neurons (iN) has generated great excitement because of the likely value of such human stem cell derived neurons (hSCNs) and iN cells in drug discovery, neuropharmacology, neurotoxicology and regenerative medicine. This review addresses the current state of our knowledge of functional receptors and ion channels expressed in neurons derived from human stem cells and iNeurons and identifies gaps and questions that might be investigated in future studies; it focusses almost exclusively on what is known about the electrophysiological properties of neurons derived from human stem cells and iN cells in vitro with an emphasis on voltage and ligand gated ion channels, since these mediate synaptic signalling in the nervous system and they are at the heart of neuropharmacology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Vasculo-Neuronal Coupling: Retrograde Vascular Communication to Brain Neurons.

    Science.gov (United States)

    Kim, Ki Jung; Ramiro Diaz, Juan; Iddings, Jennifer A; Filosa, Jessica A

    2016-12-14

    Continuous cerebral blood flow is essential for neuronal survival, but whether vascular tone influences resting neuronal function is not known. Using a multidisciplinary approach in both rat and mice brain slices, we determined whether flow/pressure-evoked increases or decreases in parenchymal arteriole vascular tone, which result in arteriole constriction and dilation, respectively, altered resting cortical pyramidal neuron activity. We present evidence for intercellular communication in the brain involving a flow of information from vessel to astrocyte to neuron, a direction opposite to that of classic neurovascular coupling and referred to here as vasculo-neuronal coupling (VNC). Flow/pressure increases within parenchymal arterioles increased vascular tone and simultaneously decreased resting pyramidal neuron firing activity. On the other hand, flow/pressure decreases evoke parenchymal arteriole dilation and increased resting pyramidal neuron firing activity. In GLAST-CreERT2; R26-lsl-GCaMP3 mice, we demonstrate that increased parenchymal arteriole tone significantly increased intracellular calcium in perivascular astrocyte processes, the onset of astrocyte calcium changes preceded the inhibition of cortical pyramidal neuronal firing activity. During increases in parenchymal arteriole tone, the pyramidal neuron response was unaffected by blockers of nitric oxide, GABA A , glutamate, or ecto-ATPase. However, VNC was abrogated by TRPV4 channel, GABA B , as well as an adenosine A 1 receptor blocker. Differently to pyramidal neuron responses, increases in flow/pressure within parenchymal arterioles increased the firing activity of a subtype of interneuron. Together, these data suggest that VNC is a complex constitutive active process that enables neurons to efficiently adjust their resting activity according to brain perfusion levels, thus safeguarding cellular homeostasis by preventing mismatches between energy supply and demand. We present evidence for vessel-to-neuron

  8. Neuronal survival in the brain: neuron type-specific mechanisms

    DEFF Research Database (Denmark)

    Pfisterer, Ulrich Gottfried; Khodosevich, Konstantin

    2017-01-01

    Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial...... numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether...... for survival in a certain brain region. This review focuses on how immature neurons survive during normal and impaired brain development, both in the embryonic/neonatal brain and in brain regions associated with adult neurogenesis, and emphasizes neuron type-specific mechanisms that help to survive for various...

  9. Novel cell separation method for molecular analysis of neuron-astrocyte cocultures

    Directory of Open Access Journals (Sweden)

    Andrea eGoudriaan

    2014-01-01

    Full Text Available Over the last decade, the importance of astrocyte-neuron communication in neuronal development and synaptic plasticity has become increasingly clear. Since neuron-astrocyte interactions represent highly dynamic and reciprocal processes, we hypothesized that many astrocyte genes may be regulated as a consequence of their interactions with maturing neurons. In order to identify such neuron-responsive astrocyte genes in vitro, we sought to establish an expedite technique for separation of neurons from co-cultured astrocytes. Our newly established method makes use of cold jet, which exploits different adhesion characteristics of subpopulations of cells (Jirsova et al., 1997, and is rapid, performed under ice-cold conditions and avoids protease-mediated isolation of astrocytes or time-consuming centrifugation, yielding intact astrocyte mRNA with approximately 90% of neuronal RNA removed. Using this purification method, we executed genome-wide profiling in which RNA derived from astrocyte-only cultures was compared with astrocyte RNA derived from differentiating neuron-astrocyte co-cultures. Data analysis determined that many astrocytic mRNAs and biological processes are regulated by neuronal interaction. Our results validate the cold jet as an efficient method to separate astrocytes from neurons in co-culture, and reveals that neurons induce robust gene-expression changes in co-cultured astrocytes.

  10. Neuronal synchrony: peculiarity and generality.

    Science.gov (United States)

    Nowotny, Thomas; Huerta, Ramon; Rabinovich, Mikhail I

    2008-09-01

    Synchronization in neuronal systems is a new and intriguing application of dynamical systems theory. Why are neuronal systems different as a subject for synchronization? (1) Neurons in themselves are multidimensional nonlinear systems that are able to exhibit a wide variety of different activity patterns. Their "dynamical repertoire" includes regular or chaotic spiking, regular or chaotic bursting, multistability, and complex transient regimes. (2) Usually, neuronal oscillations are the result of the cooperative activity of many synaptically connected neurons (a neuronal circuit). Thus, it is necessary to consider synchronization between different neuronal circuits as well. (3) The synapses that implement the coupling between neurons are also dynamical elements and their intrinsic dynamics influences the process of synchronization or entrainment significantly. In this review we will focus on four new problems: (i) the synchronization in minimal neuronal networks with plastic synapses (synchronization with activity dependent coupling), (ii) synchronization of bursts that are generated by a group of nonsymmetrically coupled inhibitory neurons (heteroclinic synchronization), (iii) the coordination of activities of two coupled neuronal networks (partial synchronization of small composite structures), and (iv) coarse grained synchronization in larger systems (synchronization on a mesoscopic scale). (c) 2008 American Institute of Physics.

  11. From Neurons to Newtons

    DEFF Research Database (Denmark)

    Nielsen, Bjørn Gilbert

    2001-01-01

    proteins generate forces, to the macroscopic levels where overt arm movements are vol- untarily controlled within an unpredictable environment by legions of neurons¯ring in orderly fashion. An extensive computer simulation system has been developed for this thesis, which at present contains a neural...... network scripting language for specifying arbitrary neural architectures, de¯nition ¯les for detailed spinal networks, various biologically realistic models of neurons, and dynamic synapses. Also included are structurally accurate models of intrafusal and extra-fusal muscle ¯bers and a general body...... that an explicit function may be derived which expresses the force that the spindle contractile elements must produce to exactly counter spindle unloading during muscle shortening. This information was used to calculate the corresponding "optimal" °-motoneuronal activity level. For some simple arm movement tasks...

  12. Criticality in Neuronal Networks

    Science.gov (United States)

    Friedman, Nir; Ito, Shinya; Brinkman, Braden A. W.; Shimono, Masanori; Deville, R. E. Lee; Beggs, John M.; Dahmen, Karin A.; Butler, Tom C.

    2012-02-01

    In recent years, experiments detecting the electrical firing patterns in slices of in vitro brain tissue have been analyzed to suggest the presence of scale invariance and possibly criticality in the brain. Much of the work done however has been limited in two ways: 1) the data collected is from local field potentials that do not represent the firing of individual neurons; 2) the analysis has been primarily limited to histograms. In our work we examine data based on the firing of individual neurons (spike data), and greatly extend the analysis by considering shape collapse and exponents. Our results strongly suggest that the brain operates near a tuned critical point of a highly distinctive universality class.

  13. Why our brains cherish humanity: Mirror neurons and colamus humanitatem

    Directory of Open Access Journals (Sweden)

    John R. Skoyles

    2008-06-01

    Full Text Available Commonsense says we are isolated. After all, our bodies are physically separate. But Seneca’s colamus humanitatem, and John Donne’s observation that “no man is an island” suggests we are neither entirely isolated nor separate. A recent discovery in neuroscience—that of mirror neurons—argues that the brain and the mind is neither built nor functions remote from what happens in other individuals. What are mirror neurons? They are brain cells that process both what happens to or is done by an individual, and, as it were, its perceived “refl ection,” when that same thing happens or is done by another individual. Thus, mirror neurons are both activated when an individual does a particular action, and when that individual perceives that same action done by another. The discovery of mirror neurons suggests we need to radically revise our notions of human nature since they offer a means by which we may not be so separated as we think. Humans unlike other apes are adapted to mirror interact nonverbally when together. Notably, our faces have been evolved to display agile and nimble movements. While this is usually explained as enabling nonverbal communication, a better description would be nonverbal commune based upon mirror neurons. I argue we cherish humanity, colamus humanitatem, because mirror neurons and our adapted mirror interpersonal interface blur the physical boundaries that separate us.

  14. Dopamine suppresses neuronal activity of Helisoma B5 neurons via a D2-like receptor, activating PLC and K channels.

    Science.gov (United States)

    Zhong, L R; Artinian, L; Rehder, V

    2013-01-03

    Dopamine (DA) plays fundamental roles as a neurotransmitter and neuromodulator in the central nervous system. How DA modulates the electrical excitability of individual neurons to elicit various behaviors is of great interest in many systems. The buccal ganglion of the freshwater pond snail Helisoma trivolvis contains the neuronal circuitry for feeding and DA is known to modulate the feeding motor program in Helisoma. The buccal neuron B5 participates in the control of gut contractile activity and is surrounded by dopaminergic processes, which are expected to release DA. In order to study whether DA modulates the electrical activity of individual B5 neurons, we performed experiments on physically isolated B5 neurons in culture and on B5 neurons within the buccal ganglion in situ. We report that DA application elicited a strong hyperpolarization in both conditions and turned the electrical activity from a spontaneously firing state to an electrically silent state. Using the cell culture system, we demonstrated that the strong hyperpolarization was inhibited by the D2 receptor antagonist sulpiride and the phospholipase C (PLC) inhibitor U73122, indicating that DA affected the membrane potential of B5 neurons through the activation of a D2-like receptor and PLC. Further studies revealed that the DA-induced hyperpolarization was inhibited by the K channel blockers 4-aminopyridine and tetraethylammonium, suggesting that K channels might serve as the ultimate target of DA signaling. Through its modulatory effect on the electrical activity of B5 neurons, the release of DA in vivo may contribute to a neuronal output that results in a variable feeding motor program. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Neurons are MHC class I-dependent targets for CD8 T cells upon neurotropic viral infection.

    Directory of Open Access Journals (Sweden)

    Grégoire Chevalier

    2011-11-01

    Full Text Available Following infection of the central nervous system (CNS, the immune system is faced with the challenge of eliminating the pathogen without causing significant damage to neurons, which have limited capacities of renewal. In particular, it was thought that neurons were protected from direct attack by cytotoxic T lymphocytes (CTL because they do not express major histocompatibility class I (MHC I molecules, at least at steady state. To date, most of our current knowledge on the specifics of neuron-CTL interaction is based on studies artificially inducing MHC I expression on neurons, loading them with exogenous peptide and applying CTL clones or lines often differentiated in culture. Thus, much remains to be uncovered regarding the modalities of the interaction between infected neurons and antiviral CD8 T cells in the course of a natural disease. Here, we used the model of neuroinflammation caused by neurotropic Borna disease virus (BDV, in which virus-specific CTL have been demonstrated as the main immune effectors triggering disease. We tested the pathogenic properties of brain-isolated CD8 T cells against pure neuronal cultures infected with BDV. We observed that BDV infection of cortical neurons triggered a significant up regulation of MHC I molecules, rendering them susceptible to recognition by antiviral CTL, freshly isolated from the brains of acutely infected rats. Using real-time imaging, we analyzed the spatio-temporal relationships between neurons and CTL. Brain-isolated CTL exhibited a reduced mobility and established stable contacts with BDV-infected neurons, in an antigen- and MHC-dependent manner. This interaction induced rapid morphological changes of the neurons, without immediate killing or impairment of electrical activity. Early signs of neuronal apoptosis were detected only hours after this initial contact. Thus, our results show that infected neurons can be recognized efficiently by brain-isolated antiviral CD8 T cells and

  16. Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus.

    Science.gov (United States)

    Hernández, Vivian M; Hegeman, Daniel J; Cui, Qiaoling; Kelver, Daniel A; Fiske, Michael P; Glajch, Kelly E; Pitt, Jason E; Huang, Tina Y; Justice, Nicholas J; Chan, C Savio

    2015-08-26

    Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction. Until recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping expression of the

  17. Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus

    Science.gov (United States)

    Hernández, Vivian M.; Hegeman, Daniel J.; Cui, Qiaoling; Kelver, Daniel A.; Fiske, Michael P.; Glajch, Kelly E.; Pitt, Jason E.; Huang, Tina Y.; Justice, Nicholas J.

    2015-01-01

    Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction. SIGNIFICANCE STATEMENT Until recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping

  18. Metabolic reprogramming during neuronal differentiation.

    Science.gov (United States)

    Agostini, M; Romeo, F; Inoue, S; Niklison-Chirou, M V; Elia, A J; Dinsdale, D; Morone, N; Knight, R A; Mak, T W; Melino, G

    2016-09-01

    Newly generated neurons pass through a series of well-defined developmental stages, which allow them to integrate into existing neuronal circuits. After exit from the cell cycle, postmitotic neurons undergo neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation and plasticity. Lack of a global metabolic analysis during early cortical neuronal development led us to explore the role of cellular metabolism and mitochondrial biology during ex vivo differentiation of primary cortical neurons. Unexpectedly, we observed a huge increase in mitochondrial biogenesis. Changes in mitochondrial mass, morphology and function were correlated with the upregulation of the master regulators of mitochondrial biogenesis, TFAM and PGC-1α. Concomitant with mitochondrial biogenesis, we observed an increase in glucose metabolism during neuronal differentiation, which was linked to an increase in glucose uptake and enhanced GLUT3 mRNA expression and platelet isoform of phosphofructokinase 1 (PFKp) protein expression. In addition, glutamate-glutamine metabolism was also increased during the differentiation of cortical neurons. We identified PI3K-Akt-mTOR signalling as a critical regulator role of energy metabolism in neurons. Selective pharmacological inhibition of these metabolic pathways indicate existence of metabolic checkpoint that need to be satisfied in order to allow neuronal differentiation.

  19. Understanding the Generation of Network Bursts by Adaptive Oscillatory Neurons

    Directory of Open Access Journals (Sweden)

    Tanguy Fardet

    2018-02-01

    Full Text Available Experimental and numerical studies have revealed that isolated populations of oscillatory neurons can spontaneously synchronize and generate periodic bursts involving the whole network. Such a behavior has notably been observed for cultured neurons in rodent's cortex or hippocampus. We show here that a sufficient condition for this network bursting is the presence of an excitatory population of oscillatory neurons which displays spike-driven adaptation. We provide an analytic model to analyze network bursts generated by coupled adaptive exponential integrate-and-fire neurons. We show that, for strong synaptic coupling, intrinsically tonic spiking neurons evolve to reach a synchronized intermittent bursting state. The presence of inhibitory neurons or plastic synapses can then modulate this dynamics in many ways but is not necessary for its appearance. Thanks to a simple self-consistent equation, our model gives an intuitive and semi-quantitative tool to understand the bursting behavior. Furthermore, it suggests that after-hyperpolarization currents are sufficient to explain bursting termination. Through a thorough mapping between the theoretical parameters and ion-channel properties, we discuss the biological mechanisms that could be involved and the relevance of the explored parameter-space. Such an insight enables us to propose experimentally-testable predictions regarding how blocking fast, medium or slow after-hyperpolarization channels would affect the firing rate and burst duration, as well as the interburst interval.

  20. 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.

  1. Imitation, mirror neurons and autism

    OpenAIRE

    Williams, Justin H.G.; Whiten, Andrew; Suddendorf, Thomas; Perrett, David I.

    2001-01-01

    Various deficits in the cognitive functioning of people with autism have been documented in recent years but these provide only partial explanations for the condition. We focus instead on an imitative disturbance involving difficulties both in copying actions and in inhibiting more stereotyped mimicking, such as echolalia. A candidate for the neural basis of this disturbance may be found in a recently discovered class of neurons in frontal cortex, 'mirror neurons' (MNs). These neurons show ac...

  2. Kv2 Channel Regulation of Action Potential Repolarization and Firing Patterns in Superior Cervical Ganglion Neurons and Hippocampal CA1 Pyramidal Neurons

    Science.gov (United States)

    Liu, Pin W.

    2014-01-01

    Kv2 family “delayed-rectifier” potassium channels are widely expressed in mammalian neurons. Kv2 channels activate relatively slowly and their contribution to action potential repolarization under physiological conditions has been unclear. We explored the function of Kv2 channels using a Kv2-selective blocker, Guangxitoxin-1E (GxTX-1E). Using acutely isolated neurons, mixed voltage-clamp and current-clamp experiments were done at 37°C to study the physiological kinetics of channel gating and action potentials. In both rat superior cervical ganglion (SCG) neurons and mouse hippocampal CA1 pyramidal neurons, 100 nm GxTX-1E produced near-saturating block of a component of current typically constituting ∼60–80% of the total delayed-rectifier current. GxTX-1E also reduced A-type potassium current (IA), but much more weakly. In SCG neurons, 100 nm GxTX-1E broadened spikes and voltage clamp experiments using action potential waveforms showed that Kv2 channels carry ∼55% of the total outward current during action potential repolarization despite activating relatively late in the spike. In CA1 neurons, 100 nm GxTX-1E broadened spikes evoked from −70 mV, but not −80 mV, likely reflecting a greater role of Kv2 when other potassium channels were partially inactivated at −70 mV. In both CA1 and SCG neurons, inhibition of Kv2 channels produced dramatic depolarization of interspike voltages during repetitive firing. In CA1 neurons and some SCG neurons, this was associated with increased initial firing frequency. In all neurons, inhibition of Kv2 channels depressed maintained firing because neurons entered depolarization block more readily. Therefore, Kv2 channels can either decrease or increase neuronal excitability depending on the time scale of excitation. PMID:24695716

  3. The biophysics of neuronal growth

    International Nuclear Information System (INIS)

    Franze, Kristian; Guck, Jochen

    2010-01-01

    For a long time, neuroscience has focused on biochemical, molecular biological and electrophysiological aspects of neuronal physiology and pathology. However, there is a growing body of evidence indicating the importance of physical stimuli for neuronal growth and development. In this review we briefly summarize the historical background of neurobiophysics and give an overview over the current understanding of neuronal growth from a physics perspective. We show how biophysics has so far contributed to a better understanding of neuronal growth and discuss current inconsistencies. Finally, we speculate how biophysics may contribute to the successful treatment of lesions to the central nervous system, which have been considered incurable until very recently.

  4. Self-recognition: a constraint on the formation of electrical coupling in neurons.

    Science.gov (United States)

    Guthrie, P B; Lee, R E; Rehder, V; Schmidt, M F; Kater, S B

    1994-03-01

    Electrical coupling between specific neurons is important for proper function of many neuronal circuits. Identified cultured neurons from the snail Helisoma show a strong correlation between electrical coupling and presence of gap junction plaques in freeze-fracture replicas. Gap junction plaques, however, were never seen between overlapping neurites from a single neuron, even though those same neurites formed gap junctions with neurites from another essentially identical identified neuron. This observation suggests that a form of self-recognition inhibits reflexive gap junction formation between sibling neurites. When one or both of those growth cones had been physically isolated from the neuronal cell body, both electrical coupling and gap junction plaques, between growth cones from the same neuron, were observed to form rapidly (within 30 min). Thus, inhibition of electrical coupling between sibling neurites apparently depends on cytoplasmic continuity between neurites, and not the molecular composition of neurite membrane. The formation of gap junctions is not likely due to the isolation process; rather, the physical isolation appears to release an inhibition of reflexive gap junction formation. These data demonstrate the existence of a previously unknown constraint on the formation of electrical synapses.

  5. The Neuronal Ceroid-Lipofuscinoses

    Science.gov (United States)

    Bennett, Michael J.; Rakheja, Dinesh

    2013-01-01

    The neuronal ceroid-lipofuscinoses (NCL's, Batten disease) represent a group of severe neurodegenerative diseases, which mostly present in childhood. The phenotypes are similar and include visual loss, seizures, loss of motor and cognitive function, and early death. At autopsy, there is massive neuronal loss with characteristic storage in…

  6. The straintronic spin-neuron

    International Nuclear Information System (INIS)

    Biswas, Ayan K; Bandyopadhyay, Supriyo; Atulasimha, Jayasimha

    2015-01-01

    In artificial neural networks, neurons are usually implemented with highly dissipative CMOS-based operational amplifiers. A more energy-efficient implementation is a ‘spin-neuron’ realized with a magneto-tunneling junction (MTJ) that is switched with a spin-polarized current (representing weighted sum of input currents) that either delivers a spin transfer torque or induces domain wall motion in the soft layer of the MTJ to mimic neuron firing. Here, we propose and analyze a different type of spin-neuron in which the soft layer of the MTJ is switched with mechanical strain generated by a voltage (representing weighted sum of input voltages) and term it straintronic spin-neuron. It dissipates orders of magnitude less energy in threshold operations than the traditional current-driven spin neuron at 0 K temperature and may even be faster. We have also studied the room-temperature firing behaviors of both types of spin neurons and find that thermal noise degrades the performance of both types, but the current-driven type is degraded much more than the straintronic type if both are optimized for maximum energy-efficiency. On the other hand, if both are designed to have the same level of thermal degradation, then the current-driven version will dissipate orders of magnitude more energy than the straintronic version. Thus, the straintronic spin-neuron is superior to current-driven spin neurons. (paper)

  7. Neuronal discrimination capacity

    International Nuclear Information System (INIS)

    Deng Yingchun; Williams, Peter; Feng Jianfeng; Liu Feng

    2003-01-01

    We explore neuronal mechanisms of discriminating between masked signals. It is found that when the correlation between input signals is zero, the output signals are separable if and only if input signals are separable. With positively (negatively) correlated signals, the output signals are separable (mixed) even when input signals are mixed (separable). Exact values of discrimination capacity are obtained for two most interesting cases: the exactly balanced inhibitory and excitatory input case and the uncorrelated input case. Interestingly, the discrimination capacity obtained in these cases is independent of model parameters, input distribution and is universal. Our results also suggest a functional role of inhibitory inputs and correlated inputs or, more generally, the large variability of efferent spike trains observed in in vivo experiments: the larger the variability of efferent spike trains, the easier it is to discriminate between masked input signals

  8. Neuronal discrimination capacity

    Energy Technology Data Exchange (ETDEWEB)

    Deng Yingchun [Department of Mathematics, Hunan Normal University 410081, Changsha (China); COGS, University of Sussex at Brighton, BN1 9QH (United Kingdom); Williams, Peter; Feng Jianfeng [COGS, University of Sussex at Brighton, BN1 9QH (United Kingdom); Liu Feng [COGS, University of Sussex at Brighton, BN1 9QH (United Kingdom); Physics Department, Nanjing University (China)

    2003-12-19

    We explore neuronal mechanisms of discriminating between masked signals. It is found that when the correlation between input signals is zero, the output signals are separable if and only if input signals are separable. With positively (negatively) correlated signals, the output signals are separable (mixed) even when input signals are mixed (separable). Exact values of discrimination capacity are obtained for two most interesting cases: the exactly balanced inhibitory and excitatory input case and the uncorrelated input case. Interestingly, the discrimination capacity obtained in these cases is independent of model parameters, input distribution and is universal. Our results also suggest a functional role of inhibitory inputs and correlated inputs or, more generally, the large variability of efferent spike trains observed in in vivo experiments: the larger the variability of efferent spike trains, the easier it is to discriminate between masked input signals.

  9. Orexin neurons receive glycinergic innervations.

    Directory of Open Access Journals (Sweden)

    Mari Hondo

    Full Text Available Glycine, a nonessential amino-acid that acts as an inhibitory neurotransmitter in the central nervous system, is currently used as a dietary supplement to improve the quality of sleep, but its mechanism of action is poorly understood. We confirmed the effects of glycine on sleep/wakefulness behavior in mice when administered peripherally. Glycine administration increased non-rapid eye movement (NREM sleep time and decreased the amount and mean episode duration of wakefulness when administered in the dark period. Since peripheral administration of glycine induced fragmentation of sleep/wakefulness states, which is a characteristic of orexin deficiency, we examined the effects of glycine on orexin neurons. The number of Fos-positive orexin neurons markedly decreased after intraperitoneal administration of glycine to mice. To examine whether glycine acts directly on orexin neurons, we examined the effects of glycine on orexin neurons by patch-clamp electrophysiology. Glycine directly induced hyperpolarization and cessation of firing of orexin neurons. These responses were inhibited by a specific glycine receptor antagonist, strychnine. Triple-labeling immunofluorescent analysis showed close apposition of glycine transporter 2 (GlyT2-immunoreactive glycinergic fibers onto orexin-immunoreactive neurons. Immunoelectron microscopic analysis revealed that GlyT2-immunoreactive terminals made symmetrical synaptic contacts with somata and dendrites of orexin neurons. Double-labeling immunoelectron microscopy demonstrated that glycine receptor alpha subunits were localized in the postsynaptic membrane of symmetrical inhibitory synapses on orexin neurons. Considering the importance of glycinergic regulation during REM sleep, our observations suggest that glycine injection might affect the activity of orexin neurons, and that glycinergic inhibition of orexin neurons might play a role in physiological sleep regulation.

  10. [The effect of enzymatic treatment using proteases on properties of persistent sodium current in CA1 pyramidal neurons of rat hippocampus].

    Science.gov (United States)

    Lun'ko, O O; Isaiev, D S; Maxymiuk, O P; Kryshtal', O O; Isaieva, O V

    2014-01-01

    We investigated the effect of proteases, widely used for neuron isolation in electrophysiological studies, on the amplitude and kinetic characteristics of persistent sodium current (I(NaP)) in hippocampal CA1 pyramidal neurons. Properties of I(NaP) were studied on neurons isolated by mechanical treatment (control group) and by mechanical and enzymatic treatment using pronase E (from Streptomyces griseus) or protease type XXIII (from Aspergillus oryzae). We show that in neurons isolated with pronase E kinetic of activation and density of I(NaP) was unaltered. Enzymatic treatment with protease type XXIII did not alter I(NaP) activation but result in significant decrease in I(NaP) density. Our data indicates that enzymatic treatment using pronase E for neuron isolation is preferable for investigation of I(NaP).

  11. Calcium activity of upper thoracic dorsal root ganglion neurons in zucker diabetic Fatty rats

    DEFF Research Database (Denmark)

    Ghorbani, Marie Louise; Nyborg, Niels C B; Fjalland, Bjarne

    2013-01-01

    The aim of the present study was to examine the calcium activity of C8-T5 dorsal root ganglion (DRG) neurons from Zucker diabetic fatty rats. In total, 8 diabetic ZDF fatty animals and 8 age-matched control ZDF lean rats were employed in the study. C8-T5 dorsal root ganglia were isolated bilatera......The aim of the present study was to examine the calcium activity of C8-T5 dorsal root ganglion (DRG) neurons from Zucker diabetic fatty rats. In total, 8 diabetic ZDF fatty animals and 8 age-matched control ZDF lean rats were employed in the study. C8-T5 dorsal root ganglia were isolated...... in calcium activity of the DRG neurons were found, potentially indicating altered neuronal responses during myocardial ischemia....

  12. Cortical neurogenesis in adult rats after ischemic brain injury: most new neurons fail to mature

    Directory of Open Access Journals (Sweden)

    Qing-quan Li

    2015-01-01

    Full Text Available The present study examines the hypothesis that endogenous neural progenitor cells isolated from the neocortex of ischemic brain can differentiate into neurons or glial cells and contribute to neural regeneration. We performed middle cerebral artery occlusion to establish a model of cerebral ischemia/reperfusion injury in adult rats. Immunohistochemical staining of the cortex 1, 3, 7, 14 or 28 days after injury revealed that neural progenitor cells double-positive for nestin and sox-2 appeared in the injured cortex 1 and 3 days post-injury, and were also positive for glial fibrillary acidic protein. New neurons were labeled using bromodeoxyuridine and different stages of maturity were identified using doublecortin, microtubule-associated protein 2 and neuronal nuclei antigen immunohistochemistry. Immature new neurons coexpressing doublecortin and bromodeoxyuridine were observed in the cortex at 3 and 7 days post-injury, and semi-mature and mature new neurons double-positive for microtubule-associated protein 2 and bromodeoxyuridine were found at 14 days post-injury. A few mature new neurons coexpressing neuronal nuclei antigen and bromodeoxyuridine were observed in the injured cortex 28 days post-injury. Glial fibrillary acidic protein/bromodeoxyuridine double-positive astrocytes were also found in the injured cortex. Our findings suggest that neural progenitor cells are present in the damaged cortex of adult rats with cerebral ischemic brain injury, and that they differentiate into astrocytes and immature neurons, but most neurons fail to reach the mature stage.

  13. Differentiation of human dental pulp stem cells into neuronal by resveratrol.

    Science.gov (United States)

    Geng, Ya-Wei; Zhang, Zhen; Liu, Ming-Yue; Hu, Wei-Ping

    2017-12-01

    Dental pulp stem cells (DPSCs) have been proposed as a promising source of stem cells in nerve regeneration due to their close embryonic origin and ease of harvest. Resveratrol (RSV) is a natural polyphenolic and possesses many biological functions such as anti-inflammatory activity and protection against atherosclerosis and neuroprotective activities. There is increasing evidence showing that RSV plays a pivotal role in neuron protection and neuronal differentiation. In this study, we isolated DPSCs from impacted third molars and investigated whether RSV induces neuronal differentiation of DPSCs. To avoid loss of DPSCs multipotency, all the experiments were conducted on cells at early passages. RT-PCR results showed that RSV-treated DPSCs (RSV-DPSCs) significantly increased the expression of the neuroprogenitor marker Nestin. When RSV-DPSCs were differentiated with neuronal induction media (RSV-dDPSCs), they showed a cell morphology similar to neurons. The expression of neuronal-specific marker genes Nestin, Musashi, and NF-M in RSV-dDPSCs was significantly increased. Immunocytochemical staining and Western blot analysis showed that the expression of neuronal marker proteins, Nestin, and NF-M, was significantly increased in RSV-dDPSCs. Therefore, we have shown that RSV treatment, along with the use of neuronal induction media, effectively promotes neuronal cell differentiation of DPSCs. © 2017 International Federation for Cell Biology.

  14. Innate Synchronous Oscillations in Freely-Organized Small Neuronal Circuits

    Science.gov (United States)

    Shein Idelson, Mark; Ben-Jacob, Eshel; Hanein, Yael

    2010-01-01

    Background Information processing in neuronal networks relies on the network's ability to generate temporal patterns of action potentials. Although the nature of neuronal network activity has been intensively investigated in the past several decades at the individual neuron level, the underlying principles of the collective network activity, such as the synchronization and coordination between neurons, are largely unknown. Here we focus on isolated neuronal clusters in culture and address the following simple, yet fundamental questions: What is the minimal number of cells needed to exhibit collective dynamics? What are the internal temporal characteristics of such dynamics and how do the temporal features of network activity alternate upon crossover from minimal networks to large networks? Methodology/Principal Findings We used network engineering techniques to induce self-organization of cultured networks into neuronal clusters of different sizes. We found that small clusters made of as few as 40 cells already exhibit spontaneous collective events characterized by innate synchronous network oscillations in the range of 25 to 100 Hz. The oscillation frequency of each network appeared to be independent of cluster size. The duration and rate of the network events scale with cluster size but converge to that of large uniform networks. Finally, the investigation of two coupled clusters revealed clear activity propagation with master/slave asymmetry. Conclusions/Significance The nature of the activity patterns observed in small networks, namely the consistent emergence of similar activity across networks of different size and morphology, suggests that neuronal clusters self-regulate their activity to sustain network bursts with internal oscillatory features. We therefore suggest that clusters of as few as tens of cells can serve as a minimal but sufficient functional network, capable of sustaining oscillatory activity. Interestingly, the frequencies of these

  15. Isolation World

    OpenAIRE

    Núñez Martín, Eugeni

    2012-01-01

    El trabajo de fin de grado tiene como nombre “Isolation World”, que en su traducción literal significa “Aislamiento del mundo”, un videojuego diseñado y creado desde cero en su totalidad, utilizando herramientas y conocimiento de lógica en programación que se han ido aprendiendo y desarrollando a lo largo de la carrera.

  16. Dysregulation of Neuronal Ca2+ Channel Linked to Heightened Sympathetic Phenotype in Prohypertensive States

    OpenAIRE

    Larsen, Hege E.; Bardsley, Emma N.; Lefkimmiatis, Konstantinos; Paterson, David J.

    2016-01-01

    Hypertension is associated with impaired nitric oxide (NO)–cyclic nucleotide (CN)-coupled intracellular calcium (Ca2+) homeostasis that enhances cardiac sympathetic neurotransmission. Because neuronal membrane Ca2+ currents are reduced by NO-activated S-nitrosylation, we tested whether CNs affect membrane channel conductance directly in neurons isolated from the stellate ganglia of spontaneously hypertensive rats (SHRs) and their normotensive controls. Using voltage-clamp and cAMP–protein kin...

  17. Pathogenesis of motor neuron disease

    Institute of Scientific and Technical Information of China (English)

    Xuefei Wang

    2006-01-01

    OBJECTIVE: To summarize and analyze the factors and theories related to the attack of motor neuron disease, and comprehensively investigate the pathogenesis of motor neuron disease.DATA SOURCES: A search of Pubmed database was undertaken to identify articles about motor neuron disease published in English from January 1994 to June 2006 by using the keywords of "neurodegenerative diseases". Other literatures were collected by retrieving specific journals and articles.STUDY SELECTION: The data were checked primarily, articles related to the pathogenesis of motor neuron disease were involved, and those obviously irrelated to the articles were excluded.DATA EXTRACTION: Totally 54 articles were collected, 30 of them were involved, and the other 24 were excluded.DATA SYNTHESIS: The pathogenesis of motor neuron disease has multiple factors, and the present related theories included free radical oxidation, excitotoxicity, genetic and immune factors, lack of neurotrophic factor,injury of neurofilament, etc. The studies mainly come from transgenic animal models, cell culture in vitro and patients with familial motor neuron disease, but there are still many restrictions and disadvantages.CONCLUSION: It is necessary to try to find whether there is internal association among different mechanisms,comprehensively investigate the pathogenesis of motor neuron diseases, in order to provide reliable evidence for the clinical treatment.

  18. Cholera Toxin Induces Sustained Hyperexcitability in Myenteric, but Not Submucosal, AH Neurons in Guinea Pig Jejunum

    Directory of Open Access Journals (Sweden)

    Joel C. Bornstein

    2017-04-01

    Full Text Available Background and Aims: Cholera toxin (CT-induced hypersecretion requires activation of secretomotor pathways in the enteric nervous system (ENS. AH neurons, which have been identified as a population of intrinsic sensory neurons (ISNs, are a source of excitatory input to the secretomotor pathways. We therefore examined effects of CT in the intestinal lumen on myenteric and submucosal AH neurons.Methods: Isolated segments of guinea pig jejunum were incubated for 90 min with saline plus CT (12.5 μg/ml or CT + neurotransmitter antagonist, or CT + tetrodotoxin (TTX in their lumen. After washing CT away, submucosal or myenteric plexus preparations were dissected keeping circumferentially adjacent mucosa intact. Submucosal AH neurons were impaled adjacent to intact mucosa and myenteric AH neurons were impaled adjacent to, more than 5 mm from, and in the absence of intact mucosa. Neuronal excitability was monitored by injecting 500 ms current pulses through the recording electrode.Results: After CT pre-treatment, excitability of myenteric AH neurons adjacent to intact mucosa (n = 29 was greater than that of control neurons (n = 24, but submucosal AH neurons (n = 33, control n = 27 were unaffected. CT also induced excitability increases in myenteric AH neurons impaled distant from the mucosa (n = 6 or in its absence (n = 5. Coincubation with tetrodotoxin or SR142801 (NK3 receptor antagonist, but not SR140333 (NK1 antagonist or granisetron (5-HT3 receptor antagonist prevented the increased excitability induced by CT. Increased excitability was associated with a reduction in the characteristic AHP and an increase in the ADP of these neurons, but not a change in the hyperpolarization-activated inward current, Ih.Conclusions: CT increases excitability of myenteric, but not submucosal, AH neurons. This is neurally mediated and depends on NK3, but not 5-HT3 receptors. Therefore, CT may act to amplify the secretomotor response to CT via an increase in the

  19. Simulating synchronization in neuronal networks

    Science.gov (United States)

    Fink, Christian G.

    2016-06-01

    We discuss several techniques used in simulating neuronal networks by exploring how a network's connectivity structure affects its propensity for synchronous spiking. Network connectivity is generated using the Watts-Strogatz small-world algorithm, and two key measures of network structure are described. These measures quantify structural characteristics that influence collective neuronal spiking, which is simulated using the leaky integrate-and-fire model. Simulations show that adding a small number of random connections to an otherwise lattice-like connectivity structure leads to a dramatic increase in neuronal synchronization.

  20. Glial tumors with neuronal differentiation.

    Science.gov (United States)

    Park, Chul-Kee; Phi, Ji Hoon; Park, Sung-Hye

    2015-01-01

    Immunohistochemical studies for neuronal differentiation in glial tumors revealed subsets of tumors having both characteristics of glial and neuronal lineages. Glial tumors with neuronal differentiation can be observed with diverse phenotypes and histologic grades. The rosette-forming glioneuronal tumor of the fourth ventricle and papillary glioneuronal tumor have been newly classified as distinct disease entities. There are other candidates for classification, such as the glioneuronal tumor without pseudopapillary architecture, glioneuronal tumor with neuropil-like islands, and the malignant glioneuronal tumor. The clinical significance of these previously unclassified tumors should be confirmed. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Mechanosensing in hypothalamic osmosensory neurons.

    Science.gov (United States)

    Prager-Khoutorsky, Masha

    2017-11-01

    Osmosensory neurons are specialized cells activated by increases in blood osmolality to trigger thirst, secretion of the antidiuretic hormone vasopressin, and elevated sympathetic tone during dehydration. In addition to multiple extrinsic factors modulating their activity, osmosensory neurons are intrinsically osmosensitive, as they are activated by increased osmolality in the absence of neighboring cells or synaptic contacts. This intrinsic osmosensitivity is a mechanical process associated with osmolality-induced changes in cell volume. This review summarises recent findings revealing molecular mechanisms underlying the mechanical activation of osmosensory neurons and highlighting important roles of microtubules, actin, and mechanosensitive ion channels in this process. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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

  3. From Neurons to Brain: Adaptive Self-Wiring of Neurons

    OpenAIRE

    Segev, Ronen; Ben-Jacob, Eshel

    1998-01-01

    During embryonic morpho-genesis, a collection of individual neurons turns into a functioning network with unique capabilities. Only recently has this most staggering example of emergent process in the natural world, began to be studied. Here we propose a navigational strategy for neurites growth cones, based on sophisticated chemical signaling. We further propose that the embryonic environment (the neurons and the glia cells) acts as an excitable media in which concentric and spiral chemical ...

  4. Imaging of intracranial neuronal and mixed neuronal-glial tumours

    International Nuclear Information System (INIS)

    Cui Shimin; Qin Jinxi; Zhang Leili; Liu Meili; Jin Song; Yan Shixin; Liu Li; Dai Weiying; Li Tao; Gao Man

    2001-01-01

    Objective: To investigate the characteristic clinical, imaging , and pathologic findings of intracranial neuronal and mixed neuronal-glial tumours. Methods: The imaging findings of surgery and pathobiology proved intracranial neuronal and mixed neuronal-glial tumours in 14 cases (7 male and 7 female, ranging in age from 6-56 years; mean age 33.8 years) were retrospectively analyzed. Results: Eight gangliogliomas were located in the frontal lobe (4 cases), temporal lobe (1 case), front- temporal lobe (2 cases), and pons (1 case). They appeared as iso-or low density on CT, iso-or low signal intensity on T 1 WI, and high signal intensity on T 2 WI on MR imaging. Two central neurocytomas were located in the supratentorial ventricles. Four desmoplastic gangliogliomas were seen as cystic masses, appearing as low signal intensity on T 1 WI and high signal intensity on T 2 WI. Conclusion: Intracranial neuronal and mixed neuronal-glial tumours had imaging characteristics. Combined with clinical history, it was possible to make a tendency preoperative diagnosis using CT or MR

  5. Tinbergen on mirror neurons

    Science.gov (United States)

    Heyes, Cecilia

    2014-01-01

    Fifty years ago, Niko Tinbergen defined the scope of behavioural biology with his four problems: causation, ontogeny, survival value and evolution. About 20 years ago, there was another highly significant development in behavioural biology—the discovery of mirror neurons (MNs). Here, I use Tinbergen's original four problems (rather than the list that appears in textbooks) to highlight the differences between two prominent accounts of MNs, the genetic and associative accounts; to suggest that the latter provides the defeasible ‘best explanation’ for current data on the causation and ontogeny of MNs; and to argue that functional analysis, of the kind that Tinbergen identified somewhat misleadingly with studies of ‘survival value’, should be a high priority for future research. In this kind of functional analysis, system-level theories would assign MNs a small, but potentially important, role in the achievement of action understanding—or another social cognitive function—by a production line of interacting component processes. These theories would be tested by experimental intervention in human and non-human animal samples with carefully documented and controlled developmental histories. PMID:24778376

  6. Neurons on the couch.

    Science.gov (United States)

    Marić, Nadja P; Jašović-Gašić, Miroslava

    2010-12-01

    A hundred years after psychoanalysis was introduced, neuroscience has taken a giant step forward. It seems nowadays that effects of psychotherapy could be monitored and measured by state-of-the art brain imaging techniques. Today, the psychotherapy is considered as a strategic and purposeful environmental influence intended to enhance learning. Since gene expression is regulated by environmental influences throughout life and these processes create brain architecture and influence the strength of synaptic connections, psychotherapy (as a kind of learning) should be explored in the context of aforementioned paradigm. In other words, when placing a client on the couch, therapist actually placed client's neuronal network; while listening and talking, expressing and analyzing, experiencing transference and counter transference, therapist tends to stabilize synaptic connections and influence dendritic growth by regulating gene-transcriptional activity. Therefore, we strongly believe that, in the near future, an increasing knowledge on cellular and molecular interactions and mechanisms of action of different psycho- and pharmaco-therapeutic procedures will enable us to tailor a sophisticated therapeutic approach toward a person, by combining major therapeutic strategies in psychiatry on the basis of rational goals and evidence-based therapeutic expectations.

