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Sample records for catecholaminergic neurons isolated

  1. Molecular basis for catecholaminergic neuron diversity

    OpenAIRE

    Grimm, Jan; Mueller, Anne; Hefti, Franz; Rosenthal, Arnon

    2004-01-01

    Catecholaminergic neurons control diverse cognitive, motor, and endocrine functions and are associated with multiple psychiatric and neurodegenerative disorders. We present global gene-expression profiles that define the four major classes of dopaminergic (DA) and noradrenergic neurons in the brain. Hypothalamic DA neurons and noradrenergic neurons in the locus coeruleus display distinct group-specific signatures of transporters, channels, transcription, plasticity, axon-guidance, and surviva...

  2. Stress- and diet-induced fat gain is controlled by NPY in catecholaminergic neurons.

    Science.gov (United States)

    Zhang, Lei; Lee, I-Chieh J; Enriquez, Rondaldo F; Lau, Jackie; Vähätalo, Laura H; Baldock, Paul A; Savontaus, Eriika; Herzog, Herbert

    2014-08-01

    Neuropeptide Y (NPY) and noradrenaline are commonly co-expressed in sympathetic neurons. Both are key regulators of energy homeostasis and critical for stress-coping. However, little is known about the specific function of NPY in the catecholaminergic system in these regulations. Here we show that mice with NPY expression only in the noradrenergic and adrenergic cells of the catecholaminergic system (catNPY) exhibited exacerbated diet-induced obesity, lower body and brown adipose tissue temperatures compared to WT and NPY(-/-) mice under a HFD. Furthermore, chronic stress increased adiposity and serum corticosterone level in WT but not NPY(-/-) mice. Re-introducing NPY specifically to the catecholaminergic system in catNPY mice restored stress responsiveness associated with increased respiratory exchange ratio and decreased liver pACC to tACC ratio. These results demonstrate catecholaminergic NPY signalling is critical in mediating diet- and chronic stress-induced fat gain via effects on diet-induced thermogenesis and stress-induced increases in corticosterone levels and lipogenic capacity.

  3. Neuromelanin, neurotransmitter status and brainstem location determine the differential vulnerability of catecholaminergic neurons to mitochondrial DNA deletions

    Directory of Open Access Journals (Sweden)

    Elstner Matthias

    2011-12-01

    Full Text Available Abstract Background Deletions of the mitochondrial DNA (mtDNA accumulate to high levels in dopaminergic neurons of the substantia nigra pars compacta (SNc in normal aging and in patients with Parkinson's disease (PD. Human nigral neurons characteristically contain the pigment neuromelanin (NM, which is believed to alter the cellular redox-status. The impact of neuronal pigmentation, neurotransmitter status and brainstem location on the susceptibility to mtDNA damage remains unclear. We quantified mtDNA deletions (ΔmtDNA in single pigmented and non-pigmented catecholaminergic, as well as non-catecholaminergic neurons of the human SNc, the ventral tegmental area (VTA and the locus coeruleus (LC, using laser capture microdissection and single-cell real-time PCR. Results In healthy aged individuals, ΔmtDNA levels were highest in pigmented catecholaminergic neurons (25.2 ± 14.9%, followed by non-pigmented catecholamergic (18.0 ± 11.2% and non-catecholaminergic neurons (12.3 ± 12.3%; p Conclusions Catecholaminergic brainstem neurons are differentially susceptible to mtDNA damage. Pigmented dopaminergic neurons of the SNc show the highest ΔmtDNA levels, possibly explaining the exceptional vulnerability of the nigro-striatal system in PD and aging. Although loss of pigmented noradrenergic LC neurons also is an early feature of PD pathology, mtDNA levels are not elevated in this nucleus in healthy controls. Thus, ΔmtDNA are neither an inevitable consequence of catecholamine metabolism nor a universal explanation for the regional vulnerability seen in PD.

  4. Involvement of catecholaminergic neurons in motor innervation of striated muscle in the mouse esophagus.

    Science.gov (United States)

    van der Keylen, Piet; Garreis, Fabian; Steigleder, Ruth; Sommer, Daniel; Neuhuber, Winfried L; Wörl, Jürgen

    2016-05-01

    Enteric co-innervation is a peculiar innervation pattern of striated esophageal musculature. Both anatomical and functional data on enteric co-innervation related to various transmitters have been collected in different species, although its function remains enigmatic. However, it is unclear whether catecholaminergic components are involved in such a co-innervation. Thus, we examined to identify catecholaminergic neuronal elements and clarify their relationship to other innervation components in the esophagus, using immunohistochemistry with antibodies against tyrosine hydroxylase (TH), vesicular acetylcholine transporter (VAChT), choline acetyltransferase (ChAT) and protein gene product 9.5 (PGP 9.5), α-bungarotoxin (α-BT) and PCR with primers for amplification of cDNA encoding TH and dopamine-β-hydroxylase (DBH). TH-positive nerve fibers were abundant throughout the myenteric plexus and localized on about 14% of α-BT-labelled motor endplates differing from VAChT-positive vagal nerve terminals. TH-positive perikarya represented a subpopulation of only about 2.8% of all PGP 9.5-positive myenteric neurons. Analysis of mRNA showed both TH and DBH transcripts in the mouse esophagus. As ChAT-positive neurons in the compact formation of the nucleus ambiguus were negative for TH, the TH-positive nerve varicosities on motor endplates are presumably of enteric origin, although a sympathetic origin cannot be excluded. In the medulla oblongata, the cholinergic ambiguus neurons were densely supplied with TH-positive varicosities. Thus, catecholamines may modulate vagal motor innervation of esophageal-striated muscles not only at the peripheral level via enteric co-innervation but also at the central level via projections to the nucleus ambiguus. As Parkinson's disease, with a loss of central dopaminergic neurons, also affects the enteric nervous system and dysphagia is prevalent in patients with this disease, investigation of intrinsic catecholamines in the esophagus may

  5. An optogenetic mouse model of rett syndrome targeting on catecholaminergic neurons.

    Science.gov (United States)

    Zhang, Shuang; Johnson, Christopher M; Cui, Ningren; Xing, Hao; Zhong, Weiwei; Wu, Yang; Jiang, Chun

    2016-10-01

    Rett syndrome (RTT) is a neurodevelopmental disorder affecting multiple functions, including the norepinephrine (NE) system. In the CNS, NE is produced mostly by neurons in the locus coeruleus (LC), where defects in intrinsic neuronal properties, NE biosynthetic enzymes, neuronal CO2 sensitivity, and synaptic currents have been reported in mouse models of RTT. LC neurons in methyl-CpG-binding protein 2 gene (Mecp2) null mice show a high rate of spontaneous firing, although whether such hyperexcitability might increase or decrease the NE release from synapses is unknown. To activate the NEergic axonal terminals selectively, we generated an optogenetic mouse model of RTT in which NEergic neuronal excitability can be manipulated with light. Using commercially available mouse breeders, we produced a new strain of double-transgenic mice with Mecp2 knockout and channelrhodopsin (ChR) knockin in catecholaminergic neurons. Several RTT-like phenotypes were found in the tyrosine hydroxylase (TH)-ChR-Mecp2(-/Y) mice, including hypoactivity, low body weight, hindlimb clasping, and breathing disorders. In brain slices, optostimulation produced depolarization and an increase in the firing rate of LC neurons from TH-ChR control mice. In TH-ChR control mice, optostimulation of presynaptic NEergic neurons augmented the firing rate of hypoglossal neurons (HNs), which was blocked by the α-adrenoceptor antagonist phentolamine. Such optostimulation of NEergic terminals had almost no effect on HNs from two or three TH-ChR-Mecp2(-/Y) mice, indicating that excessive excitation of presynaptic neurons does not benefit NEergic modulation in mice with Mecp2 disruption. These results also demonstrate the feasibility of generating double-transgenic mice for studies of RTT with commercially available mice, which are inexpensive, labor/time efficient, and promising for cell-specific stimulation. © 2016 Wiley Periodicals, Inc. PMID:27317352

  6. An optogenetic mouse model of rett syndrome targeting on catecholaminergic neurons.

    Science.gov (United States)

    Zhang, Shuang; Johnson, Christopher M; Cui, Ningren; Xing, Hao; Zhong, Weiwei; Wu, Yang; Jiang, Chun

    2016-10-01

    Rett syndrome (RTT) is a neurodevelopmental disorder affecting multiple functions, including the norepinephrine (NE) system. In the CNS, NE is produced mostly by neurons in the locus coeruleus (LC), where defects in intrinsic neuronal properties, NE biosynthetic enzymes, neuronal CO2 sensitivity, and synaptic currents have been reported in mouse models of RTT. LC neurons in methyl-CpG-binding protein 2 gene (Mecp2) null mice show a high rate of spontaneous firing, although whether such hyperexcitability might increase or decrease the NE release from synapses is unknown. To activate the NEergic axonal terminals selectively, we generated an optogenetic mouse model of RTT in which NEergic neuronal excitability can be manipulated with light. Using commercially available mouse breeders, we produced a new strain of double-transgenic mice with Mecp2 knockout and channelrhodopsin (ChR) knockin in catecholaminergic neurons. Several RTT-like phenotypes were found in the tyrosine hydroxylase (TH)-ChR-Mecp2(-/Y) mice, including hypoactivity, low body weight, hindlimb clasping, and breathing disorders. In brain slices, optostimulation produced depolarization and an increase in the firing rate of LC neurons from TH-ChR control mice. In TH-ChR control mice, optostimulation of presynaptic NEergic neurons augmented the firing rate of hypoglossal neurons (HNs), which was blocked by the α-adrenoceptor antagonist phentolamine. Such optostimulation of NEergic terminals had almost no effect on HNs from two or three TH-ChR-Mecp2(-/Y) mice, indicating that excessive excitation of presynaptic neurons does not benefit NEergic modulation in mice with Mecp2 disruption. These results also demonstrate the feasibility of generating double-transgenic mice for studies of RTT with commercially available mice, which are inexpensive, labor/time efficient, and promising for cell-specific stimulation. © 2016 Wiley Periodicals, Inc.

  7. Vesicular glutamate transporter 2 is required for the respiratory and parasympathetic activation produced by optogenetic stimulation of catecholaminergic neurons in the rostral ventrolateral medulla of mice in vivo.

    Science.gov (United States)

    Abbott, Stephen B G; Holloway, Benjamin B; Viar, Kenneth E; Guyenet, Patrice G

    2014-01-01

    Catecholaminergic neurons of the rostral ventrolateral medulla (RVLM-CA neurons; C1 neurons) contribute to the sympathetic, parasympathetic and neuroendocrine responses elicited by physical stressors such as hypotension, hypoxia, hypoglycemia, and infection. Most RVLM-CA neurons express vesicular glutamate transporter (VGLUT)2, and may use glutamate as a ionotropic transmitter, but the importance of this mode of transmission in vivo is uncertain. To address this question, we genetically deleted VGLUT2 from dopamine-β-hydroxylase-expressing neurons in mice [DβH(Cre/0) ;VGLUT2(flox/flox) mice (cKO mice)]. We compared the in vivo effects of selectively stimulating RVLM-CA neurons in cKO vs. control mice (DβH(Cre/0) ), using channelrhodopsin-2 (ChR2-mCherry) optogenetics. ChR2-mCherry was expressed by similar numbers of rostral ventrolateral medulla (RVLM) neurons in each strain (~400 neurons), with identical selectivity for catecholaminergic neurons (90-99% colocalisation with tyrosine hydroxylase). RVLM-CA neurons had similar morphology and axonal projections in DβH(Cre/0) and cKO mice. Under urethane anesthesia, photostimulation produced a similar pattern of activation of presumptive ChR2-positive RVLM-CA neurons in DβH(Cre/0) and cKO mice. Photostimulation in conscious mice produced frequency-dependent respiratory activation in DβH(Cre/0) mice but no effect in cKO mice. Similarly, photostimulation under urethane anesthesia strongly activated efferent vagal nerve activity in DβH(Cre/0) mice only. Vagal responses were unaffected by α1 -adrenoreceptor blockade. In conclusion, two responses evoked by RVLM-CA neuron stimulation in vivo require the expression of VGLUT2 by these neurons, suggesting that the acute autonomic responses driven by RVLM-CA neurons are mediated by glutamate.

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

    Science.gov (United States)

    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

  9. Hypoxia and electrical stimulation of the carotid sinus nerve induce Fos-like immunoreactivity within catecholaminergic and serotoninergic neurons of the rat brainstem.

    Science.gov (United States)

    Erickson, J T; Millhorn, D E

    1994-10-01

    A complete understanding of the neural mechanisms responsible for the chemoreceptor and baroreceptor reflexes requires precise knowledge of the locations and chemical phenotypes of higher-order neurons within these reflex pathways. In the present study, the protein product (Fos) of the c-fos protooncogene was used as a metabolic marker to trace central neural pathways following activation of carotid sinus nerve afferent fibers. In addition, immunohistochemical double-labeling techniques were used to define the chemical phenotypes of activated neurons. Both electrical stimulation of the carotid sinus nerve and physiological stimulation of the carotid bodies by hypoxia induced Fos-like immunoreactivity in catecholaminergic neurons containing tyrosine hydroxylase or phenylethanolamine-N-methyltransferase in the ventrolateral medulla oblongata and, to a lesser degree, in the dorsal vagal complex. Tyrosine hydroxylase/Fos colocalization was also observed in the locus coeruleus and the A5 noradrenergic cell group in pons. Many serotoninergic neurons in nucleus raphe pallidus, nucleus raphe magnus, and along the ventral medullary surface contained Fos-like immunoreactivity. In pons and midbrain, Fos-like immunoreactivity was observed in the lateral parabrachial and Kölliker-Fuse nuclei, the inferior colliculus, the cuneiform nucleus, and in the vicinity of the Edinger-Westphal nucleus, but no catecholaminergic or serotoninergic colocalization was observed in these regions. Although Fos-labeled cells were observed within and lateral to the dorsal raphe nucleus, few were catecholaminergic or serotoninergic. This study further defines a potential central neuroanatomical substrate for the chemoreceptor and/or baroreceptor reflexes. PMID:7814687

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Christopher L Petersen

    Full Text Available 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

  12. Neurotrophic requirements of rat embryonic catecholaminergic neurons from the rostral ventrolateral medulla

    NARCIS (Netherlands)

    Copray, JCVM; Gibbons, H; van Roon, WMC; Comer, AM; Lipski, J

    1999-01-01

    The factors that regulate the ontogeny and differentiation of C1 adrenergic neurons located in the rostral ventrolateral medulla (RVLM) are completely unknown. In the present study, we have investigated the effects of a number of neurotrophic factors on the survival of E18-19 rat C1 adrenergic neuro

  13. PYY(3-36) Induces Fos in the Arcuate Nucleus and in both Catecholaminergic and Non-catecholaminergic Neurons in the Nucleus Tractus Solitarius of Rats

    OpenAIRE

    Blevins, J. E.; Chelikani, P. K.; Haver, A. C.; Reidelberger, R. D.

    2007-01-01

    Peptide YY (3-36) [PYY(3-36)] inhibits feeding in rodents, nonhuman primates and humans, yet the neural circuits underlying this action remain to be determined. Here we assessed whether PYY(3-36) inhibits feeding by activating neurons in forebrain and hindbrain sites containing Y2 receptors and linked to control of food intake, or in hindbrain sites immediately downstream of vagal afferent neurons. Rats received an anorexigenic dose of PYY(3-36), and the number of neurons expressing Fos, an i...

  14. Presence of a dynorphin-like peptide in a restricted subpopulation of catecholaminergic neurons in rat nucleus tractus solitarii.

    Science.gov (United States)

    Ceccatelli, S; Seroogy, K B; Millhorn, D E; Terenius, L

    1992-09-01

    Immunofluorescence colocalization techniques were used to examine the extent of coexistence of the endogenous opioid peptide dynorphin with catecholamines and the related opioid peptide enkephalin within neurons of the rat medulla oblongata. Immunoreactivities for dynorphin and the catecholamine-synthesizing enzyme tyrosine hydroxylase were found to coexist within a limited subpopulation of A2 catecholamine cells, localized to the medial nucleus of the nucleus tractus solitarii. Colocalization of the two opioid peptides was found mainly within perikarya situated in the medial and ventrolateral nuclei of the nucleus tractus solitarii. Triple-labeling studies revealed only rare cases of catecholamine/dynorphin/enkephalin coexistence. These data demonstrate that dynorphin is present within a restricted subpopulation of catecholamine neurons in the dorsal medulla oblongata. In addition, the content of either of the opioids enkephalin or dynorphin appears to distinguish subsets of medullary catecholamine neurons. PMID:1356595

  15. Columnar Distribution of Catecholaminergic Neurons in the Ventrolateral Periaqueductal Gray (vlPAG) and Their Relationship to Efferent Pathways

    OpenAIRE

    Suckow, Shelby K.; Deichsel, Emily L.; Ingram, Susan L; Morgan, Michael M; Aicher, Sue A.

    2012-01-01

    The periaqueductal gray (PAG) is a critical brain region involved in opioid analgesia and provides efferents to descending pathways that modulate nociception. In addition, the PAG contains ascending pathways to regions involved in the regulation of reward, including the substantia nigra (SN) and the ventral tegmental area (VTA). SN and VTA contain dopaminergic neurons that are critical for the maintenance of positive reinforcement. Interestingly, the PAG is also reported to contain a populati...

  16. Sexually dimorphic neuronal responses to social isolation

    Science.gov (United States)

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

    2016-01-01

    Many species use social networks to buffer the effects of stress. The mere absence of a social network, however, may also be stressful. We examined neuroendocrine, PVN CRH neurons and report that social isolation alters the intrinsic properties of these cells in sexually dimorphic fashion. Specifically, isolating preadolescent female mice from littermates for neurons. These changes were not evident in age-matched males. By contrast, subjecting either males (isolated or grouped) or group housed females to acute physical stress (swim), increased FSL. The increase in FSL following either social isolation or acute physical stress was blocked by the glucocorticoid synthesis inhibitor, metyrapone and mimicked by exogenous corticosterone. The increase in FSL results in a decrease in the excitability of CRH neurons. Our observations demonstrate that social isolation, but not acute physical stress has sex-specific effects on PVN CRH neurons. DOI: http://dx.doi.org/10.7554/eLife.18726.001 PMID:27725087

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

    Science.gov (United States)

    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

    2016-02-11

    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.

  18. Catecholaminergic projections from the solitary tract nucleus to the perifornical hypothalamus.

    Science.gov (United States)

    Pierret, P; Christolomme, A; Bosler, O; Perrin, J; Orsini, J C

    1994-01-01

    The source of adrenergic and other catecholaminergic fibers innervating the perifornical lateral hypothalamus was localized in the medulla after combination of Fluoro-Gold retrograde tracing and immunohistochemistry for either tyrosine-hydroxylase or phenylethanolamine-N-methyltransferase. Following perifornical injections, Fluoro-Gold-labeled neurons were observed mainly in regions including the noradrenergic and adrenergic cell groups. In the caudal solitary tract nucleus, two kinds of doubly labeled neurons were found: a) numerous noradrenergic neurons in the A2 group at the level of, or caudal to the area postrema; b) some adrenergic neurons in the C2 group at a level immediately rostral to the area postrema. These catecholaminergic neurons connecting the caudal solitary tract nucleus to the perifornical hypothalamus might convey feeding relevant information such as glycemic level or satiety signals.

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

    OpenAIRE

    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.

    2015-01-01

    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 ...

  20. Catecholaminergic neurotransmission in heart and brain, development of tracers for positron emission tomography

    OpenAIRE

    Langer, Claus Oliver

    2000-01-01

    The catecholamines norepinephrine and its biosynthetic precursor dopamine are two principal neurotransmitters in the human central nervous system (CNS). Moreover, norepinephrine is a major transmitter substance in the peripheral, autonomic nervous system. Positron emission tomography (PET) is a non-invasive imaging technique that uses positron-labeled molecules to image and measure the function of biological processes in vivo. Neuronal catecholaminergic pathways, both in CNS...

  1. Modafinil as a catecholaminergic agent: empirical evidence and unanswered questions

    Directory of Open Access Journals (Sweden)

    Jonathan P Wisor

    2013-10-01

    Full Text Available Modafinil, in its two clinical formulations (Provigil® and Nuvigil®, is a widely prescribed wake-promoting therapeutic agent. It binds competitively to the cell membrane dopamine transporter and is dependent on catecholaminergic (dopaminergic and adrenergic signaling for its wake-promoting effects. The clinical spectrum of effects for modafinil is distinct from the effects seen with other catecholaminergic agents. Relative to other commonly used agents that act through catecholaminergic mechanisms, modafinil has a relatively low abuse potential, produces wakefulness with an attenuated compensatory sleep recovery thereafter, and does not ameliorate cataplexy in narcolepsy. These clinically relevant phenomenological differences between modafinil and agents such as amphetamines and cocaine do not eliminate catecholaminergic effects as a possible mediator of its wake-promoting action; they merely reflect its unique pharmacological profile. Modafinil is an exceptionally weak, but apparently very selective, dopamine transporter inhibitor. The pharmacodynamic response to modafinil, as measured by dopamine levels in brain microdialysate, is protracted relative to other agents that act via catecholaminergic mechanisms. The conformational constraints on the interaction of modafinil with the dopamine transporter—and probably, as a consequence, its effects on trace amine receptor signaling in the catecholaminergic cell—are unique among catecholaminergic agents. These unique pharmacological properties of modafinil should be considered both in seeking to thoroughly understand its putatively elusive mechanism of action and in the design of novel therapeutic agents.

  2. Clinical Challenges in Catecholaminergic Polymorphic Ventricular Tachycardia.

    Science.gov (United States)

    Imberti, Jacopo F; Underwood, Katherine; Mazzanti, Andrea; Priori, Silvia G

    2016-08-01

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inheritable cardiac disorder associated with exercise- and stress-induced sudden death in young individuals. Although important steps forward have been made in the comprehension and treatment of this disease, several aspects remain unclear. Firstly, from an epidemiological standpoint the actual prevalence of CPVT is still unknown and possibly underestimated. In addition, the diagnostic process remains very challenging and can be supported by genetic analysis in only about half of the cases. Finally, up to one third of CPVT patients continue to present complex arrhythmias despite beta blocker treatment; the role of newer therapeutic options, such as flecainide and left cardiac sympathetic denervation, needs to be further elucidated. All these points constitute challenges for the cardiologist in the management of CPVT patients and fuel research into new diagnostic, prognostic and therapeutic approaches. PMID:26948768

  3. Anopheles gambiae mosquito isolated neurons : a new biological model for optimizing insecticide/repellent efficacy

    OpenAIRE

    Lavialle-Defaix, C.; Apaire-Marchais, V; Legros, C.; Pennetier, Cédric; Mohamed, A; P. Licznar; Corbel, Vincent; Lapied, B

    2011-01-01

    To understand better the mode of action of insecticides and repellents used in vector-borne diseases control, we developed a new biological model based on mosquito neurons isolated from adults Anopheles gambiae heads. This cellular model is well adapted to multidisciplinary approaches: electrophysiology, pharmacology, molecular biology and biochemical assays. Using RT-PCR, we demonstrated that isolated neurons express the nicotinic acetylcholine receptor subunit alpha 1 (Ag alpha 1 nAchR), tw...

  4. [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...

  5. Localization of Biogenic Amines in the Foregut of Aplysia californica: Catecholaminergic and Serotonergic Innervation

    Science.gov (United States)

    Martínez-Rubio, Clarissa; Serrano, Geidy E.; Miller, Mark W.

    2009-01-01

    This study examined the catecholaminergic and serotonergic innervation of the foregut of Aplysia californica, a model system in which the control of feeding behaviors can be investigated at the cellular level. Similar numbers (15-25) of serotonin-like-immunoreactive (5HTli) and tyrosine hydroxylase-like-immunoreactive (THli) fibers were present in each (bilateral) esophageal nerve (En), the major source of pregastric neural innervation in this system. The majority of En 5HTli and THli fibers originated from the anterior branch (En2), which innervates the pharynx and the anterior esophagus. Fewer fibers were present in the posterior branch (En1), which innervates the majority of the esophagus and the crop. Backfills of the two En branches toward the central nervous system (CNS) labeled a single, centrifugally projecting serotonergic fiber, originating from the metacerebral cell (MCC). The MCC fiber projected only to En2. No central THli neurons were found to project to the En. Surveys of the pharynx and esophagus revealed major differences between their patterns of catecholaminergic (CA) and serotonergic innervation. Whereas THli fibers and cell bodies were distributed throughout the foregut, 5HTli fibers were present in restricted plexi, and no 5HTli somata were detected. Double-labeling experiments in the periphery revealed THli neurons projecting toward the buccal ganglion via En2. Other afferents received dense perisomatic serotonergic innervation. Finally, qualitative and quantitative differences were observed between the buccal motor programs (BMPs) produced by stimulation of the two En branches. These observations increase our understanding of aminergic contributions to the pregastric regulation of Aplysia feeding behaviors. PMID:19330814

  6. Sudden Death and Myocardial Lesions after Damage to Catecholamine Neurons of the Nucleus Tractus Solitarii in Rat

    OpenAIRE

    Talman, William T.; Dragon, Deidre Nitschke; Jones, Susan Y.; Moore, Steven A.; Lin, Li-Hsien

    2012-01-01

    Lesions that remove neurons expressing neurokinin-1 (NK1) receptors from the nucleus tractus solitarii (NTS) without removing catecholaminergic neurons lead to loss of baroreflexes, labile arterial pressure, myocardial lesions and sudden death. Because destruction of NTS catecholaminergic neurons expressing tyrosine hydroxylase (TH) may also cause lability of arterial pressure and loss of baroreflexes, we sought to test the hypothesis that cardiac lesions associated with lability are not depe...

  7. Isolation of specific neurons from C. elegans larvae for gene expression profiling.

    Directory of Open Access Journals (Sweden)

    W Clay Spencer

    Full Text Available The simple and well-described structure of the C. elegans nervous system offers an unprecedented opportunity to identify the genetic programs that define the connectivity and function of individual neurons and their circuits. A correspondingly precise gene expression map of C. elegans neurons would facilitate the application of genetic methods toward this goal. Here we describe a powerful new approach, SeqCeL (RNA-Seq of C. elegans cells for producing gene expression profiles of specific larval C. elegans neurons.We have exploited available GFP reporter lines for FACS isolation of specific larval C. elegans neurons for RNA-Seq analysis. Our analysis showed that diverse classes of neurons are accessible to this approach. To demonstrate the applicability of this strategy to rare neuron types, we generated RNA-Seq profiles of the NSM serotonergic neurons that occur as a single bilateral pair of cells in the C. elegans pharynx. These data detected >1,000 NSM enriched transcripts, including the majority of previously known NSM-expressed genes.This work offers a simple and robust protocol for expression profiling studies of post-embryonic C. elegans neurons and thus provides an important new method for identifying candidate genes for key roles in neuron-specific development and function.

  8. 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.