  7. Tinbergen on mirror neurons.

    Science.gov (United States)

    Heyes, Cecilia

    2014-01-01

    Fifty years ago, Niko Tinbergen defined the scope of behavioural biology with his four problems: causation, ontogeny, survival value and evolution. About 20 years ago, there was another highly significant development in behavioural biology-the discovery of mirror neurons (MNs). Here, I use Tinbergen's original four problems (rather than the list that appears in textbooks) to highlight the differences between two prominent accounts of MNs, the genetic and associative accounts; to suggest that the latter provides the defeasible 'best explanation' for current data on the causation and ontogeny of MNs; and to argue that functional analysis, of the kind that Tinbergen identified somewhat misleadingly with studies of 'survival value', should be a high priority for future research. In this kind of functional analysis, system-level theories would assign MNs a small, but potentially important, role in the achievement of action understanding-or another social cognitive function-by a production line of interacting component processes. These theories would be tested by experimental intervention in human and non-human animal samples with carefully documented and controlled developmental histories.

  8. Understanding Neuronal Mechanisms of Epilepsy ...

    Indian Academy of Sciences (India)

    Admin

    α subunit of Rat Brain type IIA Voltage Gated Sodium Channel and geneticin selection ..... scaling the mother wavelet. Scale = 1/ .... through dynamic clamp. Dynamic Clamp ... It has been shown that like in vivo neurons, cortical networks in.

  9. Imitation, mirror neurons and autism.

    Science.gov (United States)

    Williams, J H; Whiten, A; Suddendorf, T; Perrett, D I

    2001-06-01

    Various deficits in the cognitive functioning of people with autism have been documented in recent years but these provide only partial explanations for the condition. We focus instead on an imitative disturbance involving difficulties both in copying actions and in inhibiting more stereotyped mimicking, such as echolalia. A candidate for the neural basis of this disturbance may be found in a recently discovered class of neurons in frontal cortex, 'mirror neurons' (MNs). These neurons show activity in relation both to specific actions performed by self and matching actions performed by others, providing a potential bridge between minds. MN systems exist in primates without imitative and 'theory of mind' abilities and we suggest that in order for them to have become utilized to perform social cognitive functions, sophisticated cortical neuronal systems have evolved in which MNs function as key elements. Early developmental failures of MN systems are likely to result in a consequent cascade of developmental impairments characterised by the clinical syndrome of autism.

  10. Information processing by neuronal populations

    National Research Council Canada - National Science Library

    Hölscher, Christian; Munk, Matthias

    2009-01-01

    ... simultaneously recorded spike trains 120 Mark Laubach, Nandakumar S. Narayanan, and Eyal Y. Kimchi Part III Neuronal population information coding and plasticity in specific brain areas 149 7 F...

  11. Chimera states in bursting neurons

    OpenAIRE

    Bera, Bidesh K.; Ghosh, Dibakar; Lakshmanan, M.

    2015-01-01

    We study the existence of chimera states in pulse-coupled networks of bursting Hindmarsh-Rose neurons with nonlocal, global and local (nearest neighbor) couplings. Through a linear stability analysis, we discuss the behavior of stability function in the incoherent (i.e. disorder), coherent, chimera and multi-chimera states. Surprisingly, we find that chimera and multi-chimera states occur even using local nearest neighbor interaction in a network of identical bursting neurons alone. This is i...

  12. Studies on Anti-Depressant Activity of Four Flavonoids Isolated from ...

    African Journals Online (AJOL)

    glucose and quercetin-3-O-β-D-glucose isolated from Apocynum venetum Linn. ... may be due to increased NE, DA and 5-HT and reduced 5-HT metabolism. ..... monoaminergic neuronal activity. Biochem. Pharmacol 1985; 34: 1127-1131. 30.

  13. Communication among neurons.

    Science.gov (United States)

    Marner, Lisbeth

    2012-04-01

    The communication among neurons is the prerequisite for the working brain. To understand the cellular, neurochemical, and structural basis of this communication, and the impacts of aging and disease on brain function, quantitative measures are necessary. This thesis evaluates several quantitative neurobiological methods with respect to possible bias and methodological issues. Stereological methods are suited for the unbiased estimation of number, length, and volumes of components of the nervous system. Stereological estimates of the total length of myelinated nerve fibers were made in white matter of post mortem brains, and the impact of aging and diseases as Schizophrenia and Alzheimer's disease were evaluated. Although stereological methods are in principle unbiased, shrinkage artifacts are difficult to account for. Positron emission tomography (PET) recordings, in conjunction with kinetic modeling, permit the quantitation of radioligand binding in brain. The novel serotonin 5-HT4 antagonist [11C]SB207145 was used as an example of the validation process for quantitative PET receptor imaging. Methods based on reference tissue as well as methods based on an arterial plasma input function were evaluated with respect to precision and accuracy. It was shown that [11C]SB207145 binding had high sensitivity to occupancy by unlabeled ligand, necessitating high specific activity in the radiosynthesis to avoid bias. The established serotonin 5-HT2A ligand [18F]altanersin was evaluated in a two-year follow-up study in elderly subjects. Application of partial volume correction of the PET data diminished the reliability of the measures, but allowed for the correct distinction between changes due to brain atrophy and receptor availability. Furthermore, a PET study of patients with Alzheimer's disease with the serotonin transporter ligand [11C]DASB showed relatively preserved serotonergic projections, despite a marked decrease in 5-HT2A receptor binding. Possible confounders are

  14. Lack of functional relevance of isolated cell damage in transplants of Parkinson's disease patients

    DEFF Research Database (Denmark)

    Cooper, Oliver; Astradsson, Arnar; Hallett, Penny

    2009-01-01

    Postmortem analyses from clinical neural transplantation trials of several subjects with Parkinson's disease revealed surviving grafted dopaminergic neurons after more than a decade. A subset of these subjects displayed isolated dopaminergic neurons within the grafts that contained Lewy body......-like structures. In this review, we discuss why this isolated cell damage is unlikely to affect the overall graft function and how we can use these observations to help us to understand age-related neurodegeneration and refine our future cell replacement therapies....

  15. Arctigenin protects against neuronal hearing loss by promoting neural stem cell survival and differentiation.

    Science.gov (United States)

    Huang, Xinghua; Chen, Mo; Ding, Yan; Wang, Qin

    2017-03-01

    Neuronal hearing loss has become a prevalent health problem. This study focused on the function of arctigenin (ARC) in promoting survival and neuronal differentiation of mouse cochlear neural stem cells (NSCs), and its protection against gentamicin (GMC) induced neuronal hearing loss. Mouse cochlea was used to isolate NSCs, which were subsequently cultured in vitro. The effects of ARC on NSC survival, neurosphere formation, differentiation of NSCs, neurite outgrowth, and neural excitability in neuronal network in vitro were examined. Mechanotransduction ability demonstrated by intact cochlea, auditory brainstem response (ABR), and distortion product optoacoustic emissions (DPOAE) amplitude in mice were measured to evaluate effects of ARC on GMC-induced neuronal hearing loss. ARC increased survival, neurosphere formation, neuron differentiation of NSCs in mouse cochlear in vitro. ARC also promoted the outgrowth of neurites, as well as neural excitability of the NSC-differentiated neuron culture. Additionally, ARC rescued mechanotransduction capacity, restored the threshold shifts of ABR and DPOAE in our GMC ototoxicity murine model. This study supports the potential therapeutic role of ARC in promoting both NSCs proliferation and differentiation in vitro to functional neurons, thus supporting its protective function in the therapeutic treatment of neuropathic hearing loss in vivo. © 2017 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    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

  17. 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.

  18. Communication between mast cells and rat submucosal neurons.

    Science.gov (United States)

    Bell, Anna; Althaus, Mike; Diener, Martin

    2015-08-01

    Histamine is a mast cell mediator released e.g. during food allergy. The aim of the project was to identify the effect of histamine on rat submucosal neurons and the mechanisms involved. Cultured submucosal neurons from rat colon express H1, H2 and H3 receptors as shown by immunocytochemical staining confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) with messenger RNA (mRNA) isolated from submucosal homogenates as starting material. Histamine evoked a biphasic rise of the cytosolic Ca(2+) concentration in cultured submucosal neurons, consisting in a release of intracellularly stored Ca(2+) followed by an influx from the extracellular space. Although agonists of all three receptor subtypes evoked an increase in the cytosolic Ca(2+) concentration, experiments with antagonists revealed that mainly H1 (and to a lesser degree H2) receptors mediate the response to histamine. In coculture experiments with RBL-2H3 cells, a mast cell equivalent, compound 48/80, evoked an increase in the cytosolic Ca(2+) concentration of neighbouring neurons. Like the response to native histamine, the neuronal response to the mast cell degranulator was strongly inhibited by the H1 receptor antagonist pyrilamine and reduced by the H2 receptor antagonist cimetidine. In rats sensitized against ovalbumin, exposure to the antigen induced a rise in short-circuit current (I sc) across colonic mucosa-submucosa preparations without a significant increase in paracellular fluorescein fluxes. Pyrilamine strongly inhibited the increase in I sc, a weaker inhibition was observed after blockade of protease receptors or 5-lipoxygenase. Consequently, H1 receptors on submucosal neurons seem to play a pivotal role in the communication between mast cells and the enteric nervous system.

  19. Large-scale Reconstructions and Independent, Unbiased Clustering Based on Morphological Metrics to Classify Neurons in Selective Populations.

    Science.gov (United States)

    Bragg, Elise M; Briggs, Farran

    2017-02-15

    This protocol outlines large-scale reconstructions of neurons combined with the use of independent and unbiased clustering analyses to create a comprehensive survey of the morphological characteristics observed among a selective neuronal population. Combination of these techniques constitutes a novel approach for the collection and analysis of neuroanatomical data. Together, these techniques enable large-scale, and therefore more comprehensive, sampling of selective neuronal populations and establish unbiased quantitative methods for describing morphologically unique neuronal classes within a population. The protocol outlines the use of modified rabies virus to selectively label neurons. G-deleted rabies virus acts like a retrograde tracer following stereotaxic injection into a target brain structure of interest and serves as a vehicle for the delivery and expression of EGFP in neurons. Large numbers of neurons are infected using this technique and express GFP throughout their dendrites, producing "Golgi-like" complete fills of individual neurons. Accordingly, the virus-mediated retrograde tracing method improves upon traditional dye-based retrograde tracing techniques by producing complete intracellular fills. Individual well-isolated neurons spanning all regions of the brain area under study are selected for reconstruction in order to obtain a representative sample of neurons. The protocol outlines procedures to reconstruct cell bodies and complete dendritic arborization patterns of labeled neurons spanning multiple tissue sections. Morphological data, including positions of each neuron within the brain structure, are extracted for further analysis. Standard programming functions were utilized to perform independent cluster analyses and cluster evaluations based on morphological metrics. To verify the utility of these analyses, statistical evaluation of a cluster analysis performed on 160 neurons reconstructed in the thalamic reticular nucleus of the thalamus

  20. In vitro differentiation of bone marrow stromal cells into neurons and glial cells and differential protein expression in a two-compartment bone marrow stromal cell/neuron co-culture system.

    Science.gov (United States)

    Qi, Xu; Shao, Ming; Peng, Haisheng; Bi, Zhenggang; Su, Zhiqiang; Li, Hulun

    2010-07-01

    This study was performed to establish a bone marrow stromal cell (BMSC)/neuron two-compartment co-culture model in which differentiation of BMSCs into neurons could occur without direct contact between the two cell types, and to investigate protein expression changes during differentiation of this entirely BMSC-derived population. Cultured BMSCs isolated from Wistar rats were divided into three groups: BMSC culture, BMSC/neuron co-culture and BMSC/neuron two-compartment co-culture. Cells were examined for neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP) expression. The electrophysiological behavior of the BMSCs was examined using patch clamping. Proteins that had significantly different expression levels in BMSCs cultured alone and co-cultured with neurons were studied using a protein chip-mass spectroscopy technique. Expression of NSE and GFAP were significantly higher in co-culture cells than in two-compartment co-culture cells, and significantly higher in both co-culture groups than in BMSCs cultured alone. Five proteins showed significant changes in expression during differentiation: TIP39_RAT and CALC_RAT underwent increases, and INSL6_RAT, PNOC_RAT and PCSK1_RAT underwent decreases in expression. We conclude that BMSCs can differentiate into neurons during both contact co-culture with neurons and two-compartment co-culture with neurons. The rate at which BMSCs differentiated into neurons was higher in contact co-culture than in non-contact co-culture.

  1. Probing the dynamics of identified neurons with a data-driven modeling approach.

    Directory of Open Access Journals (Sweden)

    Thomas Nowotny

    2008-07-01

    Full Text Available In controlling animal behavior the nervous system has to perform within the operational limits set by the requirements of each specific behavior. The implications for the corresponding range of suitable network, single neuron, and ion channel properties have remained elusive. In this article we approach the question of how well-constrained properties of neuronal systems may be on the neuronal level. We used large data sets of the activity of isolated invertebrate identified cells and built an accurate conductance-based model for this cell type using customized automated parameter estimation techniques. By direct inspection of the data we found that the variability of the neurons is larger when they are isolated from the circuit than when in the intact system. Furthermore, the responses of the neurons to perturbations appear to be more consistent than their autonomous behavior under stationary conditions. In the developed model, the constraints on different parameters that enforce appropriate model dynamics vary widely from some very tightly controlled parameters to others that are almost arbitrary. The model also allows predictions for the effect of blocking selected ionic currents and to prove that the origin of irregular dynamics in the neuron model is proper chaoticity and that this chaoticity is typical in an appropriate sense. Our results indicate that data driven models are useful tools for the in-depth analysis of neuronal dynamics. The better consistency of responses to perturbations, in the real neurons as well as in the model, suggests a paradigm shift away from measuring autonomous dynamics alone towards protocols of controlled perturbations. Our predictions for the impact of channel blockers on the neuronal dynamics and the proof of chaoticity underscore the wide scope of our approach.

  2. Learning of time series through neuron-to-neuron instruction

    Energy Technology Data Exchange (ETDEWEB)

    Miyazaki, Y [Department of Physics, Kyoto University, Kyoto 606-8502, (Japan); Kinzel, W [Institut fuer Theoretische Physik, Universitaet Wurzburg, 97074 Wurzburg (Germany); Shinomoto, S [Department of Physics, Kyoto University, Kyoto (Japan)

    2003-02-07

    A model neuron with delayline feedback connections can learn a time series generated by another model neuron. It has been known that some student neurons that have completed such learning under the instruction of a teacher's quasi-periodic sequence mimic the teacher's time series over a long interval, even after instruction has ceased. We found that in addition to such faithful students, there are unfaithful students whose time series eventually diverge exponentially from that of the teacher. In order to understand the circumstances that allow for such a variety of students, the orbit dimension was estimated numerically. The quasi-periodic orbits in question were found to be confined in spaces with dimensions significantly smaller than that of the full phase space.

  3. Learning of time series through neuron-to-neuron instruction

    International Nuclear Information System (INIS)

    Miyazaki, Y; Kinzel, W; Shinomoto, S

    2003-01-01

    A model neuron with delayline feedback connections can learn a time series generated by another model neuron. It has been known that some student neurons that have completed such learning under the instruction of a teacher's quasi-periodic sequence mimic the teacher's time series over a long interval, even after instruction has ceased. We found that in addition to such faithful students, there are unfaithful students whose time series eventually diverge exponentially from that of the teacher. In order to understand the circumstances that allow for such a variety of students, the orbit dimension was estimated numerically. The quasi-periodic orbits in question were found to be confined in spaces with dimensions significantly smaller than that of the full phase space

  4. Parallel Stochastic discrete event simulation of calcium dynamics in neuron.

    Science.gov (United States)

    Ishlam Patoary, Mohammad Nazrul; Tropper, Carl; McDougal, Robert A; Zhongwei, Lin; Lytton, William W

    2017-09-26

    The intra-cellular calcium signaling pathways of a neuron depends on both biochemical reactions and diffusions. Some quasi-isolated compartments (e.g. spines) are so small and calcium concentrations are so low that one extra molecule diffusing in by chance can make a nontrivial difference in its concentration (percentage-wise). These rare events can affect dynamics discretely in such way that they cannot be evaluated by a deterministic simulation. Stochastic models of such a system provide a more detailed understanding of these systems than existing deterministic models because they capture their behavior at a molecular level. Our research focuses on the development of a high performance parallel discrete event simulation environment, Neuron Time Warp (NTW), which is intended for use in the parallel simulation of stochastic reaction-diffusion systems such as intra-calcium signaling. NTW is integrated with NEURON, a simulator which is widely used within the neuroscience community. We simulate two models, a calcium buffer and a calcium wave model. The calcium buffer model is employed in order to verify the correctness and performance of NTW by comparing it to a serial deterministic simulation in NEURON. We also derived a discrete event calcium wave model from a deterministic model using the stochastic IP3R structure.

  5. PERIPHERAL SENSORY NEURONS EXPRESSING MELANOPSIN RESPOND TO LIGHT

    Directory of Open Access Journals (Sweden)

    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.

  6. Relating neuronal firing patterns to functional differentiation of cerebral cortex.

    Directory of Open Access Journals (Sweden)

    Shigeru Shinomoto

    2009-07-01

    Full Text Available It has been empirically established that the cerebral cortical areas defined by Brodmann one hundred years ago solely on the basis of cellular organization are closely correlated to their function, such as sensation, association, and motion. Cytoarchitectonically distinct cortical areas have different densities and types of neurons. Thus, signaling patterns may also vary among cytoarchitectonically unique cortical areas. To examine how neuronal signaling patterns are related to innate cortical functions, we detected intrinsic features of cortical firing by devising a metric that efficiently isolates non-Poisson irregular characteristics, independent of spike rate fluctuations that are caused extrinsically by ever-changing behavioral conditions. Using the new metric, we analyzed spike trains from over 1,000 neurons in 15 cortical areas sampled by eight independent neurophysiological laboratories. Analysis of firing-pattern dissimilarities across cortical areas revealed a gradient of firing regularity that corresponded closely to the functional category of the cortical area; neuronal spiking patterns are regular in motor areas, random in the visual areas, and bursty in the prefrontal area. Thus, signaling patterns may play an important role in function-specific cerebral cortical computation.

  7. The mirror-neuron system.

    Science.gov (United States)

    Rizzolatti, Giacomo; Craighero, Laila

    2004-01-01

    A category of stimuli of great importance for primates, humans in particular, is that formed by actions done by other individuals. If we want to survive, we must understand the actions of others. Furthermore, without action understanding, social organization is impossible. In the case of humans, there is another faculty that depends on the observation of others' actions: imitation learning. Unlike most species, we are able to learn by imitation, and this faculty is at the basis of human culture. In this review we present data on a neurophysiological mechanism--the mirror-neuron mechanism--that appears to play a fundamental role in both action understanding and imitation. We describe first the functional properties of mirror neurons in monkeys. We review next the characteristics of the mirror-neuron system in humans. We stress, in particular, those properties specific to the human mirror-neuron system that might explain the human capacity to learn by imitation. We conclude by discussing the relationship between the mirror-neuron system and language.

  8. Neuronal factors determining high intelligence.

    Science.gov (United States)

    Dicke, Ursula; Roth, Gerhard

    2016-01-05

    Many attempts have been made to correlate degrees of both animal and human intelligence with brain properties. With respect to mammals, a much-discussed trait concerns absolute and relative brain size, either uncorrected or corrected for body size. However, the correlation of both with degrees of intelligence yields large inconsistencies, because although they are regarded as the most intelligent mammals, monkeys and apes, including humans, have neither the absolutely nor the relatively largest brains. The best fit between brain traits and degrees of intelligence among mammals is reached by a combination of the number of cortical neurons, neuron packing density, interneuronal distance and axonal conduction velocity--factors that determine general information processing capacity (IPC), as reflected by general intelligence. The highest IPC is found in humans, followed by the great apes, Old World and New World monkeys. The IPC of cetaceans and elephants is much lower because of a thin cortex, low neuron packing density and low axonal conduction velocity. By contrast, corvid and psittacid birds have very small and densely packed pallial neurons and relatively many neurons, which, despite very small brain volumes, might explain their high intelligence. The evolution of a syntactical and grammatical language in humans most probably has served as an additional intelligence amplifier, which may have happened in songbirds and psittacids in a convergent manner. © 2015 The Author(s).

  9. Energy Model of Neuron Activation.

    Science.gov (United States)

    Romanyshyn, Yuriy; Smerdov, Andriy; Petrytska, Svitlana

    2017-02-01

    On the basis of the neurophysiological strength-duration (amplitude-duration) curve of neuron activation (which relates the threshold amplitude of a rectangular current pulse of neuron activation to the pulse duration), as well as with the use of activation energy constraint (the threshold curve corresponds to the energy threshold of neuron activation by a rectangular current pulse), an energy model of neuron activation by a single current pulse has been constructed. The constructed model of activation, which determines its spectral properties, is a bandpass filter. Under the condition of minimum-phase feature of the neuron activation model, on the basis of Hilbert transform, the possibilities of phase-frequency response calculation from its amplitude-frequency response have been considered. Approximation to the amplitude-frequency response by the response of the Butterworth filter of the first order, as well as obtaining the pulse response corresponding to this approximation, give us the possibility of analyzing the efficiency of activating current pulses of various shapes, including analysis in accordance with the energy constraint.

  10. Optogenetic stimulation of locus ceruleus neurons augments inhibitory transmission to parasympathetic cardiac vagal neurons via activation of brainstem α1 and β1 receptors.

    Science.gov (United States)

    Wang, Xin; Piñol, Ramón A; Byrne, Peter; Mendelowitz, David

    2014-04-30

    Locus ceruleus (LC) noradrenergic neurons are critical in generating alertness. In addition to inducing cortical arousal, the LC also orchestrates changes in accompanying autonomic system function that compliments increased attention, such as during stress, excitation, and/or exposure to averse or novel stimuli. Although the association between arousal and increased heart rate is well accepted, the neurobiological link between the LC and parasympathetic neurons that control heart rate has not been identified. In this study, we test directly whether activation of noradrenergic neurons in the LC influences brainstem parasympathetic cardiac vagal neurons (CVNs). CVNs were identified in transgenic mice that express channel-rhodopsin-2 (ChR2) in LC tyrosine hydroxylase neurons. Photoactivation evoked a rapid depolarization, increased firing, and excitatory inward currents in ChR2-expressing neurons in the LC. Photostimulation of LC neurons did not alter excitatory currents, but increased inhibitory neurotransmission to CVNs. Optogenetic activation of LC neurons increased the frequency of isolated glycinergic IPSCs by 27 ± 8% (p = 0.003, n = 26) and augmented GABAergic IPSCs in CVNs by 21 ± 5% (p = 0.001, n = 26). Inhibiting α1, but not α2, receptors blocked the evoked responses. Inhibiting β1 receptors prevented the increase in glycinergic, but not GABAergic, IPSCs in CVNs. This study demonstrates LC noradrenergic neurons inhibit the brainstem CVNs that generate parasympathetic activity to the heart. This inhibition of CVNs would increase heart rate and risks associated with tachycardia. The receptors activated within this pathway, α1 and/or β1 receptors, are targets for clinically prescribed antagonists that promote slower, cardioprotective heart rates during heightened vigilant states.

  11. Turning skin into dopamine neurons

    Institute of Scientific and Technical Information of China (English)

    Malin Parmar; Johan Jakobsson

    2011-01-01

    The possibility to generate neurons from fibroblasts became a reality with the development of iPS technology a few years ago.By reprogramming somatic cells using transcription factor (TF) overexpression,it is possible to generate pluripotent stem cells that then can be differentiated into any somatic cell type including various subtypes of neurons.This raises the possibility of using donor-matched or even patientspecific cells for cell therapy of neurological disorders such as Parkinson's disease (PD),Huntington's disease and stroke.Supporting this idea,dopamine neurons,which are the cells dying in PD,derived from human iPS cells have been demonstrated to survive transplantation and reverse motor symptoms in animal models of PD [1].

  12. 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...

  13. Acetaminophen inhibits neuronal inflammation and protects neurons from oxidative stress

    Directory of Open Access Journals (Sweden)

    Grammas Paula

    2009-03-01

    Full Text Available Abstract Background Recent studies have demonstrated a link between the inflammatory response, increased cytokine formation, and neurodegeneration in the brain. The beneficial effects of anti-inflammatory drugs in neurodegenerative diseases, such as Alzheimer's disease (AD, have been documented. Increasing evidence suggests that acetaminophen has unappreciated anti-oxidant and anti-inflammatory properties. The objectives of this study are to determine the effects of acetaminophen on cultured brain neuronal survival and inflammatory factor expression when exposed to oxidative stress. Methods Cerebral cortical cultured neurons are pretreated with acetaminophen and then exposed to the superoxide-generating compound menadione (5 μM. Cell survival is assessed by MTT assay and inflammatory protein (tumor necrosis factor alpha, interleukin-1, macrophage inflammatory protein alpha, and RANTES release quantitated by ELISA. Expression of pro- and anti-apoptotic proteins is assessed by western blots. Results Acetaminophen has pro-survival effects on neurons in culture. Menadione, a superoxide releasing oxidant stressor, causes a significant (p Conclusion These data show that acetaminophen has anti-oxidant and anti-inflammatory effects on neurons and suggest a heretofore unappreciated therapeutic potential for this drug in neurodegenerative diseases such as AD that are characterized by oxidant and inflammatory stress.

  14. Neuronal coherence and its functional role in communication between neurons

    NARCIS (Netherlands)

    Zeitler-Geurds, M.

    2010-01-01

    Neuronal oscillations are observed in many brain areas in various frequency bands. Each of the frequency bands is associated with a particular functional role. Gamma oscillations (30-80 Hz) are thought to be related to cognitive tasks like memory and attention and possibly also involved in the

  15. Bursting neurons and ultrasound avoidance in crickets

    Directory of Open Access Journals (Sweden)

    Gary eMarsat

    2012-07-01

    Full Text Available Decision making in invertebrates often relies on simple neural circuits composed of only a few identified neurons. The relative simplicity of these circuits makes it possible to identify the key computation and neural properties underlying decisions. In this review, we summarize recent research on the neural basis of ultrasound avoidance in crickets, a response that allows escape from echolocating bats. The key neural property shaping behavioral output is high-frequency bursting of an identified interneuron, AN2, which carries information about ultrasound stimuli from receptor neurons to the brain. AN2's spike train consists of clusters of spikes –bursts– that may be interspersed with isolated, non-burst spikes. AN2 firing is necessary and sufficient to trigger avoidance steering but only high-rate firing, such as occurs in bursts, evokes this response. AN2 bursts are therefore at the core of the computation involved in deciding whether or not to steer away from ultrasound. Bursts in AN2 are triggered by synaptic input from nearly synchronous bursts in ultrasound receptors. Thus the population response at the very first stage of sensory processing –the auditory receptor- already differentiates the features of the stimulus that will trigger a behavioral response from those that will not. Adaptation, both intrinsic to AN2 and within ultrasound receptors, scales the burst-generating features according to the stimulus statistics, thus filtering out background noise and ensuring that bursts occur selectively in response to salient peaks in ultrasound intensity. Furthermore AN2’s sensitivity to ultrasound varies adaptively with predation pressure, through both developmental and evolutionary mechanisms. We discuss how this key relationship between bursting and the triggering of avoidance behavior is also observed in other invertebrate systems such as the avoidance of looming visual stimuli in locusts or heat avoidance in beetles.

  16. Effects of activated ACM on expression of signal transducers in cerebral cortical neurons of rats.

    Science.gov (United States)

    Wang, Xiaojing; Li, Zhengli; Zhu, Changgeng; Li, Zhongyu

    2007-06-01

    To explore the roles of astrocytes in the epileptogenesis, astrocytes and neurons were isolated, purified and cultured in vitro from cerebral cortex of rats. The astrocytes were activated by ciliary neurotrophic factor (CNTF) and astrocytic conditioned medium (ACM) was collected to treat neurons for 4, 8 and 12 h. By using Western blot, the expression of calmodulin dependent protein kinase II (CaMK II), inducible nitric oxide synthase (iNOS) and adenylate cyclase (AC) was detected in neurons. The results showed that the expression of CaMK II, iNOS and AC was increased significantly in the neurons treated with ACM from 4 h to 12 h (PACM and such signal pathways as NOS-NO-cGMP, Ca2+/CaM-CaMK II and AC-cAMP-PKA might take part in the signal transduction of epileptogenesis.

  17. Neuronal type-specific gene expression profiling and laser-capture microdissection.

    Science.gov (United States)

    Pietersen, Charmaine Y; Lim, Maribel P; Macey, Laurel; Woo, Tsung-Ung W; Sonntag, Kai C

    2011-01-01

    The human brain is an exceptionally heterogeneous structure. In order to gain insight into the neurobiological basis of neural circuit disturbances in various neurologic or psychiatric diseases, it is often important to define the molecular cascades that are associated with these disturbances in a neuronal type-specific manner. This can be achieved by the use of laser microdissection, in combination with molecular techniques such as gene expression profiling. To identify neurons in human postmortem brain tissue, one can use the inherent properties of the neuron, such as pigmentation and morphology or its structural composition through immunohistochemistry (IHC). Here, we describe the isolation of homogeneous neuronal cells and high-quality RNA from human postmortem brain material using a combination of rapid IHC, Nissl staining, or simple morphology with Laser-Capture Microdissection (LCM) or Laser Microdissection (LMD).

  18. Axon Guidance of Sympathetic Neurons to Cardiomyocytes by Glial Cell Line-Derived Neurotrophic Factor (GDNF)

    NARCIS (Netherlands)

    Miwa, Keiko; Lee, Jong-Kook; Takagishi, Yoshiko; Opthof, Tobias; Fu, Xianming; Hirabayashi, Masumi; Watabe, Kazuhiko; Jimbo, Yasuhiko; Kodama, Itsuo; Komuro, Issei

    2013-01-01

    Molecular signaling of cardiac autonomic innervation is an unresolved issue. Here, we show that glial cell line-derived neurotrophic factor (GDNF) promotes cardiac sympathetic innervation in vitro and in vivo. In vitro, ventricular myocytes (VMs) and sympathetic neurons (SNs) isolated from neonatal

  19. Microelectrode array-induced neuronal alignment directs neurite outgrowth: analysis using a fast Fourier transform (FFT).

    Science.gov (United States)

    Radotić, Viktorija; Braeken, Dries; Kovačić, Damir

    2017-12-01

    Many studies have shown that the topography of the substrate on which neurons are cultured can promote neuronal adhesion and guide neurite outgrowth in the same direction as the underlying topography. To investigate this effect, isotropic substrate-complementary metal-oxide-semiconductor (CMOS) chips were used as one example of microelectrode arrays (MEAs) for directing neurite growth of spiral ganglion neurons. Neurons were isolated from 5 to 7-day-old rat pups, cultured 1 day in vitro (DIV) and 4 DIV, and then fixed with 4% paraformaldehyde. For analysis of neurite alignment and orientation, fast Fourier transformation (FFT) was used. Results revealed that on the micro-patterned surface of a CMOS chip, neurons orient their neurites along three directional axes at 30, 90, and 150° and that neurites aligned in straight lines between adjacent pillars and mostly followed a single direction while occasionally branching perpendicularly. We conclude that the CMOS substrate guides neurites towards electrodes by means of their structured pillar organization and can produce electrical stimulation of aligned neurons as well as monitoring their neural activities once neurites are in the vicinity of electrodes. These findings are of particular interest for neural tissue engineering with the ultimate goal of developing a new generation of MEA essential for improved electrical stimulation of auditory neurons.

  20. Automatic parameter estimation of multicompartmental neuron models via minimization of trace error with control adjustment.

    Science.gov (United States)

    Brookings, Ted; Goeritz, Marie L; Marder, Eve

    2014-11-01

    We describe a new technique to fit conductance-based neuron models to intracellular voltage traces from isolated biological neurons. The biological neurons are recorded in current-clamp with pink (1/f) noise injected to perturb the activity of the neuron. The new algorithm finds a set of parameters that allows a multicompartmental model neuron to match the recorded voltage trace. Attempting to match a recorded voltage trace directly has a well-known problem: mismatch in the timing of action potentials between biological and model neuron is inevitable and results in poor phenomenological match between the model and data. Our approach avoids this by applying a weak control adjustment to the model to promote alignment during the fitting procedure. This approach is closely related to the control theoretic concept of a Luenberger observer. We tested this approach on synthetic data and on data recorded from an anterior gastric receptor neuron from the stomatogastric ganglion of the crab Cancer borealis. To test the flexibility of this approach, the synthetic data were constructed with conductance models that were different from the ones used in the fitting model. For both synthetic and biological data, the resultant models had good spike-timing accuracy. Copyright © 2014 the American Physiological Society.

  1. Characterization of neuronal damage by iomazenil binding and cerebral blood flow in an ischemic rat model

    International Nuclear Information System (INIS)

    Toyama, Hiroshi; Takeuchi, Akira; Koga, Sukehiko; Matsumura, Kaname; Nakashima, Hiromichi; Takeda, Kan; Yoshida, Toshimichi; Ichise, Masanori

    1998-01-01

    I-123-iomazenil is a SPECT probe for central benzodiazepine receptors (BZR) which may reflect intact cortical neuron density after ischemic insults. We evaluated whether neuronal damage in rats could be characterized by iomazenil as compared with cerebral blood flow (CBF). Serial changes in I-125-iomazenil for BZR and I-123-IMP for CBF were analyzed after the unilateral middle cerebral artery occlusion in rats by using an in vivo dualtracer technique. Uptake ratios of affected to contralateral regions were calculated. The iomazenil as well as IMP were decreased in all regions except for the cerebellum (remote area). Both iomazenil and IMP increased over time except in the temporal region (ischemic core). The iomazenil uptake was higher than IMP except in the ischemic core between 1 and 3-4 wk when iomazenil was lower than IMP. Iomazenil showed a moderate decrease in the proximal and middle parietal regions (peri-infarct areas) at 3-4 wk. The triphenyl-tetrazolium-chloride (TTC) stain at 1 wk demonstrated unstained tissue in the temporal region indicating tissue necrosis. With hematoxylin-eosin (HE) stain at 1 wk, widespread neuronal necrosis with occasional intact neurons were found in the proximal parietal region, and isolated necrotic neurons were represented in the distal parietal region. Iomazenil correlated well with the neuron distribution and the finding of a discrepancy between iomazenil and IMP might be useful in evaluating the neuronal damage. (author)

  2. Pretreatment with apoaequorin protects hippocampal CA1 neurons from oxygen-glucose deprivation.

    Science.gov (United States)

    Detert, Julia A; Adams, Erin L; Lescher, Jacob D; Lyons, Jeri-Anne; Moyer, James R

    2013-01-01

    Ischemic stroke affects ∼795,000 people each year in the U.S., which results in an estimated annual cost of $73.7 billion. Calcium is pivotal in a variety of neuronal signaling cascades, however, during ischemia, excess calcium influx can trigger excitotoxic cell death. Calcium binding proteins help neurons regulate/buffer intracellular calcium levels during ischemia. Aequorin is a calcium binding protein isolated from the jellyfish Aequorea victoria, and has been used for years as a calcium indicator, but little is known about its neuroprotective properties. The present study used an in vitro rat brain slice preparation to test the hypothesis that an intra-hippocampal infusion of apoaequorin (the calcium binding component of aequorin) protects neurons from ischemic cell death. Bilaterally cannulated rats received an apoaequorin infusion in one hemisphere and vehicle control in the other. Hippocampal slices were then prepared and subjected to 5 minutes of oxygen-glucose deprivation (OGD), and cell death was assayed by trypan blue exclusion. Apoaequorin dose-dependently protected neurons from OGD--doses of 1% and 4% (but not 0.4%) significantly decreased the number of trypan blue-labeled neurons. This effect was also time dependent, lasting up to 48 hours. This time dependent effect was paralleled by changes in cytokine and chemokine expression, indicating that apoaequorin may protect neurons via a neuroimmunomodulatory mechanism. These data support the hypothesis that pretreatment with apoaequorin protects neurons against ischemic cell death, and may be an effective neurotherapeutic.

  3. Unbalanced Neuronal Circuits in Addiction

    OpenAIRE

    Volkow, Nora D.; Wang, Gen-Jack; Tomasi, Dardo; Baler, Ruben D.

    2013-01-01

    Through sequential waves of drug-induced neurochemical stimulation, addiction co-opts the brain's neuronal circuits that mediate reward, motivation, , to behavioral inflexibility and a severe disruption of self-control and compulsive drug intake. Brain imaging technologies have allowed neuroscientists to map out the neural landscape of addiction in the human brain and to understand how drugs modify it.

  4. Computing with Spiking Neuron Networks

    NARCIS (Netherlands)

    H. Paugam-Moisy; S.M. Bohte (Sander); G. Rozenberg; T.H.W. Baeck (Thomas); J.N. Kok (Joost)

    2012-01-01

    htmlabstractAbstract Spiking Neuron Networks (SNNs) are often referred to as the 3rd gener- ation of neural networks. Highly inspired from natural computing in the brain and recent advances in neurosciences, they derive their strength and interest from an ac- curate modeling of synaptic interactions

  5. What do mirror neurons mirror?

    NARCIS (Netherlands)

    Uithol, S.; Rooij, I.J.E.I. van; Bekkering, H.; Haselager, W.F.G.

    2011-01-01

    Single cell recordings in monkeys provide strong evidence for an important role of the motor system in action understanding. This evidence is backed up by data from studies of the (human) mirror neuron system using neuroimaging or TMS techniques, and behavioral experiments. Although the data

  6. Optimal compensation for neuron loss

    Science.gov (United States)

    Barrett, David GT; Denève, Sophie; Machens, Christian K

    2016-01-01

    The brain has an impressive ability to withstand neural damage. Diseases that kill neurons can go unnoticed for years, and incomplete brain lesions or silencing of neurons often fail to produce any behavioral effect. How does the brain compensate for such damage, and what are the limits of this compensation? We propose that neural circuits instantly compensate for neuron loss, thereby preserving their function as much as possible. We show that this compensation can explain changes in tuning curves induced by neuron silencing across a variety of systems, including the primary visual cortex. We find that compensatory mechanisms can be implemented through the dynamics of networks with a tight balance of excitation and inhibition, without requiring synaptic plasticity. The limits of this compensatory mechanism are reached when excitation and inhibition become unbalanced, thereby demarcating a recovery boundary, where signal representation fails and where diseases may become symptomatic. DOI: http://dx.doi.org/10.7554/eLife.12454.001 PMID:27935480

  7. Hypothalamic neurones governing glucose homeostasis.

    Science.gov (United States)

    Coppari, R

    2015-06-01

    The notion that the brain directly controls the level of glucose in the blood (glycaemia) independent of its known action on food intake and body weight has been known ever since 1849. That year, the French physiologist Dr Claude Bernard reported that physical puncture of the floor of the fourth cerebral ventricle rapidly leads to an increased level of sugar in the blood (and urine) in rabbits. Despite this important discovery, it took approximately 150 years before significant efforts aimed at understanding the underlying mechanism of brain-mediated control of glucose metabolism were made. Technological developments allowing for genetically-mediated manipulation of selected molecular pathways in a neurone-type-specific fashion unravelled the importance of specific molecules in specific neuronal populations. These neuronal pathways govern glucose metabolism in the presence and even in the absence of insulin. Also, a peculiarity of these pathways is that certain biochemically-defined neurones govern glucose metabolism in a tissue-specific fashion. © 2015 British Society for Neuroendocrinology.

  8. Comparative Analysis of Human and Rodent Brain Primary Neuronal Culture Spontaneous Activity Using Micro-Electrode Array Technology.