  9. Catecholaminergic polymorphic ventricular tachycardia: An exciting new era.

    Science.gov (United States)

    Behere, Shashank P; Weindling, Steven N

    2016-01-01

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a highly malignant inheritable cardiac channelopathy. The past decade and a half has provided exciting new discoveries elucidating the genetic etiology and pathophysiology of CPVT. This review of the current literature on CPVT aims to summarize the state of the art in our understanding of the genetic etiology and the molecular pathogenesis of CPVT, and how these relate to our current approach to diagnosis and management. We will also shed light on groundbreaking new work that will continue to refine the management of CPVT in the future. As our knowledge of CPVT continues to grow, further studies will yield a better understanding of the efficacy and pitfalls of established diagnostic approaches and therapies as well as help shape newer diagnostic and treatment strategies. Two separate searches were run on the National Center for Biotechnology Information's (NCBI) website. The first used the medical subject headings (MeSH) database using the term "catecholaminergic polymorphic ventricular tachycardia" that was run on the PubMed database using the age filter (birth to 18 years), and it yielded 58 results. The second search using the MeSH database with the search term "catecholaminergic polymorphic ventricular tachycardia," applying no filters yielded 178 results. The abstracts of all these articles were studied and the articles were categorized and organized. Articles of relevance were read in full. As and where applicable, relevant references and citations from the primary articles were further explored and read in full.

  10. Catecholaminergic polymorphic ventricular tachycardia: An exciting new era

    Directory of Open Access Journals (Sweden)

    Shashank P Behere

    2016-01-01

    Full Text Available Catecholaminergic polymorphic ventricular tachycardia (CPVT is a highly malignant inheritable cardiac channelopathy. The past decade and a half has provided exciting new discoveries elucidating the genetic etiology and pathophysiology of CPVT. This review of the current literature on CPVT aims to summarize the state of the art in our understanding of the genetic etiology and the molecular pathogenesis of CPVT, and how these relate to our current approach to diagnosis and management. We will also shed light on groundbreaking new work that will continue to refine the management of CPVT in the future. As our knowledge of CPVT continues to grow, further studies will yield a better understanding of the efficacy and pitfalls of established diagnostic approaches and therapies as well as help shape newer diagnostic and treatment strategies. Two separate searches were run on the National Center for Biotechnology Information's (NCBI website. The first used the medical subject headings (MeSH database using the term “catecholaminergic polymorphic ventricular tachycardia” that was run on the PubMed database using the age filter (birth to 18 years, and it yielded 58 results. The second search using the MeSH database with the search term “catecholaminergic polymorphic ventricular tachycardia,” applying no filters yielded 178 results. The abstracts of all these articles were studied and the articles were categorized and organized. Articles of relevance were read in full. As and where applicable, relevant references and citations from the primary articles were further explored and read in full.

  11. 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.

  12. Bursts and isolated spikes code for opposite movement directions in midbrain electrosensory neurons.

    Directory of Open Access Journals (Sweden)

    Navid Khosravi-Hashemi

    Full Text Available Directional selectivity, in which neurons respond strongly to an object moving in a given direction but weakly or not at all to the same object moving in the opposite direction, is a crucial computation that is thought to provide a neural correlate of motion perception. However, directional selectivity has been traditionally quantified by using the full spike train, which does not take into account particular action potential patterns. We investigated how different action potential patterns, namely bursts (i.e. packets of action potentials followed by quiescence and isolated spikes, contribute to movement direction coding in a mathematical model of midbrain electrosensory neurons. We found that bursts and isolated spikes could be selectively elicited when the same object moved in opposite directions. In particular, it was possible to find parameter values for which our model neuron did not display directional selectivity when the full spike train was considered but displayed strong directional selectivity when bursts or isolated spikes were instead considered. Further analysis of our model revealed that an intrinsic burst mechanism based on subthreshold T-type calcium channels was not required to observe parameter regimes for which bursts and isolated spikes code for opposite movement directions. However, this burst mechanism enhanced the range of parameter values for which such regimes were observed. Experimental recordings from midbrain neurons confirmed our modeling prediction that bursts and isolated spikes can indeed code for opposite movement directions. Finally, we quantified the performance of a plausible neural circuit and found that it could respond more or less selectively to isolated spikes for a wide range of parameter values when compared with an interspike interval threshold. Our results thus show for the first time that different action potential patterns can differentially encode movement and that traditional measures of

  13. Deadly proposal: a case of catecholaminergic polymorphic ventricular tachycardia.

    Science.gov (United States)

    Heiner, Jason D; Bullard-Berent, Jeffrey H; Inbar, Shmuel

    2011-11-01

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare adrenergically mediated arrhythmogenic disorder classically induced by exercise or emotional stress and found in structurally normal hearts. It is an important cause of cardiac syncope and sudden death in childhood. Catecholaminergic polymorphic ventricular tachycardia is a genetic cardiac channelopathy with known mutations involving genes affecting intracellular calcium regulation. We present a case of a 14-year-old boy who had cardiopulmonary arrest after an emotionally induced episode of CPVT while attempting to invite a girl to the school dance. Review of his presenting cardiac rhythm, induction of concerning ventricular arrhythmias during an exercise stress test, and genetic testing confirmed the diagnosis of CPVT. He recovered fully and was treated with β-blocker therapy and placement of an implantable cardioverter-defibrillator. In this report, we discuss this rare but important entity, including its molecular foundation, clinical presentation, basics of diagnosis, therapeutic options, and implications of genetic testing for family members. We also compare CPVT to other notable cardiomyopathic and channelopathic causes of sudden death in youth including hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia, long QT syndrome, short QT syndrome, and Brugada syndrome. PMID:22068070

  14. A Method to Target and Isolate Airway-innervating Sensory Neurons in Mice.

    Science.gov (United States)

    Kaelberer, Melanie Maya; Jordt, Sven-Eric

    2016-01-01

    Somatosensory nerves transduce thermal, mechanical, chemical, and noxious stimuli caused by both endogenous and environmental agents. The cell bodies of these afferent neurons are located within the sensory ganglia. Sensory ganglia innervate a specific organ or portion of the body. For instance, the dorsal root ganglia (DRG) are located in the vertebral column and extend processes throughout the body and limbs. The trigeminal ganglia are located in the skull and innervate the face, and upper airways. Vagal afferents of the nodose ganglia extend throughout the gut, heart, and lungs. The nodose neurons control a diverse array of functions such as: respiratory rate, airway irritation, and cough reflexes. Thus, to understand and manipulate their function, it is critical to identify and isolate airway specific neuronal sub-populations. In the mouse, the airways are exposed to a fluorescent tracer dye, Fast Blue, for retrograde tracing of airway-specific nodose neurons. The nodose ganglia are dissociated and fluorescence activated cell (FAC) sorting is used to collect dye positive cells. Next, high quality ribonucleic acid (RNA) is extracted from dye positive cells for next generation sequencing. Using this method airway specific neuronal gene expression is determined. PMID:27168016

  15. 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, paraganglio

  16. Effects of lithium chloride on outward potassium currents in acutely isolated hippocampal CA1 pyramidal neurons

    Institute of Scientific and Technical Information of China (English)

    ZHANG Chaofeng; DU Huizhi; YANG Pin

    2006-01-01

    Although lithium possesses neuroprotective functions, the molecular mechanism underlying its actions has not been fully elucidated. In the present paper, the effects of lithium chloride on voltage-dependent potassium currents in the CA1 pyramidal neurons acutely isolated from rat hippocampus were studied using the whole-cell patch-clamp technique. Depolarizing test pulses activated two components of outward potassium currents: a rapidly activating and inactivating component, IA and a delayed component, IK. Results showed that lithium chloride increased the amplitude of IA in a concentration-dependent manner. Half enhancement concentration (EC50) was 22.80±5.45 μmol·L-1. Lithium chloride of 25 μmol·L-1 shifted the steady-state activation curve and inactivation curve of IA to more negative potentials, but mainly affected the activation kinetics. The amplitude and the activation processes of IK were not affected by lithium chloride. The effects of lithium chloride on potassium channel appear to possess neuroprotective properties by Ca2+-lowing effects modulate neuronal excitability by activating IA in rat hippocampal neurons.

  17. Monosynaptic glutamatergic activation of locus coeruleus and other lower brainstem noradrenergic neurons by the C1 cells in mice.

    Science.gov (United States)

    Holloway, Benjamin B; Stornetta, Ruth L; Bochorishvili, Genrieta; Erisir, Alev; Viar, Kenneth E; Guyenet, Patrice G

    2013-11-27

    The C1 neurons, located in the rostral ventrolateral medulla (VLM), are activated by pain, hypotension, hypoglycemia, hypoxia, and infection, as well as by psychological stress. Prior work has highlighted the ability of these neurons to increase sympathetic tone, hence peripheral catecholamine release, probably via their direct excitatory projections to sympathetic preganglionic neurons. In this study, we use channelrhodopsin-2 (ChR2) optogenetics to test whether the C1 cells are also capable of broadly activating the brain's noradrenergic system. We selectively expressed ChR2(H134R) in rostral VLM catecholaminergic neurons by injecting Cre-dependent adeno-associated viral vectors into the brain of adult dopamine-β-hydroxylase (DβH)(Cre/0) mice. Most ChR2-expressing VLM neurons (75%) were immunoreactive for phenylethanolamine N-methyl transferease, thus were C1 cells, and most of the ChR2-positive axonal varicosities were immunoreactive for vesicular glutamate transporter-2 (78%). We produced light microscopic evidence that the axons of rostral VLM (RVLM) catecholaminergic neurons contact locus coeruleus, A1, and A2 noradrenergic neurons, and ultrastructural evidence that these contacts represent asymmetric synapses. Using optogenetics in tissue slices, we show that RVLM catecholaminergic neurons activate the locus coeruleus as well as A1 and A2 noradrenergic neurons monosynaptically by releasing glutamate. In conclusion, activation of RVLM catecholaminergic neurons, predominantly C1 cells, by somatic or psychological stresses has the potential to increase the firing of both peripheral and central noradrenergic neurons.

  18. Catecholaminergic Fiber Innervation of the Vocal Motor System Is Intrasexually Dimorphic in a Teleost with Alternative Reproductive Tactics.

    Science.gov (United States)

    Ghahramani, Zachary N; Timothy, Miky; Kaur, Gurpreet; Gorbonosov, Michelle; Chernenko, Alena; Forlano, Paul M

    2015-01-01

    Catecholamines, which include the neurotransmitters dopamine and noradrenaline, are known modulators of sensorimotor function, reproduction, and sexually motivated behaviors across vertebrates, including vocal-acoustic communication. Recently, we demonstrated robust catecholaminergic (CA) innervation throughout the vocal motor system in the plainfin midshipman fish Porichthys notatus, a seasonal breeding marine teleost that produces vocal signals for social communication. There are 2 distinct male reproductive morphs in this species: type I males establish nests and court females with a long-duration advertisement call, while type II males sneak spawn to steal fertilizations from type I males. Like females, type II males can only produce brief, agonistic, grunt type vocalizations. Here, we tested the hypothesis that intrasexual differences in the number of CA neurons and their fiber innervation patterns throughout the vocal motor pathway may provide neural substrates underlying divergence in reproductive behavior between morphs. We employed immunofluorescence (-ir) histochemistry to measure tyrosine hydroxylase (TH; a rate-limiting enzyme in catecholamine synthesis) neuron numbers in several forebrain and hindbrain nuclei as well as TH-ir fiber innervation throughout the vocal pathway in type I and type II males collected from nests during the summer reproductive season. After controlling for differences in body size, only one group of CA neurons displayed an unequivocal difference between male morphs: the extraventricular vagal-associated TH-ir neurons, located just lateral to the dimorphic vocal motor nucleus (VMN), were significantly greater in number in type II males. In addition, type II males exhibited greater TH-ir fiber density within the VMN and greater numbers of TH-ir varicosities with putative contacts on vocal motor neurons. This strong inverse relationship between the predominant vocal morphotype and the CA innervation of vocal motor neurons suggests

  19. Catecholaminergic fiber innervation of the vocal motor system is intrasexually dimorphic in a teleost with alternative reproductive tactics

    Science.gov (United States)

    Ghahramani, Zachary N.; Timothy, Miky; Kaur, Gurpreet; Gorbonosov, Michelle; Chernenko, Alena; Forlano, Paul M.

    2015-01-01

    Catecholamines, which include the neurotransmitters dopamine and noradrenaline, are known modulators of sensorimotor function, reproduction, and sexually motivated behaviors across vertebrates, including vocal-acoustic communication. Recently, we demonstrated robust catecholaminergic (CA) innervation throughout the vocal-motor system in the plainfin midshipman fish, Porichtys notatus, a seasonal breeding marine teleost that produces vocal signals for social communication. There are two distinct male reproductive morphs in this species: Type I males establish nests and court females with a long duration advertisement call, while type II males sneak-spawn to steal fertilizations from type I males. Like females, type II males can only produce brief, agonistic, grunt-type vocalizations. Here, we tested the hypothesis that intrasexual differences in the numbers of CA neurons and their fiber innervation patterns throughout the vocal-motor pathway may provide neural substrates underlying divergence in reproductive behavior between morphs. We employed immunofluorescence (-ir) histochemistry to measure tyrosine hydroxylase (TH, rate-limiting enzyme in catecholamine synthesis) neuron numbers in several forebrain and hindbrain nuclei as well as TH-ir fiber innervation throughout the vocal pathway in type I and type II males collected from nests during the summer reproductive season. After controlling for differences in body size, only one group of CA neurons displayed an unequivocal difference between male morphs: the extraventricular vagal-associated TH-ir neurons, located just lateral to the dimorphic vocal motor nucleus (VMN), were significantly greater in number in type II males. In addition, type II males exhibited greater TH-ir fiber density within the VMN and greater numbers of TH-ir varicosities with putative contacts on vocal motor neurons. This strong inverse relationship between the predominant vocal morphotype and CA innervation of vocal motor neurons suggests

  20. c-fos Expression in mesopontine noradrenergic and cholinergic neurons of the cat during carbachol-induced active sleep: a double-labeling study.