    Science.gov (United States)

    Napoli, Alessandro; Obeid, Iyad

    2016-03-01

    Electrical activity in embryonic brain tissue has typically been studied using Micro Electrode Array (MEA) technology to make dozens of simultaneous recordings from dissociated neuronal cultures, brain stem cell progenitors, or brain slices from fetal rodents. Although these rodent neuronal primary culture electrical properties are mostly investigated, it has not been yet established to what extent the electrical characteristics of rodent brain neuronal cultures can be generalized to those of humans. A direct comparison of spontaneous spiking activity between rodent and human primary neurons grown under the same in vitro conditions using MEA technology has never been carried out before and will be described in the present study. Human and rodent dissociated fetal brain neuronal cultures were established in-vitro by culturing on a glass grid of 60 planar microelectrodes neurons under identical conditions. Three different cultures of human neurons were produced from tissue sourced from a single aborted fetus (at 16-18 gestational weeks) and these were compared with seven different cultures of embryonic rat neurons (at 18 gestational days) originally isolated from a single rat. The results show that the human and rodent cultures behaved significantly differently. Whereas the rodent cultures demonstrated robust spontaneous activation and network activity after only 10 days, the human cultures required nearly 40 days to achieve a substantially weaker level of electrical function. These results suggest that rat neuron preparations may yield inferences that do not necessarily transfer to humans. © 2015 Wiley Periodicals, Inc.

  9. BlastNeuron for Automated Comparison, Retrieval and Clustering of 3D Neuron Morphologies.

    Science.gov (United States)

    Wan, Yinan; Long, Fuhui; Qu, Lei; Xiao, Hang; Hawrylycz, Michael; Myers, Eugene W; Peng, Hanchuan

    2015-10-01

    Characterizing the identity and types of neurons in the brain, as well as their associated function, requires a means of quantifying and comparing 3D neuron morphology. Presently, neuron comparison methods are based on statistics from neuronal morphology such as size and number of branches, which are not fully suitable for detecting local similarities and differences in the detailed structure. We developed BlastNeuron to compare neurons in terms of their global appearance, detailed arborization patterns, and topological similarity. BlastNeuron first compares and clusters 3D neuron reconstructions based on global morphology features and moment invariants, independent of their orientations, sizes, level of reconstruction and other variations. Subsequently, BlastNeuron performs local alignment between any pair of retrieved neurons via a tree-topology driven dynamic programming method. A 3D correspondence map can thus be generated at the resolution of single reconstruction nodes. We applied BlastNeuron to three datasets: (1) 10,000+ neuron reconstructions from a public morphology database, (2) 681 newly and manually reconstructed neurons, and (3) neurons reconstructions produced using several independent reconstruction methods. Our approach was able to accurately and efficiently retrieve morphologically and functionally similar neuron structures from large morphology database, identify the local common structures, and find clusters of neurons that share similarities in both morphology and molecular profiles.

  10. Oscillating from Neurosecretion to Multitasking Dopamine Neurons

    Directory of Open Access Journals (Sweden)

    David R. Grattan

    2016-04-01

    Full Text Available In this issue of Cell Reports, Stagkourakis et al. (2016 report that oscillating hypothalamic TIDA neurons, previously thought to be simple neurosecretory neurons controlling pituitary prolactin secretion, control dopamine output via autoregulatory mechanisms and thus could potentially regulate other physiologically important hypothalamic neuronal circuits.

  11. Dual-energy precursor and nuclear erythroid-related factor 2 activator treatment additively improve redox glutathione levels and neuron survival in aging and Alzheimer mouse neurons upstream of reactive oxygen species.

    Science.gov (United States)

    Ghosh, Debolina; LeVault, Kelsey R; Brewer, Gregory J

    2014-01-01

    To determine whether glutathione (GSH) loss or increased reactive oxygen species (ROS) are more important to neuron loss, aging, and Alzheimer's disease (AD), we stressed or boosted GSH levels in neurons isolated from aging 3xTg-AD neurons compared with those from age-matched nontransgenic (non-Tg) neurons. Here, using titrating with buthionine sulfoximine, an inhibitor of γ-glutamyl cysteine synthetase (GCL), we observed that GSH depletion increased neuronal death of 3xTg-AD cultured neurons at increasing rates across the age span, whereas non-Tg neurons were resistant to GSH depletion until old age. Remarkably, the rate of neuron loss with ROS did not increase in old age and was the same for both genotypes, which indicates that cognitive deficits in the AD model were not caused by ROS. Therefore, we targeted for neuroprotection activation of the redox sensitive transcription factor, nuclear erythroid-related factor 2 (Nrf2) by 18 alpha glycyrrhetinic acid to stimulate GSH synthesis through GCL. This balanced stimulation of a number of redox enzymes restored the lower levels of Nrf2 and GCL seen in 3xTg-AD neurons compared with those of non-Tg neurons and promoted translocation of Nrf2 to the nucleus. By combining the Nrf2 activator together with the NADH precursor, nicotinamide, we increased neuron survival against amyloid beta stress in an additive manner. These stress tests and neuroprotective treatments suggest that the redox environment is more important for neuron survival than ROS. The dual neuroprotective treatment with nicotinamide and an Nrf2 inducer indicates that these age-related and AD-related changes are reversible. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Coherence resonance in globally coupled neuronal networks with different neuron numbers

    International Nuclear Information System (INIS)

    Ning Wei-Lian; Zhang Zheng-Zhen; Zeng Shang-You; Luo Xiao-Shu; Hu Jin-Lin; Zeng Shao-Wen; Qiu Yi; Wu Hui-Si

    2012-01-01

    Because a brain consists of tremendous neuronal networks with different neuron numbers ranging from tens to tens of thousands, we study the coherence resonance due to ion channel noises in globally coupled neuronal networks with different neuron numbers. We confirm that for all neuronal networks with different neuron numbers there exist the array enhanced coherence resonance and the optimal synaptic conductance to cause the maximal spiking coherence. Furthermoremore, the enhancement effects of coupling on spiking coherence and on optimal synaptic conductance are almost the same, regardless of the neuron numbers in the neuronal networks. Therefore for all the neuronal networks with different neuron numbers in the brain, relative weak synaptic conductance (0.1 mS/cm 2 ) is sufficient to induce the maximal spiking coherence and the best sub-threshold signal encoding. (interdisciplinary physics and related areas of science and technology)

  13. Gestational Age-Dependent Increase of Survival Motor Neuron Protein in Umbilical Cord-Derived Mesenchymal Stem Cells

    OpenAIRE

    Iwatani, Sota; Harahap, Nur Imma Fatimah; Nurputra, Dian Kesumapramudya; Tairaku, Shinya; Shono, Akemi; Kurokawa, Daisuke; Yamana, Keiji; Thwin, Khin Kyae Mon; Yoshida, Makiko; Mizobuchi, Masami; Koda, Tsubasa; Fujioka, Kazumichi; Taniguchi-Ikeda, Mariko; Yamada, Hideto; Morioka, Ichiro

    2017-01-01

    Background: Spinal muscular atrophy (SMA) is the most common genetic neurological disease leading to infant death. It is caused by loss of survival motor neuron (SMN) 1 gene and subsequent reduction of SMN protein in motor neurons. Because SMN is ubiquitously expressed and functionally linked to general RNA metabolism pathway, fibroblasts (FBs) are most widely used for the assessment of SMN expression in SMA patients but usually isolated from skin biopsy samples after the onset of overt sympt...

  14. The glucagon-like peptide 2 receptor is expressed in enteric neurons and not in the epithelium of the intestine

    DEFF Research Database (Denmark)

    Pedersen, Jens; B. Pedersen, Nis; Brix, Sophie W.

    2015-01-01

    fibrillary acidic protein in these isolated tissue fractions was quantified with qRT-PCR. Expression of the Glp2r was confined to compartments containing enteric neurons and receptor expression was absent in the epithelium. Our findings provide evidence for the expression of the GLP-2R in intestinal...... compartments rich in enteric neurons and, importantly they exclude significant expression in the epithelium of rat jejunal mucosa....

  15. Autoradiographic detection of [125I]-secondary antiserum: a sensitive light and electron microscopic labeling method compatible with peroxidase immunocytochemistry for dual localization of neuronal antigens

    International Nuclear Information System (INIS)

    Pickel, V.M.; Chan, J.; Milner, T.A.

    1986-01-01

    We examined whether autoradiographic localization of [ 125 I]-antirabbit immunoglobulin (IgG) was suitable for light and electron microscopic detection of a rabbit antiserum to the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH), and whether autoradiographic and peroxidase labeling could be combined for simultaneous immunocytochemical identification of TH and neuropeptides in brain. Adult rat brains were fixed by aortic arch perfusion with acrolein and paraformaldehyde. Vibratome sections of the fixed tissues were incubated with various dilutions of TH antiserum followed by [ 125 I]-secondary IgG. These sections were then directly processed for autoradiography or were incubated with rabbit antiserum to substance P (SP) or methionine [Met5]-enkephalin (ME). These latter sections were then processed by the peroxidase-antiperoxidase (PAP) or conjugated peroxidase methods followed by autoradiography. Exposure periods of 12-20 days for light microscopy or 90 days for electron microscopy yielded substantial accumulations of silver grains even at the highest (1:30,000) dilution of TH antiserum. At this dilution, immunoreactivity for TH was virtually nondetectable by PAP and conjugated peroxidase methods. The differential sensitivities of the autoradiographic versus peroxidase methods provided a means for separable identification of rabbit antiserum to TH and to SP or ME. Ultrastructural analysis of the catecholaminergic neurons in the medial nuclei of the solitary tract (NTS) showed selective cytoplasmic localization of silver grains for [ 125 I]-labeling of TH in perikarya, dendrites, and terminals. Within single thin sections prepared for dual labeling, the peroxidase marker for SP and for ME was differentially localized with respect to autoradiographic labeling of TH

  16. Responses of single neurons and neuronal ensembles in frog first- and second-order olfactory neurons

    Czech Academy of Sciences Publication Activity Database

    Rospars, J. P.; Šanda, Pavel; Lánský, Petr; Duchamp-Viret, P.

    2013-01-01

    Roč. 1536, NOV 6 (2013), s. 144-158 ISSN 0006-8993 R&D Projects: GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GAP103/11/0282 Institutional support: RVO:67985823 Keywords : olfaction * spiking activity * neuronal model Subject RIV: JD - Computer Applications, Robotics Impact factor: 2.828, year: 2013

  17. Identification of Genes Enriched in GnRH Neurons by Translating Ribosome Affinity Purification and RNAseq in Mice.

    Science.gov (United States)

    Burger, Laura L; Vanacker, Charlotte; Phumsatitpong, Chayarndorn; Wagenmaker, Elizabeth R; Wang, Luhong; Olson, David P; Moenter, Suzanne M

    2018-04-01

    Gonadotropin-releasing hormone (GnRH) neurons are a nexus of fertility regulation. We used translating ribosome affinity purification coupled with RNA sequencing to examine messenger RNAs of GnRH neurons in adult intact and gonadectomized (GDX) male and female mice. GnRH neuron ribosomes were tagged with green fluorescent protein (GFP) and GFP-labeled polysomes isolated by immunoprecipitation, producing one RNA fraction enhanced for GnRH neuron transcripts and one RNA fraction depleted. Complementary DNA libraries were created from each fraction and 50-base, paired-end sequencing done and differential expression (enhanced fraction/depleted fraction) determined with a threshold of >1.5- or <0.66-fold (false discovery rate P ≤ 0.05). A core of ∼840 genes was differentially expressed in GnRH neurons in all treatments, including enrichment for Gnrh1 (∼40-fold), and genes critical for GnRH neuron and/or gonadotrope development. In contrast, non-neuronal transcripts were not enriched or were de-enriched. Several epithelial markers were also enriched, consistent with the olfactory epithelial origins of GnRH neurons. Interestingly, many synaptic transmission pathways were de-enriched, in accordance with relatively low innervation of GnRH neurons. The most striking difference between intact and GDX mice of both sexes was a marked downregulation of genes associated with oxidative phosphorylation and upregulation of glucose transporters in GnRH neurons from GDX mice. This may suggest that GnRH neurons switch to an alternate fuel to increase adenosine triphosphate production in the absence of negative feedback when GnRH release is elevated. Knowledge of the GnRH neuron translatome and its regulation can guide functional studies and can be extended to disease states, such as polycystic ovary syndrome.

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

    Directory of Open Access Journals (Sweden)

    Michael Schemann

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

  19. How to make spinal motor neurons.

    Science.gov (United States)

    Davis-Dusenbery, Brandi N; Williams, Luis A; Klim, Joseph R; Eggan, Kevin

    2014-02-01

    All muscle movements, including breathing, walking, and fine motor skills rely on the function of the spinal motor neuron to transmit signals from the brain to individual muscle groups. Loss of spinal motor neuron function underlies several neurological disorders for which treatment has been hampered by the inability to obtain sufficient quantities of primary motor neurons to perform mechanistic studies or drug screens. Progress towards overcoming this challenge has been achieved through the synthesis of developmental biology paradigms and advances in stem cell and reprogramming technology, which allow the production of motor neurons in vitro. In this Primer, we discuss how the logic of spinal motor neuron development has been applied to allow generation of motor neurons either from pluripotent stem cells by directed differentiation and transcriptional programming, or from somatic cells by direct lineage conversion. Finally, we discuss methods to evaluate the molecular and functional properties of motor neurons generated through each of these techniques.

  20. Firing dynamics of an autaptic neuron

    International Nuclear Information System (INIS)

    Wang Heng-Tong; Chen Yong

    2015-01-01

    Autapses are synapses that connect a neuron to itself in the nervous system. Previously, both experimental and theoretical studies have demonstrated that autaptic connections in the nervous system have a significant physiological function. Autapses in nature provide self-delayed feedback, thus introducing an additional timescale to neuronal activities and causing many dynamic behaviors in neurons. Recently, theoretical studies have revealed that an autapse provides a control option for adjusting the response of a neuron: e.g., an autaptic connection can cause the electrical activities of the Hindmarsh–Rose neuron to switch between quiescent, periodic, and chaotic firing patterns; an autapse can enhance or suppress the mode-locking status of a neuron injected with sinusoidal current; and the firing frequency and interspike interval distributions of the response spike train can also be modified by the autapse. In this paper, we review recent studies that showed how an autapse affects the response of a single neuron. (topical review)

  1. Neurons from the adult human dentate nucleus: neural networks in the neuron classification.

    Science.gov (United States)

    Grbatinić, Ivan; Marić, Dušica L; Milošević, Nebojša T

    2015-04-07

    Topological (central vs. border neuron type) and morphological classification of adult human dentate nucleus neurons according to their quantified histomorphological properties using neural networks on real and virtual neuron samples. In the real sample 53.1% and 14.1% of central and border neurons, respectively, are classified correctly with total of 32.8% of misclassified neurons. The most important result present 62.2% of misclassified neurons in border neurons group which is even greater than number of correctly classified neurons (37.8%) in that group, showing obvious failure of network to classify neurons correctly based on computational parameters used in our study. On the virtual sample 97.3% of misclassified neurons in border neurons group which is much greater than number of correctly classified neurons (2.7%) in that group, again confirms obvious failure of network to classify neurons correctly. Statistical analysis shows that there is no statistically significant difference in between central and border neurons for each measured parameter (p>0.05). Total of 96.74% neurons are morphologically classified correctly by neural networks and each one belongs to one of the four histomorphological types: (a) neurons with small soma and short dendrites, (b) neurons with small soma and long dendrites, (c) neuron with large soma and short dendrites, (d) neurons with large soma and long dendrites. Statistical analysis supports these results (pneurons can be classified in four neuron types according to their quantitative histomorphological properties. These neuron types consist of two neuron sets, small and large ones with respect to their perykarions with subtypes differing in dendrite length i.e. neurons with short vs. long dendrites. Besides confirmation of neuron classification on small and large ones, already shown in literature, we found two new subtypes i.e. neurons with small soma and long dendrites and with large soma and short dendrites. These neurons are

  2. 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.

  3. Oscillatory integration windows in neurons

    Science.gov (United States)

    Gupta, Nitin; Singh, Swikriti Saran; Stopfer, Mark

    2016-01-01

    Oscillatory synchrony among neurons occurs in many species and brain areas, and has been proposed to help neural circuits process information. One hypothesis states that oscillatory input creates cyclic integration windows: specific times in each oscillatory cycle when postsynaptic neurons become especially responsive to inputs. With paired local field potential (LFP) and intracellular recordings and controlled stimulus manipulations we directly test this idea in the locust olfactory system. We find that inputs arriving in Kenyon cells (KCs) sum most effectively in a preferred window of the oscillation cycle. With a computational model, we show that the non-uniform structure of noise in the membrane potential helps mediate this process. Further experiments performed in vivo demonstrate that integration windows can form in the absence of inhibition and at a broad range of oscillation frequencies. Our results reveal how a fundamental coincidence-detection mechanism in a neural circuit functions to decode temporally organized spiking. PMID:27976720

  4. Unbalanced neuronal circuits in addiction.

    Science.gov (United States)

    Volkow, Nora D; Wang, Gen-Jack; Tomasi, Dardo; Baler, Ruben D

    2013-08-01

    Through sequential waves of drug-induced neurochemical stimulation, addiction co-opts the brain's neuronal circuits that mediate reward, motivation to behavioral inflexibility and a severe disruption of self-control and compulsive drug intake. Brain imaging technologies have allowed neuroscientists to map out the neural landscape of addiction in the human brain and to understand how drugs modify it. Published by Elsevier Ltd.

  5. Neurochemical phenotypes of cardiorespiratory neurons.

    Science.gov (United States)

    Pilowsky, Paul M

    2008-12-10

    Interactions between the cardiovascular and respiratory systems have been known for many years but the functional significance of the interactions is still widely debated. Here I discuss the possible role of metabotropic receptors in regulating cardiorespiratory neurons in the brainstem and spinal cord. It is clear that, although much has been discovered, cardiorespiratory regulation is certainly one area that still has a long way to go before its secrets are fully divulged and their function in controlling circulatory and respiratory function is revealed.

  6. Mirror Neurons from Associative Learning

    OpenAIRE

    Catmur, Caroline; Press, Clare; Heyes, Cecilia

    2016-01-01

    Mirror neurons fire both when executing actions and observing others perform similar actions. Their sensorimotor matching properties have generally been considered a genetic adaptation for social cognition; however, in the present chapter we argue that the evidence in favor of this account is not compelling. Instead we present evidence supporting an alternative account: that mirror neurons’ matching properties arise from associative learning during individual development. Notably, this proces...

  7. Trafficking of neuronal calcium channels

    Czech Academy of Sciences Publication Activity Database

    Weiss, Norbert; Zamponi, G. W.

    2017-01-01

    Roč. 1, č. 1 (2017), č. článku NS20160003. ISSN 2059-6553 R&D Projects: GA ČR GA15-13556S; GA MŠk 7AMB15FR015 Institutional support: RVO:61388963 Keywords : calcium channel * neuron * trafficing Subject RIV: ED - Physiology OBOR OECD: Physiology (including cytology) http://www.neuronalsignaling.org/content/1/1/NS20160003

  8. Selective serotonergic excitation of callosal projection neurons

    Directory of Open Access Journals (Sweden)

    Daniel eAvesar

    2012-03-01

    Full Text Available Serotonin (5-HT acting as a neurotransmitter in the cerebral cortex is critical for cognitive function, yet how 5-HT regulates information processing in cortical circuits is not well understood. We tested the serotonergic responsiveness of layer 5 pyramidal neurons (L5PNs of the mouse medial prefrontal cortex (mPFC, and found 3 distinct response types: long-lasting 5-HT1A (1A receptor-dependent inhibitory responses (84% of L5PNs, 5-HT2A (2A receptor-dependent excitatory responses (9%, and biphasic responses in which 2A-dependent excitation followed brief inhibition (5%. Relative to 5-HT-inhibited neurons, those excited by 5-HT had physiological properties characteristic of callosal/commissural (COM neurons that project to the contralateral cortex. We tested whether serotonergic responses in cortical pyramidal neurons are correlated with their axonal projection pattern using retrograde fluorescent labeling of COM and corticopontine-projecting (CPn neurons. 5-HT generated excitatory or biphasic responses in all 5-HT-responsive layer 5 COM neurons. Conversely, CPn neurons were universally inhibited by 5-HT. Serotonergic excitation of COM neurons was blocked by the 2A antagonist MDL 11939, while serotonergic inhibition of CPn neurons was blocked by the 1A antagonist WAY 100635, confirming a role for these two receptor subtypes in regulating pyramidal neuron activity. Selective serotonergic excitation of COM neurons was not layer-specific, as COM neurons in layer 2/3 were also selectively excited by 5-HT relative to their non-labeled pyramidal neuron neighbors. Because neocortical 2A receptors are implicated in the etiology and pathophysiology of schizophrenia, we propose that COM neurons may represent a novel cellular target for intervention in psychiatric disease.

  9. Dynamics of Time Delay-Induced Multiple Synchronous Behaviors in Inhibitory Coupled Neurons

    Science.gov (United States)

    Gu, Huaguang; Zhao, Zhiguo

    2015-01-01

    The inhibitory synapse can induce synchronous behaviors different from the anti-phase synchronous behaviors, which have been reported in recent studies. In the present paper, synchronous behaviors are investigated in the motif model composed of reciprocal inhibitory coupled neurons with endogenous bursting and time delay. When coupling strength is weak, synchronous behavior appears at a single interval of time delay within a bursting period. When coupling strength is strong, multiple synchronous behaviors appear at different intervals of time delay within a bursting period. The different bursting patterns of synchronous behaviors, and time delays and coupling strengths that can induce the synchronous bursting patterns can be well interpreted by the dynamics of the endogenous bursting pattern of isolated neuron, which is acquired by the fast-slow dissection method, combined with the inhibitory coupling current. For an isolated neuron, when a negative impulsive current with suitable strength is applied at different phases of the bursting, multiple different bursting patterns can be induced. For a neuron in the motif, the inhibitory coupling current, of which the application time and strength is modulated by time delay and coupling strength, can cause single or multiple synchronous firing patterns like the negative impulsive current when time delay and coupling strength is suitable. The difference compared to the previously reported multiple synchronous behaviors that appear at time delays wider than a period of the endogenous firing is discussed. The results present novel examples of synchronous behaviors in the neuronal network with inhibitory synapses and provide a reasonable explanation. PMID:26394224

  10. Complexity in neuronal noise depends on network interconnectivity.

    Science.gov (United States)

    Serletis, Demitre; Zalay, Osbert C; Valiante, Taufik A; Bardakjian, Berj L; Carlen, Peter L

    2011-06-01

    "Noise," or noise-like activity (NLA), defines background electrical membrane potential fluctuations at the cellular level of the nervous system, comprising an important aspect of brain dynamics. Using whole-cell voltage recordings from fast-spiking stratum oriens interneurons and stratum pyramidale neurons located in the CA3 region of the intact mouse hippocampus, we applied complexity measures from dynamical systems theory (i.e., 1/f(γ) noise and correlation dimension) and found evidence for complexity in neuronal NLA, ranging from high- to low-complexity dynamics. Importantly, these high- and low-complexity signal features were largely dependent on gap junction and chemical synaptic transmission. Progressive neuronal isolation from the surrounding local network via gap junction blockade (abolishing gap junction-dependent spikelets) and then chemical synaptic blockade (abolishing excitatory and inhibitory post-synaptic potentials), or the reverse order of these treatments, resulted in emergence of high-complexity NLA dynamics. Restoring local network interconnectivity via blockade washout resulted in resolution to low-complexity behavior. These results suggest that the observed increase in background NLA complexity is the result of reduced network interconnectivity, thereby highlighting the potential importance of the NLA signal to the study of network state transitions arising in normal and abnormal brain dynamics (such as in epilepsy, for example).

  11. Toxic effects of lead on neuronal development and function

    International Nuclear Information System (INIS)

    Freedman, R.; Olson, L.; Hoffer, B.J.

    1990-01-01

    The effects of lead on the development of the nervous system are of immediate concern to human health. While it is clear that lead can affect neuronal development at levels of exposure within the range found in the environment, the particular mechanism of the disruption is not readily ascertained. The goal of the authors research is to develop a model system in which the effects of lead on central nervous system development can be demonstrated. To study neuronal development in a system that minimizes such difficulties, the authors have grafted discrete brain regions derived from rat fetuses into the anterior chamber of the eye of adult hosts. The brain pieces continue organotypic development in the eye, but are isolated from possible secondary changes due to alterations in the development of the endocrine and other somatic systems because the adult host has these systems already fully developed. Using this system, they have discovered that lead induces a hypernoradrenergic innervation of central nervous system tissue. The increased innervation is observed not only structurally, but also functionally. Since norepinephrine is an inhibitory neurotransmitter, this ingrowth may explain the profound slowing of discharge of cerebellar neurons recorded in grafts of lead-treated animals. Studies in other tissues suggest that increased axonal ingrowth may be a general problem of lead intoxication that encompasses many brain areas, as well as peripheral sympathetic systems

  12. Results on a Binding Neuron Model and Their Implications for Modified Hourglass Model for Neuronal Network

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    Viswanathan Arunachalam

    2013-01-01

    Full Text Available The classical models of single neuron like Hodgkin-Huxley point neuron or leaky integrate and fire neuron assume the influence of postsynaptic potentials to last till the neuron fires. Vidybida (2008 in a refreshing departure has proposed models for binding neurons in which the trace of an input is remembered only for a finite fixed period of time after which it is forgotten. The binding neurons conform to the behaviour of real neurons and are applicable in constructing fast recurrent networks for computer modeling. This paper develops explicitly several useful results for a binding neuron like the firing time distribution and other statistical characteristics. We also discuss the applicability of the developed results in constructing a modified hourglass network model in which there are interconnected neurons with excitatory as well as inhibitory inputs. Limited simulation results of the hourglass network are presented.

  13. Single-cell axotomy of cultured hippocampal neurons integrated in neuronal circuits.

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    Gomis-Rüth, Susana; Stiess, Michael; Wierenga, Corette J; Meyn, Liane; Bradke, Frank

    2014-05-01

    An understanding of the molecular mechanisms of axon regeneration after injury is key for the development of potential therapies. Single-cell axotomy of dissociated neurons enables the study of the intrinsic regenerative capacities of injured axons. This protocol describes how to perform single-cell axotomy on dissociated hippocampal neurons containing synapses. Furthermore, to axotomize hippocampal neurons integrated in neuronal circuits, we describe how to set up coculture with a few fluorescently labeled neurons. This approach allows axotomy of single cells in a complex neuronal network and the observation of morphological and molecular changes during axon regeneration. Thus, single-cell axotomy of mature neurons is a valuable tool for gaining insights into cell intrinsic axon regeneration and the plasticity of neuronal polarity of mature neurons. Dissociation of the hippocampus and plating of hippocampal neurons takes ∼2 h. Neurons are then left to grow for 2 weeks, during which time they integrate into neuronal circuits. Subsequent axotomy takes 10 min per neuron and further imaging takes 10 min per neuron.

  14. Glutamate neurons are intermixed with midbrain dopamine neurons in nonhuman primates and humans

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    Root, David H.; Wang, Hui-Ling; Liu, Bing; Barker, David J.; Mód, László; Szocsics, Péter; Silva, Afonso C.; Maglóczky, Zsófia; Morales, Marisela

    2016-01-01

    The rodent ventral tegmental area (VTA) and substantia nigra pars compacta (SNC) contain dopamine neurons intermixed with glutamate neurons (expressing vesicular glutamate transporter 2; VGluT2), which play roles in reward and aversion. However, identifying the neuronal compositions of the VTA and SNC in higher mammals has remained challenging. Here, we revealed VGluT2 neurons within the VTA and SNC of nonhuman primates and humans by simultaneous detection of VGluT2 mRNA and tyrosine hydroxylase (TH; for identification of dopamine neurons). We found that several VTA subdivisions share similar cellular compositions in nonhuman primates and humans; their rostral linear nuclei have a high prevalence of VGluT2 neurons lacking TH; their paranigral and parabrachial pigmented nuclei have mostly TH neurons, and their parabrachial pigmented nuclei have dual VGluT2-TH neurons. Within nonhuman primates and humans SNC, the vast majority of neurons are TH neurons but VGluT2 neurons were detected in the pars lateralis subdivision. The demonstration that midbrain dopamine neurons are intermixed with glutamate or glutamate-dopamine neurons from rodents to humans offers new opportunities for translational studies towards analyzing the roles that each of these neurons play in human behavior and in midbrain-associated illnesses such as addiction, depression, schizophrenia, and Parkinson’s disease. PMID:27477243

  15. Evaluating the Autonomy of the Drosophila Circadian Clock in Dissociated Neuronal Culture.

    Science.gov (United States)

    Sabado, Virginie; Vienne, Ludovic; Nagoshi, Emi

    2017-01-01

    Circadian behavioral rhythms offer an excellent model to study intricate interactions between the molecular and neuronal mechanisms of behavior. In mammals, pacemaker neurons in the suprachiasmatic nucleus (SCN) generate rhythms cell-autonomously, which are synchronized by the network interactions within the circadian circuit to drive behavioral rhythms. However, whether this principle is universal to circadian systems in animals remains unanswered. Here, we examined the autonomy of the Drosophila circadian clock by monitoring transcriptional and post-transcriptional rhythms of individual clock neurons in dispersed culture with time-lapse microscopy. Expression patterns of the transcriptional reporter show that CLOCK/CYCLE (CLK/CYC)-mediated transcription is constantly active in dissociated clock neurons. In contrast, the expression profile of the post-transcriptional reporter indicates that PERIOD (PER) protein levels fluctuate and ~10% of cells display rhythms in PER levels with periods in the circadian range. Nevertheless, PER and TIM are enriched in the cytoplasm and no periodic PER nuclear accumulation was observed. These results suggest that repression of CLK/CYC-mediated transcription by nuclear PER is impaired, and thus the negative feedback loop of the molecular clock is incomplete in isolated clock neurons. We further demonstrate that, by pharmacological assays using the non-amidated form of neuropeptide pigment-dispersing factor (PDF), which could be specifically secreted from larval LNvs and adult s-LNvs, downstream events of the PDF signaling are partly impaired in dissociated larval clock neurons. Although non-amidated PDF is likely to be less active than the amidated one, these results point out the possibility that alteration in PDF downstream signaling may play a role in dampening of molecular rhythms in isolated clock neurons. Taken together, our results suggest that Drosophila clocks are weak oscillators that need to be in the intact circadian

  16. Evaluating the Autonomy of the Drosophila Circadian Clock in Dissociated Neuronal Culture

    Directory of Open Access Journals (Sweden)

    Virginie Sabado

    2017-10-01

    Full Text Available Circadian behavioral rhythms offer an excellent model to study intricate interactions between the molecular and neuronal mechanisms of behavior. In mammals, pacemaker neurons in the suprachiasmatic nucleus (SCN generate rhythms cell-autonomously, which are synchronized by the network interactions within the circadian circuit to drive behavioral rhythms. However, whether this principle is universal to circadian systems in animals remains unanswered. Here, we examined the autonomy of the Drosophila circadian clock by monitoring transcriptional and post-transcriptional rhythms of individual clock neurons in dispersed culture with time-lapse microscopy. Expression patterns of the transcriptional reporter show that CLOCK/CYCLE (CLK/CYC-mediated transcription is constantly active in dissociated clock neurons. In contrast, the expression profile of the post-transcriptional reporter indicates that PERIOD (PER protein levels fluctuate and ~10% of cells display rhythms in PER levels with periods in the circadian range. Nevertheless, PER and TIM are enriched in the cytoplasm and no periodic PER nuclear accumulation was observed. These results suggest that repression of CLK/CYC-mediated transcription by nuclear PER is impaired, and thus the negative feedback loop of the molecular clock is incomplete in isolated clock neurons. We further demonstrate that, by pharmacological assays using the non-amidated form of neuropeptide pigment-dispersing factor (PDF, which could be specifically secreted from larval LNvs and adult s-LNvs, downstream events of the PDF signaling are partly impaired in dissociated larval clock neurons. Although non-amidated PDF is likely to be less active than the amidated one, these results point out the possibility that alteration in PDF downstream signaling may play a role in dampening of molecular rhythms in isolated clock neurons. Taken together, our results suggest that Drosophila clocks are weak oscillators that need to be in the

  17. Neuronal Differentiation Modulated by Polymeric Membrane Properties.

    Science.gov (United States)

    Morelli, Sabrina; Piscioneri, Antonella; Drioli, Enrico; De Bartolo, Loredana

    2017-01-01

    In this study, different collagen-blend membranes were successfully constructed by blending collagen with chitosan (CHT) or poly(lactic-co-glycolic acid) (PLGA) to enhance their properties and thus create new biofunctional materials with great potential use for neuronal tissue engineering and regeneration. Collagen blending strongly affected membrane properties in the following ways: (i) it improved the surface hydrophilicity of both pure CHT and PLGA membranes, (ii) it reduced the stiffness of CHT membranes, but (iii) it did not modify the good mechanical properties of PLGA membranes. Then, we investigated the effect of the different collagen concentrations on the neuronal behavior of the membranes developed. Morphological observations, immunocytochemistry, and morphometric measures demonstrated that the membranes developed, especially CHT/Col30, PLGA, and PLGA/Col1, provided suitable microenvironments for neuronal growth owing to their enhanced properties. The most consistent neuronal differentiation was obtained in neurons cultured on PLGA-based membranes, where a well-developed neuronal network was achieved due to their improved mechanical properties. Our findings suggest that tensile strength and elongation at break are key material parameters that have potential influence on both axonal elongation and neuronal structure and organization, which are of fundamental importance for the maintenance of efficient neuronal growth. Hence, our study has provided new insights regarding the effects of membrane mechanical properties on neuronal behavior, and thus it may help to design and improve novel instructive biomaterials for neuronal tissue engineering. © 2017 S. Karger AG, Basel.

  18. Response of Electrical Activity in an Improved Neuron Model under Electromagnetic Radiation and Noise.

    Science.gov (United States)

    Zhan, Feibiao; Liu, Shenquan

    2017-01-01

    Electrical activities are ubiquitous neuronal bioelectric phenomena, which have many different modes to encode the expression of biological information, and constitute the whole process of signal propagation between neurons. Therefore, we focus on the electrical activities of neurons, which is also causing widespread concern among neuroscientists. In this paper, we mainly investigate the electrical activities of the Morris-Lecar (M-L) model with electromagnetic radiation or Gaussian white noise, which can restore the authenticity of neurons in realistic neural network. First, we explore dynamical response of the whole system with electromagnetic induction (EMI) and Gaussian white noise. We find that there are slight differences in the discharge behaviors via comparing the response of original system with that of improved system, and electromagnetic induction can transform bursting or spiking state to quiescent state and vice versa. Furthermore, we research bursting transition mode and the corresponding periodic solution mechanism for the isolated neuron model with electromagnetic induction by using one-parameter and bi-parameters bifurcation analysis. Finally, we analyze the effects of Gaussian white noise on the original system and coupled system, which is conducive to understand the actual discharge properties of realistic neurons.

  19. Differentiation of Dental Pulp Stem Cells into Neuron-Like Cells in Serum-Free Medium

    Directory of Open Access Journals (Sweden)

    Shahrul Hisham Zainal Ariffin

    2013-01-01

    Full Text Available Dental pulp tissue contains dental pulp stem cells (DPSCs. Dental pulp cells (also known as dental pulp-derived mesenchymal stem cells are capable of differentiating into multilineage cells including neuron-like cells. The aim of this study was to examine the capability of DPSCs to differentiate into neuron-like cells without using any reagents or growth factors. DPSCs were isolated from teeth extracted from 6- to 8-week-old mice and maintained in complete medium. The cells from the fourth passage were induced to differentiate by culturing in medium without serum or growth factors. RT-PCR molecular analysis showed characteristics of Cd146+, Cd166+, and Cd31− in DPSCs, indicating that these cells are mesenchymal stem cells rather than hematopoietic stem cells. After 5 days of neuronal differentiation, the cells showed neuron-like morphological changes and expressed MAP2 protein. The activation of Nestin was observed at low level prior to differentiation and increased after 5 days of culture in differentiation medium, whereas Tub3 was activated only after 5 days of neuronal differentiation. The proliferation of the differentiated cells decreased in comparison to that of the control cells. Dental pulp stem cells are induced to differentiate into neuron-like cells when cultured in serum- and growth factor-free medium.

  20. Mesencephalic dopaminergic neurons express a repertoire of olfactory receptors and respond to odorant-like molecules.

    Science.gov (United States)

    Grison, Alice; Zucchelli, Silvia; Urzì, Alice; Zamparo, Ilaria; Lazarevic, Dejan; Pascarella, Giovanni; Roncaglia, Paola; Giorgetti, Alejandro; Garcia-Esparcia, Paula; Vlachouli, Christina; Simone, Roberto; Persichetti, Francesca; Forrest, Alistair R R; Hayashizaki, Yoshihide; Carloni, Paolo; Ferrer, Isidro; Lodovichi, Claudia; Plessy, Charles; Carninci, Piero; Gustincich, Stefano

    2014-08-27

    The mesencephalic dopaminergic (mDA) cell system is composed of two major groups of projecting cells in the Substantia Nigra (SN) (A9 neurons) and the Ventral Tegmental Area (VTA) (A10 cells). Selective degeneration of A9 neurons occurs in Parkinson's disease (PD) while abnormal function of A10 cells has been linked to schizophrenia, attention deficit and addiction. The molecular basis that underlies selective vulnerability of A9 and A10 neurons is presently unknown. By taking advantage of transgenic labeling, laser capture microdissection coupled to nano Cap-Analysis of Gene Expression (nanoCAGE) technology on isolated A9 and A10 cells, we found that a subset of Olfactory Receptors (OR)s is expressed in mDA neurons. Gene expression analysis was integrated with the FANTOM5 Helicos CAGE sequencing datasets, showing the presence of these ORs in selected tissues and brain areas outside of the olfactory epithelium. OR expression in the mesencephalon was validated by RT-PCR and in situ hybridization. By screening 16 potential ligands on 5 mDA ORs recombinantly expressed in an heterologous in vitro system, we identified carvone enantiomers as agonists at Olfr287 and able to evoke an intracellular Ca2+ increase in solitary mDA neurons. ORs were found expressed in human SN and down-regulated in PD post mortem brains. Our study indicates that mDA neurons express ORs and respond to odor-like molecules providing new opportunities for pharmacological intervention in disease.

  1. Response of Electrical Activity in an Improved Neuron Model under Electromagnetic Radiation and Noise

    Directory of Open Access Journals (Sweden)

    Feibiao Zhan

    2017-11-01

    Full Text Available Electrical activities are ubiquitous neuronal bioelectric phenomena, which have many different modes to encode the expression of biological information, and constitute the whole process of signal propagation between neurons. Therefore, we focus on the electrical activities of neurons, which is also causing widespread concern among neuroscientists. In this paper, we mainly investigate the electrical activities of the Morris-Lecar (M-L model with electromagnetic radiation or Gaussian white noise, which can restore the authenticity of neurons in realistic neural network. First, we explore dynamical response of the whole system with electromagnetic induction (EMI and Gaussian white noise. We find that there are slight differences in the discharge behaviors via comparing the response of original system with that of improved system, and electromagnetic induction can transform bursting or spiking state to quiescent state and vice versa. Furthermore, we research bursting transition mode and the corresponding periodic solution mechanism for the isolated neuron model with electromagnetic induction by using one-parameter and bi-parameters bifurcation analysis. Finally, we analyze the effects of Gaussian white noise on the original system and coupled system, which is conducive to understand the actual discharge properties of realistic neurons.

  2. Influenza Virus Induces Inflammatory Response in Mouse Primary Cortical Neurons with Limited Viral Replication

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    Gefei Wang

    2016-01-01

    Full Text Available Unlike stereotypical neurotropic viruses, influenza A viruses have been detected in the brain tissues of human and animal models. To investigate the interaction between neurons and influenza A viruses, mouse cortical neurons were isolated, infected with human H1N1 influenza virus, and then examined for the production of various inflammatory molecules involved in immune response. We found that replication of the influenza virus in neurons was limited, although early viral transcription was not affected. Virus-induced neuron viability decreased at 6 h postinfection (p.i. but increased at 24 h p.i. depending upon the viral strain. Virus-induced apoptosis and cytopathy in primary cortical neurons were not apparent at 24 h p.i. The mRNA levels of inflammatory cytokines, chemokines, and type I interferons were upregulated at 6 h and 24 h p.i. These results indicate that the influenza virus induces inflammatory response in mouse primary cortical neurons with limited viral replication. The cytokines released in viral infection-induced neuroinflammation might play critical roles in influenza encephalopathy, rather than in viral replication-induced cytopathy.