    Science.gov (United States)

    Yamuy, J; Sampogna, S; Morales, F R; Chase, M H

    1998-01-01

    The interaction of cholinergic and catecholaminergic mechanisms in the mesopontine region has been hypothesized as being critical for the generation and maintenance of active (REM) sleep. To further examine this hypothesis, we sought to determine the pattern of neuronal activation (via c-fos expression) of catecholaminergic and cholinergic neurons in this region during active sleep induced by the pontine microapplication of carbachol (designated as active sleep-carbachol). Accordingly, we used two sets of double-labeling techniques; the first to identify tyrosine hydroxylase-containing neurons (putative catecholaminergic cells) which also express the c-fos protein product Fos, and the second to reveal choline acetyltransferase-containing neurons (putative cholinergic cells) which also express Fos. Compared to control cats, active sleep-carbachol cats exhibited a significantly greater number of Fos-expressing neurons in the dorsolateral region of the pons, which encompasses the locus coeruleus, the lateral pontine reticular formation, the peribrachial nuclei and the latero-dorsal and pedunculo-pontine tegmental nuclei. However, both control and active sleep-carbachol cats exhibited a similar number of catecholaminergic and cholinergic neurons in those regions that expressed Fos (i.e., double-labeled cells). A large number of c-fos-expressing neurons in the active sleep-carbachol cats whose neurotransmitter phenotype was not identified suggests that non-catecholaminergic, non-cholinergic neuronal populations in mesopontine regions are involved in the generation and maintenance of active sleep. The lack of increased c-fos expression in catecholaminergic neurons during active sleep-carbachol confirms and extends previous data that indicate that these cells are silent during active sleep-carbachol and naturally-occurring active sleep. The finding that cholinergic neurons of the dorsolateral pons were not activated either during wakefulness or active sleep

  1. FolR1: a novel cell surface marker for isolating midbrain dopamine neural progenitors and nascent dopamine neurons

    Science.gov (United States)

    Gennet, Nicole; Tamburini, Claudia; Nan, Xinsheng; Li, Meng

    2016-01-01

    Cell type-specific surface markers offer a powerful tool for purifying defined cell types for restorative therapies and drug screenings. Midbrain dopaminergic neurons (mesDA) are the nerve cells preferentially lost in the brains of Parkinson’s disease patients. Clinical trials of transplantation of fetal neural precursors suggest that cell therapy may offer a cure for this devastating neurological disease. Many lines of preclinical studies demonstrate that neural progenitors committed to dopaminergic fate survive and integrate better than postmitotic DA neurons. We show that the folate-receptor 1 (FolR1), a GPI-anchored cell surface molecule, specifically marks mesDA neural progenitors and immature mesDA neurons. FolR1 expression superimposes with Lmx1a, a bona-fide mesDA lineage marker, during the active phase of mesDA neurogenesis from E9.5 to E14.5 during mouse development, as well as in ESC-derived mesDA lineage. FolR1+ neural progenitors can be isolated by FACS or magnetic sorting (MAC) which give rise to dopamine neurons expressing TH and Pitx3, whilst FolR1 negative cells generate non-dopaminergic neurons and glia cells. This study identifies FolR1 as a new cell surface marker selectively expressed in mesDA progenitors in vivo and in vitro and that can be used to enrich in vitro differentiated TH neurons. PMID:27580818

  2. FolR1: a novel cell surface marker for isolating midbrain dopamine neural progenitors and nascent dopamine neurons.

    Science.gov (United States)

    Gennet, Nicole; Tamburini, Claudia; Nan, Xinsheng; Li, Meng

    2016-01-01

    Cell type-specific surface markers offer a powerful tool for purifying defined cell types for restorative therapies and drug screenings. Midbrain dopaminergic neurons (mesDA) are the nerve cells preferentially lost in the brains of Parkinson's disease patients. Clinical trials of transplantation of fetal neural precursors suggest that cell therapy may offer a cure for this devastating neurological disease. Many lines of preclinical studies demonstrate that neural progenitors committed to dopaminergic fate survive and integrate better than postmitotic DA neurons. We show that the folate-receptor 1 (FolR1), a GPI-anchored cell surface molecule, specifically marks mesDA neural progenitors and immature mesDA neurons. FolR1 expression superimposes with Lmx1a, a bona-fide mesDA lineage marker, during the active phase of mesDA neurogenesis from E9.5 to E14.5 during mouse development, as well as in ESC-derived mesDA lineage. FolR1(+) neural progenitors can be isolated by FACS or magnetic sorting (MAC) which give rise to dopamine neurons expressing TH and Pitx3, whilst FolR1 negative cells generate non-dopaminergic neurons and glia cells. This study identifies FolR1 as a new cell surface marker selectively expressed in mesDA progenitors in vivo and in vitro and that can be used to enrich in vitro differentiated TH neurons. PMID:27580818

  3. 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...

  4. A case of catecholaminergic polymorphic ventricular tachycardia caused by two calsequestrin 2 mutations

    NARCIS (Netherlands)

    De La Fuente, Sam; Van Langen, Irene M.; Postma, Alex V.; Bikker, Henni; Meijer, Albert

    2008-01-01

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an uncommon heritable disease presenting with syncope or sudden cardiac death. Two genes involved in calcium homeostasis, the ryanodine receptor gene and the calsequestrin 2 (CASQ2) gene, have been implicated in this disease. We describ

  5. 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...

  6. 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.

  7. Effects of benzodiazepines and non-benzodiazepine compounds on the GABA-induced response in frog isolated sensory neurones.

    OpenAIRE

    Yakushiji, T; Fukuda, T.; Oyama, Y.; Akaike, N.

    1989-01-01

    1. The effects of benzodiazepines and non-benzodiazepine compounds on the gamma-aminobutyric acid (GABA)-induced chloride current (ICl) were studied in frog isolated sensory neurones by use of a concentration-jump (termed 'concentration-clamp') technique, under single-electrode voltage-clamp conditions. The drugs used were classified into four categories as follows: full benzodiazepine receptor agonists (diazepam, clonazepam, nitrazepam, midazolam, clotiazepam and etizolam), partial agonists ...

  8. Postpacing abnormal repolarization in catecholaminergic polymorphic ventricular tachycardia associated with a mutation in the cardiac ryanodine receptor gene

    NARCIS (Netherlands)

    E. Nof; B. Belhassen; M. Arad; Z.A. Bhuiyan; C. Antzelevitch; R. Rosso; R. Fogelman; D. Luria; D. El-Ani; M.M.A.M. Mannens; S. Viskin; M. Eldar; A.A.M. Wilde; M. Glikson

    2011-01-01

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease for which electrophysiological studies (EPS) have shown to be of limited value. This study presents a CPVT family in which marked postpacing repolarization abnormalities during EPS were the only consistent phen

  9. 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.

  10. Catecholaminergic innervation of central and peripheral auditory circuitry varies with reproductive state in female midshipman fish, Porichthys notatus.

    Directory of Open Access Journals (Sweden)

    Paul M Forlano

    Full Text Available In seasonal breeding vertebrates, hormone regulation of catecholamines, which include dopamine and noradrenaline, may function, in part, to modulate behavioral responses to conspecific vocalizations. However, natural seasonal changes in catecholamine innervation of auditory nuclei is largely unexplored, especially in the peripheral auditory system, where encoding of social acoustic stimuli is initiated. The plainfin midshipman fish, Porichthys notatus, has proven to be an excellent model to explore mechanisms underlying seasonal peripheral auditory plasticity related to reproductive social behavior. Recently, we demonstrated robust catecholaminergic (CA innervation throughout the auditory system in midshipman. Most notably, dopaminergic neurons in the diencephalon have widespread projections to auditory circuitry including direct innervation of the saccule, the main endorgan of hearing, and the cholinergic octavolateralis efferent nucleus (OE which also projects to the inner ear. Here, we tested the hypothesis that gravid, reproductive summer females show differential CA innervation of the auditory system compared to non-reproductive winter females. We utilized quantitative immunofluorescence to measure tyrosine hydroxylase immunoreactive (TH-ir fiber density throughout central auditory nuclei and the sensory epithelium of the saccule. Reproductive females exhibited greater density of TH-ir innervation in two forebrain areas including the auditory thalamus and greater density of TH-ir on somata and dendrites of the OE. In contrast, non-reproductive females had greater numbers of TH-ir terminals in the saccule and greater TH-ir fiber density in a region of the auditory hindbrain as well as greater numbers of TH-ir neurons in the preoptic area. These data provide evidence that catecholamines may function, in part, to seasonally modulate the sensitivity of the inner ear and, in turn, the appropriate behavioral response to reproductive acoustic

  11. Effect of helium-neon laser on fast excitatory postsynaptic potential of neurons in the isolated rat superior cervical ganglia

    Institute of Scientific and Technical Information of China (English)

    Hua Mo(莫华); Ping He(何萍); Ning Mo(莫宁)

    2004-01-01

    The aim of this study is to further measure the effect of 632.8-nm helium-neon laser on fast excitatory postsynaptic potential(f-EPSP)of postganglionic neurons in isolated rat superior cervical ganglia by means of intracellular recording techniques.The neurons with f-EPSP were irradiated by different power densities(1 - 5 mW/cm2)laser.Irradiated by the 2-mW/cm2 laser,the amplitude of the f-EPSP could augment(P < 0.05,paired t test)and even cause action potential at the end of the first 1 - 2 minutes,the f-EPSP could descend and last for 3 - 8 minutes.But the amplitude of the f-EPSP of neurons irradiated by the 5-mW/cm2 laser could depress for the irradiating periods.The results show that:1)the variation of the amplitude of f-EPSP caused by laser is power density-dependent and time-dependent; 2)there exist the second-order phases in the interaction of the helium-neon laser with neurons.These findings may provide certain evidence in explanation of the mechanisms of clinical helium-neon laser therapy.

  12. Isolation of Specific Neurons from C. elegans Larvae for Gene Expression Profiling

    OpenAIRE

    W Clay Spencer; Rebecca McWhirter; Tyne Miller; Pnina Strasbourger; Owen Thompson; Hillier, LaDeana W.; Waterston, Robert H.; Miller, David M.

    2014-01-01

    Background The simple and well-described structure of the C. elegans nervous system offers an unprecedented opportunity to identify the genetic programs that define the connectivity and function of individual neurons and their circuits. A correspondingly precise gene expression map of C. elegans neurons would facilitate the application of genetic methods toward this goal. Here we describe a powerful new approach, SeqCeL (RNA-Seq of C. elegans cells) for producing gene expression profiles of s...

  13. Leptin receptor immunoreactivity is present in ascending serotonergic and catecholaminergic neurons of the rat

    DEFF Research Database (Denmark)

    Hay-Schmidt, Anders; Helboe, Lone; Larsen, Philip J.

    2001-01-01

    Obesity, tyrosine hydroxylase, arcuate nucleus, paracentricular nucleus, raphe nuclei, leptin, serotonin, catecholamines......Obesity, tyrosine hydroxylase, arcuate nucleus, paracentricular nucleus, raphe nuclei, leptin, serotonin, catecholamines...

  14. Isolation and Culture of Pig Spermatogonial Stem Cells and Their in Vitro Differentiation into Neuron-Like Cells and Adipocytes

    Directory of Open Access Journals (Sweden)

    Xiaoyan Wang

    2015-11-01

    Full Text Available Spermatogonial stem cells (SSCs renew themselves throughout the life of an organism and also differentiate into sperm in the adult. They are multipopent and therefore, can be induced to differentiate into many cells types in vitro. SSCs from pigs, considered an ideal animal model, are used in studies of male infertility, regenerative medicine, and preparation of transgenic animals. Here, we report on a culture system for porcine SSCs and the differentiation of these cells into neuron-like cells and adipocytes. SSCs and Sertoli cells were isolated from neonatal piglet testis by differential adhesion and SSCs were cultured on a feeder layer of Sertoli cells. Third-generation SSCs were induced to differentiate into neuron-like cells by addition of retinoic acid, β-mercaptoethanol, and 3-isobutyl-1-methylxanthine (IBMX to the induction media and into adipocytes by the addition of hexadecadrol, insulin, and IBMX to the induction media. The differentiated cells were characterized by biochemical staining, qRT-PCR, and immunocytochemistry. The cells were positive for SSC markers, including alkaline phosphatase and SSC-specific genes, consistent with the cells being undifferentiated. The isolated SSCs survived on the Sertoli cells for 15 generations. Karyotyping confirmed that the chromosomal number of the SSCs were normal for pig (2n = 38, n = 19. Pig SSCs were successfully induced into neuron-like cells eight days after induction and into adipocytes 22 days after induction as determined by biochemical and immunocytochemical staining. qPCR results also support this conclusion. The nervous tissue markers genes, Nestin and β-tubulin, were expressed in the neuron-like cells and the adipocyte marker genes, PPARγ and C/EBPα, were expressed in the adipocytes.

  15. Genetic Isolation of Hypothalamic Neurons that Regulate Context-Specific Male Social Behavior.

    Science.gov (United States)

    Soden, Marta E; Miller, Samara M; Burgeno, Lauren M; Phillips, Paul E M; Hnasko, Thomas S; Zweifel, Larry S

    2016-07-12

    Nearly all animals engage in a complex assortment of social behaviors that are essential for the survival of the species. In mammals, these behaviors are regulated by sub-nuclei within the hypothalamus, but the specific cell types within these nuclei responsible for coordinating behavior in distinct contexts are only beginning to be resolved. Here, we identify a population of neurons in the ventral premammillary nucleus of the hypothalamus (PMV) that are strongly activated in male intruder mice in response to a larger resident male but that are not responsive to females. Using a combination of molecular and genetic approaches, we demonstrate that these PMV neurons regulate intruder-specific male social behavior and social novelty recognition in a manner dependent on synaptic release of the excitatory neurotransmitter glutamate. These data provide direct evidence for a unique population of neurons that regulate social behaviors in specific contexts. PMID:27346361

  16. Effects of SO2 derivatives on sodium currents in acutely isolated rat hippocampal lead-exposed neurons

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    In this study, the effects of acute SO2 derivatives and chronic lead exposure together on sodium cur-rents (INa) were investigated in acutely isolated rat hippocampal neurons by using the whole-cell patch clamp techniques. We found that chronic lead exposure hardly reduced the amplitudes of INa. In the normal condition, sodium current started to appear at around ?70 mV, and reached the peak current at around ?40 mV. After chronic lead exposure, the data changed to ?70 and ?30 mV. After adding SO2 derivatives, the data changed to ?80 and ?40 mV, respectively. SO2 derivatives caused a significant in-crease of INa in hippocampal chronic-lead exposed neurons. Chronic lead exposure induced a right shift of the activation curve and a left shift of the inactivation curve of sodium channels. SO2 derivatives caused negative shifts of the activation and inactivation curves of INa in hippocampal chronic-lead ex-posed neurons. Lead exposure put off the time reaching the peak of INa activation. SO2 derivatives in-creased the time constants of inactivation after lead exposure. The interaction of lead and SO2 deriva-tives with voltage-dependent sodium channels may lead to changes in electrical activity and contribute to worsening the neurotoxicological damage.