  3. Gamma Radiation (5-10 Gy) Impairs Neuronal Function in the Guinea Pig Hippocampus

    Science.gov (United States)

    1993-01-01

    Radiation (5-10 Gy) Impairs Neuronal Function in the Guinea Pig Hippocampus TERRY C. PELLMAR AND DENNIS L. LEPINSKI Ph.vsiology Department..Irmned Forces...L. Gamma Radiation ioral effects. Within hours of irradiation with 10 Gy and (5- 10 Gy) Impairs Neuronal Function in the Guinea Pig Hippo- less...acti v- Guinea pigs were exposed to 5 and 10 Gy ’y radiation. Hippo- ity (9) are evident. campal brain slices were isolated 30 min, I day, 3 days and 5

  4. 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

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  6. Astrocytes expressing ALS‐linked mutant FUS induce motor neuron death through release of tumor necrosis factor‐alpha

    Science.gov (United States)

    Kia, Azadeh; McAvoy, Kevin; Krishnamurthy, Karthik; Trotti, Davide

    2018-01-01

    Mutations in fused in sarcoma (FUS) are linked to amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease affecting both upper and lower motor neurons. While it is established that astrocytes contribute to the death of motor neurons in ALS, the specific contribution of mutant FUS (mutFUS) through astrocytes has not yet been studied. Here, we used primary astrocytes expressing a N‐terminally GFP tagged R521G mutant or wild‐type FUS (WTFUS) and show that mutFUS‐expressing astrocytes undergo astrogliosis, damage co‐cultured motor neurons via activation of an inflammatory response and produce conditioned medium (ACM) that is toxic to motor neurons in isolation. Time lapse imaging shows that motor neuron cultures exposed to mutFUS ACM, but not WTFUS ACM, undergo significant cell loss, which is preceded by progressive degeneration of neurites. We found that Tumor Necrosis Factor‐Alpha (TNFα) is secreted into ACM of mutFUS‐expressing astrocytes. Accordingly, mutFUS astrocyte‐mediated motor neuron toxicity is blocked by targeting soluble TNFα with neutralizing antibodies. We also found that mutant astrocytes trigger changes to motor neuron AMPA receptors (AMPAR) that render them susceptible to excitotoxicity and AMPAR‐mediated cell death. Our data provide the first evidence of astrocytic involvement in FUS‐ALS, identify TNFα as a mediator of this toxicity, and provide several potential therapeutic targets to protect motor neurons in FUS‐linked ALS. PMID:29380416

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-03-10

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

  8. Decoupled choice-driven and stimulus-related activity in parietal neurons may be misrepresented by choice probabilities.

    Science.gov (United States)

    Zaidel, Adam; DeAngelis, Gregory C; Angelaki, Dora E

    2017-09-28

    Trial-by-trial correlations between neural responses and choices (choice probabilities) are often interpreted to reflect a causal contribution of neurons to task performance. However, choice probabilities may arise from top-down, rather than bottom-up, signals. We isolated distinct sensory and decision contributions to single-unit activity recorded from the dorsal medial superior temporal (MSTd) and ventral intraparietal (VIP) areas of monkeys during perception of self-motion. Superficially, neurons in both areas show similar tuning curves during task performance. However, tuning in MSTd neurons primarily reflects sensory inputs, whereas choice-related signals dominate tuning in VIP neurons. Importantly, the choice-related activity of VIP neurons is not predictable from their stimulus tuning, and these factors are often confounded in choice probability measurements. This finding was confirmed in a subset of neurons for which stimulus tuning was measured during passive fixation. Our findings reveal decoupled stimulus and choice signals in the VIP area, and challenge our understanding of choice signals in the brain.Choice-related signals in neuronal activity may reflect bottom-up sensory processes, top-down decision-related influences, or a combination of the two. Here the authors report that choice-related activity in VIP neurons is not predictable from their stimulus tuning, and that dominant choice signals can bias the standard metric of choice preference (choice probability).

  9. Bursting as a source of non-linear determinism in the firing patterns of nigral dopamine neurons.

    Science.gov (United States)

    Jeong, Jaeseung; Shi, Wei-Xing; Hoffman, Ralph; Oh, Jihoon; Gore, John C; Bunney, Benjamin S; Peterson, Bradley S

    2012-11-01

    Nigral dopamine (DA) neurons in vivo exhibit complex firing patterns consisting of tonic single-spikes and phasic bursts that encode information for certain types of reward-related learning and behavior. Non-linear dynamical analysis has previously demonstrated the presence of a non-linear deterministic structure in complex firing patterns of DA neurons, yet the origin of this non-linear determinism remains unknown. In this study, we hypothesized that bursting activity is the primary source of non-linear determinism in the firing patterns of DA neurons. To test this hypothesis, we investigated the dimension complexity of inter-spike interval data recorded in vivo from bursting and non-bursting DA neurons in the chloral hydrate-anesthetized rat substantia nigra. We found that bursting DA neurons exhibited non-linear determinism in their firing patterns, whereas non-bursting DA neurons showed truly stochastic firing patterns. Determinism was also detected in the isolated burst and inter-burst interval data extracted from firing patterns of bursting neurons. Moreover, less bursting DA neurons in halothane-anesthetized rats exhibited higher dimensional spiking dynamics than do more bursting DA neurons in chloral hydrate-anesthetized rats. These results strongly indicate that bursting activity is the main source of low-dimensional, non-linear determinism in the firing patterns of DA neurons. This finding furthermore suggests that bursts are the likely carriers of meaningful information in the firing activities of DA neurons. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  10. Calretinin as a marker for premotor neurons involved in upgaze in human brainstem

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    Christopher eAdamczyk

    2015-12-01

    indicated by co-expression of glutamate decarboxylase in a subpopulation. Calretinin-positive neurons ensheathed by perineuronal nets in the human y-group are considered as the homologue premotor neurons described in monkey, projecting to superior rectus and inferior oblique motoneurons. In conclusion, combined immunostaining for parvalbumin, perineuronal nets and calretinin may well be suited for the specific identification and subsequent analysis of premotor upgaze pathways in clinical cases of isolated up- or downgaze deficits.

  11. Liposomes to target peripheral neurons and Schwann cells.

    Directory of Open Access Journals (Sweden)

    Sooyeon Lee

    Full Text Available While a wealth of literature for tissue-specific liposomes is emerging, optimal formulations to target the cells of the peripheral nervous system (PNS are lacking. In this study, we asked whether a novel formulation of phospholipid-based liposomes could be optimized for preferential uptake by microvascular endothelia, peripheral neurons and Schwann cells. Here, we report a unique formulation consisting of a phospholipid, a polymer surfactant and cholesterol that result in enhanced uptake by targeted cells. Using fluorescently labeled liposomes, we followed particle internalization and trafficking through a distinct route from dextran and escape from degradative compartments, such as lysosomes. In cultures of non-myelinating Schwann cells, liposomes associate with the lipid raft marker Cholera toxin, and their internalization is inhibited by disruption of lipid rafts or actin polymerization. In contrast, pharmacological inhibition of clathrin-mediated endocytosis does not significantly impact liposome entry. To evaluate the efficacy of liposome targeting in tissues, we utilized myelinating explant cultures of dorsal root ganglia and isolated diaphragm preparations, both of which contain peripheral neurons and myelinating Schwann cells. In these models, we detected preferential liposome uptake into neurons and glial cells in comparison to surrounding muscle tissue. Furthermore, in vivo liposome administration by intramuscular or intravenous injection confirmed that the particles were delivered to myelinated peripheral nerves. Within the CNS, we detected the liposomes in choroid epithelium, but not in myelinated white matter regions or in brain parenchyma. The described nanoparticles represent a novel neurophilic delivery vehicle for targeting small therapeutic compounds, biological molecules, or imaging reagents into peripheral neurons and Schwann cells, and provide a major advancement toward developing effective therapies for peripheral

  12. Hindbrain Catecholamine Neurons Activate Orexin Neurons During Systemic Glucoprivation in Male Rats.

    Science.gov (United States)

    Li, Ai-Jun; Wang, Qing; Elsarelli, Megan M; Brown, R Lane; Ritter, Sue

    2015-08-01

    Hindbrain catecholamine neurons are required for elicitation of feeding responses to glucose deficit, but the forebrain circuitry required for these responses is incompletely understood. Here we examined interactions of catecholamine and orexin neurons in eliciting glucoprivic feeding. Orexin neurons, located in the perifornical lateral hypothalamus (PeFLH), are heavily innervated by hindbrain catecholamine neurons, stimulate food intake, and increase arousal and behavioral activation. Orexin neurons may therefore contribute importantly to appetitive responses, such as food seeking, during glucoprivation. Retrograde tracing results showed that nearly all innervation of the PeFLH from the hindbrain originated from catecholamine neurons and some raphe nuclei. Results also suggested that many catecholamine neurons project collaterally to the PeFLH and paraventricular hypothalamic nucleus. Systemic administration of the antiglycolytic agent, 2-deoxy-D-glucose, increased food intake and c-Fos expression in orexin neurons. Both responses were eliminated by a lesion of catecholamine neurons innervating orexin neurons using the retrogradely transported immunotoxin, anti-dopamine-β-hydroxylase saporin, which is specifically internalized by dopamine-β-hydroxylase-expressing catecholamine neurons. Using designer receptors exclusively activated by designer drugs in transgenic rats expressing Cre recombinase under the control of tyrosine hydroxylase promoter, catecholamine neurons in cell groups A1 and C1 of the ventrolateral medulla were activated selectively by peripheral injection of clozapine-N-oxide. Clozapine-N-oxide injection increased food intake and c-Fos expression in PeFLH orexin neurons as well as in paraventricular hypothalamic nucleus neurons. In summary, catecholamine neurons are required for the activation of orexin neurons during glucoprivation. Activation of orexin neurons may contribute to appetitive responses required for glucoprivic feeding.

  13. Atypical PKC, PKCλ/ι, activates β-secretase and increases Aβ1-40/42 and phospho-tau in mouse brain and isolated neuronal cells, and may link hyperinsulinemia and other aPKC activators to development of pathological and memory abnormalities in Alzheimer's disease.

    Science.gov (United States)

    Sajan, Mini P; Hansen, Barbara C; Higgs, Margaret G; Kahn, C Ron; Braun, Ursula; Leitges, Michael; Park, Collin R; Diamond, David M; Farese, Robert V

    2018-01-01

    Hyperinsulinemia activates brain Akt and PKC-λ/ι and increases Aβ 1-40/42 and phospho-tau in insulin-resistant animals. Here, we examined underlying mechanisms in mice, neuronal cells, and mouse hippocampal slices. Like Aβ 1-40/42 , β-secretase activity was increased in insulin-resistant mice and monkeys. In insulin-resistant mice, inhibition of hepatic PKC-λ/ι sufficient to correct hepatic abnormalities and hyperinsulinemia simultaneously reversed increases in Akt, atypical protein kinase C (aPKC), β-secretase, and Aβ 1-40/42 , and restored acute Akt activation. However, 2 aPKC inhibitors additionally blocked insulin's ability to activate brain PKC-λ/ι and thereby increase β-secretase and Aβ 1-40/42 . Furthermore, direct blockade of brain aPKC simultaneously corrected an impairment in novel object recognition in high-fat-fed insulin-resistant mice. In neuronal cells and/or mouse hippocampal slices, PKC-ι/λ activation by insulin, metformin, or expression of constitutive PKC-ι provoked increases in β-secretase, Aβ 1-40/42 , and phospho-thr-231-tau that were blocked by various PKC-λ/ι inhibitors, but not by an Akt inhibitor. PKC-λ/ι provokes increases in brain β-secretase, Aβ 1-40/42 , and phospho-thr-231-tau. Excessive signaling via PKC-λ/ι may link hyperinsulinemia and other PKC-λ/ι activators to pathological and functional abnormalities in Alzheimer's disease. Published by Elsevier Inc.

  14. A chimeric path to neuronal synchronization

    Science.gov (United States)

    Essaki Arumugam, Easwara Moorthy; Spano, Mark L.

    2015-01-01

    Synchronization of neuronal activity is associated with neurological disorders such as epilepsy. This process of neuronal synchronization is not fully understood. To further our understanding, we have experimentally studied the progression of this synchronization from normal neuronal firing to full synchronization. We implemented nine FitzHugh-Nagumo neurons (a simplified Hodgkin-Huxley model) via discrete electronics. For different coupling parameters (synaptic strengths), the neurons in the ring were either unsynchronized or completely synchronized when locally coupled in a ring. When a single long-range connection (nonlocal coupling) was introduced, an intermediate state known as a chimera appeared. The results indicate that (1) epilepsy is likely not only a dynamical disease but also a topological disease, strongly tied to the connectivity of the underlying network of neurons, and (2) the synchronization process in epilepsy may not be an "all or none" phenomenon, but can pass through an intermediate stage (chimera).

  15. A chimeric path to neuronal synchronization

    Energy Technology Data Exchange (ETDEWEB)

    Essaki Arumugam, Easwara Moorthy; Spano, Mark L. [School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona 85287-9709 (United States)

    2015-01-15

    Synchronization of neuronal activity is associated with neurological disorders such as epilepsy. This process of neuronal synchronization is not fully understood. To further our understanding, we have experimentally studied the progression of this synchronization from normal neuronal firing to full synchronization. We implemented nine FitzHugh-Nagumo neurons (a simplified Hodgkin-Huxley model) via discrete electronics. For different coupling parameters (synaptic strengths), the neurons in the ring were either unsynchronized or completely synchronized when locally coupled in a ring. When a single long-range connection (nonlocal coupling) was introduced, an intermediate state known as a chimera appeared. The results indicate that (1) epilepsy is likely not only a dynamical disease but also a topological disease, strongly tied to the connectivity of the underlying network of neurons, and (2) the synchronization process in epilepsy may not be an “all or none” phenomenon, but can pass through an intermediate stage (chimera)

  16. Mini Review: Biomaterials for Enhancing Neuronal Repair

    Science.gov (United States)

    Cangellaris, Olivia V.; Gillette, Martha U.

    2018-04-01

    As they differentiate from neuroblasts, nascent neurons become highly polarized and elongate. Neurons extend and elaborate fine and fragile cellular extensions that form circuits enabling long-distance communication and signal integration within the body. While other organ systems are developing, projections of differentiating neurons find paths to distant targets. Subsequent post-developmental neuronal damage is catastrophic because the cues for reinnervation are no longer active. Advances in biomaterials are enabling fabrication of micro-environments that encourage neuronal regrowth and restoration of function by recreating these developmental cues. This mini-review considers new materials that employ topographical, chemical, electrical, and/or mechanical cues for use in neuronal repair. Manipulating and integrating these elements in different combinations will generate new technologies to enhance neural repair.

  17. 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.

  18. A chimeric path to neuronal synchronization

    International Nuclear Information System (INIS)

    Essaki Arumugam, Easwara Moorthy; Spano, Mark L.

    2015-01-01

    Synchronization of neuronal activity is associated with neurological disorders such as epilepsy. This process of neuronal synchronization is not fully understood. To further our understanding, we have experimentally studied the progression of this synchronization from normal neuronal firing to full synchronization. We implemented nine FitzHugh-Nagumo neurons (a simplified Hodgkin-Huxley model) via discrete electronics. For different coupling parameters (synaptic strengths), the neurons in the ring were either unsynchronized or completely synchronized when locally coupled in a ring. When a single long-range connection (nonlocal coupling) was introduced, an intermediate state known as a chimera appeared. The results indicate that (1) epilepsy is likely not only a dynamical disease but also a topological disease, strongly tied to the connectivity of the underlying network of neurons, and (2) the synchronization process in epilepsy may not be an “all or none” phenomenon, but can pass through an intermediate stage (chimera)

  19. Gene expression profiling of two distinct neuronal populations in the rodent spinal cord.

    Directory of Open Access Journals (Sweden)

    Jesper Ryge

    Full Text Available BACKGROUND: In the field of neuroscience microarray gene expression profiles on anatomically defined brain structures are being used increasingly to study both normal brain functions as well as pathological states. Fluorescent tracing techniques in brain tissue that identifies distinct neuronal populations can in combination with global gene expression profiling potentially increase the resolution and specificity of such studies to shed new light on neuronal functions at the cellular level. METHODOLOGY/PRINCIPAL FINDINGS: We examine the microarray gene expression profiles of two distinct neuronal populations in the spinal cord of the neonatal rat, the principal motor neurons and specific interneurons involved in motor control. The gene expression profiles of the respective cell populations were obtained from amplified mRNA originating from 50-250 fluorescently identified and laser microdissected cells. In the data analysis we combine a new microarray normalization procedure with a conglomerate measure of significant differential gene expression. Using our methodology we find 32 genes to be more expressed in the interneurons compared to the motor neurons that all except one have not previously been associated with this neuronal population. As a validation of our method we find 17 genes to be more expressed in the motor neurons than in the interneurons and of these only one had not previously been described in this population. CONCLUSIONS/SIGNIFICANCE: We provide an optimized experimental protocol that allows isolation of gene transcripts from fluorescent retrogradely labeled cell populations in fresh tissue, which can be used to generate amplified aRNA for microarray hybridization from as few as 50 laser microdissected cells. Using this optimized experimental protocol in combination with our microarray analysis methodology we find 49 differentially expressed genes between the motor neurons and the interneurons that reflect the functional

  20. 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

  1. 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.

  2. Neuronal Networks on Nanocellulose Scaffolds.

    Science.gov (United States)

    Jonsson, Malin; Brackmann, Christian; Puchades, Maja; Brattås, Karoline; Ewing, Andrew; Gatenholm, Paul; Enejder, Annika

    2015-11-01

    Proliferation, integration, and neurite extension of PC12 cells, a widely used culture model for cholinergic neurons, were studied in nanocellulose scaffolds biosynthesized by Gluconacetobacter xylinus to allow a three-dimensional (3D) extension of neurites better mimicking neuronal networks in tissue. The interaction with control scaffolds was compared with cationized nanocellulose (trimethyl ammonium betahydroxy propyl [TMAHP] cellulose) to investigate the impact of surface charges on the cell interaction mechanisms. Furthermore, coatings with extracellular matrix proteins (collagen, fibronectin, and laminin) were investigated to determine the importance of integrin-mediated cell attachment. Cell proliferation was evaluated by a cellular proliferation assay, while cell integration and neurite propagation were studied by simultaneous label-free Coherent anti-Stokes Raman Scattering and second harmonic generation microscopy, providing 3D images of PC12 cells and arrangement of nanocellulose fibrils, respectively. Cell attachment and proliferation were enhanced by TMAHP modification, but not by protein coating. Protein coating instead promoted active interaction between the cells and the scaffold, hence lateral cell migration and integration. Irrespective of surface modification, deepest cell integration measured was one to two cell layers, whereas neurites have a capacity to integrate deeper than the cell bodies in the scaffold due to their fine dimensions and amoeba-like migration pattern. Neurites with lengths of >50 μm were observed, successfully connecting individual cells and cell clusters. In conclusion, TMAHP-modified nanocellulose scaffolds promote initial cellular scaffold adhesion, which combined with additional cell-scaffold treatments enables further formation of 3D neuronal networks.

  3. C. elegans model of neuronal aging

    OpenAIRE

    Peng, Chiu-Ying; Chen, Chun-Hao; Hsu, Jiun-Min; Pan, Chun-Liang

    2011-01-01

    Aging of the nervous system underlies the behavioral and cognitive decline associated with senescence. Understanding the molecular and cellular basis of neuronal aging will therefore contribute to the development of effective treatments for aging and age-associated neurodegenerative disorders. Despite this pressing need, there are surprisingly few animal models that aim at recapitulating neuronal aging in a physiological context. We recently developed a C. elegans model of neuronal aging, and...

  4. 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.

  5. Do enteric neurons make hypocretin? ☆

    OpenAIRE

    Baumann, Christian R.; Clark, Erika L.; Pedersen, Nigel P.; Hecht, Jonathan L.; Scammell, Thomas E.

    2007-01-01

    Hypocretins (orexins) are wake-promoting neuropeptides produced by hypothalamic neurons. These hypocretin-producing cells are lost in people with narcolepsy, possibly due to an autoimmune attack. Prior studies described hypocretin neurons in the enteric nervous system, and these cells could be an additional target of an autoimmune process. We sought to determine whether enteric hypocretin neurons are lost in narcoleptic subjects. Even though we tried several methods (including whole mounts, s...

  6. High-Degree Neurons Feed Cortical Computations.

    Directory of Open Access Journals (Sweden)

    Nicholas M Timme

    2016-05-01

    Full Text Available Recent work has shown that functional connectivity among cortical neurons is highly varied, with a small percentage of neurons having many more connections than others. Also, recent theoretical developments now make it possible to quantify how neurons modify information from the connections they receive. Therefore, it is now possible to investigate how information modification, or computation, depends on the number of connections a neuron receives (in-degree or sends out (out-degree. To do this, we recorded the simultaneous spiking activity of hundreds of neurons in cortico-hippocampal slice cultures using a high-density 512-electrode array. This preparation and recording method combination produced large numbers of neurons recorded at temporal and spatial resolutions that are not currently available in any in vivo recording system. We utilized transfer entropy (a well-established method for detecting linear and nonlinear interactions in time series and the partial information decomposition (a powerful, recently developed tool for dissecting multivariate information processing into distinct parts to quantify computation between neurons where information flows converged. We found that computations did not occur equally in all neurons throughout the networks. Surprisingly, neurons that computed large amounts of information tended to receive connections from high out-degree neurons. However, the in-degree of a neuron was not related to the amount of information it computed. To gain insight into these findings, we developed a simple feedforward network model. We found that a degree-modified Hebbian wiring rule best reproduced the pattern of computation and degree correlation results seen in the real data. Interestingly, this rule also maximized signal propagation in the presence of network-wide correlations, suggesting a mechanism by which cortex could deal with common random background input. These are the first results to show that the extent to

  7. Design of memristive interface between electronic neurons

    Science.gov (United States)

    Gerasimova, S. A.; Mikhaylov, A. N.; Belov, A. I.; Korolev, D. S.; Guseinov, D. V.; Lebedeva, A. V.; Gorshkov, O. N.; Kazantsev, V. B.

    2018-05-01

    Nonlinear dynamics of two electronic oscillators coupled via a memristive device has been investigated. Such model mimics the interaction between synaptically coupled brain neurons with the memristive device imitating neuron axon. The synaptic connection is provided by the adaptive behavior of memristive device that changes its resistance under the action of spike-like activity. Mathematical model of such a memristive interface has been developed to describe and predict the experimentally observed regularities of forced synchronization of neuron-like oscillators.

  8. Mirror neurons: From origin to function

    OpenAIRE

    Cook, R; Bird, G; Catmur, C; Press, C; Heyes, C

    2014-01-01

    This article argues that mirror neurons originate in sensorimotor associative learning and therefore a new approach is needed to investigate their functions. Mirror neurons were discovered about 20 years ago in the monkey brain, and there is now evidence that they are also present in the human brain. The intriguing feature of many mirror neurons is that they fire not only when the animal is performing an action, such as grasping an object using a power grip, but also when the animal passively...

  9. Geometrical Determinants of Neuronal Actin Waves

    OpenAIRE

    Tomba, Caterina; Bra?ni, C?line; Bugnicourt, Ghislain; Cohen, Floriane; Friedrich, Benjamin M.; Gov, Nir S.; Villard, Catherine

    2017-01-01

    Hippocampal neurons produce in their early stages of growth propagative, actin-rich dynamical structures called actin waves. The directional motion of actin waves from the soma to the tip of neuronal extensions has been associated with net forward growth, and ultimately with the specification of neurites into axon and dendrites. Here, geometrical cues are used to control actin wave dynamics by constraining neurons on adhesive stripes of various widths. A key observable, the average time betwe...

  10. The Relevance of AgRP Neuron-Derived GABA Inputs to POMC Neurons Differs for Spontaneous and Evoked Release

    OpenAIRE

    Rau, Andrew R.; Hentges, Shane T.

    2017-01-01

    Hypothalamic agouti-related peptide (AgRP) neurons potently stimulate food intake, whereas proopiomelanocortin (POMC) neurons inhibit feeding. Whether AgRP neurons exert their orexigenic actions, at least in part, by inhibiting anorexigenic POMC neurons remains unclear. Here, the connectivity between GABA-releasing AgRP neurons and POMC neurons was examined in brain slices from male and female mice. GABA-mediated spontaneous IPSCs (sIPSCs) in POMC neurons were unaffected by disturbing GABA re...

  11. 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

  12. 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.

  13. 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...

  14. 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.

  15. Mechanisms of Neuronal Apoptosis In Vivo

    National Research Council Canada - National Science Library

    Martin, Lee J

    2004-01-01

    .... Neuronal cell death in the form of apoptosis or necrosis occurs after exposure to neurotoxins, chemical warfare agents, radiation, viruses, and after seizures, trauma, limb amputation, and hypoxic...

  16. Autosomal dominant adult neuronal ceroid lipofuscinosis

    NARCIS (Netherlands)

    Nijssen, Peter C.G.

    2011-01-01

    this thesis investigates a family with autosomal dominant neuronal ceroid lipofuscinosis, with chapters on clinical neurology, neuropathology, neurogenetics, neurophysiology, auditory and visual aspects.

  17. Neurochemistry of olivocochlear neurons in the hamster.

    Science.gov (United States)

    Reuss, Stefan; Disque-Kaiser, Ursula; Antoniou-Lipfert, Patricia; Gholi, Maryam Najaf; Riemann, Elke; Riemann, Randolf

    2009-04-01

    The present study was conducted to characterize the superior olivary complex (SOC) of the lower brain stem in the pigmented Djungarian hamster Phodopus sungorus. Using Nissl-stained serial cryostat sections from fresh-frozen brains, we determined the borders of the SOC nuclei. We also identified olivocochlear (OC) neurons by retrograde neuronal tracing upon injection of Fluoro-Gold into the scala tympani. To evaluate the SOC as a putative source of neuronal nitric oxide synthase (nNOS), arginine-vasopressin (AVP), oxytocin (OT), vasoactive intestinal polypeptide (VIP), or pituitary adenylate cyclase-activating polypeptide (PACAP) that were all found in the cochlea, we conducted immunohistochemistry on sections exhibiting retrogradely labeled neurons. We did not observe AVP-, OT-, or VIP-immunoreactivity, neither in OC neurons nor in the SOC at all, revealing that cochlear AVP, OT, and VIP are of nonolivary origin. However, we found nNOS, the enzyme responsible for nitric oxide synthesis in neurons, and PACAP in neuronal perikarya of the SOC. Retrogradely labeled neurons of the lateral olivocochlear (LOC) system in the lateral superior olive did not contain PACAP and were only infrequently nNOS-immunoreactive. In contrast, some shell neurons and some of the medial OC (MOC) system exhibited immunofluorescence for either substance. Our data obtained from the dwarf hamster Phodopus sungorus confirm previous observations that a part of the LOC system is nitrergic. They further demonstrate that the medial olivocochlear system is partly nitrergic and use PACAP as neurotransmitter or modulator.

  18. Mirror neurons and language in schizophrenia

    OpenAIRE

    Bendová, Marie

    2016-01-01

    Mirror neurons are a specific kind of visuomotor neurons that are involved in action execution and also in action perception. The mirror mechanism is linked to a variety of complex psychological functions such as social-cognitive functions and language. People with schizophrenia have often difficulties both in mirror neuron system and in language skills. In the first part of our research we studied the connectivity of mirror neuron areas (such as IFG, STG, PMC, SMC and so on) by fMRI in resti...

  19. Beyond Critical Exponents in Neuronal Avalanches

    Science.gov (United States)

    Friedman, Nir; Butler, Tom; Deville, Robert; Beggs, John; Dahmen, Karin

    2011-03-01

    Neurons form a complex network in the brain, where they interact with one another by firing electrical signals. Neurons firing can trigger other neurons to fire, potentially causing avalanches of activity in the network. In many cases these avalanches have been found to be scale independent, similar to critical phenomena in diverse systems such as magnets and earthquakes. We discuss models for neuronal activity that allow for the extraction of testable, statistical predictions. We compare these models to experimental results, and go beyond critical exponents.

  20. Glutamate mediated astrocytic filtering of neuronal activity.

    Directory of Open Access Journals (Sweden)

    Gilad Wallach

    2014-12-01

    Full Text Available Neuron-astrocyte communication is an important regulatory mechanism in various brain functions but its complexity and role are yet to be fully understood. In particular, the temporal pattern of astrocyte response to neuronal firing has not been fully characterized. Here, we used neuron-astrocyte cultures on multi-electrode arrays coupled to Ca2+ imaging and explored the range of neuronal stimulation frequencies while keeping constant the amount of stimulation. Our results reveal that astrocytes specifically respond to the frequency of neuronal stimulation by intracellular Ca2+ transients, with a clear onset of astrocytic activation at neuron firing rates around 3-5 Hz. The cell-to-cell heterogeneity of the astrocyte Ca2+ response was however large and increasing with stimulation frequency. Astrocytic activation by neurons was abolished with antagonists of type I metabotropic glutamate receptor, validating the glutamate-dependence of this neuron-to-astrocyte pathway. Using a realistic biophysical model of glutamate-based intracellular calcium signaling in astrocytes, we suggest that the stepwise response is due to the supralinear dynamics of intracellular IP3 and that the heterogeneity of the responses may be due to the heterogeneity of the astrocyte-to-astrocyte couplings via gap junction channels. Therefore our results present astrocyte intracellular Ca2+ activity as a nonlinear integrator of glutamate-dependent neuronal activity.

  1. Glutamate Mediated Astrocytic Filtering of Neuronal Activity

    Science.gov (United States)

    Herzog, Nitzan; De Pittà, Maurizio; Jacob, Eshel Ben; Berry, Hugues; Hanein, Yael

    2014-01-01

    Neuron-astrocyte communication is an important regulatory mechanism in various brain functions but its complexity and role are yet to be fully understood. In particular, the temporal pattern of astrocyte response to neuronal firing has not been fully characterized. Here, we used neuron-astrocyte cultures on multi-electrode arrays coupled to Ca2+ imaging and explored the range of neuronal stimulation frequencies while keeping constant the amount of stimulation. Our results reveal that astrocytes specifically respond to the frequency of neuronal stimulation by intracellular Ca2+ transients, with a clear onset of astrocytic activation at neuron firing rates around 3-5 Hz. The cell-to-cell heterogeneity of the astrocyte Ca2+ response was however large and increasing with stimulation frequency. Astrocytic activation by neurons was abolished with antagonists of type I metabotropic glutamate receptor, validating the glutamate-dependence of this neuron-to-astrocyte pathway. Using a realistic biophysical model of glutamate-based intracellular calcium signaling in astrocytes, we suggest that the stepwise response is due to the supralinear dynamics of intracellular IP3 and that the heterogeneity of the responses may be due to the heterogeneity of the astrocyte-to-astrocyte couplings via gap junction channels. Therefore our results present astrocyte intracellular Ca2+ activity as a nonlinear integrator of glutamate-dependent neuronal activity. PMID:25521344

  2. Spiking Neurons for Analysis of Patterns

    Science.gov (United States)

    Huntsberger, Terrance

    2008-01-01

    Artificial neural networks comprising spiking neurons of a novel type have been conceived as improved pattern-analysis and pattern-recognition computational systems. These neurons are represented by a mathematical model denoted the state-variable model (SVM), which among other things, exploits a computational parallelism inherent in spiking-neuron geometry. Networks of SVM neurons offer advantages of speed and computational efficiency, relative to traditional artificial neural networks. The SVM also overcomes some of the limitations of prior spiking-neuron models. There are numerous potential pattern-recognition, tracking, and data-reduction (data preprocessing) applications for these SVM neural networks on Earth and in exploration of remote planets. Spiking neurons imitate biological neurons more closely than do the neurons of traditional artificial neural networks. A spiking neuron includes a central cell body (soma) surrounded by a tree-like interconnection network (dendrites). Spiking neurons are so named because they generate trains of output pulses (spikes) in response to inputs received from sensors or from other neurons. They gain their speed advantage over traditional neural networks by using the timing of individual spikes for computation, whereas traditional artificial neurons use averages of activity levels over time. Moreover, spiking neurons use the delays inherent in dendritic processing in order to efficiently encode the information content of incoming signals. Because traditional artificial neurons fail to capture this encoding, they have less processing capability, and so it is necessary to use more gates when implementing traditional artificial neurons in electronic circuitry. Such higher-order functions as dynamic tasking are effected by use of pools (collections) of spiking neurons interconnected by spike-transmitting fibers. The SVM includes adaptive thresholds and submodels of transport of ions (in imitation of such transport in biological

  3. Life-long stability of neurons: a century of research on neurogenesis, neuronal death and neuron quantification in adult CNS.

    Science.gov (United States)

    Turlejski, Kris; Djavadian, Ruzanna

    2002-01-01

    In this chapter we provide an extensive review of 100 years of research on the stability of neurons in the mammalian brain, with special emphasis on humans. Although Cajal formulated the Neuronal Doctrine, he was wrong in his beliefs that adult neurogenesis did not occur and adult neurons are dying throughout life. These two beliefs became accepted "common knowledge" and have shaped much of neuroscience research and provided much of the basis for clinical treatment of age-related brain diseases. In this review, we consider adult neurogenesis from a historical and evolutionary perspective. It is concluded, that while adult neurogenesis is a factor in the dynamics of the dentate gyrus and olfactory bulb, it is probably not a major factor during the life-span in most brain areas. Likewise, the acceptance of neuronal death as an explanation for normal age-related senility is challenged with evidence collected over the last fifty years. Much of the problem in changing this common belief of dying neurons was the inadequacies of neuronal counting methods. In this review we discuss in detail implications of recent improvements in neuronal quantification. We conclude: First, age-related neuronal atrophy is the major factor in functional deterioration of existing neurons and could be slowed down, or even reversed by various pharmacological interventions. Second, in most cases neuronal degeneration during aging is a pathology that in principle may be avoided. Third, loss of myelin and of the white matter is more frequent and important than the limited neuronal death in normal aging.

  4. Effect of immobilization stress on gene expression of catecholamine biosynthetic enzymes in heart auricles of socially isolated rats

    Directory of Open Access Journals (Sweden)

    L. Gavrilovic

    2009-12-01

    Full Text Available Chronic stress is associated with the development of cardiovascular diseases. The sympathoneural system plays an important role in the regulation of cardiac function both in health and disease. In the present study, the changes in gene expression of the catecholamine biosynthetic enzymes tyrosine hydroxylase (TH, dopamine-β-hydroxylase (DBH and phenylethanolamine N-methyltransferase (PNMT and protein levels in the right and left heart auricles of naive control and long-term (12 weeks socially isolated rats were investigated by Taqman RT-PCR and Western blot analysis. The response of these animals to additional immobilization stress (2 h was also examined. Long-term social isolation produced a decrease in TH mRNA level in left auricles (about 70% compared to the corresponding control. Expression of the DBH gene was markedly decreased both in the right (about 62% and left (about 81% auricles compared to the corresponding control, group-maintained rats, whereas PNMT mRNA levels remained unchanged. Exposure of group-housed rats to acute immobilization for 2 h led to a significant increase of mRNA levels of TH (about 267%, DBH (about 37% and PNMT (about 60% only in the right auricles. Additional 2-h immobilization of individually housed rats did not affect gene expression of these enzymes in either the right or left auricle. Protein levels of TH, DBH and PNMT in left and right heart auricles were unchanged either in both individually housed and immobilized rats. The unchanged mRNA levels of the enzymes examined after short-term immobilization suggest that the catecholaminergic system of the heart auricles of animals previously exposed to chronic psychosocial stress was adapted to maintain appropriate cardiovascular homeostasis.

  5. Endorphinic neurons are contacting the tuberoinfundibular dopaminergic neurons in the rat brain

    International Nuclear Information System (INIS)

    Morel, G.; Pelletier, G.

    1986-01-01

    The anatomical relationships between endorphinic neurons and dopaminergic neurons were evaluated in the rat hypothalamus using a combination of immunocytochemistry and autoradiography. In the arcuate nucleus, endorphinic endings were seen making contacts with dopaminergic cell bodies and dendrites. No synapsis could be observed at the sites of contacts. These results strongly suggest that the endorphinic neurons are directly acting on dopaminergic neurons to modify the release of dopamine into the pituitary portal system

  6. Discrimination of communication vocalizations by single neurons and groups of neurons in the auditory midbrain.

    Science.gov (United States)

    Schneider, David M; Woolley, Sarah M N

    2010-06-01

    Many social animals including songbirds use communication vocalizations for individual recognition. The perception of vocalizations depends on the encoding of complex sounds by neurons in the ascending auditory system, each of which is tuned to a particular subset of acoustic features. Here, we examined how well the responses of single auditory neurons could be used to discriminate among bird songs and we compared discriminability to spectrotemporal tuning. We then used biologically realistic models of pooled neural responses to test whether the responses of groups of neurons discriminated among songs better than the responses of single neurons and whether discrimination by groups of neurons was related to spectrotemporal tuning and trial-to-trial response variability. The responses of single auditory midbrain neurons could be used to discriminate among vocalizations with a wide range of abilities, ranging from chance to 100%. The ability to discriminate among songs using single neuron responses was not correlated with spectrotemporal tuning. Pooling the responses of pairs of neurons generally led to better discrimination than the average of the two inputs and the most discriminating input. Pooling the responses of three to five single neurons continued to improve neural discrimination. The increase in discriminability was largest for groups of neurons with similar spectrotemporal tuning. Further, we found that groups of neurons with correlated spike trains achieved the largest gains in discriminability. We simulated neurons with varying levels of temporal precision and measured the discriminability of responses from single simulated neurons and groups of simulated neurons. Simulated neurons with biologically observed levels of temporal precision benefited more from pooling correlated inputs than did neurons with highly precise or imprecise spike trains. These findings suggest that pooling correlated neural responses with the levels of precision observed in the

  7. BigNeuron: Large-scale 3D Neuron Reconstruction from Optical Microscopy Images

    OpenAIRE

    Peng, Hanchuan; Hawrylycz, Michael; Roskams, Jane; Hill, Sean; Spruston, Nelson; Meijering, Erik; Ascoli, Giorgio A.

    2015-01-01

    textabstractUnderstanding the structure of single neurons is critical for understanding how they function within neural circuits. BigNeuron is a new community effort that combines modern bioimaging informatics, recent leaps in labeling and microscopy, and the widely recognized need for openness and standardization to provide a community resource for automated reconstruction of dendritic and axonal morphology of single neurons. Understanding the structure of single neurons is critical for unde...

  8. Leptin Action on GABAergic Neurons Prevents Obesity and Reduces Inhibitory Tone to POMC Neurons

    OpenAIRE

    Vong, Linh; Ye, Chianping; Yang, Zongfang; Choi, Brian; Chua, Streamson; Lowell, Bradford B.

    2011-01-01

    Leptin acts in the brain to prevent obesity. The underlying neurocircuitry responsible for this is poorly understood, in part due to incomplete knowledge regarding first order, leptin-responsive neurons. To address this, we and others have been removing leptin receptors from candidate first order neurons. While functionally relevant neurons have been identified, the observed effects have been small suggesting that most first order neurons remain unidentified. Here we take an alternative appro...

  9. Essential roles of mitochondrial depolarization in neuron loss through microglial activation and attraction toward neurons.

    Science.gov (United States)

    Nam, Min-Kyung; Shin, Hyun-Ah; Han, Ji-Hye; Park, Dae-Wook; Rhim, Hyangshuk

    2013-04-10

    As life spans increased, neurodegenerative disorders that affect aging populations have also increased. Progressive neuronal loss in specific brain regions is the most common cause of neurodegenerative disease; however, key determinants mediating neuron loss are not fully understood. Using a model of mitochondrial membrane potential (ΔΨm) loss, we found only 25% cell loss in SH-SY5Y (SH) neuronal mono-cultures, but interestingly, 85% neuronal loss occurred when neurons were co-cultured with BV2 microglia. SH neurons overexpressing uncoupling protein 2 exhibited an increase in neuron-microglia interactions, which represent an early step in microglial phagocytosis of neurons. This result indicates that ΔΨm loss in SH neurons is an important contributor to recruitment of BV2 microglia. Notably, we show that ΔΨm loss in BV2 microglia plays a crucial role in microglial activation and phagocytosis of damaged SH neurons. Thus, our study demonstrates that ΔΨm loss in both neurons and microglia is a critical determinant of neuron loss. These findings also offer new insights into neuroimmunological and bioenergetical aspects of neurodegenerative disease. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Cerebellar Nuclear Neurons Use Time and Rate Coding to Transmit Purkinje Neuron Pauses.

    Science.gov (United States)

    Sudhakar, Shyam Kumar; Torben-Nielsen, Benjamin; De Schutter, Erik

    2015-12-01

    Neurons of the cerebellar nuclei convey the final output of the cerebellum to their targets in various parts of the brain. Within the cerebellum their direct upstream connections originate from inhibitory Purkinje neurons. Purkinje neurons have a complex firing pattern of regular spikes interrupted by intermittent pauses of variable length. How can the cerebellar nucleus process this complex input pattern? In this modeling study, we investigate different forms of Purkinje neuron simple spike pause synchrony and its influence on candidate coding strategies in the cerebellar nuclei. That is, we investigate how different alignments of synchronous pauses in synthetic Purkinje neuron spike trains affect either time-locking or rate-changes in the downstream nuclei. We find that Purkinje neuron synchrony is mainly represented by changes in the firing rate of cerebellar nuclei neurons. Pause beginning synchronization produced a unique effect on nuclei neuron firing, while the effect of pause ending and pause overlapping synchronization could not be distinguished from each other. Pause beginning synchronization produced better time-locking of nuclear neurons for short length pauses. We also characterize the effect of pause length and spike jitter on the nuclear neuron firing. Additionally, we find that the rate of rebound responses in nuclear neurons after a synchronous pause is controlled by the firing rate of Purkinje neurons preceding it.