  17. Gene Expression Analysis of Neurons and Astrocytes Isolated by Laser Capture Microdissection from Frozen Human Brain Tissues.

    Science.gov (United States)

    Tagliafierro, Lidia; Bonawitz, Kirsten; Glenn, Omolara C; Chiba-Falek, Ornit

    2016-01-01

    Different cell types and multiple cellular connections characterize the human brain. Gene expression analysis using a specific population of cells is more accurate than conducting analysis of the whole tissue homogenate, particularly in the context of neurodegenerative diseases, where a specific subset of cells is affected by the different pathology. Due to the difficulty of obtaining homogenous cell populations, gene expression in specific cell-types (neurons, astrocytes, etc.) has been understudied. To leverage the use of archive resources of frozen human brains in studies of neurodegenerative diseases, we developed and calibrated a method to quantify cell-type specific-neuronal, astrocytes-expression profiles of genes implicated in neurodegenerative diseases, including Parkinson's and Alzheimer's diseases. Archive human frozen brain tissues were used to prepare slides for rapid immunostaining using cell-specific antibodies. The immunoreactive-cells were isolated by Laser Capture Microdissection (LCM). The enrichment for a particular cell-type of interest was validated in post-analysis stage by the expression of cell-specific markers. We optimized the technique to preserve the RNA integrity, so that the RNA was suitable for downstream expression analyses. Following RNA extraction, the expression levels were determined digitally using nCounter Single Cell Gene Expression assay (NanoString Technologies®). The results demonstrated that using our optimized technique we successfully isolated single neurons and astrocytes from human frozen brain tissues and obtained RNA of a good quality that was suitable for mRNA expression analysis. We present here new advancements compared to previous reported methods, which improve the method's feasibility and its applicability for a variety of downstream molecular analyses. Our new developed method can be implemented in genetic and functional genomic research of neurodegenerative diseases and has the potential to significantly

  18. Acetylcholine modulates transient outward potassium channel in acutely isolated cerebral cortical neurons of rats

    Institute of Scientific and Technical Information of China (English)

    Lanwei Cui; Tao Sun; Lihui Qu; Yurong Li; Haixia Wen

    2009-01-01

    BACKGROUND:The neuronal transient outward potassium channel has been shown to be highly associated with acetylcholine.However,the influence of acetylcholine on the transient outward potassium current in cerebral cortical neurons remains poorly understood.OBJECTIVE:To investigate acetylcholine modulation on transient outward potassium current in rat parietal cortical neurons using the whole-cell patch-clamp technique.DESIGN,TIME AND SETTING:A neuroelectrophysiology study was performed at the Department of Physiology,Harbin Medical University between January 2005 and January 2006.MATERIALS:Wistar rats were provided by the Animal Research Center,the Second Hospital of Harbin Medical University;PC-IIC patch-clamp amplifier and IBBClamp data collection analysis system were provided by Huazhong University for Science and Technology,Wuhan,China;PP-83 microelectrode puller was purchased from Narrishage,Japan.METHODS:The parietal somatosensory cortical neurons were acutely dissociated,and the modulation of acetylcholine (0.1,1,10,100 μmol/L) on transient outward potassium channel was recorded using the whole-cell patch-clamp technique.MAIN OUTCOME MEASURES:Influence of acetylcholine on transient outward potassium current,potassium channel activation,and inactivation.RESULTS:The inhibitory effect of acetylcholine on transient outward potassium current was dose- and voltage-dependent (P<0.01).Acetylcholine was found to significantly affect the activation process of transient outward potassium current,i.e.,the activation curve of transient outward potassium current was left-shifted,while the inactivation curve was shifted to hyperpolarization.Acetylcholine significantly prolonged the time constant of recovery from inactivation of transient outward potassium current (P<0.01).CONCLUSION:These results suggest that acetylcholine inhibits transient outward potassium current by regulating activation and inactivation processes of the transient outward potassium channel.

  19. Estradiol-dependent catecholaminergic innervation of auditory areas in a seasonally breeding songbird.

    Science.gov (United States)

    Matragrano, Lisa L; Sanford, Sara E; Salvante, Katrina G; Sockman, Keith W; Maney, Donna L

    2011-08-01

    A growing body of evidence suggests that gonadal steroids such as estradiol (E2) alter neural responses not only in brain regions associated with reproductive behavior but also in sensory areas. Because catecholamine systems are involved in sensory processing and selective attention, and because they are sensitive to E2 in many species, they may mediate the neural effects of E2 in sensory areas. Here, we tested the effects of E2 on catecholaminergic innervation, synthesis and activity in the auditory system of white-throated sparrows, a seasonally breeding songbird in which E2 promotes selective auditory responses to song. Non-breeding females with regressed ovaries were held on a winter-like photoperiod and implanted with silastic capsules containing either no hormone or E2. In one hemisphere of the brain, we used immunohistochemistry to quantify fibers immunoreactive for tyrosine hydroxylase or dopamine beta-hydroxylase in the auditory forebrain, thalamus and midbrain. E2 treatment increased catecholaminergic innervation in the same areas of the auditory system in which E2 promotes selectivity for song. In the contralateral hemisphere we quantified dopamine, norepinephrine and their metabolites in tissue punches using HPLC. Norepinephrine increased in the auditory forebrain, but not the midbrain, after E2 treatment. We found that evidence of interhemispheric differences, both in immunoreactivity and catecholamine content that did not depend on E2 treatment. Overall, our results show that increases in plasma E2 typical of the breeding season enhanced catecholaminergic innervation and synthesis in some parts of the auditory system, raising the possibility that catecholamines play a role in E2-dependent auditory plasticity in songbirds.

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

    OpenAIRE

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

    2005-01-01

    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 μ-opioid receptor (MOP) regulation of voltage-gated calcium channel currents (ICa) 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 protoc...

  1. Pentobarbitone modulation of NMDA receptors in neurones isolated from the rat olfactory brain.

    OpenAIRE

    Charlesworth, P; Jacobson, I; Richards, C. D.

    1995-01-01

    1. The action of pentobarbitone on the N-methyl-D-aspartate (NMDA) receptors of neurones freshly dissociated from the olfactory bulb and olfactory tubercle has been studied using patch-clamp techniques. 2. Pentobarbitone produced a concentration-dependent depression of the currents evoked by NMDA with an IC50 value of c. 250 microM. 3. Analysis of the NMDA-evoked noise produced power spectra that could be fitted by the sum of two Lorentzians with corner frequencies of 17 and 82 Hz. Pentobarbi...

  2. Effect of etomidate on voltage-dependent potassium currents in rat isolated hippocampal pyramidal neurons

    Institute of Scientific and Technical Information of China (English)

    TAN Hong-yu; SUN Li-na; WANG Xiao-liang; YE Tie-hu

    2010-01-01

    Background Previous studies demonstrated general anesthetics affect potassium ion channels, which may be one of the mechanisms of general anesthesia. Because the effect of etomidate on potassium channels in rat hippocampus which is involved in memory function has not been studied, we investigated the effects of etomidate on both delayed rectifier potassium current (I_((K(DR))) and transient outward potassium current (I_((K(A))) in acutely dissociated rat hippocampal pyramidal neurons.Methods Single rat hippocampal pyramidal neurons from male Wistar rats of 7-10 days were acutely dissociated by enzymatic digestion and mechanical dispersion according to the methods of Kay and Wong with slight modification. Voltage-clamp recordings were performed in the whole-cell patch clamp configuration. Currents were recorded with a List EPC-10 amplifier and data were stored in a computer using Pulse 8.5. Student's paired two-tail t test was used for data analysis. Results At the concentration of 100 μmol/L, etomidate significantly inhibited I_(K(DR)) by 49.2% at +40 mV when depolarized from -110 mV (P 0.05). The IC_(50) value of etomidate for blocking I_(K(DR)) was calculated as 5.4 μmol/L, with a Hill slope of 2.45. At the presence of 10 μmol/L etomidate, the V_(1/2) of activation curve was shifted from (17.3±1.5) mV to (10.7±9.9) mV (n=8, P <0.05), the V_(1/2) of inactivation curve was shifted from (-18.3±2.2) mV to (-45.3±9.4) mV (n=8, P <0.05). Etomidate 10 μmol/L shifted both the activation curve and inactivation curve of I_(K(DR)) to negative potential, but mainly affected the inactivation kinetics.Conclusions Etomidate potently inhibited I_(K(DR)) but not I_(K(A)) in rat hippocampal pyramidal neurons. I_(K(DR)) was inhibited by etomidate in a concentration-dependent manner, while I_(K(A)) remained unaffected.

  3. Familial Evaluation in Catecholaminergic Polymorphic Ventricular Tachycardia Disease Penetrance and Expression in Cardiac Ryanodine Receptor Mutation-Carrying Relatives

    NARCIS (Netherlands)

    van der Werf, Christian; Nederend, Ineke; Hofman, Nynke; van Geloven, Nan; Ebink, Corne; Frohn-Mulder, Ingrid M. E.; Alings, A. Marco W.; Bosker, Hans A.; Bracke, Frank A.; van den Heuvel, Freek; Waalewijn, Reinier A.; Bikker, Hennie; van Tintelen, J. Peter; Bhuiyan, Zahurul A.; van den Berg, Maarten P.; Wilde, Arthur A. M.

    2012-01-01

    Background-Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome associated with mutations in the cardiac ryanodine receptor gene (RYR2) in the majority of patients. Previous studies of CPVT patients mainly involved probands, so current insight into disease

  4. Radioautographic identification of central monoaminergic neurons after local micro-instillation of tritiated serotonin and norepinephrine in the cat

    International Nuclear Information System (INIS)

    Monoaminergic neurons in nuclei raphe dorsalis and locus coeruleus of the cat may be visualized by radioautography after local micro-instillation of tritiated serotonin and noradrenaline. The concomitant administration of the appropriate tracer with the other biogenic amine in non radioactive form permits a specific identification of serotoninergic and catecholaminergic nerve cell bodies. A small contingent of presumptive serotoninergic neurons is thus demonstrated in the region of the locus coeruleus

  5. Super-resolution imaging of ciliary microdomains in isolated olfactory sensory neurons using a custom STED microscope

    Science.gov (United States)

    Meyer, Stephanie A.; Ozbay, Baris; Restrepo, Diego; Gibson, Emily A.

    2014-03-01

    We performed super-resolution imaging of isolated olfactory sensory neurons (OSNs) using a custom-built Stimulated Emission Depletion (STED) microscope. The design for the STED microscope is based on the system developed in the laboratory of Dr. Stefan Hell1. Our system is capable of imaging with sub-diffraction limited resolution simultaneously in two color channels (at Atto 590/Atto 647N wavelengths). A single, pulsed laser source (ALP; Fianium, Inc.) generates all four laser beams, two excitation and two STED. The two STED beams are coupled into one polarization maintaining (PM) fiber and the two excitation beams into another. They are then collimated and both STED beams pass through a vortex phase plate (RPC Photonics) to allow shaping into a donut at the focus of the objective lens. The beams are then combined and sent into an inverted research microscope (IX-71; Olympus Inc.) allowing widefield epifluorescence, brightfield and DIC imaging on the same field of view as STED imaging. A fast piezo stage scans the sample during STED and confocal imaging. The fluorescent signals from the two color channels are detected with two avalanche photodiodes (APD) after appropriate spectral filtering. The resolution of the system was characterized by imaging 40 nm fluorescent beads as ~60 nm (Atto 590) and ~50 nm (Atto 647N). We performed STED imaging on immunolabeled isolated OSNs tagged at the CNGA2 and ANO2 proteins. The STED microscope allows us to resolve ciliary CNGA2 microdomains of ~54 nm that were blurred in confocal.

  6. Effects of benzodiazepines and non-benzodiazepine compounds on the GABA-induced response in frog isolated sensory neurones.

    Science.gov (United States)

    Yakushiji, T; Fukuda, T; Oyama, Y; Akaike, N

    1989-11-01

    1. The effects of benzodiazepines and non-benzodiazepine compounds on the gamma-aminobutyric acid (GABA)-induced chloride current (ICl) were studied in frog isolated sensory neurones by use of a concentration-jump (termed 'concentration-clamp') technique, under single-electrode voltage-clamp conditions. The drugs used were classified into four categories as follows: full benzodiazepine receptor agonists (diazepam, clonazepam, nitrazepam, midazolam, clotiazepam and etizolam), partial agonists (CL 218,872, Ro 16-6028, Ro 17-1812 and Ro 23-0364), inverse agonists (Ro 15-3505, FG 7142 and beta-CCE) and a benzodiazepine receptor antagonist, Ro 15-1788 (flumazenil). 2. All full agonists at concentrations of 3 x 10(-6) M or less increased dose-dependently the peak amplitude of ICl elicited by 3 x 10(-6) M GABA to twice to three times larger than the control. However, no further augmentation of the GABA response was observed at concentrations of 1 x 10(-5) M or higher. Partial agonists also showed a dose-dependent augmentation of the GABA response at concentrations ranging from 3 x 10(-8) M to 3 x 10(-5) M, but their efficacies of augmentation of the GABA response were only about half or less of those of full agonists. Of the inverse agonists, beta-CCE had a unique dose-dependent effect on the GABA response. Beta-CCE reduced dose-dependently the GABA response at concentrations of less than 3 x 10(-6) M, but augmented it at concentrations of 3 x 10(-5) M and 6 x 10(-5) M. The inverse agonists reduced dose-dependently the GABA response. The benzodiazepine antagonist, flumazenil, slightly augmented the GABA response at concentrations between 3 x 10 7M and 3 x 10 5 M. 3. These results show clear differences in the effects on the GABA response between these four categories of compounds known to affect the benzodiazepine recognition site of the GABA/ benzodiazepine receptor-chloride channel complex. Our experimental system of frog isolated sensory neurones and a 'concentration

  7. Cell model of catecholaminergic polymorphic ventricular tachycardia reveals early and delayed afterdepolarizations.

    Directory of Open Access Journals (Sweden)

    Kirsi Kujala

    Full Text Available BACKGROUND: Induced pluripotent stem cells (iPSC provide means to study the pathophysiology of genetic disorders. Catecholaminergic polymorphic ventricular tachycardia (CPVT is a malignant inherited ion channel disorder predominantly caused by mutations in the cardiac ryanodine receptor (RyR2. In this study the cellular characteristics of CPVT are investigated and whether the electrophysiological features of this mutation can be mimicked using iPSC -derived cardiomyocytes (CM. METHODOLOGY/PRINCIPAL FINDINGS: Spontaneously beating CMs were differentiated from iPSCs derived from a CPVT patient carrying a P2328S mutation in RyR2 and from two healthy controls. Calcium (Ca(2+ cycling and electrophysiological properties were studied by Ca(2+ imaging and patch-clamp techniques. Monophasic action potential (MAP recordings and 24h-ECGs of CPVT-P2328S patients were analyzed for the presence of afterdepolarizations. We found defects in Ca(2+ cycling and electrophysiology in CPVT CMs, reflecting the cardiac phenotype observed in the patients. Catecholaminergic stress led to abnormal Ca(2+ signaling and induced arrhythmias in CPVT CMs. CPVT CMs also displayed reduced sarcoplasmic reticulum (SR Ca(2+ content, indicating leakage of Ca(2+ from the SR. Patch-clamp recordings of CPVT CMs revealed both delayed afterdepolarizations (DADs during spontaneous beating and in response to adrenaline and also early afterdepolarizations (EADs during spontaneous beating, recapitulating the changes seen in MAP and 24h-ECG recordings of patients carrying the same mutation. CONCLUSIONS/SIGNIFICANCE: This cell model shows aberrant Ca(2+ cycling characteristic of CPVT and in addition to DADs it displays EADs. This cell model for CPVT provides a platform to study basic pathology, to screen drugs, and to optimize drug therapy.

  8. Transient voltage-dependent potassium currents are reduced in NTS neurons isolated from renal wrap hypertensive rats.

    Science.gov (United States)

    Belugin, Sergei; Mifflin, Steve

    2005-12-01

    Whole cell patch-clamp measurements were made in neurons enzymatically dispersed from the nucleus of the solitary tract (NTS) to determine if alterations occur in voltage-dependent potassium channels from rats made hypertensive (HT) by unilateral nephrectomy/renal wrap for 4 wk. Some rats had the fluorescent tracer DiA applied to the aortic nerve before the experiment to identify NTS neurons receiving monosynaptic baroreceptor afferent inputs. Mean arterial pressure (MAP) was greater in 4-wk HT (165 +/- 5 mmHg, n = 26, P NTS neurons from NT and HT rats. At activation voltages from -10 to +10 mV, TOCs were significantly less in HT neurons compared with those observed in NT neurons (P NTS neurons from NT and HT rats and was not different comparing neurons from NT and HT rats. However, examination of the subset of NTS neurons exhibiting somatic DiA fluorescence revealed that DiA-labeled neurons from HT rats had a significantly shorter duration delayed excitation (n = 8 cells, P = 0.022) than DiA-labeled neurons from NT rats (n = 7 cells). Neurons with delayed excitation from HT rats had a significantly broader first action potential (AP) and a slower maximal downstroke velocity of repolarization compared with NT neurons with delayed excitation (P = 0.016 and P = 0.014, respectively). The number of APs in the first 200 ms of a sustained depolarization was greater in HT than NT neurons (P = 0.012). These results suggest that HT of 4-wk duration reduces TOCs in NTS neurons, and this contributes to reduced delayed excitation and increased AP responses to depolarizing inputs. Such changes could alter baroreflex function in hypertension.

  9. 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. PMID:25756794

  10. Isolation of Multipotent Nestin-Expressing Stem Cells Derived from the Epidermis of Elderly Humans and TAT-VHL Peptide-Mediated Neuronal Differentiation of These Cells

    Directory of Open Access Journals (Sweden)

    Jiro Maegawa

    2013-05-01

    Full Text Available A specialized population of cells residing in the hair follicle is quiescent but shows pluripotency for differentiating into epithelial-mesenchymal lineage cells. Therefore, such cells are hoped to be useful as implantable donor cells for regenerative therapy. Recently, it was reported that intracellular delivery of TAT-VHL peptide induces neuronal differentiation of skin-derived precursors. In the present study, we successfully isolated multipotent stem cells derived from the epidermis of elderly humans, characterized these cells as being capable of sphere formation and strong expression of nestin, fibronectin, and CD34 but not of keratin 15, and identified the niche of these cells as being the outer root sheath of the hair follicles. In addition, we showed that TAT-VHL peptide induced their neuronal differentiation in vitro, and confirmed by fluorescence immunohistochemistry the neuronal differentiation of such peptide-treated cells implanted into rodent brains. These multipotent nestin-expressing stem cells derived from human epidermis are easily accessible and should be useful as donor cells for neuronal regenerative cell therapy.

  11. Modeling Catecholaminergic Polymorphic Ventricular Tachycardia using Induced Pluripotent Stem Cell-derived Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Atara Novak

    2012-07-01

    Full Text Available Catecholaminergic polymorphic ventricular tachycardia (CPVT is an inherited arrhythmogenic cardiac disorder characterized by life-threatening arrhythmias induced by physical or emotional stress, in the absence structural heart abnormalities. The arrhythmias may cause syncope or degenerate into cardiac arrest and sudden death which usually occurs during childhood. Recent studies have shown that CPVT is caused by mutations in the cardiac ryanodine receptor type 2 (RyR2 or calsequestrin 2 (CASQ2 genes. Both proteins are key contributors to the intracellular Ca2+ handling process and play a pivotal role in Ca2+ release from the sarcoplasmic reticulum to the cytosol during systole. Although the molecular pathogenesis of CPVT is not entirely clear, it was suggested that the CPVT mutations promote excessive sarcoplasmic reticulum Ca2+ leak, which initiates delayed afterdepolarizations (DADs and triggered arrhythmias in cardiac myocytes. The recent breakthrough discovery of induced pluripotent stem cells (iPSC generated from somatic cells (e.g. fibroblasts, keratinocytes now enables researches to investigate mutated cardiomyocytes generated from the patient’s iPSC. To this end, in the present article we review recent studies on CPVT iPSC-derived cardiomyocytes, thus demonstrating in the mutated cells catecholamine-induced DADs and triggered arrhythmias.

  12. Alternans in genetically modified Langendorff-perfused murine hearts modeling catecholaminergic polymorphic ventricular tachycardia

    Directory of Open Access Journals (Sweden)

    Ian N Sabir

    2010-10-01

    Full Text Available The relationship between alternans and arrhythmogenicity was studied in genetically modified murine hearts modeling catecholaminergic polymorphic ventricular tachycardia (CPVT during Langendorff perfusion, before and after treatment with catecholamines and a β-adrenergic antagonist. Heterozygous (RyR2p/s and homozygous (RyR2s/s RyR2-P2328S hearts, and wild-type (WT controls, were studied before and after treatment with epinephrine (100 nM and 1 µM and propranolol (100 nM. Monophasic action potential recordings demonstrated significantly greater incidences of arrhythmia in RyR2s/p and RyR2s/s hearts as compared to WTs. Arrhythmogenicity in RyR2s/s hearts was associated with alternans, particularly at short baseline cycle lengths. Both phenomena were significantly accentuated by treatment with epinephrine and significantly diminished by treatment with propranolol, in full agreement with clinical expectations. These changes took place, however, despite an absence of changes in action potential durations, ventricular effective refractory periods or restitution curve characteristics. Furthermore pooled data from all hearts in which arrhythmia occurred demonstrated significantly greater alternans magnitudes, but similar restitution curve slopes, to hearts that did not demonstrate arrhythmia. These findings thus further validate the RyR2-P2328S murine heart as a model for human CPVT, confirming an alternans phenotype in common with murine genetic models of the Brugada syndrome and the congenital long-QT syndrome type 3. In contrast to these latter similarities, however, this report demonstrates the dissociation of alternans from changes in the properties of restitution curves for the first time in a murine model of a human arrhythmic syndrome.

  13. Divergent Projections of Catecholaminergic Neurons in the Nucleus of the Solitary Tract to Limbic Forebrain and Medullary Autonomic Brain Regions

    OpenAIRE

    Reyes, Beverly A. S.; Van Bockstaele, Elisabeth J.

    2006-01-01

    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 micr...

  14. 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.

  15. Isolation and Culture of Pig Spermatogonial Stem Cells and Their in Vitro Differentiation into Neuron-Like Cells and Adipocytes

    OpenAIRE

    Xiaoyan Wang; Tingfeng Chen; Yani Zhang; Bichun Li; Qi Xu; Chengyi Song

    2015-01-01

    Spermatogonial stem cells (SSCs) renew themselves throughout the life of an organism and also differentiate into sperm in the adult. They are multipopent and therefore, can be induced to differentiate into many cells types in vitro. SSCs from pigs, considered an ideal animal model, are used in studies of male infertility, regenerative medicine, and preparation of transgenic animals. Here, we report on a culture system for porcine SSCs and the differentiation of these cells into neuron-like c...

  16. Isolation Rearing Reduces Neuronal Excitability in Dentate Gyrus Granule Cells of Adolescent C57BL/6J Mice: Role of GABAergic Tonic Currents and Neurosteroids.

    Science.gov (United States)

    Talani, Giuseppe; Biggio, Francesca; Licheri, Valentina; Locci, Valentina; Biggio, Giovanni; Sanna, Enrico

    2016-01-01

    Early-life exposure to stress, by impacting on a brain still under development, is considered a critical factor for the increased vulnerability to psychiatric disorders and abuse of psychotropic substances during adulthood. As previously reported, rearing C57BL/6J weanling mice in social isolation (SI) from their peers for several weeks, a model of prolonged stress, is associated with a decreased plasma and brain levels of neuroactive steroids such as 3α,5α-THP, with a parallel up-regulation of extrasynaptic GABAA receptors (GABAAR) in dentate gyrus (DG) granule cells compared to group-housed (GH) mice. In the present study, together with the SI-induced decrease in plasma concentration of both progesterone and 3α,5α-THP, and an increase in THIP-stimulated GABAergic tonic currents, patch-clamp analysis of DG granule cells revealed a significant decrease in membrane input resistance and action potential (AP) firing rate, in SI compared to GH mice, suggesting that SI exerts an inhibitory action on neuronal excitability of these neurons. Voltage-clamp recordings of glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs) revealed a SI-associated decrease in frequency as well as a shift from paired-pulse (PP) depression to PP facilitation (PPF) of evoked EPSCs, indicative of a reduced probability of glutamate release. Daily administration of progesterone during isolation reverted the changes in plasma 3α,5α-THP as well as in GABAergic tonic currents and neuronal excitability caused by SI, but it had only a limited effect on the changes in the probability of presynaptic glutamate release. Overall, the results obtained in this work, together with those previously published, indicate that exposure of mice to SI during adolescence reduces neuronal excitability of DG granule cells, an effect that may be linked to the increased GABAergic tonic currents as a consequence of the sustained decrease in plasma and hippocampal levels of neurosteroids. All these

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

    Directory of Open Access Journals (Sweden)

    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

  18. Effect of angiotensin Ⅱ type 1 receptor on delayed rectifier potassium current in catecholaminergic CATH.a cells

    Institute of Scientific and Technical Information of China (English)

    Jian-qing DU; Cheng-wen SUN; Jing-shi TANG

    2004-01-01

    AIM: To study the modulatory effects of angiotensin Ⅱ (Ang Ⅱ) on the delayed rectifier potassium (Kv) current(IKv) and its underlying intracellular mechanism in the catecholaminergic system of rats. METHODS: AT1 and AT2receptors of the differentiated and undifferentiated CATH.a cells were determined by radioligands binding assay.The IKv was recorded with the whole cell patch-clamp configuration in voltage clamp mode on CATH.a cells.RESULTS: The Ang Ⅱ receptor proteins including AT1 and AT2 receptors were expressed in CATH.a cells, and the number of the former was significantly more than the latter (P<0.01). The IKv of CATH.a cells was reduced by superfusion with the Ang Ⅱ (100 nmol/L) (P<0.05) in the presence of the AT2 receptor antagonist PD123319, but was not affected by only superfusion with PD123319. The effect of Ang Ⅱ on IKv in CATH.a cells was completely inhibited by addition of AT1 receptor antagonist losartan. Superfusion with Ang Ⅱ (100 nmol/L) plus U73122, an inhibitor of phospholipase C (PLC) in the presence of PD 123319 had no effect on the IKv [(20.2+2.8) pA/pF]. AngⅡ-induced reduction of IKv was attenuated (P<0.05) but not abolished by PKC inhibitor calphostin C (Cal) and selective CaMK Ⅱ inhibitor KN-93 (10 μmol/L) respectively. However, IKv reduction was completely abolished by superfusion with both Cal and KN-93. CONCLUSION: The inhibition of Kv currents in CATH.a cells by Ang Ⅱ is mediated by AT1 receptor, and the PLC, PKC and CaMK Ⅱ may be involved in signal transduction of AT1 receptor.The differentiated CATH.a cell is a useful cell model to study Ang Ⅱ receptor-mediated functional modulation of catecholaminergic system.