  11. Cerebellar Nuclear Neurons Use Time and Rate Coding to Transmit Purkinje Neuron Pauses

    Science.gov (United States)

    Sudhakar, Shyam Kumar; Torben-Nielsen, Benjamin; De Schutter, Erik

    2015-01-01

    Neurons of the cerebellar nuclei convey the final output of the cerebellum to their targets in various parts of the brain. Within the cerebellum their direct upstream connections originate from inhibitory Purkinje neurons. Purkinje neurons have a complex firing pattern of regular spikes interrupted by intermittent pauses of variable length. How can the cerebellar nucleus process this complex input pattern? In this modeling study, we investigate different forms of Purkinje neuron simple spike pause synchrony and its influence on candidate coding strategies in the cerebellar nuclei. That is, we investigate how different alignments of synchronous pauses in synthetic Purkinje neuron spike trains affect either time-locking or rate-changes in the downstream nuclei. We find that Purkinje neuron synchrony is mainly represented by changes in the firing rate of cerebellar nuclei neurons. Pause beginning synchronization produced a unique effect on nuclei neuron firing, while the effect of pause ending and pause overlapping synchronization could not be distinguished from each other. Pause beginning synchronization produced better time-locking of nuclear neurons for short length pauses. We also characterize the effect of pause length and spike jitter on the nuclear neuron firing. Additionally, we find that the rate of rebound responses in nuclear neurons after a synchronous pause is controlled by the firing rate of Purkinje neurons preceding it. PMID:26630202

  12. Stages of neuronal network formation

    International Nuclear Information System (INIS)

    Woiterski, Lydia; Käs, Josef A; Claudepierre, Thomas; Luxenhofer, Robert; Jordan, Rainer

    2013-01-01

    Graph theoretical approaches have become a powerful tool for investigating the architecture and dynamics of complex networks. The topology of network graphs revealed small-world properties for very different real systems among these neuronal networks. In this study, we observed the early development of mouse retinal ganglion cell (RGC) networks in vitro using time-lapse video microscopy. By means of a time-resolved graph theoretical analysis of the connectivity, shortest path length and the edge length, we were able to discover the different stages during the network formation. Starting from single cells, at the first stage neurons connected to each other ending up in a network with maximum complexity. In the further course, we observed a simplification of the network which manifested in a change of relevant network parameters such as the minimization of the path length. Moreover, we found that RGC networks self-organized as small-world networks at both stages; however, the optimization occurred only in the second stage. (paper)

  13. [Infantile autism and mirror neurons].

    Science.gov (United States)

    Cornelio-Nieto, J O

    2009-02-27

    Infantile autism is a disorder that is characterised by alterations affecting reciprocal social interactions, abnormal verbal and non-verbal communication, poor imaginative activity and a restricted repertoire of activities and interests. The causes of autism remain unknown, but there are a number of different approaches that attempt to explain the neurobiological causes of the syndrome. A recent theory that has been considered is that of a dysfunction in the mirror neuron system (MNS). The MNS is a neuronal complex, originally described in monkeys and also found in humans, that is related with our movements and which offers specific responses to the movements and intended movements of other subjects. This system is believed to underlie processes of imitation and our capacity to learn by imitation. It is also thought to play a role in language acquisition, in expressing the emotions, in understanding what is happening to others and in empathy. Because these functions are altered in children with autism, it has been suggested that there is some dysfunction present in the MNS of those with autism. Dysfunction of the MNS could account for the symptoms that are observed in children with autism.

  14. Inhibitory neurons modulate spontaneous signaling in cultured cortical neurons: density-dependent regulation of excitatory neuronal signaling

    International Nuclear Information System (INIS)

    Serra, Michael; Guaraldi, Mary; Shea, Thomas B

    2010-01-01

    Cortical neuronal activity depends on a balance between excitatory and inhibitory influences. Culturing of neurons on multi-electrode arrays (MEAs) has provided insight into the development and maintenance of neuronal networks. Herein, we seeded MEAs with murine embryonic cortical/hippocampal neurons at different densities ( 1000 cells mm −2 ) and monitored resultant spontaneous signaling. Sparsely seeded cultures displayed a large number of bipolar, rapid, high-amplitude individual signals with no apparent temporal regularity. By contrast, densely seeded cultures instead displayed clusters of signals at regular intervals. These patterns were observed even within thinner and thicker areas of the same culture. GABAergic neurons (25% of total neurons in our cultures) mediated the differential signal patterns observed above, since addition of the inhibitory antagonist bicuculline to dense cultures and hippocampal slice cultures induced the signal pattern characteristic of sparse cultures. Sparsely seeded cultures likely lacked sufficient inhibitory neurons to modulate excitatory activity. Differential seeding of MEAs can provide a unique model for analyses of pertubation in the interaction between excitatory and inhibitory function during aging and neuropathological conditions where dysregulation of GABAergic neurons is a significant component

  15. Optimum Shock Isolation

    National Research Council Canada - National Science Library

    Bolotnik, Nikolai

    2001-01-01

    .... Several types of performance criteria for isolation are considered, the most important of which are the peak force transmitted to the body to be isolated and the maximum displacement of the body relative to the base...

  16. Isolated patellofemoral osteoarthritis.

    NARCIS (Netherlands)

    Jonbergen, J.P.W. van; Poolman, R.W.; Kampen, A. van

    2010-01-01

    BACKGROUND AND PURPOSE: The optimal treatment for isolated patellofemoral osteoarthritis is unclear at present. We systematically reviewed the highest level of available evidence on the nonoperative and operative treatment of isolated patellofemoral osteoarthritis to develop an evidenced-based

  17. Anti-correlated cortical networks arise from spontaneous neuronal dynamics at slow timescales.

    Science.gov (United States)

    Kodama, Nathan X; Feng, Tianyi; Ullett, James J; Chiel, Hillel J; Sivakumar, Siddharth S; Galán, Roberto F

    2018-01-12

    In the highly interconnected architectures of the cerebral cortex, recurrent intracortical loops disproportionately outnumber thalamo-cortical inputs. These networks are also capable of generating neuronal activity without feedforward sensory drive. It is unknown, however, what spatiotemporal patterns may be solely attributed to intrinsic connections of the local cortical network. Using high-density microelectrode arrays, here we show that in the isolated, primary somatosensory cortex of mice, neuronal firing fluctuates on timescales from milliseconds to tens of seconds. Slower firing fluctuations reveal two spatially distinct neuronal ensembles, which correspond to superficial and deeper layers. These ensembles are anti-correlated: when one fires more, the other fires less and vice versa. This interplay is clearest at timescales of several seconds and is therefore consistent with shifts between active sensing and anticipatory behavioral states in mice.

  18. Interactive Exploration for Continuously Expanding Neuron Databases.

    Science.gov (United States)

    Li, Zhongyu; Metaxas, Dimitris N; Lu, Aidong; Zhang, Shaoting

    2017-02-15

    This paper proposes a novel framework to help biologists explore and analyze neurons based on retrieval of data from neuron morphological databases. In recent years, the continuously expanding neuron databases provide a rich source of information to associate neuronal morphologies with their functional properties. We design a coarse-to-fine framework for efficient and effective data retrieval from large-scale neuron databases. In the coarse-level, for efficiency in large-scale, we employ a binary coding method to compress morphological features into binary codes of tens of bits. Short binary codes allow for real-time similarity searching in Hamming space. Because the neuron databases are continuously expanding, it is inefficient to re-train the binary coding model from scratch when adding new neurons. To solve this problem, we extend binary coding with online updating schemes, which only considers the newly added neurons and update the model on-the-fly, without accessing the whole neuron databases. In the fine-grained level, we introduce domain experts/users in the framework, which can give relevance feedback for the binary coding based retrieval results. This interactive strategy can improve the retrieval performance through re-ranking the above coarse results, where we design a new similarity measure and take the feedback into account. Our framework is validated on more than 17,000 neuron cells, showing promising retrieval accuracy and efficiency. Moreover, we demonstrate its use case in assisting biologists to identify and explore unknown neurons. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Structural and functional effects of social isolation on the hippocampus of rats with traumatic brain injury.

    Science.gov (United States)

    Khodaie, Babak; Lotfinia, Ahmad Ali; Ahmadi, Milad; Lotfinia, Mahmoud; Jafarian, Maryam; Karimzadeh, Fariba; Coulon, Philippe; Gorji, Ali

    2015-02-01

    Social isolation has significant long-term psychological and physiological consequences. Both social isolation and traumatic brain injury (TBI) alter normal brain function and structure. However, the influence of social isolation on recovery from TBI is unclear. This study aims to evaluate if social isolation exacerbates the anatomical and functional deficits after TBI in young rats. Juvenile male rats were divided into four groups; sham operated control with social contacts, sham control with social isolation, TBI with social contacts, and TBI with social isolation. During four weeks after brain injury in juvenile rats, we evaluated the animal behaviors by T-maze and open-field tests, recorded brain activity with electrocorticograms and assessed structural changes by histological procedures in the hippocampal dentate gyrus, CA1, and CA3 areas. Our findings revealed significant memory impairments and hyperactivity conditions in rats with TBI and social isolation compared to the other groups. Histological assessments showed an increase of the mean number of dark neurons, apoptotic cells, and caspase-3 positive cells in all tested areas of the hippocampus in TBI rats with and without social isolation compared to sham rats. Furthermore, social isolation significantly increased the number of dark cells, apoptotic neurons, and caspase-3 positive cells in the hippocampal CA3 region in rats with TBI. This study indicates the harmful effect of social isolation on anatomical and functional deficits induced by TBI in juvenile rats. Prevention of social isolation may improve the outcome of TBI. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. High-voltage-activated calcium current subtypes in mouse DRG neurons adapt in a subpopulation-specific manner after nerve injury.

    Science.gov (United States)

    Murali, Swetha S; Napier, Ian A; Mohammadi, Sarasa A; Alewood, Paul F; Lewis, Richard J; Christie, MacDonald J

    2015-03-01

    Changes in ion channel function and expression are characteristic of neuropathic pain. Voltage-gated calcium channels (VGCCs) are integral for neurotransmission and membrane excitability, but relatively little is known about changes in their expression after nerve injury. In this study, we investigate whether peripheral nerve ligation is followed by changes in the density and proportion of high-voltage-activated (HVA) VGCC current subtypes in dorsal root ganglion (DRG) neurons, the contribution of presynaptic N-type calcium channels in evoked excitatory postsynaptic currents (EPSCs) recorded from dorsal horn neurons in the spinal cord, and the changes in expression of mRNA encoding VGCC subunits in DRG neurons. Using C57BL/6 mice [8- to 11-wk-old males (n = 91)] for partial sciatic nerve ligation or sham surgery, we performed whole cell patch-clamp recordings on isolated DRG neurons and dorsal horn neurons and measured the expression of all VGCC subunits with RT-PCR in DRG neurons. After nerve injury, the density of P/Q-type current was reduced overall in DRG neurons. There was an increase in the percentage of N-type and a decrease in that of P/Q-type current in medium- to large-diameter neurons. No changes were found in the contribution of presynaptic N-type calcium channels in evoked EPSCs recorded from dorsal horn neurons. The α2δ-1 subunit was upregulated by 1.7-fold and γ-3, γ-2, and β-4 subunits were all downregulated 1.7-fold in injured neurons compared with sham-operated neurons. This comprehensive characterization of HVA VGCC subtypes in mouse DRG neurons after nerve injury revealed changes in N- and P/Q-type current proportions only in medium- to large-diameter neurons. Copyright © 2015 the American Physiological Society.

  1. Intratelencephalic corticostriatal neurons equally excite striatonigral and striatopallidal neurons and their discharge activity is selectively reduced in experimental parkinsonism

    OpenAIRE

    Ballion, B. (B.); Mallet, N. (Nicolas); Bezard, E. (E.); Lanciego, J.L. (José Luis); Gonon, F. (Francois)

    2008-01-01

    Striatonigral and striatopallidal neurons form distinct populations of striatal projection neurons. Their discharge activity is imbalanced after dopaminergic degeneration in Parkinson's disease. Striatal projection neurons receive massive cortical excitatory inputs from bilateral intratelencephalic (IT) neurons projecting to both the ipsilateral and contralateral striatum and from collateral axons of ipsilateral neurons that send their main axon through the pyramidal tract (PT). Previous anat...

  2. Heavy metals in locus ceruleus and motor neurons in motor neuron disease.

    Science.gov (United States)

    Pamphlett, Roger; Kum Jew, Stephen

    2013-12-12

    The causes of sporadic amyotrophic lateral sclerosis (SALS) and other types of motor neuron disease (MND) remain largely unknown. Heavy metals have long been implicated in MND, and it has recently been shown that inorganic mercury selectively enters human locus ceruleus (LC) and motor neurons. We therefore used silver nitrate autometallography (AMG) to look for AMG-stainable heavy metals (inorganic mercury and bismuth) in LC and motor neurons of 24 patients with MND (18 with SALS and 6 with familial MND) and in the LC of 24 controls. Heavy metals in neurons were found in significantly more MND patients than in controls when comparing: (1) the presence of any versus no heavy metal-containing LC neurons (MND 88%, controls 42%), (2) the median percentage of heavy metal-containing LC neurons (MND 9.5%, control 0.0%), and (3) numbers of individuals with heavy metal-containing LC neurons in the upper half of the percentage range (MND 75%, controls 25%). In MND patients, 67% of remaining spinal motor neurons contained heavy metals; smaller percentages were found in hypoglossal, nucleus ambiguus and oculomotor neurons, but none in cortical motor neurons. The majority of MND patients had heavy metals in both LC and spinal motor neurons. No glia or other neurons, including neuromelanin-containing neurons of the substantia nigra, contained stainable heavy metals. Uptake of heavy metals by LC and lower motor neurons appears to be fairly common in humans, though heavy metal staining in the LC, most likely due to inorganic mercury, was seen significantly more often in MND patients than in controls. The LC innervates many cell types that are affected in MND, and it is possible that MND is triggered by toxicant-induced interactions between LC and motor neurons.

  3. Heavy metals in locus ceruleus and motor neurons in motor neuron disease

    Science.gov (United States)

    2013-01-01

    Background The causes of sporadic amyotrophic lateral sclerosis (SALS) and other types of motor neuron disease (MND) remain largely unknown. Heavy metals have long been implicated in MND, and it has recently been shown that inorganic mercury selectively enters human locus ceruleus (LC) and motor neurons. We therefore used silver nitrate autometallography (AMG) to look for AMG-stainable heavy metals (inorganic mercury and bismuth) in LC and motor neurons of 24 patients with MND (18 with SALS and 6 with familial MND) and in the LC of 24 controls. Results Heavy metals in neurons were found in significantly more MND patients than in controls when comparing: (1) the presence of any versus no heavy metal-containing LC neurons (MND 88%, controls 42%), (2) the median percentage of heavy metal-containing LC neurons (MND 9.5%, control 0.0%), and (3) numbers of individuals with heavy metal-containing LC neurons in the upper half of the percentage range (MND 75%, controls 25%). In MND patients, 67% of remaining spinal motor neurons contained heavy metals; smaller percentages were found in hypoglossal, nucleus ambiguus and oculomotor neurons, but none in cortical motor neurons. The majority of MND patients had heavy metals in both LC and spinal motor neurons. No glia or other neurons, including neuromelanin-containing neurons of the substantia nigra, contained stainable heavy metals. Conclusions Uptake of heavy metals by LC and lower motor neurons appears to be fairly common in humans, though heavy metal staining in the LC, most likely due to inorganic mercury, was seen significantly more often in MND patients than in controls. The LC innervates many cell types that are affected in MND, and it is possible that MND is triggered by toxicant-induced interactions between LC and motor neurons. PMID:24330485

  4. Human Embryonic Stem Cell-Derived Neurons Are Highly Permissive for Varicella-Zoster Virus Lytic Infection.

    Science.gov (United States)

    Sadaoka, Tomohiko; Schwartz, Cindi L; Rajbhandari, Labchan; Venkatesan, Arun; Cohen, Jeffrey I

    2018-01-01

    Varicella-zoster virus (VZV) is highly cell associated when grown in culture and has a much higher (4,000- to 20,000-fold increased) particle-to-PFU ratio in vitro than herpes simplex virus (HSV). In contrast, VZV is highly infectious in vivo by airborne transmission. Neurons are major targets for VZV in vivo ; in neurons, the virus can establish latency and reactivate to produce infectious virus. Using neurons derived from human embryonic stem cells (hESC) and cell-free wild-type (WT) VZV, we demonstrated that neurons are nearly 100 times more permissive for WT VZV infection than very-early-passage human embryonic lung cells or MRC-5 diploid human fibroblasts, the cells used for vaccine production or virus isolation. The peak titers achieved after infection were ∼10-fold higher in human neurons than in MRC-5 cells, and the viral genome copy number-to-PFU ratio for VZV in human neurons was 500, compared with 50,000 for MRC-5 cells. Thus, VZV may not necessarily have a higher particle-to-PFU ratio than other herpesviruses; instead, the cells previously used to propagate virus in vitro may have been suboptimal. Furthermore, based on electron microscopy, neurons infected with VZV produced fewer defective or incomplete viral particles than MRC-5 cells. Our data suggest that neurons derived from hESC may have advantages compared to other cells for studies of VZV pathogenesis, for obtaining stocks of virus with high titers, and for isolating VZV from clinical specimens. IMPORTANCE Varicella-zoster virus (VZV) causes chickenpox and shingles. Cell-free VZV has been difficult to obtain, both for in vitro studies and for vaccine production. While numerous cells lines have been tested for their ability to produce high titers of VZV, the number of total virus particles relative to the number of viral particles that can form plaques in culture has been reported to be extremely high relative to that in other viruses. We show that VZV grows to much higher titers in human

  5. Isolation of Synaptosomes, Synaptic Plasma Membranes, and Synaptic Junctional Complexes.

    Science.gov (United States)

    Michaelis, Mary L; Jiang, Lei; Michaelis, Elias K

    2017-01-01

    Isolation of synaptic nerve terminals or synaptosomes provides an opportunity to study the process of neurotransmission at many levels and with a variety of approaches. For example, structural features of the synaptic terminals and the organelles within them, such as synaptic vesicles and mitochondria, have been elucidated with electron microscopy. The postsynaptic membranes are joined to the presynaptic "active zone" of transmitter release through cell adhesion molecules and remain attached throughout the isolation of synaptosomes. These "post synaptic densities" or "PSDs" contain the receptors for the transmitters released from the nerve terminals and can easily be seen with electron microscopy. Biochemical and cell biological studies with synaptosomes have revealed which proteins and lipids are most actively involved in synaptic release of neurotransmitters. The functional properties of the nerve terminals, such as responses to depolarization and the uptake or release of signaling molecules, have also been characterized through the use of fluorescent dyes, tagged transmitters, and transporter substrates. In addition, isolated synaptosomes can serve as the starting material for the isolation of relatively pure synaptic plasma membranes (SPMs) that are devoid of organelles from the internal environment of the nerve terminal, such as mitochondria and synaptic vesicles. The isolated SPMs can reseal and form vesicular structures in which transport of ions such as sodium and calcium, as well as solutes such as neurotransmitters can be studied. The PSDs also remain associated with the presynaptic membranes during isolation of SPM fractions, making it possible to isolate the synaptic junctional complexes (SJCs) devoid of the rest of the plasma membranes of the nerve terminals and postsynaptic membrane components. Isolated SJCs can be used to identify the proteins that constitute this highly specialized region of neurons. In this chapter, we describe the steps involved

  6. Transfection in Primary Cultured Neuronal Cells.

    Science.gov (United States)

    Marwick, Katie F M; Hardingham, Giles E

    2017-01-01

    Transfection allows the introduction of foreign nucleic acid into eukaryotic cells. It is an important tool in understanding the roles of NMDARs in neurons. Here, we describe using lipofection-mediated transfection to introduce cDNA encoding NMDAR subunits into postmitotic rodent primary cortical neurons maintained in culture.

  7. IGF-1: elixir for motor neuron diseases.

    Science.gov (United States)

    Papanikolaou, Theodora; Ellerby, Lisa M

    2009-08-13

    Modulation of testosterone levels is a therapeutic approach for spinal and bulbar muscular atrophy (SBMA), a polyglutamine disorder that affects the motor neurons. The article by Palazzolo et al. in this issue of Neuron provides compelling evidence that the expression of insulin growth hormone is a potential therapeutic for SBMA.

  8. Neuromodulation of vertebrate motor neuron membrane properties

    DEFF Research Database (Denmark)

    Hultborn, Hans; Kiehn, Ole

    1992-01-01

    The short-term function of motor neurons is to integrate synaptic inputs converging onto the somato-dendritic membrane and to transform the net synaptic drive into spike trains. A set of voltage-gated ion channels determines the electro-responsiveness and thereby the motor neuron's input-output f...

  9. Neuronal hyperplasia in the anal canal

    DEFF Research Database (Denmark)

    Fenger, C; Schrøder, H D

    1990-01-01

    In a consecutive series of minor surgical specimens from the anal canal, neuronal hyperplasia was found in nine of 56 haemorrhoidectomy specimens and in four of 23 fibrous polyps. In an additional series of 14 resections of the anal canal, neuronal hyperplasia was present in six cases, of which f...

  10. Life and Death of a Neuron

    Science.gov (United States)

    ... order to clear debris. Hope Through Research Scientists hope that by understanding more about the life and death of neurons they can develop new ... NIH is appreciated. Patient & Caregiver Education ... Your Brain Preventing Stroke Understanding Sleep The Life and Death of a Neuron Genes At Work ...

  11. The Mirror Neuron System and Action Recognition

    Science.gov (United States)

    Buccino, Giovanni; Binkofski, Ferdinand; Riggio, Lucia

    2004-01-01

    Mirror neurons, first described in the rostral part of monkey ventral premotor cortex (area F5), discharge both when the animal performs a goal-directed hand action and when it observes another individual performing the same or a similar action. More recently, in the same area mirror neurons responding to the observation of mouth actions have been…

  12. Mirror neurons: functions, mechanisms and models.

    Science.gov (United States)

    Oztop, Erhan; Kawato, Mitsuo; Arbib, Michael A

    2013-04-12

    Mirror neurons for manipulation fire both when the animal manipulates an object in a specific way and when it sees another animal (or the experimenter) perform an action that is more or less similar. Such neurons were originally found in macaque monkeys, in the ventral premotor cortex, area F5 and later also in the inferior parietal lobule. Recent neuroimaging data indicate that the adult human brain is endowed with a "mirror neuron system," putatively containing mirror neurons and other neurons, for matching the observation and execution of actions. Mirror neurons may serve action recognition in monkeys as well as humans, whereas their putative role in imitation and language may be realized in human but not in monkey. This article shows the important role of computational models in providing sufficient and causal explanations for the observed phenomena involving mirror systems and the learning processes which form them, and underlines the need for additional circuitry to lift up the monkey mirror neuron circuit to sustain the posited cognitive functions attributed to the human mirror neuron system. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  13. Where do mirror neurons come from?

    Science.gov (United States)

    Heyes, Cecilia

    2010-03-01

    Debates about the evolution of the 'mirror neuron system' imply that it is an adaptation for action understanding. Alternatively, mirror neurons may be a byproduct of associative learning. Here I argue that the adaptation and associative hypotheses both offer plausible accounts of the origin of mirror neurons, but the associative hypothesis has three advantages. First, it provides a straightforward, testable explanation for the differences between monkeys and humans that have led some researchers to question the existence of a mirror neuron system. Second, it is consistent with emerging evidence that mirror neurons contribute to a range of social cognitive functions, but do not play a dominant, specialised role in action understanding. Finally, the associative hypothesis is supported by recent data showing that, even in adulthood, the mirror neuron system can be transformed by sensorimotor learning. The associative account implies that mirror neurons come from sensorimotor experience, and that much of this experience is obtained through interaction with others. Therefore, if the associative account is correct, the mirror neuron system is a product, as well as a process, of social interaction. (c) 2009 Elsevier Ltd. All rights reserved.

  14. Evidence that OGG1 glycosylase protects neurons against oxidative DNA damage and cell death under ischemic conditions

    DEFF Research Database (Denmark)

    Liu, Dong; Croteau, Deborah L; Souza-Pinto, Nadja

    2011-01-01

    to ischemic and oxidative stress. After exposure of cultured neurons to oxidative and metabolic stress levels of OGG1 in the nucleus were elevated and mitochondria exhibited fragmentation and increased levels of the mitochondrial fission protein dynamin-related protein 1 (Drp1) and reduced membrane potential......7,8-Dihydro-8-oxoguanine DNA glycosylase (OGG1) is a major DNA glycosylase involved in base-excision repair (BER) of oxidative DNA damage to nuclear and mitochondrial DNA (mtDNA). We used OGG1-deficient (OGG1(-/-)) mice to examine the possible roles of OGG1 in the vulnerability of neurons....... Cortical neurons isolated from OGG1(-/-) mice were more vulnerable to oxidative insults than were OGG1(+/+) neurons, and OGG1(-/-) mice developed larger cortical infarcts and behavioral deficits after permanent middle cerebral artery occlusion compared with OGG1(+/+) mice. Accumulations of oxidative DNA...

  15. Interleukin-1 beta activates specific populations of enteric neurons and enteric glia in the guinea pig ileum and colon

    NARCIS (Netherlands)

    Tjwa, ETTL; Bradley, JM; Keenan, CM; Kroese, ABA; Sharkey, KA

    2003-01-01

    Fos expression was used to assess whether the proinflammatory cytokine interleukin-1beta (IL-1beta) activated specific, chemically coded neuronal populations in isolated preparations of guinea pig ileum and colon. Whether the effects of IL-1beta were mediated through a prostaglandin pathway and

  16. Investigation of Mitochondrial Dysfunction by Sequential Microplate-Based Respiration Measurements from Intact and Permeabilized Neurons

    Science.gov (United States)

    Clerc, Pascaline; Polster, Brian M.

    2012-01-01

    Mitochondrial dysfunction is a component of many neurodegenerative conditions. Measurement of oxygen consumption from intact neurons enables evaluation of mitochondrial bioenergetics under conditions that are more physiologically realistic compared to isolated mitochondria. However, mechanistic analysis of mitochondrial function in cells is complicated by changing energy demands and lack of substrate control. Here we describe a technique for sequentially measuring respiration from intact and saponin-permeabilized cortical neurons on single microplates. This technique allows control of substrates to individual electron transport chain complexes following permeabilization, as well as side-by-side comparisons to intact cells. To illustrate the utility of the technique, we demonstrate that inhibition of respiration by the drug KB-R7943 in intact neurons is relieved by delivery of the complex II substrate succinate, but not by complex I substrates, via acute saponin permeabilization. In contrast, methyl succinate, a putative cell permeable complex II substrate, failed to rescue respiration in intact neurons and was a poor complex II substrate in permeabilized cells. Sequential measurements of intact and permeabilized cell respiration should be particularly useful for evaluating indirect mitochondrial toxicity due to drugs or cellular signaling events which cannot be readily studied using isolated mitochondria. PMID:22496810

  17. Mitochondrial permeability transition pore inhibitors prevent ethanol-induced neuronal death in mice.

    Science.gov (United States)

    Lamarche, Frederic; Carcenac, Carole; Gonthier, Brigitte; Cottet-Rousselle, Cecile; Chauvin, Christiane; Barret, Luc; Leverve, Xavier; Savasta, Marc; Fontaine, Eric

    2013-01-18

    Ethanol induces brain injury by a mechanism that remains partly unknown. Mitochondria play a key role in cell death processes, notably through the opening of the permeability transition pore (PTP). Here, we tested the effect of ethanol and PTP inhibitors on mitochondrial physiology and cell viability both in vitro and in vivo. Direct addition of ethanol up to 100 mM on isolated mouse brain mitochondria slightly decreased oxygen consumption but did not affect PTP regulation. In comparison, when isolated from ethanol-treated (two doses of 2 g/kg, 2 h apart) 7-day-old mouse pups, brain mitochondria displayed a transient decrease in oxygen consumption but no change in PTP regulation or H2O2 production. Conversely, exposure of primary cultured astrocytes and neurons to 20 mM ethanol for 3 days led to a transient PTP opening in astrocytes without affecting cell viability and to a permanent PTP opening in 10 to 20% neurons with the same percentage of cell death. Ethanol-treated mouse pups displayed a widespread caspase-3 activation in neurons but not in astrocytes and dramatic behavioral alterations. Interestingly, two different PTP inhibitors (namely, cyclosporin A and nortriptyline) prevented both ethanol-induced neuronal death in vivo and ethanol-induced behavioral modifications. We conclude that PTP opening is involved in ethanol-induced neurotoxicity in the mouse.

  18. Nicotinic activation of laterodorsal tegmental neurons

    DEFF Research Database (Denmark)

    Ishibashi, Masaru; Leonard, Christopher S; Kohlmeier, Kristi A

    2009-01-01

    Identifying the neurological mechanisms underlying nicotine reinforcement is a healthcare imperative, if society is to effectively combat tobacco addiction. The majority of studies of the neurobiology of addiction have focused on dopamine (DA)-containing neurons of the ventral tegmental area (VTA......). However, recent data suggest that neurons of the laterodorsal tegmental (LDT) nucleus, which sends cholinergic, GABAergic, and glutamatergic-containing projections to DA-containing neurons of the VTA, are critical to gating normal functioning of this nucleus. The actions of nicotine on LDT neurons...... are unknown. We addressed this issue by examining the effects of nicotine on identified cholinergic and non-cholinergic LDT neurons using whole-cell patch clamp and Ca(2+)-imaging methods in brain slices from mice (P12-P45). Nicotine applied by puffer pipette or bath superfusion elicited membrane...

  19. Timing control by redundant inhibitory neuronal circuits

    Energy Technology Data Exchange (ETDEWEB)

    Tristan, I., E-mail: itristan@ucsd.edu; Rulkov, N. F.; Huerta, R.; Rabinovich, M. [BioCircuits Institute, University of California, San Diego, La Jolla, California 92093-0402 (United States)

    2014-03-15

    Rhythms and timing control of sequential activity in the brain is fundamental to cognition and behavior. Although experimental and theoretical studies support the understanding that neuronal circuits are intrinsically capable of generating different time intervals, the dynamical origin of the phenomenon of functionally dependent timing control is still unclear. Here, we consider a new mechanism that is related to the multi-neuronal cooperative dynamics in inhibitory brain motifs consisting of a few clusters. It is shown that redundancy and diversity of neurons within each cluster enhances the sensitivity of the timing control with the level of neuronal excitation of the whole network. The generality of the mechanism is shown to work on two different neuronal models: a conductance-based model and a map-based model.

  20. Neuronal migration, apoptosis and bipolar disorder.

    Science.gov (United States)

    Uribe, Ezequiel; Wix, Richard

    2012-01-01

    Bipolar disorder, like the majority of psychiatric disorders, is considered a neurodevelopment disease of neurodevelopment. There is an increased rate of neuronal birth and death during this development period. In the particular case of the processes that determine neuronal death, it is known that those neurons that establish connections have to be removed from the central nervous system. There is a deficit of GABAergic interneurons in the cerebral cortex in bipolar disorder, accompanied by overexpression of proapoptic genes. There is also an alteration in the expression of molecules that mediate in the migration of these neurons and their inclusion in functional synapsis during the foetal stage. The role of these molecules in the neuronal death pathways by apoptosis will be reviewed here in an attempt to establish biological hypotheses of the genesis of bipolar disorder. Copyright © 2011 SEP y SEPB. Published by Elsevier Espana. All rights reserved.

  1. Chromatin Regulation of Neuronal Maturation and Plasticity.

    Science.gov (United States)

    Gallegos, David A; Chan, Urann; Chen, Liang-Fu; West, Anne E

    2018-05-01

    Neurons are dynamic cells that respond and adapt to stimuli throughout their long postmitotic lives. The structural and functional plasticity of neurons requires the regulated transcription of new gene products, and dysregulation of transcription in either the developing or adult brain impairs cognition. We discuss how mechanisms of chromatin regulation help to orchestrate the transcriptional programs that underlie the maturation of developing neurons and the plasticity of adult neurons. We review how chromatin regulation acts locally to modulate the expression of specific genes and more broadly to coordinate gene expression programs during transitions between cellular states. These data highlight the importance of epigenetic transcriptional mechanisms in postmitotic neurons. We suggest areas where emerging methods may advance understanding in the future. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. A COMPUTATIONAL MODEL OF MOTOR NEURON DEGENERATION

    Science.gov (United States)

    Le Masson, Gwendal; Przedborski, Serge; Abbott, L.F.

    2014-01-01

    SUMMARY To explore the link between bioenergetics and motor neuron degeneration, we used a computational model in which detailed morphology and ion conductance are paired with intracellular ATP production and consumption. We found that reduced ATP availability increases the metabolic cost of a single action potential and disrupts K+/Na+ homeostasis, resulting in a chronic depolarization. The magnitude of the ATP shortage at which this ionic instability occurs depends on the morphology and intrinsic conductance characteristic of the neuron. If ATP shortage is confined to the distal part of the axon, the ensuing local ionic instability eventually spreads to the whole neuron and involves fasciculation-like spiking events. A shortage of ATP also causes a rise in intracellular calcium. Our modeling work supports the notion that mitochondrial dysfunction can account for salient features of the paralytic disorder amyotrophic lateral sclerosis, including motor neuron hyperexcitability, fasciculation, and differential vulnerability of motor neuron subpopulations. PMID:25088365

  3. A computational model of motor neuron degeneration.

    Science.gov (United States)

    Le Masson, Gwendal; Przedborski, Serge; Abbott, L F

    2014-08-20

    To explore the link between bioenergetics and motor neuron degeneration, we used a computational model in which detailed morphology and ion conductance are paired with intracellular ATP production and consumption. We found that reduced ATP availability increases the metabolic cost of a single action potential and disrupts K+/Na+ homeostasis, resulting in a chronic depolarization. The magnitude of the ATP shortage at which this ionic instability occurs depends on the morphology and intrinsic conductance characteristic of the neuron. If ATP shortage is confined to the distal part of the axon, the ensuing local ionic instability eventually spreads to the whole neuron and involves fasciculation-like spiking events. A shortage of ATP also causes a rise in intracellular calcium. Our modeling work supports the notion that mitochondrial dysfunction can account for salient features of the paralytic disorder amyotrophic lateral sclerosis, including motor neuron hyperexcitability, fasciculation, and differential vulnerability of motor neuron subpopulations. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Interaction function of coupled bursting neurons

    International Nuclear Information System (INIS)

    Shi Xia; Zhang Jiadong

    2016-01-01

    The interaction functions of electrically coupled Hindmarsh–Rose (HR) neurons for different firing patterns are investigated in this paper. By applying the phase reduction technique, the phase response curve (PRC) of the spiking neuron and burst phase response curve (BPRC) of the bursting neuron are derived. Then the interaction function of two coupled neurons can be calculated numerically according to the PRC (or BPRC) and the voltage time course of the neurons. Results show that the BPRC is more and more complicated with the increase of the spike number within a burst, and the curve of the interaction function oscillates more and more frequently with it. However, two certain things are unchanged: ϕ = 0, which corresponds to the in-phase synchronization state, is always the stable equilibrium, while the anti-phase synchronization state with ϕ = 0.5 is an unstable equilibrium. (paper)

  5. Timing control by redundant inhibitory neuronal circuits

    International Nuclear Information System (INIS)

    Tristan, I.; Rulkov, N. F.; Huerta, R.; Rabinovich, M.

    2014-01-01

    Rhythms and timing control of sequential activity in the brain is fundamental to cognition and behavior. Although experimental and theoretical studies support the understanding that neuronal circuits are intrinsically capable of generating different time intervals, the dynamical origin of the phenomenon of functionally dependent timing control is still unclear. Here, we consider a new mechanism that is related to the multi-neuronal cooperative dynamics in inhibitory brain motifs consisting of a few clusters. It is shown that redundancy and diversity of neurons within each cluster enhances the sensitivity of the timing control with the level of neuronal excitation of the whole network. The generality of the mechanism is shown to work on two different neuronal models: a conductance-based model and a map-based model

  6. Reflections on mirror neurons and speech perception

    Science.gov (United States)

    Lotto, Andrew J.; Hickok, Gregory S.; Holt, Lori L.

    2010-01-01

    The discovery of mirror neurons, a class of neurons that respond when a monkey performs an action and also when the monkey observes others producing the same action, has promoted a renaissance for the Motor Theory (MT) of speech perception. This is because mirror neurons seem to accomplish the same kind of one to one mapping between perception and action that MT theorizes to be the basis of human speech communication. However, this seeming correspondence is superficial, and there are theoretical and empirical reasons to temper enthusiasm about the explanatory role mirror neurons might have for speech perception. In fact, rather than providing support for MT, mirror neurons are actually inconsistent with the central tenets of MT. PMID:19223222

  7. Attractor dynamics in local neuronal networks

    Directory of Open Access Journals (Sweden)

    Jean-Philippe eThivierge

    2014-03-01

    Full Text Available Patterns of synaptic connectivity in various regions of the brain are characterized by the presence of synaptic motifs, defined as unidirectional and bidirectional synaptic contacts that follow a particular configuration and link together small groups of neurons. Recent computational work proposes that a relay network (two populations communicating via a third, relay population of neurons can generate precise patterns of neural synchronization. Here, we employ two distinct models of neuronal dynamics and show that simulated neural circuits designed in this way are caught in a global attractor of activity that prevents neurons from modulating their response on the basis of incoming stimuli. To circumvent the emergence of a fixed global attractor, we propose a mechanism of selective gain inhibition that promotes flexible responses to external stimuli. We suggest that local neuronal circuits may employ this mechanism to generate precise patterns of neural synchronization whose transient nature delimits the occurrence of a brief stimulus.

  8. 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.

  9. A single-neuron tracing study of arkypallidal and prototypic neurons in healthy rats.

    Science.gov (United States)

    Fujiyama, Fumino; Nakano, Takashi; Matsuda, Wakoto; Furuta, Takahiro; Udagawa, Jun; Kaneko, Takeshi

    2016-12-01

    The external globus pallidus (GP) is known as a relay nucleus of the indirect pathway of the basal ganglia. Recent studies in dopamine-depleted and healthy rats indicate that the GP comprises two main types of pallidofugal neurons: the so-called "prototypic" and "arkypallidal" neurons. However, the reconstruction of complete arkypallidal neurons in healthy rats has not been reported. Here we visualized the entire axonal arborization of four single arkypallidal neurons and six single prototypic neurons in rat brain using labeling with a viral vector expressing membrane-targeted green fluorescent protein and examined the distribution of axon boutons in the target nuclei. Results revealed that not only the arkypallidal neurons but nearly all of the prototypic neurons projected to the striatum with numerous axon varicosities. Thus, the striatum is a major target nucleus for pallidal neurons. Arkypallidal and prototypic GP neurons located in the calbindin-positive and calbindin-negative regions mainly projected to the corresponding positive and negative regions in the striatum. Because the GP and striatum calbindin staining patterns reflect the topographic organization of the striatopallidal projection, the striatal neurons in the sensorimotor and associative regions constitute the reciprocal connection with the GP neurons in the corresponding regions.

  10. Neuron-derived IgG protects neurons from complement-dependent cytotoxicity.

    Science.gov (United States)

    Zhang, Jie; Niu, Na; Li, Bingjie; McNutt, Michael A

    2013-12-01

    Passive immunity of the nervous system has traditionally been thought to be predominantly due to the blood-brain barrier. This concept must now be revisited based on the existence of neuron-derived IgG. The conventional concept is that IgG is produced solely by mature B lymphocytes, but it has now been found to be synthesized by murine and human neurons. However, the function of this endogenous IgG is poorly understood. In this study, we confirm IgG production by rat cortical neurons at the protein and mRNA levels, with 69.0 ± 5.8% of cortical neurons IgG-positive. Injury to primary-culture neurons was induced by complement leading to increases in IgG production. Blockage of neuron-derived IgG resulted in more neuronal death and early apoptosis in the presence of complement. In addition, FcγRI was found in microglia and astrocytes. Expression of FcγR I in microglia was increased by exposure to neuron-derived IgG. Release of NO from microglia triggered by complement was attenuated by neuron-derived IgG, and this attenuation could be reversed by IgG neutralization. These data demonstrate that neuron-derived IgG is protective of neurons against injury induced by complement and microglial activation. IgG appears to play an important role in maintaining the stability of the nervous system.

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

    International Nuclear Information System (INIS)

    Born, D.E.

    1986-01-01

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

  12. A central pattern generator producing alternative outputs: phase relations of leech heart motor neurons with respect to premotor synaptic input.

    Science.gov (United States)

    Norris, Brian J; Weaver, Adam L; Wenning, Angela; García, Paul S; Calabrese, Ronald L

    2007-11-01

    The central pattern generator (CPG) for heartbeat in leeches consists of seven identified pairs of segmental heart interneurons and one unidentified pair. Four of the identified pairs and the unidentified pair of interneurons make inhibitory synaptic connections with segmental heart motor neurons. The CPG produces a side-to-side asymmetric pattern of intersegmental coordination among ipsilateral premotor interneurons corresponding to a similarly asymmetric fictive motor pattern in heart motor neurons, and asymmetric constriction pattern of the two tubular hearts: synchronous and peristaltic. Using extracellular techniques, we recorded, in 61 isolated nerve cords, the activity of motor neurons in conjunction with the phase reference premotor heart interneuron, HN(4), and another premotor interneuron that allowed us to assess the coordination mode. These data were then coupled with a previous description of the temporal pattern of premotor interneuron activity in the two coordination modes to synthesize a global phase diagram for the known elements of the CPG and the entire motor neuron ensemble. These average data reveal the stereotypical side-to-side asymmetric patterns of intersegmental coordination among the motor neurons and show how this pattern meshes with the activity pattern of premotor interneurons. Analysis of animal-to-animal variability in this coordination indicates that the intersegmental phase progression of motor neuron activity in the midbody in the peristaltic coordination mode is the most stereotypical feature of the fictive motor pattern. Bilateral recordings from motor neurons corroborate the main features of the asymmetric motor pattern.