  19. Vestibular Neuronitis

    Science.gov (United States)

    ... Prevent Painful Swimmer's Ear Additional Content Medical News Vestibular Neuronitis By Lawrence R. Lustig, MD NOTE: This ... Drugs Herpes Zoster Oticus Meniere Disease Purulent Labyrinthitis Vestibular Neuronitis Vestibular neuronitis is a disorder characterized by ...

  20. 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.

  1. Evidence for the occurrence of an enkephalin-like peptide in adrenaline and noradrenaline neurons of the rat medulla oblongata.

    Science.gov (United States)

    Ceccatelli, S; Millhorn, D E; Hökfelt, T; Goldstein, M

    1989-01-01

    The indirect immunofluorescence technique was used to analyze the catecholaminergic neurons in the medulla oblongata of the rat for the presence of enkephalin (ENK)- and neuropeptide Y (NPY)-like immunoreactivity (LI). In colchicine pretreated animals, using a double staining technique with mouse and rabbit antibodies against ENK and tyrosine hydroxylase (TH) or phenylethanolamine N-methyltransferase (PNMT), it was demonstrated that both TH- and ENK-LI occurred in the same neurons, particularly in many neurons of the A1 noradrenaline cell group. In the transition zone to the C1 adrenaline cell group, a proportion of PNMT-positive cells also contained ENK-LI. In the rostral and mid portion of the C1 group only few TH/PNMT-positive cells were found to be ENK-positive. In the noradrenergic A2 region, a moderate number of cell bodies also contained TH- plus ENK-LI, whereas only a few of the adrenaline cells of the C2 and C3 groups showed ENK-LI. In addition, with an elution restaining technique it was possible to demonstrate that several of the cells containing TH- and ENK-LI were also positive for NPY-LI. The present findings demonstrate that a subpopulation of the catecholaminergic neurons in the medulla oblongata of the rat is ENK-positive, thereby indicating a possible co-release of the two compounds in their projection areas, for example the paraventricular nucleus and the spinal cord. PMID:2565245

  2. Cuneiform neurons activated during cholinergically induced active sleep in the cat.

    Science.gov (United States)

    Pose, I; Sampogna, S; Chase, M H; Morales, F R

    2000-05-01

    In the present study, we report that the cuneiform (Cun) nucleus, a brainstem structure that before now has not been implicated in sleep processes, exhibits a large number of neurons that express c-fos during carbachol-induced active sleep (AS-carbachol). Compared with control (awake) cats, during AS-carbachol, there was a 671% increase in the number of neurons that expressed c-fos in this structure. Within the Cun nucleus, three immunocytochemically distinct populations of neurons were observed. One group consisted of GABAergic neurons, which predominantly did not express c-fos during AS-carbachol. Two other different populations expressed c-fos during this state. One of the Fos-positive (Fos(+)) populations consisted of a distinct group of nitric oxide synthase (NOS)-NADPH-diaphorase (NADPH-d)-containing neurons; the neurotransmitter of the other Fos(+) population remains unknown. The Cun nucleus did not contain cholinergic, catecholaminergic, serotonergic, or glycinergic neurons. On the basis of neuronal activation during AS-carbachol, as indicated by c-fos expression, we suggest that the Cun nucleus is involved, in an as yet unknown manner, in the physiological expression of active sleep. The finding of a population of NOS-NADPH-d containing neurons, which were activated during AS-carbachol, suggests that nitrergic modulation of their target cell groups is likely to play a role in active sleep-related physiological processes. PMID:10777795

  3. A human pluripotent stem cell model of catecholaminergic polymorphic ventricular tachycardia recapitulates patient-specific drug responses

    Directory of Open Access Journals (Sweden)

    Marcela K. Preininger

    2016-09-01

    Full Text Available Although β-blockers can be used to eliminate stress-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT, this treatment is unsuccessful in ∼25% of cases. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs generated from these patients have potential for use in investigating the phenomenon, but it remains unknown whether they can recapitulate patient-specific drug responses to β-blockers. This study assessed whether the inadequacy of β-blocker therapy in an individual can be observed in vitro using patient-derived CPVT iPSC-CMs. An individual with CPVT harboring a novel mutation in the type 2 cardiac ryanodine receptor (RyR2 was identified whose persistent ventricular arrhythmias during β-blockade with nadolol were abolished during flecainide treatment. iPSC-CMs generated from this patient and two control individuals expressed comparable levels of excitation-contraction genes, but assessment of the sarcoplasmic reticulum Ca2+ leak and load relationship revealed intracellular Ca2+ homeostasis was altered in the CPVT iPSC-CMs. β-adrenergic stimulation potentiated spontaneous Ca2+ waves and unduly frequent, large and prolonged Ca2+ sparks in CPVT compared with control iPSC-CMs, validating the disease phenotype. Pursuant to the patient's in vivo responses, nadolol treatment during β-adrenergic stimulation achieved negligible reduction of Ca2+ wave frequency and failed to rescue Ca2+ spark defects in CPVT iPSC-CMs. In contrast, flecainide reduced both frequency and amplitude of Ca2+ waves and restored the frequency, width and duration of Ca2+ sparks to baseline levels. By recapitulating the improved response of an individual with CPVT to flecainide compared with β-blocker therapy in vitro, these data provide new evidence that iPSC-CMs can capture basic components of patient-specific drug responses.

  4. A human pluripotent stem cell model of catecholaminergic polymorphic ventricular tachycardia recapitulates patient-specific drug responses

    Science.gov (United States)

    Preininger, Marcela K.; Jha, Rajneesh; Maxwell, Joshua T.; Wu, Qingling; Singh, Monalisa; Dalal, Aarti; Mceachin, Zachary T.; Rossoll, Wilfried; Hales, Chadwick M.; Fischbach, Peter S.; Wagner, Mary B.

    2016-01-01

    ABSTRACT Although β-blockers can be used to eliminate stress-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), this treatment is unsuccessful in ∼25% of cases. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) generated from these patients have potential for use in investigating the phenomenon, but it remains unknown whether they can recapitulate patient-specific drug responses to β-blockers. This study assessed whether the inadequacy of β-blocker therapy in an individual can be observed in vitro using patient-derived CPVT iPSC-CMs. An individual with CPVT harboring a novel mutation in the type 2 cardiac ryanodine receptor (RyR2) was identified whose persistent ventricular arrhythmias during β-blockade with nadolol were abolished during flecainide treatment. iPSC-CMs generated from this patient and two control individuals expressed comparable levels of excitation-contraction genes, but assessment of the sarcoplasmic reticulum Ca2+ leak and load relationship revealed intracellular Ca2+ homeostasis was altered in the CPVT iPSC-CMs. β-adrenergic stimulation potentiated spontaneous Ca2+ waves and unduly frequent, large and prolonged Ca2+ sparks in CPVT compared with control iPSC-CMs, validating the disease phenotype. Pursuant to the patient's in vivo responses, nadolol treatment during β-adrenergic stimulation achieved negligible reduction of Ca2+ wave frequency and failed to rescue Ca2+ spark defects in CPVT iPSC-CMs. In contrast, flecainide reduced both frequency and amplitude of Ca2+ waves and restored the frequency, width and duration of Ca2+ sparks to baseline levels. By recapitulating the improved response of an individual with CPVT to flecainide compared with β-blocker therapy in vitro, these data provide new evidence that iPSC-CMs can capture basic components of patient-specific drug responses. PMID:27491078

  5. Energy efficiency of information transmission by electrically coupled neurons

    OpenAIRE

    Torrealdea, Francisco J.; Sarasola, Cecilia; d'Anjou, Alicia; Moujahid, Abdelmalik; de Mendizábal, N. Vélez

    2012-01-01

    The generation of spikes by neurons is energetically a costly process. This paper studies the consumption of energy and the information entropy in the signalling activity of a model neuron both when it is supposed isolated and when it is coupled to another neuron by an electrical synapse. The neuron has been modelled by a four dimensional Hindmarsh-Rose type kinetic model for which an energy function has been deduced. For the isolated neuron values of energy consumption and information entrop...

  6. Catecholaminergic Gene Variants: Contribution in ADHD and Associated Comorbid Attributes in the Eastern Indian Probands

    Directory of Open Access Journals (Sweden)

    Paramita Ghosh

    2013-01-01

    Full Text Available Contribution of genes in attention deficit hyperactivity disorder (ADHD has been explored in various populations, and several genes were speculated to contribute small but additive effects. We have assessed variants in four genes, DDC (rs3837091 and rs3735273, DRD2 (rs1800496, rs1801028, and rs1799732, DRD4 (rs4646984 and rs4646983, and COMT (rs165599 and rs740603 in Indian ADHD subjects with comorbid attributes. Cases were recruited following the Diagnostic and Statistical Manual for Mental Disorders-IV-TR after obtaining informed written consent. DNA isolated from peripheral blood leukocytes of ADHD probands (N=170, their parents (N=310, and ethnically matched controls (n=180 was used for genotyping followed by population- and family-based analyses by the UNPHASED program. DRD4 sites showed significant difference in allelic frequencies by case-control analysis, while DDC and COMT exhibited bias in familial transmission (P<0.05. rs3837091 “AGAG,” rs3735273 “A,” rs1799732 “C,” rs740603 “G,” rs165599 “G” and single repeat alleles of rs4646984/rs4646983 showed positive correlation with co-morbid characteristics (P<0.05. Multi dimensionality reduction analysis of case-control data revealed significant interactive effects of all four genes (P<0.001, while family-based data showed interaction between DDC and DRD2 (P=0.04. This first study on these gene variants in Indo-Caucasoid ADHD probands and associated co-morbid conditions indicates altered dopaminergic neurotransmission in ADHD.

  7. 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

  8. An Optimized Culture Method of Rat Dorsal Root Ganglion Neurons

    Institute of Scientific and Technical Information of China (English)

    LIUYin; CHENJing-Hong; GONGZe-Hui

    2004-01-01

    AIM: To establish a primary culture technique of acutely isolated dorsal root ganglion (DRG) neurons, and provide a simple & useful in vitro model for study of analgesia. Methods: Acutely isolated dorsal root ganglion (DRG) neurons were planted and cultured; the configuration and growth characters of DRG neurons were observed through inverted microscope.

  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. c-Fos immunoreactivity in the pig brain following deoxynivalenol intoxication: focus on NUCB2/nesfatin-1 expressing neurons.

    Science.gov (United States)

    Gaigé, Stéphanie; Bonnet, Marion S; Tardivel, Catherine; Pinton, Philippe; Trouslard, Jérôme; Jean, André; Guzylack, Laurence; Troadec, Jean-Denis; Dallaporta, Michel

    2013-01-01

    Deoxynivalenol (DON), produced by the cereal-contaminating Fusarium fungi, is a major trichothecene responsible for mycotoxicoses in farm animals, including swine. The main effect of DON-intoxication is food intake reduction and the consequent body weight loss. The present study aimed to identify brain structures activated during DON intoxication in pigs. To this goal, we used c-Fos staining which constitutes a useful approach to identify activated neurons. We showed that per os administration of Fusarium graminearum extracts (containing the equivalent of 1mg DON per kg of body weight) induced an increase in c-Fos immunoreactivity in several central structures, including the ventrolateral medulla (VLM), dorsal vagal complex (DVC), paraventricular nucleus of the hypothalamus (PVN), arcuate nucleus (Arc), supraoptic nucleus (SON) and amygdala (CeA). Moreover, we coupled c-Fos staining with phenotypic markers detection in order to specify the neuronal populations activated during DON intoxication. This phenotypic characterization revealed the activation of catecholaminergic but not of serotoninergic neurons in response to the toxin. In this context, we also paid a particular attention to NUCB2/nesfatin-1 positive cells, since nesfatin-1 is known to exert a satiety effect. We report here, for the first time in the pig brain, the presence of NUCB2/nesfatin-1 neurons in the VLM, DVC, PVN, Arc and SON, and their activation during DON intoxication. Taken together, these data show that DON stimulates the main structures involved in food intake in pigs and suggest that catecholaminergic and NUCB2/nesfatin-1 neurons could contribute in the anorexigenic effects of the mycotoxin.

  11. Exposure to Advertisement Calls of Reproductive Competitors Activates Vocal-Acoustic and Catecholaminergic Neurons in the Plainfin Midshipman Fish, Porichthys notatus

    OpenAIRE

    Christopher L Petersen; Miky Timothy; D Spencer Kim; Ashwin A Bhandiwad; Robert A Mohr; 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 e...

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    Jang, Ji Yeon; Choi, Young Whan; Kim, Ha Neui; Kim, Yu Ri; Hong, Jin Woo; Bae, Dong Won; Park, Se Jin; Shin, Hwa Kyoung; Choi, Byung Tae

    2014-01-01

    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 brain disorder

  14. Cardiac ryanodine receptor gene (hRyR2) mutation underlying catecholaminergic polymorphic ventricular tachycardia in a Chinese adolescent presenting with sudden cardiac arrest and cardiac syncope

    Institute of Scientific and Technical Information of China (English)

    Ngai-Shing Mok; Ching-Wan Lam; Nai-Chung Fong; Yim-Wo Hui; Yuen-Choi Choi; Kwok-Yin Chan

    2006-01-01

    @@ Sudden cardiac death (SCD) in children and adolescents is uncommon and yet it is devastating for both victim's family and the society.Recently, it was increasingly recognized that SCD in young patients with structurally normal heart may be caused by inheritable primary electrical diseases due to the malfunction of cardiac ion channels, a disease entity known as the ion channelopathies.Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a specific form of ion channelopathy which can cause cardiac syncope or SCD in young patients by producing catecholamine-induced bi-directional ventricular tachycardia (BiVT), polymorphic VT and ventricular fibrillation (VF) during physical exertion or emotion.1-7 We reported here an index case of CPVT caused by cardiac ryanodine receptor gene (hRyR2)mutation which presented as cardiac syncope and sudden cardiac arrest in a Chinese adolescent female.