  13. Direct Reprogramming of Adult Human Somatic Stem Cells Into Functional Neurons Using Sox2, Ascl1, and Neurog2

    Directory of Open Access Journals (Sweden)

    Jessica Alves de Medeiros Araújo

    2018-06-01

    Full Text Available Reprogramming of somatic cells into induced pluripotent stem cells (iPS or directly into cells from a different lineage, including neurons, has revolutionized research in regenerative medicine in recent years. Mesenchymal stem cells are good candidates for lineage reprogramming and autologous transplantation, since they can be easily isolated from accessible sources in adult humans, such as bone marrow and dental tissues. Here, we demonstrate that expression of the transcription factors (TFs SRY (sex determining region Y-box 2 (Sox2, Mammalian achaete-scute homolog 1 (Ascl1, or Neurogenin 2 (Neurog2 is sufficient for reprogramming human umbilical cord mesenchymal stem cells (hUCMSC into induced neurons (iNs. Furthermore, the combination of Sox2/Ascl1 or Sox2/Neurog2 is sufficient to reprogram up to 50% of transfected hUCMSCs into iNs showing electrical properties of mature neurons and establishing synaptic contacts with co-culture primary neurons. Finally, we show evidence supporting the notion that different combinations of TFs (Sox2/Ascl1 and Sox2/Neurog2 may induce multiple and overlapping neuronal phenotypes in lineage-reprogrammed iNs, suggesting that neuronal fate is determined by a combination of signals involving the TFs used for reprogramming but also the internal state of the converted cell. Altogether, the data presented here contribute to the advancement of techniques aiming at obtaining specific neuronal phenotypes from lineage-converted human somatic cells to treat neurological disorders.

  14. Distinct functional and temporal requirements for zebrafish Hdac1 during neural crest-derived craniofacial and peripheral neuron development.

    Science.gov (United States)

    Ignatius, Myron S; Unal Eroglu, Arife; Malireddy, Smitha; Gallagher, Glen; Nambiar, Roopa M; Henion, Paul D

    2013-01-01

    The regulation of gene expression is accomplished by both genetic and epigenetic means and is required for the precise control of the development of the neural crest. In hdac1(b382) mutants, craniofacial cartilage development is defective in two distinct ways. First, fewer hoxb3a, dlx2 and dlx3-expressing posterior branchial arch precursors are specified and many of those that are consequently undergo apoptosis. Second, in contrast, normal numbers of progenitors are present in the anterior mandibular and hyoid arches, but chondrocyte precursors fail to terminally differentiate. In the peripheral nervous system, there is a disruption of enteric, DRG and sympathetic neuron differentiation in hdac1(b382) mutants compared to wildtype embryos. Specifically, enteric and DRG-precursors differentiate into neurons in the anterior gut and trunk respectively, while enteric and DRG neurons are rarely present in the posterior gut and tail. Sympathetic neuron precursors are specified in hdac1(b382) mutants and they undergo generic neuronal differentiation but fail to undergo noradrenergic differentiation. Using the HDAC inhibitor TSA, we isolated enzyme activity and temporal requirements for HDAC function that reproduce hdac1(b382) defects in craniofacial and sympathetic neuron development. Our study reveals distinct functional and temporal requirements for zebrafish hdac1 during neural crest-derived craniofacial and peripheral neuron development.

  15. Co-release of glutamate and GABA from single vesicles in GABAergic neurons exogenously expressing VGLUT3

    Directory of Open Access Journals (Sweden)

    Johannes eZimmermann

    2015-09-01

    Full Text Available The identity of the vesicle neurotransmitter transporter expressed by a neuron largely corresponds with the primary neurotransmitter that cell releases. However, the vesicular glutamate transporter subtype 3 (VGLUT3 is mainly expressed in non-glutamatergic neurons, including cholinergic, serotonergic, or GABAergic neurons. Though a functional role for glutamate release from these non-glutamatergic neurons has been demonstrated, the interplay between VGLUT3 and the neuron’s characteristic neurotransmitter transporter, particularly in the case of GABAergic neurons, at the synaptic and vesicular level is less clear. In this study, we explore how exogenous expression of VGLUT3 in striatal GABAergic neurons affects the packaging and release of glutamate and GABA in synaptic vesicles. We found that VGLUT3 expression in isolated, autaptic GABAergic neurons leads to action potential evoked release of glutamate. Under these conditions, glutamate and GABA could be packaged together in single vesicles release either spontaneously or asynchronously. However, the presence of glutamate in GABAergic vesicles did not affect uptake of GABA itself, suggesting a lack of synergy in vesicle filling for these transmitters. Finally, we found postsynaptic detection of glutamate released from GABAergic terminals difficult when bona fide glutamatergic synapses were present, suggesting that co-released glutamate cannot induce postsynaptic glutamate receptor clustering.

  16. Distinct functional and temporal requirements for zebrafish Hdac1 during neural crest-derived craniofacial and peripheral neuron development.

    Directory of Open Access Journals (Sweden)

    Myron S Ignatius

    Full Text Available The regulation of gene expression is accomplished by both genetic and epigenetic means and is required for the precise control of the development of the neural crest. In hdac1(b382 mutants, craniofacial cartilage development is defective in two distinct ways. First, fewer hoxb3a, dlx2 and dlx3-expressing posterior branchial arch precursors are specified and many of those that are consequently undergo apoptosis. Second, in contrast, normal numbers of progenitors are present in the anterior mandibular and hyoid arches, but chondrocyte precursors fail to terminally differentiate. In the peripheral nervous system, there is a disruption of enteric, DRG and sympathetic neuron differentiation in hdac1(b382 mutants compared to wildtype embryos. Specifically, enteric and DRG-precursors differentiate into neurons in the anterior gut and trunk respectively, while enteric and DRG neurons are rarely present in the posterior gut and tail. Sympathetic neuron precursors are specified in hdac1(b382 mutants and they undergo generic neuronal differentiation but fail to undergo noradrenergic differentiation. Using the HDAC inhibitor TSA, we isolated enzyme activity and temporal requirements for HDAC function that reproduce hdac1(b382 defects in craniofacial and sympathetic neuron development. Our study reveals distinct functional and temporal requirements for zebrafish hdac1 during neural crest-derived craniofacial and peripheral neuron development.

  17. Ferulic acid promotes survival and differentiation of neural stem cells to prevent gentamicin-induced neuronal hearing loss.

    Science.gov (United States)

    Gu, Lintao; Cui, Xinhua; Wei, Wei; Yang, Jia; Li, Xuezhong

    2017-11-15

    Neural stem cells (NSCs) have exhibited promising potential in therapies against neuronal hearing loss. Ferulic acid (FA) has been widely reported to enhance neurogenic differentiation of different stem cells. We investigated the role of FA in promoting NSC transplant therapy to prevent gentamicin-induced neuronal hearing loss. NSCs were isolated from mouse cochlear tissues to establish in vitro culture, which were then treated with FA. The survival and differentiation of NSCs were evaluated. Subsequently, neurite outgrowth and excitability of the in vitro neuronal network were assessed. Gentamicin was used to induce neuronal hearing loss in mice, in the presence and absence of FA, followed by assessments of auditory brainstem response (ABR) and distortion product optoacoustic emissions (DPOAE) amplitude. FA promoted survival, neurosphere formation and differentiation of NSCs, as well as neurite outgrowth and excitability of in vitro neuronal network. Furthermore, FA restored ABR threshold shifts and DPOAE in gentamicin-induced neuronal hearing loss mouse model in vivo. Our data, for the first time, support potential therapeutic efficacy of FA in promoting survival and differentiation of NSCs to prevent gentamicin-induced neuronal hearing loss. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. MRI of neuronal migration disorders

    International Nuclear Information System (INIS)

    Engelbrecht, V.

    1996-01-01

    Twenty-one MRI examinations of the brain were performed in 19 children with neuronal migration disorders. Multiplanar oriented spin-echo sequences were on a scanner with 1.5 T. In 8 children we performed an additional turbo-inversion recovery (TIR) sequence. Results of sonography or CT from five children were compared with MRI scans. Using the actual nomenclature, we found the following migration disorders: Lissencephaly (n=6), cobblestone lissencephaly with Walker-Warbung syndrome (WWS) (n=2), polymicrogyria and schizencephaly (n=2), focal heterotopia (n=5), diffuse heterotopie (n=2) and hemimegalencephaly (n=2). MRI was superior to CT and sonography in all children. Except for the two boys with WWS, the TIR sequence was the best to demonstrate the changes in migration disorder because of the high contrast between gray and white matter. We demonstrate the characteristic features of the different migration disorders and compare them with the existing literature. (orig.) [de

  19. Neuronal responses to physiological stress

    DEFF Research Database (Denmark)

    Kagias, Konstantinos; Nehammer, Camilla; Pocock, Roger David John

    2012-01-01

    damage during aging that results in decline and eventual death. Studies have shown that the nervous system plays a pivotal role in responding to stress. Neurons not only receive and process information from the environment but also actively respond to various stresses to promote survival. These responses......Physiological stress can be defined as any external or internal condition that challenges the homeostasis of a cell or an organism. It can be divided into three different aspects: environmental stress, intrinsic developmental stress, and aging. Throughout life all living organisms are challenged...... by changes in the environment. Fluctuations in oxygen levels, temperature, and redox state for example, trigger molecular events that enable an organism to adapt, survive, and reproduce. In addition to external stressors, organisms experience stress associated with morphogenesis and changes in inner...

  20. Responses of neurons to extreme osmomechanical stress.

    Science.gov (United States)

    Wan, X; Harris, J A; Morris, C E

    1995-05-01

    Neurons are often regarded as fragile cells, easily destroyed by mechanical and osmotic insult. The results presented here demonstrate that this perception needs revision. Using extreme osmotic swelling, we show that molluscan neurons are astonishingly robust. In distilled water, a heterogeneous population of Lymnaea stagnalis CNS neurons swelled to several times their initial volume, yet had a ST50 (survival time for 50% of cells) > 60 min. Cells that were initially bigger survived longer. On return to normal medium, survivors were able, over the next 24 hr, to rearborize. Reversible membrane capacitance changes corresponding to about 0.7 muF/cm2 of apparent surface area accompanied neuronal swelling and shrinking in hypo- and hyperosmotic solutions; reversible changes in cell surface area evidently contributed to the neurons' ability to accommodate hydrostatic pressures then recover. The reversible membrane area/capacitance changes were not dependent on extracellular Ca2+. Neurons were monitored for potassium currents during direct mechanical inflation and during osmotically driven inflation. The latter but not the former stimulus routinely elicited small potassium currents, suggesting that tension increases activate the currents only if additional disruption of the cortex has occurred. Under stress in distilled water, a third of the neurons displayed a quite unexpected behavior: prolonged writhing of peripheral regions of the soma. This suggested that a plasma membrane-linked contractile machinery (presumably actomyosin) might contribute to the neurons' mechano-osmotic robustness by restricting water influx. Consistent with this possibility, 1 mM N-ethyl-maleimide, which inhibits myosin ATPase, decreased the ST50 to 18 min, rendered the survival time independent of initial size, and abolished writhing activity. For neurons, active mechanical resistance of the submembranous cortex, along with the mechanical compliance supplied by insertion or eversion of membrane

  1. Mirror neurons: from origin to function.

    Science.gov (United States)

    Cook, Richard; Bird, Geoffrey; Catmur, Caroline; Press, Clare; Heyes, Cecilia

    2014-04-01

    This article argues that mirror neurons originate in sensorimotor associative learning and therefore a new approach is needed to investigate their functions. Mirror neurons were discovered about 20 years ago in the monkey brain, and there is now evidence that they are also present in the human brain. The intriguing feature of many mirror neurons is that they fire not only when the animal is performing an action, such as grasping an object using a power grip, but also when the animal passively observes a similar action performed by another agent. It is widely believed that mirror neurons are a genetic adaptation for action understanding; that they were designed by evolution to fulfill a specific socio-cognitive function. In contrast, we argue that mirror neurons are forged by domain-general processes of associative learning in the course of individual development, and, although they may have psychological functions, they do not necessarily have a specific evolutionary purpose or adaptive function. The evidence supporting this view shows that (1) mirror neurons do not consistently encode action "goals"; (2) the contingency- and context-sensitive nature of associative learning explains the full range of mirror neuron properties; (3) human infants receive enough sensorimotor experience to support associative learning of mirror neurons ("wealth of the stimulus"); and (4) mirror neurons can be changed in radical ways by sensorimotor training. The associative account implies that reliable information about the function of mirror neurons can be obtained only by research based on developmental history, system-level theory, and careful experimentation.

  2. Contribution of synchronized GABAergic neurons to dopaminergic neuron firing and bursting.

    Science.gov (United States)

    Morozova, Ekaterina O; Myroshnychenko, Maxym; Zakharov, Denis; di Volo, Matteo; Gutkin, Boris; Lapish, Christopher C; Kuznetsov, Alexey

    2016-10-01

    In the ventral tegmental area (VTA), interactions between dopamine (DA) and γ-aminobutyric acid (GABA) neurons are critical for regulating DA neuron activity and thus DA efflux. To provide a mechanistic explanation of how GABA neurons influence DA neuron firing, we developed a circuit model of the VTA. The model is based on feed-forward inhibition and recreates canonical features of the VTA neurons. Simulations revealed that γ-aminobutyric acid (GABA) receptor (GABAR) stimulation can differentially influence the firing pattern of the DA neuron, depending on the level of synchronization among GABA neurons. Asynchronous activity of GABA neurons provides a constant level of inhibition to the DA neuron and, when removed, produces a classical disinhibition burst. In contrast, when GABA neurons are synchronized by common synaptic input, their influence evokes additional spikes in the DA neuron, resulting in increased measures of firing and bursting. Distinct from previous mechanisms, the increases were not based on lowered firing rate of the GABA neurons or weaker hyperpolarization by the GABAR synaptic current. This phenomenon was induced by GABA-mediated hyperpolarization of the DA neuron that leads to decreases in intracellular calcium (Ca 2+ ) concentration, thus reducing the Ca 2+ -dependent potassium (K + ) current. In this way, the GABA-mediated hyperpolarization replaces Ca 2+ -dependent K + current; however, this inhibition is pulsatile, which allows the DA neuron to fire during the rhythmic pauses in inhibition. Our results emphasize the importance of inhibition in the VTA, which has been discussed in many studies, and suggest a novel mechanism whereby computations can occur locally. Copyright © 2016 the American Physiological Society.

  3. Loss of thymidine kinase 2 alters neuronal bioenergetics and leads to neurodegeneration.

    Science.gov (United States)

    Bartesaghi, Stefano; Betts-Henderson, Joanne; Cain, Kelvin; Dinsdale, David; Zhou, Xiaoshan; Karlsson, Anna; Salomoni, Paolo; Nicotera, Pierluigi

    2010-05-01

    Mutations of thymidine kinase 2 (TK2), an essential component of the mitochondrial nucleotide salvage pathway, can give rise to mitochondrial DNA (mtDNA) depletion syndromes (MDS). These clinically heterogeneous disorders are characterized by severe reduction in mtDNA copy number in affected tissues and are associated with progressive myopathy, hepatopathy and/or encephalopathy, depending in part on the underlying nuclear genetic defect. Mutations of TK2 have previously been associated with an isolated myopathic form of MDS (OMIM 609560). However, more recently, neurological phenotypes have been demonstrated in patients carrying TK2 mutations, thus suggesting that loss of TK2 results in neuronal dysfunction. Here, we directly address the role of TK2 in neuronal homeostasis using a knockout mouse model. We demonstrate that in vivo loss of TK2 activity leads to a severe ataxic phenotype, accompanied by reduced mtDNA copy number and decreased steady-state levels of electron transport chain proteins in the brain. In TK2-deficient cerebellar neurons, these abnormalities are associated with impaired mitochondrial bioenergetic function, aberrant mitochondrial ultrastructure and degeneration of selected neuronal types. Overall, our findings demonstrate that TK2 deficiency leads to neuronal dysfunction in vivo, and have important implications for understanding the mechanisms of neurological impairment in MDS.

  4. Information in a Network of Neuronal Cells: Effect of Cell Density and Short-Term Depression

    KAUST Repository

    Onesto, Valentina

    2016-05-10

    Neurons are specialized, electrically excitable cells which use electrical to chemical signals to transmit and elaborate information. Understanding how the cooperation of a great many of neurons in a grid may modify and perhaps improve the information quality, in contrast to few neurons in isolation, is critical for the rational design of cell-materials interfaces for applications in regenerative medicine, tissue engineering, and personalized lab-on-a-chips. In the present paper, we couple an integrate-and-fire model with information theory variables to analyse the extent of information in a network of nerve cells. We provide an estimate of the information in the network in bits as a function of cell density and short-term depression time. In the model, neurons are connected through a Delaunay triangulation of not-intersecting edges; in doing so, the number of connecting synapses per neuron is approximately constant to reproduce the early time of network development in planar neural cell cultures. In simulations where the number of nodes is varied, we observe an optimal value of cell density for which information in the grid is maximized. In simulations in which the posttransmission latency time is varied, we observe that information increases as the latency time decreases and, for specific configurations of the grid, it is largely enhanced in a resonance effect.

  5. Differentiation of neural crest stem cells from nasal mucosa into motor neuron-like cells.

    Science.gov (United States)

    Bagher, Zohreh; Kamrava, Seyed Kamran; Alizadeh, Rafieh; Farhadi, Mohammad; Absalan, Moloud; Falah, Masoumeh; Faghihi, Faezeh; Zare-Sadeghi, Arash; Komeili, Ali

    2018-05-25

    Cell transplantation is a potential therapeutic approach for repairing neuropathological and neurodegenerative disorders of central nervous system by replacing the degenerated cells with new ones. Among a variety of stem cell candidates to provide these new cells, olfactory ectomesenchymal stem cells (OE-MSCs) have attracted a great attention due to their neural crest origin, easy harvest, high proliferation, and autologous transplantation. Since there is no report on differentiation potential of these cells into motor neuron-like cells, we evaluated this potential using Real-time PCR, flowcytometry and immunocytochemistry after the treatment with differentiation cocktail containing retinoic acid and Sonic Hedgehog. Immunocytochemistry staining of the isolated OE-MSCs demonstrated their capability to express nestin and vimentin, as the two markers of primitive neuroectoderm. The motor neuron differentiation of OE-MSCs resulted in changing their morphology into bipolar cells with high expression of motor neuron markers of ChAT, Hb-9 and Islet-1 at the level of mRNA and protein. Consequently, we believe that the OE-MSCs have great potential to differentiate into motor neuron-like cells and can be an ideal stem cell source for the treatment of motor neuron-related disorders of central nervous system. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Information in a Network of Neuronal Cells: Effect of Cell Density and Short-Term Depression

    Directory of Open Access Journals (Sweden)

    Valentina Onesto

    2016-01-01

    Full Text Available Neurons are specialized, electrically excitable cells which use electrical to chemical signals to transmit and elaborate information. Understanding how the cooperation of a great many of neurons in a grid may modify and perhaps improve the information quality, in contrast to few neurons in isolation, is critical for the rational design of cell-materials interfaces for applications in regenerative medicine, tissue engineering, and personalized lab-on-a-chips. In the present paper, we couple an integrate-and-fire model with information theory variables to analyse the extent of information in a network of nerve cells. We provide an estimate of the information in the network in bits as a function of cell density and short-term depression time. In the model, neurons are connected through a Delaunay triangulation of not-intersecting edges; in doing so, the number of connecting synapses per neuron is approximately constant to reproduce the early time of network development in planar neural cell cultures. In simulations where the number of nodes is varied, we observe an optimal value of cell density for which information in the grid is maximized. In simulations in which the posttransmission latency time is varied, we observe that information increases as the latency time decreases and, for specific configurations of the grid, it is largely enhanced in a resonance effect.

  7. Plasma Extracellular Vesicles Enriched for Neuronal Origin: A Potential Window into Brain Pathologic Processes

    Directory of Open Access Journals (Sweden)

    Maja Mustapic

    2017-05-01

    Full Text Available Our team has been a pioneer in harvesting extracellular vesicles (EVs enriched for neuronal origin from peripheral blood and using them as a biomarker discovery platform for neurological disorders. This methodology has demonstrated excellent diagnostic and predictive performance for Alzheimer's and other neurodegenerative diseases in multiple studies, providing a strong proof of concept for this approach. Here, we describe our methodology in detail and offer further evidence that isolated EVs are enriched for neuronal origin. In addition, we present evidence that EVs enriched for neuronal origin represent a more sensitive and accurate base for biomarkers than plasma, serum, or non-enriched total plasma EVs. Finally, we proceed to investigate the protein content of EVs enriched for neuronal origin and compare it with other relevant enriched and non-enriched populations of plasma EVs. Neuronal-origin enriched plasma EVs contain higher levels of signaling molecules of great interest for cellular metabolism, survival, and repair, which may be useful as biomarkers and to follow response to therapeutic interventions in a mechanism-specific manner.

  8. Information in a Network of Neuronal Cells: Effect of Cell Density and Short-Term Depression

    KAUST Repository

    Onesto, Valentina; Cosentino, Carlo; Di Fabrizio, Enzo M.; Cesarelli, Mario; Amato, Francesco; Gentile, Francesco

    2016-01-01

    Neurons are specialized, electrically excitable cells which use electrical to chemical signals to transmit and elaborate information. Understanding how the cooperation of a great many of neurons in a grid may modify and perhaps improve the information quality, in contrast to few neurons in isolation, is critical for the rational design of cell-materials interfaces for applications in regenerative medicine, tissue engineering, and personalized lab-on-a-chips. In the present paper, we couple an integrate-and-fire model with information theory variables to analyse the extent of information in a network of nerve cells. We provide an estimate of the information in the network in bits as a function of cell density and short-term depression time. In the model, neurons are connected through a Delaunay triangulation of not-intersecting edges; in doing so, the number of connecting synapses per neuron is approximately constant to reproduce the early time of network development in planar neural cell cultures. In simulations where the number of nodes is varied, we observe an optimal value of cell density for which information in the grid is maximized. In simulations in which the posttransmission latency time is varied, we observe that information increases as the latency time decreases and, for specific configurations of the grid, it is largely enhanced in a resonance effect.

  9. Automated computation of arbor densities: a step toward identifying neuronal cell types

    Directory of Open Access Journals (Sweden)

    Uygar eSümbül

    2014-11-01

    Full Text Available The shape and position of a neuron convey information regarding its molecular and functional identity. The identification of cell types from structure, a classic method, relies on the time-consuming step of arbor tracing. However, as genetic tools and imaging methods make data-driven approaches to neuronal circuit analysis feasible, the need for automated processing increases. Here, we first establish that mouse retinal ganglion cell types can be as precise about distributing their arbor volumes across the inner plexiform layer as they are about distributing the skeletons of the arbors. Then, we describe an automated approach to computing the spatial distribution of the dendritic arbors, or arbor density, with respect to a global depth coordinate based on this observation. Our method involves three-dimensional reconstruction of neuronal arbors by a supervised machine learning algorithm, post-processing of the enhanced stacks to remove somata and isolate the neuron of interest, and registration of neurons to each other using automatically detected arbors of the starburst amacrine interneurons as fiducial markers. In principle, this method could be generalizable to other structures of the CNS, provided that they allow sparse labeling of the cells and contain a reliable axis of spatial reference.

  10. Double labelling immunohistochemical characterization of autonomic sympathetic neurons innervating the sow retractor clitoridis muscle

    Directory of Open Access Journals (Sweden)

    L Ragionieri

    2009-08-01

    Full Text Available Retrograde neuronal tracing and immunohistochemical methods were used to define the neurochemical content of sympathetic neurons projecting to the sow retractor clitoridis muscle (RCM. Differently from the other smooth muscles of genital organs, the RCM is an isolated muscle that is tonically contracted in the rest phase and relaxed in the active phase. This peculiarity makes it an interesting experimental model. The fluorescent tracer fast blue was injected into the RCM of three 50 kg subjects. After a one-week survival period, the ipsilateral paravertebral ganglion S1, that in a preliminary study showed the greatest number of cells projecting to the muscle, was collected from each animal. The co-existence of tyrosine hydroxylase with choline acetyltransferase, neuronal nitric oxide synthase, calcitonin gene-related peptide, leuenkephalin, neuropeptide Y, substance P and vasoactive intestinal polypeptide was studied under a fluorescent microscope on cryostat sections. Tyrosine hydroxylase was present in about 58% of the neurons projecting to the muscle and was found to be co-localized with each of the other tested substances.Within fast blue-labelled cells negative to the adrenergic marker, small populations of neurons singularly containing each of the other enzymatic markers or peptides were also observed. The present study documents the complexity of the neurochemical interactions that regulate the activity of the smooth myocytes of the RCM and their vascular components.

  11. AlGaN/GaN-based HEMTs for electrical stimulation of neuronal cell cultures

    International Nuclear Information System (INIS)

    Witte, H; Warnke, C; Krost, A; Voigt, T; De Lima, A; Ivanov, I; Vidakovic-Koch, T R; Sundmacher, K

    2011-01-01

    Unipolar source-drain voltage pulses of GaN/AlGaN-high electron mobility transistors (HEMTs) were used for stimulation of cultured neuronal networks obtained from embryonic rat cerebral cortex. The HEMT sensor was grown by metal organic vapour phase epitaxy on a 2 inch sapphire substrate consisting of 10 single HEMTs concentrically arranged around the wafer centre. Electrolytic reactions between the HEMT sensor surface and the culture medium were not detected using cyclic voltammetry. During voltage pulses and resulting neuronal excitation, capacitances were recharged giving indications of the contributions of the AlGaN and AlO x isolation layers between the two-dimensional electron gas channel and the neuron culture. The resulting threshold current for stimulation of neuron activity strongly depended on the culture and HEMT position on the sensor surface under consideration which was caused by different impedances of each neuron culture and position within the culture. The differences of culture impedances could be explained by variations of composition, thickness and conductivity of the culture areas.

  12. AlGaN/GaN-based HEMTs for electrical stimulation of neuronal cell cultures

    Energy Technology Data Exchange (ETDEWEB)

    Witte, H; Warnke, C; Krost, A [Institute of Experimental Physics, Otto-von-Guericke-University-Magdeburg, Magdeburg (Germany); Voigt, T; De Lima, A [Institute for Physiology, Otto-von-Guericke-University-Magdeburg, Magdeburg (Germany); Ivanov, I; Vidakovic-Koch, T R; Sundmacher, K, E-mail: hartmut.witte@physik.uni-magdeburg.de [Process Systems Engineering, Otto-von-Guericke-University-Magdeburg, Magdeburg (Germany)

    2011-09-07

    Unipolar source-drain voltage pulses of GaN/AlGaN-high electron mobility transistors (HEMTs) were used for stimulation of cultured neuronal networks obtained from embryonic rat cerebral cortex. The HEMT sensor was grown by metal organic vapour phase epitaxy on a 2 inch sapphire substrate consisting of 10 single HEMTs concentrically arranged around the wafer centre. Electrolytic reactions between the HEMT sensor surface and the culture medium were not detected using cyclic voltammetry. During voltage pulses and resulting neuronal excitation, capacitances were recharged giving indications of the contributions of the AlGaN and AlO{sub x} isolation layers between the two-dimensional electron gas channel and the neuron culture. The resulting threshold current for stimulation of neuron activity strongly depended on the culture and HEMT position on the sensor surface under consideration which was caused by different impedances of each neuron culture and position within the culture. The differences of culture impedances could be explained by variations of composition, thickness and conductivity of the culture areas.

  13. Triptolide Promotes the Clearance of α-Synuclein by Enhancing Autophagy in Neuronal Cells.

    Science.gov (United States)

    Hu, Guanzheng; Gong, Xiaoli; Wang, Le; Liu, Mengru; Liu, Yang; Fu, Xia; Wang, Wei; Zhang, Ting; Wang, Xiaomin

    2017-04-01

    Parkinson's disease (PD) is an aging-associated neurodegenerative disease with a characteristic feature of α-synuclein accumulation. Point mutations (A53T, A30P) that increase the aggregation propensity of α-synuclein result in familial early onset PD. The abnormal metabolism of α-synuclein results in aberrant level changes of α-synuclein in PD. In pathological conditions, α-synuclein is degraded mainly by the autophagy-lysosome pathway. Triptolide (T10) is a monomeric compound isolated from a traditional Chinese herb. Our group demonstrated for the first time that T10 possesses potent neuroprotective properties both in vitro and in vivo PD models. In the present study, we reported T10 as a potent autophagy inducer in neuronal cells, which helped to promote the clearance of various forms of α-synuclein in neuronal cells. We transfected neuronal cells with A53T mutant (A53T) or wild-type (WT) α-synuclein plasmids and found T10 attenuated the cytotoxicity induced by pathogenic A53T α-synuclein overexpression. We observed that T10 significantly reduced both A53T and WT α-synuclein level in neuronal cell line, as well as in primary cultured cortical neurons. Excluding the changes of syntheses, secretion, and aggregation of α-synuclein, we further added autophagy inhibitor or proteasome inhibitor with T10, and we noticed that T10 promoted the clearance of α-synuclein mainly by the autophagic pathway. Lastly, we observed increased autophagy marker LC3-II expression and autophagosomes by GFP-LC3-II accumulation and ultrastructural characterization. However, the lysosome activity and cell viability were not modulated by T10. Our study revealed that T10 could induce autophagy and promote the clearance of both WT and A53T α-synuclein in neurons. These results provide evidence of T10 as a promising mean to treat PD and other neurodegenerative diseases by reducing pathogenic proteins in neurons.

  14. Stochastic multiresonance in coupled excitable FHN neurons

    Science.gov (United States)

    Li, Huiyan; Sun, Xiaojuan; Xiao, Jinghua

    2018-04-01

    In this paper, effects of noise on Watts-Strogatz small-world neuronal networks, which are stimulated by a subthreshold signal, have been investigated. With the numerical simulations, it is surprisingly found that there exist several optimal noise intensities at which the subthreshold signal can be detected efficiently. This indicates the occurrence of stochastic multiresonance in the studied neuronal networks. Moreover, it is revealed that the occurrence of stochastic multiresonance has close relationship with the period of subthreshold signal Te and the noise-induced mean period of the neuronal networks T0. In detail, we find that noise could induce the neuronal networks to generate stochastic resonance for M times if Te is not very large and falls into the interval ( M × T 0 , ( M + 1 ) × T 0 ) with M being a positive integer. In real neuronal system, subthreshold signal detection is very meaningful. Thus, the obtained results in this paper could give some important implications on detecting subthreshold signal and propagating neuronal information in neuronal systems.

  15. Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro.

    Science.gov (United States)

    Bardy, Cedric; van den Hurk, Mark; Eames, Tameji; Marchand, Cynthia; Hernandez, Ruben V; Kellogg, Mariko; Gorris, Mark; Galet, Ben; Palomares, Vanessa; Brown, Joshua; Bang, Anne G; Mertens, Jerome; Böhnke, Lena; Boyer, Leah; Simon, Suzanne; Gage, Fred H

    2015-05-19

    Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely used to culture neurons. We found that classic basal media, as well as serum, impair action potential generation and synaptic communication. To overcome this problem, we designed a new neuronal medium (BrainPhys basal + serum-free supplements) in which we adjusted the concentrations of inorganic salts, neuroactive amino acids, and energetic substrates. We then tested that this medium adequately supports neuronal activity and survival of human neurons in culture. Long-term exposure to this physiological medium also improved the proportion of neurons that were synaptically active. The medium was designed to culture human neurons but also proved adequate for rodent neurons. The improvement in BrainPhys basal medium to support neurophysiological activity is an important step toward reducing the gap between brain physiological conditions in vivo and neuronal models in vitro.

  16. Protocol for culturing low density pure rat hippocampal neurons supported by mature mixed neuron cultures.

    Science.gov (United States)

    Yang, Qian; Ke, Yini; Luo, Jianhong; Tang, Yang

    2017-02-01

    primary hippocampal neuron cultures allow for subcellular morphological dissection, easy access to drug treatment and electrophysiology analysis of individual neurons, and is therefore an ideal model for the study of neuron physiology. While neuron and glia mixed cultures are relatively easy to prepare, pure neurons are particular hard to culture at low densities which are suitable for morphology studies. This may be due to a lack of neurotrophic factors such as brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT3) and Glial cell line-derived neurotrophic factor (GDNF). In this study we used a two step protocol in which neuron-glia mixed cultures were initially prepared for maturation to support the growth of young neurons plated at very low densities. Our protocol showed that neurotrophic support resulted in physiologically functional hippocampal neurons with larger cell body, increased neurite length and decreased branching and complexity compared to cultures prepared using a conventional method. Our protocol provides a novel way to culture highly uniformed hippocampal neurons for acquiring high quality, neuron based data. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Survival motor neuron protein in motor neurons determines synaptic integrity in spinal muscular atrophy.

    Science.gov (United States)

    Martinez, Tara L; Kong, Lingling; Wang, Xueyong; Osborne, Melissa A; Crowder, Melissa E; Van Meerbeke, James P; Xu, Xixi; Davis, Crystal; Wooley, Joe; Goldhamer, David J; Lutz, Cathleen M; Rich, Mark M; Sumner, Charlotte J

    2012-06-20

    The inherited motor neuron disease spinal muscular atrophy (SMA) is caused by deficient expression of survival motor neuron (SMN) protein and results in severe muscle weakness. In SMA mice, synaptic dysfunction of both neuromuscular junctions (NMJs) and central sensorimotor synapses precedes motor neuron cell death. To address whether this synaptic dysfunction is due to SMN deficiency in motor neurons, muscle, or both, we generated three lines of conditional SMA mice with tissue-specific increases in SMN expression. All three lines of mice showed increased survival, weights, and improved motor behavior. While increased SMN expression in motor neurons prevented synaptic dysfunction at the NMJ and restored motor neuron somal synapses, increased SMN expression in muscle did not affect synaptic function although it did improve myofiber size. Together these data indicate that both peripheral and central synaptic integrity are dependent on motor neurons in SMA, but SMN may have variable roles in the maintenance of these different synapses. At the NMJ, it functions at the presynaptic terminal in a cell-autonomous fashion, but may be necessary for retrograde trophic signaling to presynaptic inputs onto motor neurons. Importantly, SMN also appears to function in muscle growth and/or maintenance independent of motor neurons. Our data suggest that SMN plays distinct roles in muscle, NMJs, and motor neuron somal synapses and that restored function of SMN at all three sites will be necessary for full recovery of muscle power.

  18. Glass promotes the differentiation of neuronal and non-neuronal cell types in the Drosophila eye

    Science.gov (United States)

    Morrison, Carolyn A.; Chen, Hao; Cook, Tiffany; Brown, Stuart

    2018-01-01

    Transcriptional regulators can specify different cell types from a pool of equivalent progenitors by activating distinct developmental programs. The Glass transcription factor is expressed in all progenitors in the developing Drosophila eye, and is maintained in both neuronal and non-neuronal cell types. Glass is required for neuronal progenitors to differentiate as photoreceptors, but its role in non-neuronal cone and pigment cells is unknown. To determine whether Glass activity is limited to neuronal lineages, we compared the effects of misexpressing it in neuroblasts of the larval brain and in epithelial cells of the wing disc. Glass activated overlapping but distinct sets of genes in these neuronal and non-neuronal contexts, including markers of photoreceptors, cone cells and pigment cells. Coexpression of other transcription factors such as Pax2, Eyes absent, Lozenge and Escargot enabled Glass to induce additional genes characteristic of the non-neuronal cell types. Cell type-specific glass mutations generated in cone or pigment cells using somatic CRISPR revealed autonomous developmental defects, and expressing Glass specifically in these cells partially rescued glass mutant phenotypes. These results indicate that Glass is a determinant of organ identity that acts in both neuronal and non-neuronal cells to promote their differentiation into functional components of the eye. PMID:29324767

  19. Parkin Mutations Reduce the Complexity of Neuronal Processes in iPSC-derived Human Neurons

    Science.gov (United States)

    Ren, Yong; Jiang, Houbo; Hu, Zhixing; Fan, Kevin; Wang, Jun; Janoschka, Stephen; Wang, Xiaomin; Ge, Shaoyu; Feng, Jian

    2015-01-01

    Parkinson’s disease (PD) is characterized by the degeneration of nigral dopaminergic (DA) neurons and non-DA neurons in many parts of the brain. Mutations of parkin, an E3 ubiquitin ligase that strongly binds to microtubules, are the most frequent cause of recessively inherited Parkinson’s disease. The lack of robust PD phenotype in parkin knockout mice suggests a unique vulnerability of human neurons to parkin mutations. Here, we show that the complexity of neuronal processes as measured by total neurite length, number of terminals, number of branch points and Sholl analysis, was greatly reduced in induced pluripotent stem cell (iPSC)-derived TH+ or TH− neurons from PD patients with parkin mutations. Consistent with these, microtubule stability was significantly decreased by parkin mutations in iPSC-derived neurons. Overexpression of parkin, but not its PD-linked mutant nor GFP, restored the complexity of neuronal processes and the stability of microtubules. Consistent with these, the microtubule-depolymerizing agent colchicine mimicked the effect of parkin mutations by decreasing neurite length and complexity in control neurons while the microtubule-stabilizing drug taxol mimicked the effect of parkin overexpression by enhancing the morphology of parkin-deficient neurons. The results suggest that parkin maintains the morphological complexity of human neurons by stabilizing microtubules. PMID:25332110

  20. Genetic variation in glia-neuron signalling modulates ageing rate.

    Science.gov (United States)

    Yin, Jiang-An; Gao, Ge; Liu, Xi-Juan; Hao, Zi-Qian; Li, Kai; Kang, Xin-Lei; Li, Hong; Shan, Yuan-Hong; Hu, Wen-Li; Li, Hai-Peng; Cai, Shi-Qing

    2017-11-08

    The rate of behavioural decline in the ageing population is remarkably variable among individuals. Despite the considerable interest in studying natural variation in ageing rate to identify factors that control healthy ageing, no such factor has yet been found. Here we report a genetic basis for variation in ageing rates in Caenorhabditis elegans. We find that C. elegans isolates show diverse lifespan and age-related declines in virility, pharyngeal pumping, and locomotion. DNA polymorphisms in a novel peptide-coding gene, named regulatory-gene-for-behavioural-ageing-1 (rgba-1), and the neuropeptide receptor gene npr-28 influence the rate of age-related decline of worm mating behaviour; these two genes might have been subjected to recent selective sweeps. Glia-derived RGBA-1 activates NPR-28 signalling, which acts in serotonergic and dopaminergic neurons to accelerate behavioural deterioration. This signalling involves the SIR-2.1-dependent activation of the mitochondrial unfolded protein response, a pathway that modulates ageing. Thus, natural variation in neuropeptide-mediated glia-neuron signalling modulates the rate of ageing in C. elegans.

  1. Spin switches for compact implementation of neuron and synapse

    International Nuclear Information System (INIS)

    Quang Diep, Vinh; Sutton, Brian; Datta, Supriyo; Behin-Aein, Behtash

    2014-01-01

    Nanomagnets driven by spin currents provide a natural implementation for a neuron and a synapse: currents allow convenient summation of multiple inputs, while the magnet provides the threshold function. The objective of this paper is to explore the possibility of a hardware neural network implementation using a spin switch (SS) as its basic building block. SS is a recently proposed device based on established technology with a transistor-like gain and input-output isolation. This allows neural networks to be constructed with purely passive interconnections without intervening clocks or amplifiers. The weights for the neural network are conveniently adjusted through analog voltages that can be stored in a non-volatile manner in an underlying CMOS layer using a floating gate low dropout voltage regulator. The operation of a multi-layer SS neural network designed for character recognition is demonstrated using a standard simulation model based on coupled Landau-Lifshitz-Gilbert equations, one for each magnet in the network

  2. Spin switches for compact implementation of neuron and synapse

    Energy Technology Data Exchange (ETDEWEB)

    Quang Diep, Vinh, E-mail: vdiep@purdue.edu; Sutton, Brian; Datta, Supriyo [School of Electrical and Computer Engineering, Purdue University, West Lafayette, Indiana 47907 (United States); Behin-Aein, Behtash [GLOBALFOUNDRIES, Inc., Sunnyvale, California 94085 (United States)

    2014-06-02

    Nanomagnets driven by spin currents provide a natural implementation for a neuron and a synapse: currents allow convenient summation of multiple inputs, while the magnet provides the threshold function. The objective of this paper is to explore the possibility of a hardware neural network implementation using a spin switch (SS) as its basic building block. SS is a recently proposed device based on established technology with a transistor-like gain and input-output isolation. This allows neural networks to be constructed with purely passive interconnections without intervening clocks or amplifiers. The weights for the neural network are conveniently adjusted through analog voltages that can be stored in a non-volatile manner in an underlying CMOS layer using a floating gate low dropout voltage regulator. The operation of a multi-layer SS neural network designed for character recognition is demonstrated using a standard simulation model based on coupled Landau-Lifshitz-Gilbert equations, one for each magnet in the network.

  3. Mutation and premating isolation

    Science.gov (United States)

    Woodruff, R. C.; Thompson, J. N. Jr

    2002-01-01

    While premating isolation might be traceable to different genetic mechanisms in different species, evidence supports the idea that as few as one or two genes may often be sufficient to initiate isolation. Thus, new mutation can theoretically play a key role in the process. But it has long been thought that a new isolation mutation would fail, because there would be no other individuals for the isolation-mutation-carrier to mate with. We now realize that premeiotic mutations are very common and will yield a cluster of progeny carrying the same new mutant allele. In this paper, we discuss the evidence for genetically simple premating isolation barriers and the role that clusters of an isolation mutation may play in initiating allopatric, and even sympatric, species divisions.

  4. Evoking prescribed spike times in stochastic neurons

    Science.gov (United States)

    Doose, Jens; Lindner, Benjamin

    2017-09-01

    Single cell stimulation in vivo is a powerful tool to investigate the properties of single neurons and their functionality in neural networks. We present a method to determine a cell-specific stimulus that reliably evokes a prescribed spike train with high temporal precision of action potentials. We test the performance of this stimulus in simulations for two different stochastic neuron models. For a broad range of parameters and a neuron firing with intermediate firing rates (20-40 Hz) the reliability in evoking the prescribed spike train is close to its theoretical maximum that is mainly determined by the level of intrinsic noise.

  5. Response of spiking neurons to correlated inputs

    International Nuclear Information System (INIS)

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

    2002-01-01

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

  6. Physics in isolation

    International Nuclear Information System (INIS)

    Anon.

    1986-01-01

    In late May, about 330 physicists made their way up to isolated and beautiful Lake Louise high in the Canadian Rockies about 100 miles west of Calgary in a second effort to increase interactions between particle and nuclear physicists. The conference series aims to foster exciting and diverse physics by bringing the different physicists together somewhere which is so isolated that they must interact with each other. The formula worked very well and isolated Lake Louise was a huge success

  7. Physics in isolation

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1986-09-15

    In late May, about 330 physicists made their way up to isolated and beautiful Lake Louise high in the Canadian Rockies about 100 miles west of Calgary in a second effort to increase interactions between particle and nuclear physicists. The conference series aims to foster exciting and diverse physics by bringing the different physicists together somewhere which is so isolated that they must interact with each other. The formula worked very well and isolated Lake Louise was a huge success.

  8. Hierarchical clustering of gene expression patterns in the Eomes + lineage of excitatory neurons during early neocortical development

    Directory of Open Access Journals (Sweden)

    Cameron David A

    2012-08-01

    Full Text Available Abstract Background Cortical neurons display dynamic patterns of gene expression during the coincident processes of differentiation and migration through the developing cerebrum. To identify genes selectively expressed by the Eomes + (Tbr2 lineage of excitatory cortical neurons, GFP-expressing cells from Tg(Eomes::eGFP Gsat embryos were isolated to > 99% purity and profiled. Results We report the identification, validation and spatial grouping of genes selectively expressed within the Eomes + cortical excitatory neuron lineage during early cortical development. In these neurons 475 genes were expressed ≥ 3-fold, and 534 genes ≤ 3-fold, compared to the reference population of neuronal precursors. Of the up-regulated genes, 328 were represented at the Genepaint in situ hybridization database and 317 (97% were validated as having spatial expression patterns consistent with the lineage of differentiating excitatory neurons. A novel approach for quantifying in situ hybridization patterns (QISP across the cerebral wall was developed that allowed the hierarchical clustering of genes into putative co-regulated groups. Forty four candidate genes were identified that show spatial expression with Intermediate Precursor Cells, 49 candidate genes show spatial expression with Multipolar Neurons, while the remaining 224 genes achieved peak expression in the developing cortical plate. Conclusions This analysis of differentiating excitatory neurons revealed the expression patterns of 37 transcription factors, many chemotropic signaling molecules (including the Semaphorin, Netrin and Slit signaling pathways, and unexpected evidence for non-canonical neurotransmitter signaling and changes in mechanisms of glucose metabolism. Over half of the 317 identified genes are associated with neuronal disease making these findings a valuable resource for studies of neurological development and disease.

  9. The Relevance of AgRP Neuron-Derived GABA Inputs to POMC Neurons Differs for Spontaneous and Evoked Release.

    Science.gov (United States)

    Rau, Andrew R; Hentges, Shane T

    2017-08-02

    Hypothalamic agouti-related peptide (AgRP) neurons potently stimulate food intake, whereas proopiomelanocortin (POMC) neurons inhibit feeding. Whether AgRP neurons exert their orexigenic actions, at least in part, by inhibiting anorexigenic POMC neurons remains unclear. Here, the connectivity between GABA-releasing AgRP neurons and POMC neurons was examined in brain slices from male and female mice. GABA-mediated spontaneous IPSCs (sIPSCs) in POMC neurons were unaffected by disturbing GABA release from AgRP neurons either by cell type-specific deletion of the vesicular GABA transporter or by expression of botulinum toxin in AgRP neurons to prevent vesicle-associated membrane protein 2-dependent vesicle fusion. Additionally, there was no difference in the ability of μ-opioid receptor (MOR) agonists to inhibit sIPSCs in POMC neurons when MORs were deleted from AgRP neurons, and activation of the inhibitory designer receptor hM4Di on AgRP neurons did not affect sIPSCs recorded from POMC neurons. These approaches collectively indicate that AgRP neurons do not significantly contribute to the strong spontaneous GABA input to POMC neurons. Despite these observations, optogenetic stimulation of AgRP neurons reliably produced evoked IPSCs in POMC neurons, leading to the inhibition of POMC neuron firing. Thus, AgRP neurons can potently affect POMC neuron function without contributing a significant source of spontaneous GABA input to POMC neurons. Together, these results indicate that the relevance of GABAergic inputs from AgRP to POMC neurons is state dependent and highlight the need to consider different types of transmitter release in circuit mapping and physiologic regulation. SIGNIFICANCE STATEMENT Agouti-related peptide (AgRP) neurons play an important role in driving food intake, while proopiomelanocortin (POMC) neurons inhibit feeding. Despite the importance of these two well characterized neuron types in maintaining metabolic homeostasis, communication between these

  10. Effect of correlating adjacent neurons for identifying communications: Feasibility experiment in a cultured neuronal network

    OpenAIRE

    Yoshi Nishitani; Chie Hosokawa; Yuko Mizuno-Matsumoto; Tomomitsu Miyoshi; Shinichi Tamura

    2017-01-01

    Neuronal networks have fluctuating characteristics, unlike the stable characteristics seen in computers. The underlying mechanisms that drive reliable communication among neuronal networks and their ability to perform intelligible tasks remain unknown. Recently, in an attempt to resolve this issue, we showed that stimulated neurons communicate via spikes that propagate temporally, in the form of spike trains. We named this phenomenon “spike wave propagation”. In these previous studies, using ...

  11. Reconstruction of phrenic neuron identity in embryonic stem cell-derived motor neurons.

    Science.gov (United States)

    Machado, Carolina Barcellos; Kanning, Kevin C; Kreis, Patricia; Stevenson, Danielle; Crossley, Martin; Nowak, Magdalena; Iacovino, Michelina; Kyba, Michael; Chambers, David; Blanc, Eric; Lieberam, Ivo

    2014-02-01

    Air breathing is an essential motor function for vertebrates living on land. The rhythm that drives breathing is generated within the central nervous system and relayed via specialised subsets of spinal motor neurons to muscles that regulate lung volume. In mammals, a key respiratory muscle is the diaphragm, which is innervated by motor neurons in the phrenic nucleus. Remarkably, relatively little is known about how this crucial subtype of motor neuron is generated during embryogenesis. Here, we used direct differentiation of motor neurons from mouse embryonic stem cells as a tool to identify genes that direct phrenic neuron identity. We find that three determinants, Pou3f1, Hoxa5 and Notch, act in combination to promote a phrenic neuron molecular identity. We show that Notch signalling induces Pou3f1 in developing motor neurons in vitro and in vivo. This suggests that the phrenic neuron lineage is established through a local source of Notch ligand at mid-cervical levels. Furthermore, we find that the cadherins Pcdh10, which is regulated by Pou3f1 and Hoxa5, and Cdh10, which is controlled by Pou3f1, are both mediators of like-like clustering of motor neuron cell bodies. This specific Pcdh10/Cdh10 activity might provide the means by which phrenic neurons are assembled into a distinct nucleus. Our study provides a framework for understanding how phrenic neuron identity is conferred and will help to generate this rare and inaccessible yet vital neuronal subtype directly from pluripotent stem cells, thus facilitating subsequent functional investigations.

  12. Fitting neuron models to spike trains

    Directory of Open Access Journals (Sweden)

    Cyrille eRossant

    2011-02-01

    Full Text Available Computational modeling is increasingly used to understand the function of neural circuitsin systems neuroscience.These studies require models of individual neurons with realisticinput-output properties.Recently, it was found that spiking models can accurately predict theprecisely timed spike trains produced by cortical neurons in response tosomatically injected currents,if properly fitted. This requires fitting techniques that are efficientand flexible enough to easily test different candidate models.We present a generic solution, based on the Brian simulator(a neural network simulator in Python, which allowsthe user to define and fit arbitrary neuron models to electrophysiological recordings.It relies on vectorization and parallel computing techniques toachieve efficiency.We demonstrate its use on neural recordings in the barrel cortex andin the auditory brainstem, and confirm that simple adaptive spiking modelscan accurately predict the response of cortical neurons. Finally, we show how a complexmulticompartmental model can be reduced to a simple effective spiking model.

  13. 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.

  14. From quantum entanglement to mirror neuron

    International Nuclear Information System (INIS)

    Zak, Michail

    2007-01-01

    It is proposed that two fundamental phenomena: quantum entanglement in physics, and mirror neuron in biopsychology, can be described by using the same mathematical formalism, namely, the feedback from the Liouville equation to equation of motion

  15. Do enteric neurons make hypocretin? ☆

    Science.gov (United States)

    Baumann, Christian R.; Clark, Erika L.; Pedersen, Nigel P.; Hecht, Jonathan L.; Scammell, Thomas E.

    2008-01-01

    Hypocretins (orexins) are wake-promoting neuropeptides produced by hypothalamic neurons. These hypocretin-producing cells are lost in people with narcolepsy, possibly due to an autoimmune attack. Prior studies described hypocretin neurons in the enteric nervous system, and these cells could be an additional target of an autoimmune process. We sought to determine whether enteric hypocretin neurons are lost in narcoleptic subjects. Even though we tried several methods (including whole mounts, sectioned tissue, pre-treatment of mice with colchicine, and the use of various primary antisera), we could not identify hypocretin-producing cells in enteric nervous tissue collected from mice or normal human subjects. These results raise doubts about whether enteric neurons produce hypocretin. PMID:18191238

  16. Advances in 3D neuronal cell culture

    NARCIS (Netherlands)

    Frimat, Jean Philippe; Xie, Sijia; Bastiaens, Alex; Schurink, Bart; Wolbers, Floor; Den Toonder, Jaap; Luttge, Regina

    2015-01-01

    In this contribution, the authors present our advances in three-dimensional (3D) neuronal cell culture platform technology contributing to controlled environments for microtissue engineering and analysis of cellular physiological and pathological responses. First, a micromachined silicon sieving

  17. Review Paper: Polyphenolic Antioxidants and Neuronal Regeneration

    Directory of Open Access Journals (Sweden)

    Amin Ataie

    2016-05-01

    Full Text Available Many studies indicate that oxidative stress is involved in the pathophysiology of neurodegenerative diseases. Oxidative stress can induce neuronal damages, modulate intracellular signaling and ultimately leads to neuronal death by apoptosis or necrosis. To review antioxidants preventive effects on oxidative stress and neurodegenerative diseases we accumulated data from international medical journals and academic informations' sites. According to many studies, antioxidants could reduce toxic neuronal damages and many studies confirmed the efficacy of polyphenol antioxidants in fruits and vegetables to reduce neuronal death and to diminish oxidative stress. This systematic review showed the antioxidant activities of phytochemicals which play as natural neuroprotectives with low adverse effects against some neurodegenerative diseases as Parkinson or Alzheimer diseases.

  18. Review Paper: Polyphenolic Antioxidants and Neuronal Regeneration

    Directory of Open Access Journals (Sweden)

    Amin Ataie

    2016-04-01

    Full Text Available Many studies indicate that oxidative stress is involved in the pathophysiology of neurodegenerative diseases. Oxidative stress can induce neuronal damages, modulate intracellular signaling and ultimately leads to neuronal death by apoptosis or necrosis. To review antioxidants preventive effects on oxidative stress and neurodegenerative diseases we accumulated data from international medical journals and academic informations' sites. According to many studies, antioxidants could reduce toxic neuronal damages and many studies confirmed the efficacy of polyphenol antioxidants in fruits and vegetables to reduce neuronal death and to diminish oxidative stress. This systematic review showed the antioxidant activities of phytochemicals which play as natural neuroprotectives with low adverse effects against some neurodegenerative diseases as Parkinson or Alzheimer diseases.

  19. Frequency-domain analysis of intrinsic neuronal properties using high-resistant electrodes

    Directory of Open Access Journals (Sweden)

    Christian Rössert

    2009-08-01

    Full Text Available Intrinsic cellular properties of neurons in culture or slices are usually studied by the whole cell clamp method using low-resistant patch pipettes. These electrodes allow detailed analyses with standard electrophysiological methods such as current- or voltage-clamp. However, in these preparations large parts of the network and dendritic structures may be removed, thus preventing an adequate study of synaptic signal processing. Therefore, intact in vivo preparations or isolated in vitro whole brains have been used in which intracellular recordings are usually made with sharp, high-resistant electrodes to optimize the impalement of neurons. The general non-linear resistance properties of these electrodes, however, severely limit accurate quantitative studies of membrane dynamics especially needed for precise modelling. Therefore, we have developed a frequency-domain analysis of membrane properties that uses a Piece-wise Non-linear Electrode Compensation (PNEC method. The technique was tested in second-order vestibular neurons and abducens motoneurons of isolated frog whole brain preparations using sharp potassium chloride- or potassium acetate-filled electrodes. All recordings were performed without online electrode compensation. The properties of each electrode were determined separately after the neuronal recordings and were used in the frequency-domain analysis of the combined measurement of electrode and cell. This allowed detailed analysis of membrane properties in the frequency-domain with high-resistant electrodes and provided quantitative data that can be further used to model channel kinetics. Thus, sharp electrodes can be used for the characterization of intrinsic properties and synaptic inputs of neurons in intact brains.

  20. AgRP neurons regulate development of dopamine neuronal plasticity and nonfood-associated behaviors

    Science.gov (United States)

    Dietrich, Marcelo O; Bober, Jeremy; Ferreira, Jozélia G; Tellez, Luis A; Mineur, Yann S; Souza, Diogo O; Gao, Xiao-Bing; Picciotto, Marina R; Araújo, Ivan; Liu, Zhong-Wu; Horvath, Tamas L

    2012-01-01

    It is not known whether behaviors unrelated to feeding are affected by hypothalamic regulators of hunger. We found that impairment of Agouti-related protein (AgRP) circuitry by either Sirt1 knockdown in AgRP-expressing neurons or early postnatal ablation of these neurons increased exploratory behavior and enhanced responses to cocaine. In AgRP circuit–impaired mice, ventral tegmental dopamine neurons exhibited enhanced spike timing–dependent long-term potentiation, altered amplitude of miniature postsynaptic currents and elevated dopamine in basal forebrain. Thus, AgRP neurons determine the set point of the reward circuitry and associated behaviors. PMID:22729177

  1. Labeling of neuronal differentiation and neuron cells with biocompatible fluorescent nanodiamonds.

    Science.gov (United States)

    Hsu, Tzu-Chia; Liu, Kuang-Kai; Chang, Huan-Cheng; Hwang, Eric; Chao, Jui-I

    2014-05-16

    Nanodiamond is a promising carbon nanomaterial developed for biomedical applications. Here, we show fluorescent nanodiamond (FND) with the biocompatible properties that can be used for the labeling and tracking of neuronal differentiation and neuron cells derived from embryonal carcinoma stem (ECS) cells. The fluorescence intensities of FNDs were increased by treatment with FNDs in both the mouse P19 and human NT2/D1 ECS cells. FNDs were taken into ECS cells; however, FNDs did not alter the cellular morphology and growth ability. Moreover, FNDs did not change the protein expression of stem cell marker SSEA-1 of ECS cells. The neuronal differentiation of ECS cells could be induced by retinoic acid (RA). Interestingly, FNDs did not affect on the morphological alteration, cytotoxicity and apoptosis during the neuronal differentiation. Besides, FNDs did not alter the cell viability and the expression of neuron-specific marker β-III-tubulin in these differentiated neuron cells. The existence of FNDs in the neuron cells can be identified by confocal microscopy and flow cytometry. Together, FND is a biocompatible and readily detectable nanomaterial for the labeling and tracking of neuronal differentiation process and neuron cells from stem cells.

  2. Neuronal growth on L- and D-cysteine self-assembled monolayers reveals neuronal chiral sensitivity.

    Science.gov (United States)

    Baranes, Koby; Moshe, Hagay; Alon, Noa; Schwartz, Shmulik; Shefi, Orit

    2014-05-21

    Studying the interaction between neuronal cells and chiral molecules is fundamental for the design of novel biomaterials and drugs. Chirality influences all biological processes that involve intermolecular interaction. One common method used to study cellular interactions with different enantiomeric targets is the use of chiral surfaces. Based on previous studies that demonstrated the importance of cysteine in the nervous system, we studied the effect of L- and D-cysteine on single neuronal growth. L-Cysteine, which normally functions as a neuromodulator or a neuroprotective antioxidant, causes damage at elevated levels, which may occur post trauma. In this study, we grew adult neurons in culture enriched with L- and D-cysteine as free compounds or as self-assembled monolayers of chiral surfaces and examined the effect on the neuronal morphology and adhesion. Notably, we have found that exposure to the L-cysteine enantiomer inhibited, and even prevented, neuronal attachment more severely than exposure to the D-cysteine enantiomer. Atop the L-cysteine surfaces, neuronal growth was reduced and degenerated. Since the cysteine molecules were attached to the surface via the thiol groups, the neuronal membrane was exposed to the molecular chiral site. Thus, our results have demonstrated high neuronal chiral sensitivity, revealing chiral surfaces as indirect regulators of neuronal cells and providing a reference for studying chiral drugs.

  3. A neuron-astrocyte transistor-like model for neuromorphic dressed neurons.

    Science.gov (United States)

    Valenza, G; Pioggia, G; Armato, A; Ferro, M; Scilingo, E P; De Rossi, D

    2011-09-01

    Experimental evidences on the role of the synaptic glia as an active partner together with the bold synapse in neuronal signaling and dynamics of neural tissue strongly suggest to investigate on a more realistic neuron-glia model for better understanding human brain processing. Among the glial cells, the astrocytes play a crucial role in the tripartite synapsis, i.e. the dressed neuron. A well-known two-way astrocyte-neuron interaction can be found in the literature, completely revising the purely supportive role for the glia. The aim of this study is to provide a computationally efficient model for neuron-glia interaction. The neuron-glia interactions were simulated by implementing the Li-Rinzel model for an astrocyte and the Izhikevich model for a neuron. Assuming the dressed neuron dynamics similar to the nonlinear input-output characteristics of a bipolar junction transistor, we derived our computationally efficient model. This model may represent the fundamental computational unit for the development of real-time artificial neuron-glia networks opening new perspectives in pattern recognition systems and in brain neurophysiology. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. NBLAST: Rapid, Sensitive Comparison of Neuronal Structure and Construction of Neuron Family Databases.

    Science.gov (United States)

    Costa, Marta; Manton, James D; Ostrovsky, Aaron D; Prohaska, Steffen; Jefferis, Gregory S X E

    2016-07-20

    Neural circuit mapping is generating datasets of tens of thousands of labeled neurons. New computational tools are needed to search and organize these data. We present NBLAST, a sensitive and rapid algorithm, for measuring pairwise neuronal similarity. NBLAST considers both position and local geometry, decomposing neurons into short segments; matched segments are scored using a probabilistic scoring matrix defined by statistics of matches and non-matches. We validated NBLAST on a published dataset of 16,129 single Drosophila neurons. NBLAST can distinguish neuronal types down to the finest level (single identified neurons) without a priori information. Cluster analysis of extensively studied neuronal classes identified new types and unreported topographical features. Fully automated clustering organized the validation dataset into 1,052 clusters, many of which map onto previously described neuronal types. NBLAST supports additional query types, including searching neurons against transgene expression patterns. Finally, we show that NBLAST is effective with data from other invertebrates and zebrafish. VIDEO ABSTRACT. Copyright © 2016 MRC Laboratory of Molecular Biology. Published by Elsevier Inc. All rights reserved.

  5. Intrinsically active and pacemaker neurons in pluripotent stem cell-derived neuronal populations.

    Science.gov (United States)

    Illes, Sebastian; Jakab, Martin; Beyer, Felix; Gelfert, Renate; Couillard-Despres, Sébastien; Schnitzler, Alfons; Ritter, Markus; Aigner, Ludwig

    2014-03-11

    Neurons generated from pluripotent stem cells (PSCs) self-organize into functional neuronal assemblies in vitro, generating synchronous network activities. Intriguingly, PSC-derived neuronal assemblies develop spontaneous activities that are independent of external stimulation, suggesting the presence of thus far undetected intrinsically active neurons (IANs). Here, by using mouse embryonic stem cells, we provide evidence for the existence of IANs in PSC-neuronal networks based on extracellular multielectrode array and intracellular patch-clamp recordings. IANs remain active after pharmacological inhibition of fast synaptic communication and possess intrinsic mechanisms required for autonomous neuronal activity. PSC-derived IANs are functionally integrated in PSC-neuronal populations, contribute to synchronous network bursting, and exhibit pacemaker properties. The intrinsic activity and pacemaker properties of the neuronal subpopulation identified herein may be particularly relevant for interventions involving transplantation of neural tissues. IANs may be a key element in the regulation of the functional activity of grafted as well as preexisting host neuronal networks.

  6. Effects of weak electric fields on the activity of neurons and neuronal networks

    International Nuclear Information System (INIS)

    Jeffreys, J.G.R.; Deans, J.; Bikson, M.; Fox, J.

    2003-01-01

    Electric fields applied to brain tissue will affect cellular properties. They will hyperpolarise the ends of cells closest to the positive part of the field, and depolarise ends closest to the negative. In the case of neurons this affects excitability. How these changes in transmembrane potential are distributed depends on the length constant of the neuron, and on its geometry; if the neuron is electrically compact, the change in transmembrane potential becomes an almost linear function of distance in the direction of the field. Neurons from the mammalian hippocampus, maintained in tissue slices in vitro, are significantly affected by fields of around 1-5 Vm -1 . (author)

  7. Statistics of Visual Responses to Image Object Stimuli from Primate AIT Neurons to DNN Neurons.

    Science.gov (United States)

    Dong, Qiulei; Wang, Hong; Hu, Zhanyi

    2018-02-01

    Under the goal-driven paradigm, Yamins et al. ( 2014 ; Yamins & DiCarlo, 2016 ) have shown that by optimizing only the final eight-way categorization performance of a four-layer hierarchical network, not only can its top output layer quantitatively predict IT neuron responses but its penultimate layer can also automatically predict V4 neuron responses. Currently, deep neural networks (DNNs) in the field of computer vision have reached image object categorization performance comparable to that of human beings on ImageNet, a data set that contains 1.3 million training images of 1000 categories. We explore whether the DNN neurons (units in DNNs) possess image object representational statistics similar to monkey IT neurons, particularly when the network becomes deeper and the number of image categories becomes larger, using VGG19, a typical and widely used deep network of 19 layers in the computer vision field. Following Lehky, Kiani, Esteky, and Tanaka ( 2011 , 2014 ), where the response statistics of 674 IT neurons to 806 image stimuli are analyzed using three measures (kurtosis, Pareto tail index, and intrinsic dimensionality), we investigate the three issues in this letter using the same three measures: (1) the similarities and differences of the neural response statistics between VGG19 and primate IT cortex, (2) the variation trends of the response statistics of VGG19 neurons at different layers from low to high, and (3) the variation trends of the response statistics of VGG19 neurons when the numbers of stimuli and neurons increase. We find that the response statistics on both single-neuron selectivity and population sparseness of VGG19 neurons are fundamentally different from those of IT neurons in most cases; by increasing the number of neurons in different layers and the number of stimuli, the response statistics of neurons at different layers from low to high do not substantially change; and the estimated intrinsic dimensionality values at the low

  8. 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.

  9. Progranulin regulates neuronal outgrowth independent of Sortilin

    Directory of Open Access Journals (Sweden)

    Gass Jennifer

    2012-07-01

    Full Text Available Abstract Background Progranulin (PGRN, a widely secreted growth factor, is involved in multiple biological functions, and mutations located within the PGRN gene (GRN are a major cause of frontotemporal lobar degeneration with TDP-43-positive inclusions (FLTD-TDP. In light of recent reports suggesting PGRN functions as a protective neurotrophic factor and that sortilin (SORT1 is a neuronal receptor for PGRN, we used a Sort1-deficient (Sort1−/− murine primary hippocampal neuron model to investigate whether PGRN’s neurotrophic effects are dependent on SORT1. We sought to elucidate this relationship to determine what role SORT1, as a regulator of PGRN levels, plays in modulating PGRN’s neurotrophic effects. Results As the first group to evaluate the effect of PGRN loss in Grn knockout primary neuronal cultures, we show neurite outgrowth and branching are significantly decreased in Grn−/− neurons compared to wild-type (WT neurons. More importantly, we also demonstrate that PGRN overexpression can rescue this phenotype. However, the recovery in outgrowth is not observed following treatment with recombinant PGRN harboring missense mutations p.C139R, p.P248L or p.R432C, indicating that these mutations adversely affect the neurotrophic properties of PGRN. In addition, we also present evidence that cleavage of full-length PGRN into granulin peptides is required for increased neuronal outgrowth, suggesting that the neurotrophic functions of PGRN are contained within certain granulins. To further characterize the mechanism by which PGRN impacts neuronal morphology, we assessed the involvement of SORT1. We demonstrate that PGRN induced-outgrowth occurs in the absence of SORT1 in Sort1−/− cultures. Conclusion We demonstrate that loss of PGRN impairs proper neurite outgrowth and branching, and that exogenous PGRN alleviates this impairment. Furthermore, we determined that exogenous PGRN induces outgrowth independent of SORT1, suggesting another

  10. Action observation: Inferring intentions without mirror neurons

    DEFF Research Database (Denmark)

    Frith, Christopher; Kilner, James M

    2008-01-01

    A recent study has shown, using fMRI, that the mirror neuron system does not mediate action understanding when the observed action is novel or when it is hard to understand.......A recent study has shown, using fMRI, that the mirror neuron system does not mediate action understanding when the observed action is novel or when it is hard to understand....

  11. Unidirectional synchronization of Hodgkin-Huxley neurons

    Energy Technology Data Exchange (ETDEWEB)

    Cornejo-Perez, Octavio [Division de Matematicas Aplicadas y Sistemas, Computacionales, IPICYT, Apdo. Postal 3-74 Tangamanga, 78231 San Luis Potosi (Mexico)]. E-mail: octavio@ipicyt.edu.mx; Femat, Ricardo [Division de Matematicas Aplicadas y Sistemas, Computacionales, IPICYT, Apdo. Postal 3-74 Tangamanga, 78231 San Luis Potosi (Mexico)]. E-mail: rfemat@ipicyt.edu.mx

    2005-07-01

    Synchronization dynamics of two noiseless Hodgkin-Huxley (HH) neurons under the action of feedback control is studied. The spiking patterns of the action potentials evoked by periodic external modulations attain synchronization states under the feedback action. Numerical simulations for the synchronization dynamics of regular-irregular desynchronized spiking sequences are displayed. The results are discussed in context of generalized synchronization. It is also shown that the HH neurons can be synchronized in face of unmeasured states.

  12. Arsenic Trioxide Modulates the Central Snail Neuron Action Potential

    Directory of Open Access Journals (Sweden)

    Guan-Ling Lu

    2009-09-01

    Conclusion: As2O3 at 10 mM elicits BoPs in central snail neurons and this effect may relate to the PLC activity of the neuron, rather than protein kinase A activity, or calcium influxes of the neuron. As2O3 at higher concentration irreversibly abolishes the spontaneous action potentials of the neuron.

  13. Isolated optic nerve pseudotumour

    International Nuclear Information System (INIS)

    Patankar, T.; Prasad, S.; Krishnan, A.; Laxminarayan, R.

    2000-01-01

    Isolated optic nerve involvement by the idiopathic inflammatory process is a rare finding and very few reports are available. Here a case of an isolated optic nerve inflammatory pseudotumour presenting with gradually progressive unilateral loss of vision is described. It showed dramatic response to a trial of steroids and its differential diagnoses are discussed. Copyright (1999) Blackwell Science Pty Ltd

  14. 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

  15. The transfer function of neuron spike.

    Science.gov (United States)

    Palmieri, Igor; Monteiro, Luiz H A; Miranda, Maria D

    2015-08-01

    The mathematical modeling of neuronal signals is a relevant problem in neuroscience. The complexity of the neuron behavior, however, makes this problem a particularly difficult task. Here, we propose a discrete-time linear time-invariant (LTI) model with a rational function in order to represent the neuronal spike detected by an electrode located in the surroundings of the nerve cell. The model is presented as a cascade association of two subsystems: one that generates an action potential from an input stimulus, and one that represents the medium between the cell and the electrode. The suggested approach employs system identification and signal processing concepts, and is dissociated from any considerations about the biophysical processes of the neuronal cell, providing a low-complexity alternative to model the neuronal spike. The model is validated by using in vivo experimental readings of intracellular and extracellular signals. A computational simulation of the model is presented in order to assess its proximity to the neuronal signal and to observe the variability of the estimated parameters. The implications of the results are discussed in the context of spike sorting. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Endocannabinoids mediate neuron-astrocyte communication.

    Science.gov (United States)

    Navarrete, Marta; Araque, Alfonso

    2008-03-27

    Cannabinoid receptors play key roles in brain function, and cannabinoid effects in brain physiology and drug-related behavior are thought to be mediated by receptors present in neurons. Neuron-astrocyte communication relies on the expression by astrocytes of neurotransmitter receptors. Yet, the expression of cannabinoid receptors by astrocytes in situ and their involvement in the neuron-astrocyte communication remain largely unknown. We show that hippocampal astrocytes express CB1 receptors that upon activation lead to phospholipase C-dependent Ca2+ mobilization from internal stores. These receptors are activated by endocannabinoids released by neurons, increasing astrocyte Ca2+ levels, which stimulate glutamate release that activates NMDA receptors in pyramidal neurons. These results demonstrate the existence of endocannabinoid-mediated neuron-astrocyte communication, revealing that astrocytes are targets of cannabinoids and might therefore participate in the physiology of cannabinoid-related addiction. They also reveal the existence of an endocannabinoid-glutamate signaling pathway where astrocytes serve as a bridge for nonsynaptic interneuronal communication.

  17. (-)1-(Benzofuran-2-yl)-2-propylaminopentane, [(-)BPAP], a selective enhancer of the impulse propagation mediated release of catecholamines and serotonin in the brain.

    Science.gov (United States)

    Knoll, J; Yoneda, F; Knoll, B; Ohde, H; Miklya, I

    1999-12-01

    1. The brain constituents beta-phenylethylamine (PEA) and tryptamine enhance the impulse propagation mediated transmitter release (exocytosis) from the catecholaminergic and serotoninergic neurons in the brain ('catecholaminergic/serotoninergic activity enhancer, CAE/SAE, effect'). (-)Deprenyl (Selegiline) and (-)1-phenyl-2-propylaminopentane [(-)PPAP] are amphetamine derived CAE substances devoid of the catecholamine releasing property. 2. By changing the aromatic ring in PPAP we developed highly potent and selective CAE/SAE substances, structurally unrelated to the amphetamines. Out of 65 newly synthetized compounds, a tryptamine derived structure, (-)1-(benzofuran-2-yl)-2-propylaminopentane [(-)BPAP] was selected as a potential follower of (-)deprenyl in the clinic and as a reference compound for further analysis of the CAE/SAE mechanism in the mammalian brain. 3. (-)BPAP significantly enhanced in 0.18 micromol 1(-1) concentration the impulse propagation mediated release of [(3)H]-noradrenaline and [(3)H]-dopamine and in 36 nmol 1(-1) concentration the release of [(3)H]-serotonin from the isolated brain stem of rats. The amount of catecholamines and serotonin released from isolated discrete rat brain regions (dopamine from the striatum, substantia nigra and tuberculum olfactorium, noradrenaline from the locus coeruleus and serotonin from the raphe) enhanced significantly in the presence of 10(-12) - 10(-14) M (-)BPAP. BPAP protected cultured hippocampal neurons from the neurotoxic effect of beta-amyloid in 10(-14) M concentration. In rats (-)BPAP significantly enhanced the activity of the catecholaminergic and serotoninergic neurons in the brain 30 min after acute injection of 0.1 microg kg(-1) s.c. In the shuttle box, (-)BPAP in rats was about 130 times more potent than (-)deprenyl in antagonizing tetrabenazine induced inhibition of performance.

  18. (−)1-(Benzofuran-2-yl)-2-propylaminopentane, [(−)BPAP], a selective enhancer of the impulse propagation mediated release of catecholamines and serotonin in the brain

    Science.gov (United States)

    Knoll, Joseph; Yoneda, Fumio; Knoll, Berta; Ohde, Hironori; Miklya, Ildikó

    1999-01-01

    The brain constituents β-phenylethylamine (PEA) and tryptamine enhance the impulse propagation mediated transmitter release (exocytosis) from the catecholaminergic and serotoninergic neurons in the brain (‘catecholaminergic/serotoninergic activity enhancer, CAE/SAE, effect'). (−)Deprenyl (Selegiline) and (−)1-phenyl-2-propylaminopentane [(−)PPAP] are amphetamine derived CAE substances devoid of the catecholamine releasing property.By changing the aromatic ring in PPAP we developed highly potent and selective CAE/SAE substances, structurally unrelated to the amphetamines. Out of 65 newly synthetized compounds, a tryptamine derived structure, (−)1-(benzofuran-2-yl)-2-propylaminopentane [(−)BPAP] was selected as a potential follower of (−)deprenyl in the clinic and as a reference compound for further analysis of the CAE/SAE mechanism in the mammalian brain.(−)BPAP significantly enhanced in 0.18 μmol 1−1 concentration the impulse propagation mediated release of [3H]-noradrenaline and [3H]-dopamine and in 36 nmol 1−1 concentration the release of [3H]-serotonin from the isolated brain stem of rats. The amount of catecholamines and serotonin released from isolated discrete rat brain regions (dopamine from the striatum, substantia nigra and tuberculum olfactorium, noradrenaline from the locus coeruleus and serotonin from the raphe) enhanced significantly in the presence of 10−12–10−14 M (−)BPAP. BPAP protected cultured hippocampal neurons from the neurotoxic effect of β-amyloid in 10−14 M concentration. In rats (−)BPAP significantly enhanced the activity of the catecholaminergic and serotoninergic neurons in the brain 30 min after acute injection of 0.1 μg kg−1 s.c. In the shuttle box, (−)BPAP in rats was about 130 times more potent than (−)deprenyl in antagonizing tetrabenazine induced inhibition of performance. PMID:10588928

  19. Graphene foam as a biocompatible scaffold for culturing human neurons

    Science.gov (United States)

    Mattei, Cristiana; Nasr, Babak; Hudson, Emma J.; Alshawaf, Abdullah J.; Chana, Gursharan; Everall, Ian P.; Dottori, Mirella; Skafidas, Efstratios

    2018-01-01

    In this study, we explore the use of electrically active graphene foam as a scaffold for the culture of human-derived neurons. Human embryonic stem cell (hESC)-derived cortical neurons fated as either glutamatergic or GABAergic neuronal phenotypes were cultured on graphene foam. We show that graphene foam is biocompatible for the culture of human neurons, capable of supporting cell viability and differentiation of hESC-derived cortical neurons. Based on the findings, we propose that graphene foam represents a suitable scaffold for engineering neuronal tissue and warrants further investigation as a model for understanding neuronal maturation, function and circuit formation. PMID:29657752

  20. Neuroglobin overexpression inhibits oxygen-glucose deprivation-induced mitochondrial permeability transition pore opening in primary cultured mouse cortical neurons.

    Science.gov (United States)

    Yu, Zhanyang; Liu, Ning; Li, Yadan; Xu, Jianfeng; Wang, Xiaoying

    2013-08-01

    Neuroglobin (Ngb) is an endogenous neuroprotective molecule against hypoxic/ischemic brain injury, but the underlying mechanisms remain largely undefined. Our recent study revealed that Ngb can bind to voltage-dependent anion channel (VDAC), a regulator of mitochondria permeability transition (MPT). In this study we examined the role of Ngb in MPT pore (mPTP) opening following oxygen-glucose deprivation (OGD) in primary cultured mouse cortical neurons. Co-immunoprecipitation (Co-IP) and immunocytochemistry showed that the binding between Ngb and VDAC was increased after OGD compared to normoxia, indicating the OGD-enhanced Ngb-VDAC interaction. Ngb overexpression protected primary mouse cortical neurons from OGD-induced neuronal death, to an extent comparable to mPTP opening inhibitor, cyclosporine A (CsA) pretreatment. We further measured the role of Ngb in OGD-induced mPTP opening using Ngb overexpression and knockdown approaches in primary cultured neurons, and recombinant Ngb exposure to isolated mitochondria. Same as CsA pretreatment, Ngb overexpression significantly reduced OGD-induced mPTP opening markers including mitochondria swelling, mitochondrial NAD(+) release, and cytochrome c (Cyt c) release in primary cultured neurons. Recombinant Ngb incubation significantly reduced OGD-induced NAD(+) release and Cyt c release from isolated mitochondria. In contrast, Ngb knockdown significantly increased OGD-induced neuron death, and increased OGD-induced mitochondrial NAD(+) release and Cyt c release as well, and these outcomes could be rescued by CsA pretreatment. In summary, our results demonstrated that Ngb overexpression can inhibit OGD-induced mPTP opening in primary cultured mouse cortical neurons, which may be one of the molecular mechanisms of Ngb's neuroprotection. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Effects of Social Isolation on Glucocorticoid Regulation in Social Mammals

    Science.gov (United States)

    Hawkley, Louise C.; Cole, Steve W.; Capitanio, John P.; Norman, Greg J.; Cacioppo, John T.

    2012-01-01

    The regulation and function of the hypothalamic-pituitary-adrenocortical (HPA) axis and glucocorticoids have been well conserved across vertebrate species. Glucocorticoids influence a wide range of physiological functions that include glucose regulation, metabolism, inflammatory control, as well as cardiovascular, reproductive, and neuronal effects. Some of these are relatively quick-acting non-genomic effects, but most are slower-acting genomic effects. Thus, any stimulus that affects HPA function has the potential to exert wide-ranging short-term and long-term effects on much of vertebrate physiology. Here, we review the effects of social isolation on the functioning of the HPA axis in social species, and on glucocorticoid physiology in social mammals in particular. Evidence indicates that objective and perceived social isolation alter HPA regulation, although the nature and direction of the HPA response differs among species and across age. The inconsistencies in the direction and nature of HPA effects have implications for drawing cross-species conclusions about the effects of social isolation, and are particularly problematic for understanding HPA-related physiological processes in humans. The animal and human data are incommensurate because, for example, animal studies of objective isolation have typically not been modeled on, or for comparability with, the subjective experience of isolation in humans. An animal model of human isolation must be taken more seriously if we want to advance our understanding of the mechanisms for the effects of objective and perceived isolation in humans. PMID:22663934

  2. Neuron matters: electric activation of neuronal tissue is dependent on the interaction between the neuron and the electric field.

    Science.gov (United States)

    Ye, Hui; Steiger, Amanda

    2015-08-12

    In laboratory research and clinical practice, externally-applied electric fields have been widely used to control neuronal activity. It is generally accepted that neuronal excitability is controlled by electric current that depolarizes or hyperpolarizes the excitable cell membrane. What determines the amount of polarization? Research on the mechanisms of electric stimulation focus on the optimal control of the field properties (frequency, amplitude, and direction of the electric currents) to improve stimulation outcomes. Emerging evidence from modeling and experimental studies support the existence of interactions between the targeted neurons and the externally-applied electric fields. With cell-field interaction, we suggest a two-way process. When a neuron is positioned inside an electric field, the electric field will induce a change in the resting membrane potential by superimposing an electrically-induced transmembrane potential (ITP). At the same time, the electric field can be perturbed and re-distributed by the cell. This cell-field interaction may play a significant role in the overall effects of stimulation. The redistributed field can cause secondary effects to neighboring cells by altering their geometrical pattern and amount of membrane polarization. Neurons excited by the externally-applied electric field can also affect neighboring cells by ephaptic interaction. Both aspects of the cell-field interaction depend on the biophysical properties of the neuronal tissue, including geometric (i.e., size, shape, orientation to the field) and electric (i.e., conductivity and dielectricity) attributes of the cells. The biophysical basis of the cell-field interaction can be explained by the electromagnetism theory. Further experimental and simulation studies on electric stimulation of neuronal tissue should consider the prospect of a cell-field interaction, and a better understanding of tissue inhomogeneity and anisotropy is needed to fully appreciate the neural

  3. Distinct Laterality in Forelimb-Movement Representations of Rat Primary and Secondary Motor Cortical Neurons with Intratelencephalic and Pyramidal Tract Projections.

    Science.gov (United States)

    Soma, Shogo; Saiki, Akiko; Yoshida, Junichi; Ríos, Alain; Kawabata, Masanori; Sakai, Yutaka; Isomura, Yoshikazu

    2017-11-08

    Two distinct motor areas, the primary and secondary motor cortices (M1 and M2), play crucial roles in voluntary movement in rodents. The aim of this study was to characterize the laterality in motor cortical representations of right and left forelimb movements. To achieve this goal, we developed a novel behavioral task, the Right-Left Pedal task, in which a head-restrained male rat manipulates a right or left pedal with the corresponding forelimb. This task enabled us to monitor independent movements of both forelimbs with high spatiotemporal resolution. We observed phasic movement-related neuronal activity (Go-type) and tonic hold-related activity (Hold-type) in isolated unilateral movements. In both M1 and M2, Go-type neurons exhibited bias toward contralateral preference, whereas Hold-type neurons exhibited no bias. The contralateral bias was weaker in M2 than M1. Moreover, we differentiated between intratelencephalic (IT) and pyramidal tract (PT) neurons using optogenetically evoked spike collision in rats expressing channelrhodopsin-2. Even in identified PT and IT neurons, Hold-type neurons exhibited no lateral bias. Go-type PT neurons exhibited bias toward contralateral preference, whereas IT neurons exhibited no bias. Our findings suggest a different laterality of movement representations of M1 and M2, in each of which IT neurons are involved in cooperation of bilateral movements, whereas PT neurons control contralateral movements. SIGNIFICANCE STATEMENT In rodents, the primary and secondary motor cortices (M1 and M2) are involved in voluntary movements via distinct projection neurons: intratelencephalic (IT) neurons and pyramidal tract (PT) neurons. However, it remains unclear whether the two motor cortices (M1 vs M2) and the two classes of projection neurons (IT vs PT) have different laterality of movement representations. We optogenetically identified these neurons and analyzed their functional activity using a novel behavioral task to monitor movements

  4. Adult neuronal ceroid-lipofuscinosis.

    Science.gov (United States)

    Goebel, H H; Braak, H

    1989-01-01

    Among the different clinical forms of neuronal ceroid-lipofuscinosis (NCL), the adult type is the least frequent, most sporadic and most difficult one to diagnose. Clinical symptomatology differs from the classical childhood NCL forms in that ocular symptoms are absent while changes of behavior, dementia and seizures dominate the clinical picture. Excessive accumulation of NCL-specific lipopigments has largely been explored in the nervous system, where pigmento-architectonic investigations disclose layer-specific cortical pathology similar to but less pronounced than that of juvenile and protracted juvenile NCL. Ultrastructural analysis of lipopigments in adult NCL reveals diversity of lipopigment fine structure, but less impressive than in the childhood forms of NCL. Abnormal accretion of lipopigments outside the nervous system has rarely been demonstrated and requires ampler documentation, making in vivo diagnosis of adult NCL often difficult and sometimes equivocal. Adult NCL is now frequently considered identical to "Kufs' disease". However, in the past, the latter term has comprised a heterogeneous spectrum of lipidoses the NCL-nature of which had not been unequivocally established. Thus, one may either speak of "Kufs' syndrome" or abandon this term altogether. Although patients afflicted with adult NCL may suffer from Kufs' disease, not all who have and had Kufs disease may have or have had adult NCL. The current debate on adult NCL centers around scepticism concerning many of the earlier reports, on incorporating diagnostic studies of non-CNS organs in presumptive patients and on distinguishing adult NCL from "atypical" patients or forms of NCL, as well as other disorders marked by non-specific abnormal accumulation of lipofuscin.

  5. A central pattern generator producing alternative outputs: pattern, strength, and dynamics of premotor synaptic input to leech heart motor neurons.

    Science.gov (United States)

    Norris, Brian J; Weaver, Adam L; Wenning, Angela; García, Paul S; Calabrese, Ronald L

    2007-11-01

    The central pattern generator (CPG) for heartbeat in medicinal leeches consists of seven identified pairs of segmental heart interneurons and one unidentified pair. Four of the identified pairs and the unidentified pair of interneurons make inhibitory synaptic connections with segmental heart motor neurons. The CPG produces a side-to-side asymmetric pattern of intersegmental coordination among ipsilateral premotor interneurons corresponding to a similarly asymmetric fictive motor pattern in heart motor neurons, and asymmetric constriction pattern of the two tubular hearts, synchronous and peristaltic. Using extracellular recordings from premotor interneurons and voltage-clamp recordings of ipsilateral segmental motor neurons in 69 isolated nerve cords, we assessed the strength and dynamics of premotor inhibitory synaptic output onto the entire ensemble of heart motor neurons and the associated conduction delays in both coordination modes. We conclude that premotor interneurons establish a stereotypical pattern of intersegmental synaptic connectivity, strengths, and dynamics that is invariant across coordination modes, despite wide variations among preparations. These data coupled with a previous description of the temporal pattern of premotor interneuron activity and relative phasing of motor neuron activity in the two coordination modes enable a direct assessment of how premotor interneurons through their temporal pattern of activity and their spatial pattern of synaptic connectivity, strengths, and dynamics coordinate segmental motor neurons into a functional pattern of activity.

  6. Expression profile of vesicular nucleotide transporter (VNUT, SLC17A9) in subpopulations of rat dorsal root ganglion neurons.

    Science.gov (United States)

    Nishida, Kentaro; Nomura, Yuka; Kawamori, Kanako; Moriyama, Yoshinori; Nagasawa, Kazuki

    2014-09-05

    ATP plays an important role in the signal transduction between sensory neurons and satellite cells in dorsal root ganglia (DRGs). In primary cultured DRG neurons, ATP is known to be stored in lysosomes via a vesicular nucleotide transporter (VNUT), and to be released into the intercellular space through exocytosis. DRGs consist of large-, medium- and small-sized neurons, which play different roles in sensory transmission, but there is no information on the expression profiles of VNUT in DRG subpopulations. Here, we obtained detailed expression profiles of VNUT in isolated rat DRG tissues. On immunohistochemical analysis, VNUT was found in DRG neurons, and was predominantly expressed by the small- and medium-sized DRG ones, as judged upon visual inspection, and this was compatible with the finding that the number of VNUT-positive DRG neurons in IB4-positive cells was greater than that in NF200-positive ones. These results suggest that VNUT play a role in ATP accumulation in DRG neurons, especially in small- and medium-sized ones, and might be involved in ATP-mediated nociceptive signaling in DRGs. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Synchronization of Coupled Neurons Controlled by a Pacemaker

    International Nuclear Information System (INIS)

    Li Mei-Sheng; Zhang Hong-Hui; Zhao Yong; Shi Xia

    2011-01-01

    We investigate synchronization of Hindmarsh—Rose neurons with gap junctions under the control of a pacemaker. In a ring Hindmarsh—Rose neuronal network, the coupled neurons with the pacemaker can occur in synchronization more easily than those without the pacemaker. Furthermore, the pacemaker can induce phase synchronization or nearly-complete synchronization of nonidentical neurons. This synchronization can occur more easily when time delay is considered. Theses results can be helpful to understand the activities of the real neuronal system. (general)

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

    Science.gov (United States)

    O'Mullane, Lauren M; Keast, Janet R; Osborne, Peregrine B

    2013-08-01

    Recent evidence suggests that the urothelium functions as a sensory transducer of chemical, mechanical or thermal stimuli and signals to nerve terminals and other cells in the bladder wall. The cellular and molecular basis of neuro-urothelial communication is not easily studied in the intact bladder. This led us to establish a method of co-culturing dorsal root ganglion sensory neurons and bladder urothelial cells. Sensory neurons and urothelial cells obtained from dorsal root ganglia and bladders dissected from adult female Sprague-Dawley® rats were isolated by enzyme treatment and mechanical dissociation. They were plated together or separately on collagen coated substrate and cultured in keratinocyte medium for 48 to 72 hours. Retrograde tracer labeling was performed to identify bladder afferents used for functional testing. Neurite growth and complexity in neurons co-cultured with urothelial cells was increased relative to that in neuronal monocultures. The growth promoting effect of urothelial cells was reduced by the tyrosine kinase inhibitor K252a but upstream inhibition of nerve growth factor signaling with TrkA-Fc had no effect. Fura-2 calcium imaging of urothelial cells showed responses to adenosine triphosphate (100 μM) and activation of TRPV4 (4α-PDD, 10 μM) but not TRPV1 (capsaicin, 1 μM), TRPV3 (farnesyl pyrophosphate, 1 μM) or TRPA1 (mustard oil, 100 μM). In contrast, co-cultured neurons were activated by all agonists except farnesyl pyrophosphate. Co-culturing provides a new methodology for investigating neuro-urothelial interactions in animal models of urological conditions. Results suggest that neuronal properties are maintained in the presence of urothelium and neurite growth is potentiated by a nerve growth factor independent mechanism. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  9. Hyccin, the Molecule Mutated in the Leukodystrophy Hypomyelination and Congenital Cataract (HCC), Is a Neuronal Protein

    Science.gov (United States)

    Giacomini, Caterina; Musante, Veronica; Fruscione, Floriana; La Padula, Veronica; Biancheri, Roberta; Scarfì, Sonia; Prada, Valeria; Sotgia, Federica; Duncan, Ian D.; Zara, Federico; Werner, Hauke B.; Lisanti, Michael P.; Nobbio, Lucilla; Corradi, Anna; Minetti, Carlo

    2012-01-01

    “Hypomyelination and Congenital Cataract”, HCC (MIM #610532), is an autosomal recessive disorder characterized by congenital cataract and diffuse cerebral and peripheral hypomyelination. HCC is caused by deficiency of Hyccin, a protein whose biological role has not been clarified yet. Since the identification of the cell types expressing a protein of unknown function can contribute to define the physiological context in which the molecule is explicating its function, we analyzed the pattern of Hyccin expression in the central and peripheral nervous system (CNS and PNS). Using heterozygous mice expressing the b-galactosidase (LacZ) gene under control of the Hyccin gene regulatory elements, we show that the gene is primarily expressed in neuronal cells. Indeed, Hyccin-LacZ signal was identified in CA1 hippocampal pyramidal neurons, olfactory bulb, and cortical pyramidal neurons, while it did not colocalize with oligodendroglial or astrocytic markers. In the PNS, Hyccin was detectable only in axons isolated from newborn mice. In the brain, Hyccin transcript levels were higher in early postnatal development (postnatal days 2 and 10) and then declined in adult mice. In a model of active myelinogenesis, organotypic cultures of rat Schwann cells (SC)/Dorsal Root Ganglion (DRG) sensory neurons, Hyccin was detected along the neurites, while it was absent from SC. Intriguingly, the abundance of the molecule was upregulated at postnatal days 10 and 15, in the initial steps of myelinogenesis and then declined at 30 days when the process is complete. As Hyccin is primarily expressed in neurons and its mutation leads to hypomyelination in human patients, we suggest that the protein is involved in neuron-to-glia signalling to initiate or maintain myelination. PMID:22461884

  10. Hyccin, the molecule mutated in the leukodystrophy hypomyelination and congenital cataract (HCC, is a neuronal protein.

    Directory of Open Access Journals (Sweden)

    Elisabetta Gazzerro

    Full Text Available "Hypomyelination and Congenital Cataract", HCC (MIM #610532, is an autosomal recessive disorder characterized by congenital cataract and diffuse cerebral and peripheral hypomyelination. HCC is caused by deficiency of Hyccin, a protein whose biological role has not been clarified yet. Since the identification of the cell types expressing a protein of unknown function can contribute to define the physiological context in which the molecule is explicating its function, we analyzed the pattern of Hyccin expression in the central and peripheral nervous system (CNS and PNS. Using heterozygous mice expressing the b-galactosidase (LacZ gene under control of the Hyccin gene regulatory elements, we show that the gene is primarily expressed in neuronal cells. Indeed, Hyccin-LacZ signal was identified in CA1 hippocampal pyramidal neurons, olfactory bulb, and cortical pyramidal neurons, while it did not colocalize with oligodendroglial or astrocytic markers. In the PNS, Hyccin was detectable only in axons isolated from newborn mice. In the brain, Hyccin transcript levels were higher in early postnatal development (postnatal days 2 and 10 and then declined in adult mice. In a model of active myelinogenesis, organotypic cultures of rat Schwann cells (SC/Dorsal Root Ganglion (DRG sensory neurons, Hyccin was detected along the neurites, while it was absent from SC. Intriguingly, the abundance of the molecule was upregulated at postnatal days 10 and 15, in the initial steps of myelinogenesis and then declined at 30 days when the process is complete. As Hyccin is primarily expressed in neurons and its mutation leads to hypomyelination in human patients, we suggest that the protein is involved in neuron-to-glia signalling to initiate or maintain myelination.

  11. A reanalysis of "Two types of asynchronous activity in networks of excitatory and inhibitory spiking neurons".

    Science.gov (United States)

    Engelken, Rainer; Farkhooi, Farzad; Hansel, David; van Vreeswijk, Carl; Wolf, Fred

    2016-01-01

    Neuronal activity in the central nervous system varies strongly in time and across neuronal populations. It is a longstanding proposal that such fluctuations generically arise from chaotic network dynamics. Various theoretical studies predict that the rich dynamics of rate models operating in the chaotic regime can subserve circuit computation and learning. Neurons in the brain, however, communicate via spikes and it is a theoretical challenge to obtain similar rate fluctuations in networks of spiking neuron models. A recent study investigated spiking balanced networks of leaky integrate and fire (LIF) neurons and compared their dynamics to a matched rate network with identical topology, where single unit input-output functions were chosen from isolated LIF neurons receiving Gaussian white noise input. A mathematical analogy between the chaotic instability in networks of rate units and the spiking network dynamics was proposed. Here we revisit the behavior of the spiking LIF networks and these matched rate networks. We find expected hallmarks of a chaotic instability in the rate network: For supercritical coupling strength near the transition point, the autocorrelation time diverges. For subcritical coupling strengths, we observe critical slowing down in response to small external perturbations. In the spiking network, we found in contrast that the timescale of the autocorrelations is insensitive to the coupling strength and that rate deviations resulting from small input perturbations rapidly decay. The decay speed even accelerates for increasing coupling strength. In conclusion, our reanalysis demonstrates fundamental differences between the behavior of pulse-coupled spiking LIF networks and rate networks with matched topology and input-output function. In particular there is no indication of a corresponding chaotic instability in the spiking network.

  12. Regulation of neuronal excitability by interaction of fragile X mental retardation protein with slack potassium channels.

    Science.gov (United States)

    Zhang, Yalan; Brown, Maile R; Hyland, Callen; Chen, Yi; Kronengold, Jack; Fleming, Matthew R; Kohn, Andrea B; Moroz, Leonid L; Kaczmarek, Leonard K

    2012-10-31

    Loss of the RNA-binding protein fragile X mental retardation protein (FMRP) represents the most common form of inherited intellectual disability. Studies with heterologous expression systems indicate that FMRP interacts directly with Slack Na(+)-activated K(+) channels (K(Na)), producing an enhancement of channel activity. We have now used Aplysia bag cell (BC) neurons, which regulate reproductive behaviors, to examine the effects of Slack and FMRP on excitability. FMRP and Slack immunoreactivity were colocalized at the periphery of isolated BC neurons, and the two proteins could be reciprocally coimmunoprecipitated. Intracellular injection of FMRP lacking its mRNA binding domain rapidly induced a biphasic outward current, with an early transient tetrodotoxin-sensitive component followed by a slowly activating sustained component. The properties of this current matched that of the native Slack potassium current, which was identified using an siRNA approach. Addition of FMRP to inside-out patches containing native Aplysia Slack channels increased channel opening and, in current-clamp recordings, produced narrowing of action potentials. Suppression of Slack expression did not alter the ability of BC neurons to undergo a characteristic prolonged discharge in response to synaptic stimulation, but prevented recovery from a prolonged inhibitory period that normally follows the discharge. Recovery from the inhibited period was also inhibited by the protein synthesis inhibitor anisomycin. Our studies indicate that, in BC neurons, Slack channels are required for prolonged changes in neuronal excitability that require new protein synthesis, and raise the possibility that channel-FMRP interactions may link changes in neuronal firing to changes in protein translation.

  13. Mitochondrial DNA Depletion in Respiratory Chain–Deficient Parkinson Disease Neurons

    Science.gov (United States)

    Rygiel, Karolina A.; Hepplewhite, Philippa D.; Morris, Christopher M.; Picard, Martin; Turnbull, Doug M.

    2016-01-01

    Objective To determine the extent of respiratory chain abnormalities and investigate the contribution of mtDNA to the loss of respiratory chain complexes (CI–IV) in the substantia nigra (SN) of idiopathic Parkinson disease (IPD) patients at the single‐neuron level. Methods Multiple‐label immunofluorescence was applied to postmortem sections of 10 IPD patients and 10 controls to quantify the abundance of CI–IV subunits (NDUFB8 or NDUFA13, SDHA, UQCRC2, and COXI) and mitochondrial transcription factors (TFAM and TFB2M) relative to mitochondrial mass (porin and GRP75) in dopaminergic neurons. To assess the involvement of mtDNA in respiratory chain deficiency in IPD, SN neurons, isolated with laser‐capture microdissection, were assayed for mtDNA deletions, copy number, and presence of transcription/replication‐associated 7S DNA employing a triplex real‐time polymerase chain reaction (PCR) assay. Results Whereas mitochondrial mass was unchanged in single SN neurons from IPD patients, we observed a significant reduction in the abundances of CI and II subunits. At the single‐cell level, CI and II deficiencies were correlated in patients. The CI deficiency concomitantly occurred with low abundances of the mtDNA transcription factors TFAM and TFB2M, which also initiate transcription‐primed mtDNA replication. Consistent with this, real‐time PCR analysis revealed fewer transcription/replication‐associated mtDNA molecules and an overall reduction in mtDNA copy number in patients. This effect was more pronounced in single IPD neurons with severe CI deficiency. Interpretation Respiratory chain dysfunction in IPD neurons not only involves CI, but also extends to CII. These deficiencies are possibly a consequence of the interplay between nDNA and mtDNA‐encoded factors mechanistically connected via TFAM. ANN NEUROL 2016;79:366–378 PMID:26605748

  14. Leptin signaling in GABA neurons, but not glutamate neurons, is required for reproductive function.

    Science.gov (United States)

    Zuure, Wieteke A; Roberts, Amy L; Quennell, Janette H; Anderson, Greg M

    2013-11-06

    The adipocyte-derived hormone leptin acts in the brain to modulate the central driver of fertility: the gonadotropin releasing hormone (GnRH) neuronal system. This effect is indirect, as GnRH neurons do not express leptin receptors (LEPRs). Here we test whether GABAergic or glutamatergic neurons provide the intermediate pathway between the site of leptin action and the GnRH neurons. Leptin receptors were deleted from GABA and glutamate neurons using Cre-Lox transgenics, and the downstream effects on puberty onset and reproduction were examined. Both mouse lines displayed the expected increase in body weight and region-specific loss of leptin signaling in the hypothalamus. The GABA neuron-specific LEPR knock-out females and males showed significantly delayed puberty onset. Adult fertility observations revealed that these knock-out animals have decreased fecundity. In contrast, glutamate neuron-specific LEPR knock-out mice displayed normal fertility. Assessment of the estrogenic hypothalamic-pituitary-gonadal axis regulation in females showed that leptin action on GABA neurons is not necessary for estradiol-mediated suppression of tonic luteinizing hormone secretion (an indirect measure of GnRH neuron activity) but is required for regulation of a full preovulatory-like luteinizing hormone surge. In conclusion, leptin signaling in GABAergic (but not glutamatergic neurons) plays a critical role in the timing of puberty onset and is involved in fertility regulation throughout adulthood in both sexes. These results form an important step in explaining the role of central leptin signaling in the reproductive system. Limiting the leptin-to-GnRH mediators to GABAergic cells will enable future research to focus on a few specific types of neurons.

  15. Noradrenaline from Locus Coeruleus Neurons Acts on Pedunculo-Pontine Neurons to Prevent REM Sleep and Induces Its Loss-Associated Effects in Rats.

    Science.gov (United States)

    Khanday, Mudasir Ahmad; Somarajan, Bindu I; Mehta, Rachna; Mallick, Birendra Nath

    2016-01-01

    Normally, rapid eye movement sleep (REMS) does not appear during waking or non-REMS. Isolated, independent studies showed that elevated noradrenaline (NA) levels inhibit REMS and induce REMS loss-associated cytomolecular, cytomorphological, psychosomatic changes and associated symptoms. However, the source of NA and its target in the brain for REMS regulation and function in health and diseases remained to be confirmed in vivo . Using tyrosine hydroxylase (TH)-siRNA and virus-coated TH-shRNA in normal freely moving rats, we downregulated NA synthesis in locus coeruleus (LC) REM-OFF neurons in vivo . These TH-downregulated rats showed increased REMS, which was prevented by infusing NA into the pedunculo-pontine tegmentum (PPT), the site of REM-ON neurons, normal REMS returned after recovery. Moreover, unlike normal or control-siRNA- or shRNA-injected rats, upon REMS deprivation (REMSD) TH-downregulated rat brains did not show elevated Na-K ATPase (molecular changes) expression and activity. To the best of our knowledge, these are the first in vivo findings in an animal model confirming that NA from the LC REM-OFF neurons (1) acts on the PPT REM-ON neurons to prevent appearance of REMS, and (2) are responsible for inducing REMSD-associated molecular changes and symptoms. These observations clearly show neuro-physio-chemical mechanism of why normally REMS does not appear during waking. Also, that LC neurons are the primary source of NA, which in turn causes some, if not many, REMSD-associated symptoms and behavioral changes. The findings are proof-of-principle for the first time and hold potential to be exploited for confirmation toward treating REMS disorder and amelioration of REMS loss-associated symptoms in patients.

  16. Targeted Ablation and Reorganization of the Principal Preplate Neurons and Their Neuroblasts Identified by Golli Promoter Transgene Expression in the Neocortex of Mice

    Directory of Open Access Journals (Sweden)

    Yuan-Yun Xie

    2009-10-01

    Full Text Available The present study delineates the cellular responses of dorsal pallium to targeted genetic ablation of the principal preplate neurons of the neocortex. Ganciclovir treatment during prenatal development (E11-E13; where E is embryonic day of mice selectively killed cells with shared S-phase vulnerability and targeted expression of a GPT [golli promoter transgene, linked to HSV-TK (herpes simplex virus-thymidine kinase, τ-eGFP (τ-enhanced green fluorescent protein and lacZ (lacZ galactosidase reporters] localized in preplate neurons. Morphogenetic fates of attacked neurons and neuroblasts, and their successors, were assessed by multiple labelling in time-series comparisons between ablated (HSV-TK+/0 and control (HSV-TK0/0 littermates. During ablation generation, neocortical growth was suppressed, and compensatory reorganization of non-GPT ventricular zone progenitors of dorsal pallium produced replacements for killed GPT neuroblasts. Replacement and surviving GPT neuroblasts then produced replacements for killed GPT neurons. Near-normal restoration of their complement delayed the settlement of GPT neurons into the reconstituted preplate, which curtailed the outgrowth of pioneer corticofugal axons. Based on this evidence, we conclude that specific cell killing in ablated mice can eliminate a major fraction of GPT neurons, with insignificant bystander killing. Also, replacement GPT neurons in ablated mice originate exclusively by proliferation from intermediate progenitor GPT neuroblasts, whose complement is maintained by non-GPT progenitors for inductive regulation of the total complement of GPT neurons. Finally, GPT neurons in both normal and ablated mice meet all morphogenetic criteria, including the ‘outside-in’ vertical gradient of settlement, presently used to identify principal preplate neurons. In ablated mice, delayed organization of these neurons desynchronizes and isolates developing neocortex from the rest of the brain, and

  17. Isolation and characterization of neural stem cells from human fetal striatum

    International Nuclear Information System (INIS)

    Li Xiaoxia; Xu Jinchong; Bai Yun; Wang Xuan; Dai Xin; Liu Yinan; Zhang Jun; Zou Junhua; Shen Li; Li Lingsong

    2005-01-01

    This paper described that neural stem cells (hsNSCs) were isolated and expanded rapidly from human fetal striatum in adherent culture. The population was serum- and growth factor-dependent and expressed neural stem cell markers. They were capable of multi-differentiation into neurons, astrocytes, and oligodendrocytes. When plated in the dopaminergic neuron inducing medium, human striatum neural stem cells could differentiate into tyrosine hydroxylase positive neurons. hsNSCs were morphologically homogeneous and possessed high proliferation ability. The population doubled every 44.28 h and until now it has divided for more than 82 generations in vitro. Normal human diploid karyotype was unchanged throughout the in vitro culture period. Together, this study has exploited a method for continuous and rapid expansion of human neural stem cells as pure population, which maintained the capacity to generate almost fifty percent neurons. The availability of such cells may hold great interest for basic and applied neuroscience

  18. A novel perspective on neuron study: damaging and promoting effects in different neurons induced by mechanical stress.

    Science.gov (United States)

    Wang, Yazhou; Wang, Wei; Li, Zong; Hao, Shilei; Wang, Bochu

    2016-10-01

    A growing volume of experimental evidence demonstrates that mechanical stress plays a significant role in growth, proliferation, apoptosis, gene expression, electrophysiological properties and many other aspects of neurons. In this review, first, the mechanical microenvironment and properties of neurons under in vivo conditions are introduced and analyzed. Second, research works in recent decades on the effects of different mechanical forces, especially compression and tension, on various neurons, including dorsal root ganglion neurons, retinal ganglion cells, cerebral cortex neurons, hippocampus neurons, neural stem cells, and other neurons, are summarized. Previous research results demonstrate that mechanical stress can not only injure neurons by damaging their morphology, impacting their electrophysiological characteristics and gene expression, but also promote neuron self-repair. Finally, some future perspectives in neuron research are discussed.

  19. Neuronal 3',3,5-triiodothyronine (T3) uptake and behavioral phenotype of mice deficient in Mct8, the neuronal T3 transporter mutated in Allan-Herndon-Dudley syndrome.

    Science.gov (United States)

    Wirth, Eva K; Roth, Stephan; Blechschmidt, Cristiane; Hölter, Sabine M; Becker, Lore; Racz, Ildiko; Zimmer, Andreas; Klopstock, Thomas; Gailus-Durner, Valerie; Fuchs, Helmut; Wurst, Wolfgang; Naumann, Thomas; Bräuer, Anja; de Angelis, Martin Hrabé; Köhrle, Josef; Grüters, Annette; Schweizer, Ulrich

    2009-07-29

    Thyroid hormone transport into cells requires plasma membrane transport proteins. Mutations in one of these, monocarboxylate transporter 8 (MCT8), have been identified as underlying cause for the Allan-Herndon-Dudley syndrome, an X-linked mental retardation in which the patients also present with abnormally high 3',3,5-triiodothyronine (T(3)) plasma levels. Mice deficient in Mct8 replicate the thyroid hormone abnormalities observed in the human condition. However, no neurological deficits have been described in mice lacking Mct8. Therefore, we subjected Mct8-deficient mice to a comprehensive immunohistochemical, neurological, and behavioral screen. Several behavioral abnormalities were found in the mutants. Interestingly, some of these behavioral changes are compatible with hypothyroidism, whereas others rather indicate hyperthyroidism. We thus hypothesized that neurons exclusively dependent on Mct8 are in a hypothyroid state, whereas neurons expressing other T(3) transporters become hyperthyroid, if they are exposed directly to the high plasma T(3). The majority of T(3) uptake in primary cortical neurons is mediated by Mct8, but pharmacological inhibition suggested functional expression of additional T(3) transporter classes. mRNAs encoding six T(3) transporters, including L-type amino acid transporters (LATs), were coexpressed with Mct8 in isolated neurons. We then demonstrated Lat2 expression in cultured neurons and throughout murine brain development. In contrast, LAT2 is expressed in microglia in the developing human brain during gestation, but not in neurons. We suggest that lack of functional complementation by alternative thyroid hormone transporters in developing human neurons precipitates the devastating neurodevelopmental phenotype in MCT8-deficient patients, whereas Mct8-deficient mouse neurons are functionally complemented by other transporters, for possibly Lat2.

  20. Isolation and culture of larval cells from C. elegans.

    Directory of Open Access Journals (Sweden)

    Sihui Zhang

    Full Text Available Cell culture is an essential tool to study cell function. In C. elegans the ability to isolate and culture cells has been limited to embryonically derived cells. However, cells or blastomeres isolated from mixed stage embryos terminally differentiate within 24 hours of culture, thus precluding post-embryonic stage cell culture. We have developed an efficient and technically simple method for large-scale isolation and primary culture of larval-stage cells. We have optimized the treatment to maximize cell number and minimize cell death for each of the four larval stages. We obtained up to 7.8×10(4 cells per microliter of packed larvae, and up to 97% of adherent cells isolated by this method were viable for at least 16 hours. Cultured larval cells showed stage-specific increases in both cell size and multinuclearity and expressed lineage- and cell type-specific reporters. The majority (81% of larval cells isolated by our method were muscle cells that exhibited stage-specific phenotypes. L1 muscle cells developed 1 to 2 wide cytoplasmic processes, while L4 muscle cells developed 4 to 14 processes of various thicknesses. L4 muscle cells developed bands of myosin heavy chain A thick filaments at the cell center and spontaneously contracted ex vivo. Neurons constituted less than 10% of the isolated cells and the majority of neurons developed one or more long, microtubule-rich protrusions that terminated in actin-rich growth cones. In addition to cells such as muscle and neuron that are high abundance in vivo, we were also able to isolate M-lineage cells that constitute less than 0.2% of cells in vivo. Our novel method of cell isolation extends C. elegans cell culture to larval developmental stages, and allows use of the wealth of cell culture tools, such as cell sorting, electrophysiology, co-culture, and high-resolution imaging of subcellular dynamics, in investigation of post-embryonic development and physiology.

  1. Resveratrol stimulates AMP kinase activity in neurons.

    Science.gov (United States)

    Dasgupta, Biplab; Milbrandt, Jeffrey

    2007-04-24

    Resveratrol is a polyphenol produced by plants that has multiple beneficial activities similar to those associated with caloric restriction (CR), such as increased life span and delay in the onset of diseases associated with aging. CR improves neuronal health, and the global beneficial effects of CR have been postulated to be mediated by the nervous system. One key enzyme thought to be activated during CR is the AMP-activated kinase (AMPK), a sensor of cellular energy levels. AMPK is activated by increases in the cellular AMP:ATP ratio, whereupon it functions to help preserve cellular energy. In this regard, the regulation of dietary food intake by hypothalamic neurons is mediated by AMPK. The suppression of nonessential energy expenditure by activated AMPK along with the CR mimetic and neuroprotective properties of resveratrol led us to hypothesize that neuronal activation of AMPK could be an important component of resveratrol activity. Here, we show that resveratrol activated AMPK in Neuro2a cells and primary neurons in vitro as well as in the brain. Resveratrol and the AMPK-activating compound 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) promoted robust neurite outgrowth in Neuro2a cells, which was blocked by genetic and pharmacologic inhibition of AMPK. Resveratrol also stimulated mitochondrial biogenesis in an AMPK-dependent manner. Resveratrol-stimulated AMPK activity in neurons depended on LKB1 activity but did not require the NAD-dependent protein deacetylase SIRT1 during this time frame. These findings suggest that neuronal activation of AMPK by resveratrol could affect neuronal energy homeostasis and contribute to the neuroprotective effects of resveratrol.

  2. 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.

  3. Estradiol Protects Proopiomelanocortin Neurons Against Insulin Resistance.

    Science.gov (United States)

    Qiu, Jian; Bosch, Martha A; Meza, Cecilia; Navarro, Uyen-Vy; Nestor, Casey C; Wagner, Edward J; Rønnekleiv, Oline K; Kelly, Martin J

    2018-02-01

    Insulin resistance is at the core of the metabolic syndrome, and men exhibit a higher incidence of metabolic syndrome than women in early adult life, but this sex advantage diminishes sharply when women reach the postmenopausal state. Because 17β-estradiol (E2) augments the excitability of the anorexigenic proopiomelanocortin (POMC) neurons, we investigated the neuroprotective effects of E2 against insulin resistance in POMC neurons from diet-induced obese (DIO) female and male mice. The efficacy of insulin to activate canonical transient receptor potential 5 (TRPC5) channels and depolarize POMC neurons was significantly reduced in DIO male mice but not in DIO female mice. However, the insulin response in POMC neurons was abrogated in ovariectomized DIO females but restored with E2 replacement. E2 increased T-type calcium channel Cav3.1 messenger RNA (mRNA) expression and whole-cell currents but downregulated stromal-interaction molecule 1 mRNA, which rendered POMC neurons more excitable and responsive to insulin-mediated TRPC5 channel activation. Moreover, E2 prevented the increase in suppressor of cytokine signaling-3 mRNA expression with DIO as seen in DIO males. As proof of principle, insulin [intracerebroventricular injection into the third ventricle (ICV)] decreased food intake and increased metabolism in female but not male guinea pigs fed a high-fat diet. The uncoupling of the insulin receptor from its downstream effector system was corroborated by the reduced expression of phosphorylated protein kinase B in the arcuate nucleus of male but not female guinea pigs following insulin. Therefore, E2 protects female POMC neurons from insulin resistance by enhancing POMC neuronal excitability and the coupling of insulin receptor to TRPC5 channel activation. Copyright © 2018 Endocrine Society.

  4. MOX Fabrication Isolation Considerations

    Energy Technology Data Exchange (ETDEWEB)

    Eric L. Shaber; Bradley J Schrader

    2005-08-01

    This document provides a technical position on the preferred level of isolation to fabricate demonstration quantities of mixed oxide transmutation fuels. The Advanced Fuel Cycle Initiative should design and construct automated glovebox fabrication lines for this purpose. This level of isolation adequately protects the health and safety of workers and the general public for all mixed oxide (and other transmutation fuel) manufacturing efforts while retaining flexibility, allowing parallel development and setup, and minimizing capital expense. The basis regulations, issues, and advantages/disadvantages of five potential forms of isolation are summarized here as justification for selection of the preferred technical position.

  5. Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro

    NARCIS (Netherlands)

    Bardy, C.; Hurk, M. van den; Eames, T.; Marchand, C.; Hernandez, R.V.; Kellogg, M.; Gorris, M.A.J.; Galet, B.; Palomares, V.; Brown, J.; Bang, A.G.; Mertens, J.; Bohnke, L.; Boyer, L.; Simon, S.; Gage, F.H.

    2015-01-01

    Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely

  6. Morphine disinhibits glutamatergic input to VTA dopamine neurons and promotes dopamine neuron excitation.

    Science.gov (United States)

    Chen, Ming; Zhao, Yanfang; Yang, Hualan; Luan, Wenjie; Song, Jiaojiao; Cui, Dongyang; Dong, Yi; Lai, Bin; Ma, Lan; Zheng, Ping

    2015-07-24

    One reported mechanism for morphine activation of dopamine (DA) neurons of the ventral tegmental area (VTA) is the disinhibition model of VTA-DA neurons. Morphine inhibits GABA inhibitory neurons, which shifts the balance between inhibitory and excitatory input to VTA-DA neurons in favor of excitation and then leads to VTA-DA neuron excitation. However, it is not known whether morphine has an additional strengthening effect on excitatory input. Our results suggest that glutamatergic input to VTA-DA neurons is inhibited by GABAergic interneurons via GABAB receptors and that morphine promotes presynaptic glutamate release by removing this inhibition. We also studied the contribution of the morphine-induced disinhibitory effect on the presynaptic glutamate release to the overall excitatory effect of morphine on VTA-DA neurons and related behavior. Our results suggest that the disinhibitory action of morphine on presynaptic glutamate release might be the main mechanism for morphine-induced increase in VTA-DA neuron firing and related behaviors.

  7. Transgenic tools to characterize neuronal properties of discrete populations of zebrafish neurons.

    Science.gov (United States)

    Satou, Chie; Kimura, Yukiko; Hirata, Hiromi; Suster, Maximiliano L; Kawakami, Koichi; Higashijima, Shin-ichi

    2013-09-01

    The developing nervous system consists of a variety of cell types. Transgenic animals expressing reporter genes in specific classes of neuronal cells are powerful tools for the study of neuronal network formation. We generated a wide variety of transgenic zebrafish that expressed reporter genes in specific classes of neurons or neuronal progenitors. These include lines in which neurons of specific neurotransmitter phenotypes expressed fluorescent proteins or Gal4, and lines in which specific subsets of the dorsal progenitor domain in the spinal cord expressed fluorescent proteins. Using these, we examined domain organization in the developing dorsal spinal cord, and found that there are six progenitor domains in zebrafish, which is similar to the domain organization in mice. We also systematically characterized neurotransmitter properties of the neurons that are produced from each domain. Given that reporter gene expressions occurs in a wide area of the nervous system in the lines generated, these transgenic fish should serve as powerful tools for the investigation of not only the neurons in the dorsal spinal cord but also neuronal structures and functions in many other regions of the nervous system.

  8. CRISPR Epigenome Editing of AKAP150 in DRG Neurons Abolishes Degenerative IVD-Induced Neuronal Activation.

    Science.gov (United States)

    Stover, Joshua D; Farhang, Niloofar; Berrett, Kristofer C; Gertz, Jason; Lawrence, Brandon; Bowles, Robby D

    2017-09-06

    Back pain is a major contributor to disability and has significant socioeconomic impacts worldwide. The degenerative intervertebral disc (IVD) has been hypothesized to contribute to back pain, but a better understanding of the interactions between the degenerative IVD and nociceptive neurons innervating the disc and treatment strategies that directly target these interactions is needed to improve our understanding and treatment of back pain. We investigated degenerative IVD-induced changes to dorsal root ganglion (DRG) neuron activity and utilized CRISPR epigenome editing as a neuromodulation strategy. By exposing DRG neurons to degenerative IVD-conditioned media under both normal and pathological IVD pH levels, we demonstrate that degenerative IVDs trigger interleukin (IL)-6-induced increases in neuron activity to thermal stimuli, which is directly mediated by AKAP and enhanced by acidic pH. Utilizing this novel information on AKAP-mediated increases in nociceptive neuron activity, we developed lentiviral CRISPR epigenome editing vectors that modulate endogenous expression of AKAP150 by targeted promoter histone methylation. When delivered to DRG neurons, these epigenome-modifying vectors abolished degenerative IVD-induced DRG-elevated neuron activity while preserving non-pathologic neuron activity. This work elucidates the potential for CRISPR epigenome editing as a targeted gene-based pain neuromodulation strategy. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  9. BigNeuron: Large-Scale 3D Neuron Reconstruction from Optical Microscopy Images

    NARCIS (Netherlands)

    H. Peng (Hanchuan); M. Hawrylycz (Michael); J. Roskams (Jane); S. Hill (Sean); N. Spruston (Nelson); E. Meijering (Erik); G.A. Ascoli (Giorgio A.)

    2015-01-01

    textabstractUnderstanding the structure of single neurons is critical for understanding how they function within neural circuits. BigNeuron is a new community effort that combines modern bioimaging informatics, recent leaps in labeling and microscopy, and the widely recognized need for openness and

  10. Prion propagation and toxicity occur in vitro with two-phase kinetics specific to strain and neuronal type.

    Science.gov (United States)

    Hannaoui, Samia; Maatouk, Layal; Privat, Nicolas; Levavasseur, Etienne; Faucheux, Baptiste A; Haïk, Stéphane

    2013-03-01

    Prion diseases, or transmissible spongiform encephalopathies (TSEs), are fatal neurodegenerative disorders that occur in humans and animals. The neuropathological hallmarks of TSEs are spongiosis, glial proliferation, and neuronal loss. The only known specific molecular marker of TSEs is the abnormal isoform (PrP(Sc)) of the host-encoded prion protein (PrP(C)), which accumulates in the brain of infected subjects and forms infectious prion particles. Although this transmissible agent lacks a specific nucleic acid component, several prion strains have been isolated. Prion strains are characterized by differences in disease outcome, PrP(Sc) distribution patterns, and brain lesion profiles at the terminal stage of the disease. The molecular factors and cellular mechanisms involved in strain-specific neuronal tropism and toxicity remain largely unknown. Currently, no cellular model exists to facilitate in vitro studies of these processes. A few cultured cell lines that maintain persistent scrapie infections have been developed, but only two of them have shown the cytotoxic effects associated with prion propagation. In this study, we have developed primary neuronal cultures to assess in vitro neuronal tropism and toxicity of different prion strains (scrapie strains 139A, ME7, and 22L). We have tested primary neuronal cultures enriched in cerebellar granular, striatal, or cortical neurons. Our results showed that (i) a strain-specific neuronal tropism operated in vitro; (ii) the cytotoxic effect varied among strains and neuronal