  15. INTERACTION OF VESICULAR MONOAMINE TRANSPORTER 2 (VMAT2 AND NEUROMELANIN PIGMENT AMONG THE MIDBRAIN DOPAMINERGIC NEURONS, IN MAN

    Directory of Open Access Journals (Sweden)

    P. Pasbakhsh

    2004-05-01

    Full Text Available Neuromelanin (NM pigment accumulates with age in catecholaminergic neurons in man, and the ventral substantia nigra dopaminergic neurons that are the most vulnerable to degeneration in Parkinson's disease (PD contain the greatest amount of this pigment. In vitro data indicate that NM pigment is formed from the excess cytosolic catecholamine that is not accumulated into synaptic vesicles via the vesicular monoamine transporter2 (VMAT2. Using semi-quantitative immunohistochemical methods in human postmortem brain, we sought to examine the relationship between the contents of VMAT2 and NM pigment. The immunostaining intensity (ISI was measured for VMAT2 in two regions of the midbrain dopaminergic cell complex. The ISI of the cells was related to the density of NM pigment within the cells. We also measured the ISI for tyrosine hydroxylase (TH and examined the noradrenergic neurons in the locus coeruleus (LC. In brains 22-65 years of age: 1 ventral substantia nigra neurons had the lowest VMAT2 ISI of all neurons in the midbrain cell complex, whereas over 2-fold higher levels are found in most ventral tegmental area neurons; 2 there was an inverse relationship between VMAT2 ISI and neuromelanin pigment in the midbrain dompaminergic neurons; 3 neurons with the highest VMAT2 ISI resided in the LC; 4 neurons with high VMAT2 ISI also had high TH ISI; and 5 in the newborn brain, which has not yet accumulated neuromelanin pigment in the aminergic neurons, the regional distribution of VMAT2 and TH-ISI was similar to that found in the adult brain. These data support the hypothesis that among the midbrain dopaminergic neurons, the ventral substantia nigra dopamine neurons accumulate the highest levels of NM pigment because they have the lowest levels of VMAT2, which thereby renders them especially vulnerable to degeneration in PD.

  16. Neuronal avalanches and coherence potentials

    Science.gov (United States)

    Plenz, D.

    2012-05-01

    The mammalian cortex consists of a vast network of weakly interacting excitable cells called neurons. Neurons must synchronize their activities in order to trigger activity in neighboring neurons. Moreover, interactions must be carefully regulated to remain weak (but not too weak) such that cascades of active neuronal groups avoid explosive growth yet allow for activity propagation over long-distances. Such a balance is robustly realized for neuronal avalanches, which are defined as cortical activity cascades that follow precise power laws. In experiments, scale-invariant neuronal avalanche dynamics have been observed during spontaneous cortical activity in isolated preparations in vitro as well as in the ongoing cortical activity of awake animals and in humans. Theory, models, and experiments suggest that neuronal avalanches are the signature of brain function near criticality at which the cortex optimally responds to inputs and maximizes its information capacity. Importantly, avalanche dynamics allow for the emergence of a subset of avalanches, the coherence potentials. They emerge when the synchronization of a local neuronal group exceeds a local threshold, at which the system spawns replicas of the local group activity at distant network sites. The functional importance of coherence potentials will be discussed in the context of propagating structures, such as gliders in balanced cellular automata. Gliders constitute local population dynamics that replicate in space after a finite number of generations and are thought to provide cellular automata with universal computation. Avalanches and coherence potentials are proposed to constitute a modern framework of cortical synchronization dynamics that underlies brain function.

  17. [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.

  18. Nursing of Patients with Catecholaminergic Polymorphic Ventricular Tachycardia%儿茶酚胺敏感性室性心动过速患者的护理

    Institute of Scientific and Technical Information of China (English)

    蒋欣

    2012-01-01

    目的 探讨儿茶酚胺敏感性室性心动过速(catecholaminergic polymorphic ventricular tachycardia,CPVT)患者的护理特点.方法 回顾性分析2005年6月至2011年6月宁波市医疗中心李惠利医院心内科收治的5例CPVT患者的临床资料,并总结其护理经验.结果 β受体阻滞剂对大多数CPVT患者效果良好,但对长期足量应用β受体阻滞剂仍不能满意控制心律失常发生的患者,需要采用植入式心律转复除颤器(implantable cardioverter defibrillator,ICD)治疗.结论 CPVT患者护理各有特点,药物治疗为主的CPVT患者应重视解释疏导和心理护理,而安装植入式心律转复除颤器(implantable cardioverter defibrillator,ICD)患者的应重视术后护理工作.%Objective To summarizes the nursing Features in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT). Methods The clinical data of five CPVT patients in our hospital during June 2005 and June 2011 were analyzed retrospectivley. The nursing features were summarized according ly. Results The β-blockers are effective in the most patients but the long-term adequate doses of beta blockers are still not satisfied with the control of arrhythmia in patients. Implantable cardioverter defibril- lator (ICD) is the only option for the high risk patients. Conclusion Both treatments have different nurs ing features:one focuses on the interpretation of treatment guidelines and psychological care,and the other emphasizes the post-operative care.

  19. Differential regulation of the zebrafish orthopedia1 gene during fate determination of diencephalic neurons

    Directory of Open Access Journals (Sweden)

    Tarallo Raffaella

    2006-10-01

    Full Text Available Abstract Background The homeodomain transcription factor Orthopedia (Otp is essential in restricting the fate of multiple classes of secreting neurons in the neuroendocrine hypothalamus of vertebrates. However, there is little information on the intercellular factors that regulate Otp expression during development. Results Here, we identified two otp orthologues in zebrafish (otp1 and otp2 and explored otp1 in the context of the morphogenetic pathways that specify neuroectodermal regions. During forebrain development, otp1 is expressed in anterior groups of diencephalic cells, positioned in the preoptic area (PO (anterior alar plate and the posterior tuberculum (PT (posterior basal plate. The latter structure is characterized by Tyrosine Hydroxylase (TH-positive cells, suggesting a role for otp1 in the lineage restriction of catecholaminergic (CA neurons. Disruptions of Hedgehog (HH and Fibroblast Growth Factor (FGF pathways point to the ability of SHH protein to trigger otp1 expression in PO presumptive neuroblasts, with the attenuating effect of Dzip1 and FGF8. In addition, our data disclose otp1 as a determinant of CA neurons in the PT, where otp1 activity is strictly dependent on Nodal signaling and it is not responsive to SHH and FGF. Conclusion In this study, we pinpoint the evolutionary importance of otp1 transcription factor in cell states of the diencephalon anlage and early neuronal progenitors. Furthermore, our data indicate that morphogenetic mechanisms differentially regulate otp1 expression in alar and basal plates.

  20. Isolation Rearing Reduces Neuronal Excitability in Dentate Gyrus Granule Cells of Adolescent C57BL/6J Mice: Role of GABAergic Tonic Currents and Neurosteroids

    OpenAIRE

    Talani, Giuseppe; Biggio, Francesca; Licheri, Valentina; Locci, Valentina; Biggio, Giovanni; Sanna, Enrico

    2016-01-01

    Early-life exposure to stress, by impacting on a brain still under development, is considered a critical factor for the increased vulnerability to psychiatric disorders and abuse of psychotropic substances during adulthood. As previously reported, rearing C57BL/6J weanling mice in social isolation (SI) from their peers for several weeks, a model of prolonged stress, is associated with a decreased plasma and brain levels of neuroactive steroids such as 3α,5α-THP, with a parallel up-regulation ...

  1. Isolation rearing reduces neuronal excitability in dentate gyrus granule cells of adolescent C57BL/6J mice: role of GABAergic tonic currents and neurosteroids

    OpenAIRE

    Giuseppe Talani; Francesca Biggio; Valentina Licheri; Valentina Locci; Giovanni Biggio; Enrico Sanna

    2016-01-01

    Early-life exposure to stress, by impacting on a brain still under development, is considered a critical factor for the increased vulnerability to psychiatric disorders and abuse of psychotropic substances during adulthood. As previously reported, rearing C57BL/6J weanling mice in isolation (SI) from their peers for several weeks, a model of prolonged stress, is associated with a decreased plasma and brain levels of neuroactive steroids such as 3α,5α-THP, with a parallel up-regulation of extr...

  2. Post-natal heart adaptation in a knock-in mouse model of calsequestrin 2-linked recessive catecholaminergic polymorphic ventricular tachycardia.

    Science.gov (United States)

    Valle, Giorgia; Boncompagni, Simona; Sacchetto, Roberta; Protasi, Feliciano; Volpe, Pompeo

    2014-02-15

    Cardiac calsequestrin (CASQ2) contributes to intracellular Ca(2+) homeostasis by virtue of its low-affinity/high-capacity Ca(2+) binding properties, maintains sarcoplasmic reticulum (SR) architecture and regulates excitation-contraction coupling, especially or exclusively upon β-adrenergic stimulation. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease associated with cardiac arrest in children or young adults. Recessive CPVT variants are due to mutations in the CASQ2 gene. Molecular and ultra-structural properties were studied in hearts of CASQ2(R33Q/R33Q) and of CASQ2(-/-) mice from post-natal day 2 to week 8. The drastic reduction of CASQ2-R33Q is an early developmental event and is accompanied by down-regulation of triadin and junctin, and morphological changes of jSR and of SR-transverse-tubule junctions. Although endoplasmic reticulum stress is activated, no signs of either apoptosis or autophagy are detected. The other model of recessive CPVT, the CASQ2(-/-) mouse, does not display the same adaptive pattern. Expression of CASQ2-R33Q influences molecular and ultra-structural heart development; post-natal, adaptive changes appear capable of ensuring until adulthood a new pathophysiological equilibrium. PMID:24370574

  3. Electrophysiological effects of trace amines on mesencephalic dopaminergic neurons

    Directory of Open Access Journals (Sweden)

    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

  4. Calcium signals in olfactory neurons.

    Science.gov (United States)

    Tareilus, E; Noé, J; Breer, H

    1995-11-01

    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. PMID:7488645

  5. Calcium signals in olfactory neurons.

    Science.gov (United States)

    Tareilus, E; Noé, J; Breer, H

    1995-11-01

    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.

  6. Catecholamine metabolism drives generation of mitochondrial DNA deletions in dopaminergic neurons.

    Science.gov (United States)

    Neuhaus, Johannes F G; Baris, Olivier R; Hess, Simon; Moser, Natasha; Schröder, Hannsjörg; Chinta, Shankar J; Andersen, Julie K; Kloppenburg, Peter; Wiesner, Rudolf J

    2014-02-01

    Accumulation of mitochondrial DNA deletions is observed especially in dopaminergic neurons of the substantia nigra during ageing and even more in Parkinson's disease. The resulting mitochondrial dysfunction is suspected to play an important role in neurodegeneration. However, the molecular mechanisms involved in the preferential generation of mitochondrial DNA deletions in dopaminergic neurons are still unknown. To study this phenomenon, we developed novel polymerase chain reaction strategies to detect distinct mitochondrial DNA deletions and monitor their accumulation patterns. Applying these approaches in in vitro and in vivo models, we show that catecholamine metabolism drives the generation and accumulation of these mitochondrial DNA mutations. As in humans, age-related accumulation of mitochondrial DNA deletions is most prominent in dopaminergic areas of mouse brain and even higher in the catecholaminergic adrenal medulla. Dopamine treatment of terminally differentiated neuroblastoma cells, as well as stimulation of dopamine turnover in mice over-expressing monoamine oxidase B both induce multiple mitochondrial DNA deletions. Our results thus identify catecholamine metabolism as the driving force behind mitochondrial DNA deletions, probably being an important factor in the ageing-associated degeneration of dopaminergic neurons.

  7. SURVIVAL AND NEURITE FORMATION OF MESENCEPHALIC TRIGEMINAL NEURONS OF THE RAT IN-VITRO

    NARCIS (Netherlands)

    COPRAY, JCVM; LIEM, RSB

    1993-01-01

    In order to study the development and functional properties of single, isolated, rat mesencephalic trigeminal neurones, a cell-culture procedure was developed for these specific primary sensory neurones. Mesencephalic trigeminal neurones were isolated from the brainstem of 16-day-old rat embryos. Va

  8. Degenerative alterations in noradrenergic neurons of the locus coeruleus in Alzheimer’s disease****

    Institute of Scientific and Technical Information of China (English)

    Lihua Liu; Saiping Luo; Leping Zeng; Weihong Wang; Liming Yuan; Xiaohong Jian

    2013-01-01

    Mice carrying mutant amyloid-β precursor protein and presenilin-1 genes (APP/PS1 double trans-genic mice) have frequently been used in studies of Alzheimer’s disease; however, such studies have focused mainly on hippocampal and cortical changes. The severity of Alzheimer’s disease is known to correlate with the amount of amyloid-βprotein deposition and the number of dead neurons in the locus coeruleus. In the present study, we assigned APP/PS1 double transgenic mice to two groups according to age: young mice (5–6 months old) and aged mice (16–17 months old). Age-matched wild-type mice were used as controls. Immunohistochemistry for tyrosine hydroxylase (a marker of catecholaminergic neurons in the locus coeruleus) revealed that APP/PS1 mice had 23%fewer cel s in the locus coeruleus compared with aged wild-type mice. APP/PS1 mice also had increased numbers of cel bodies of neurons positive for tyrosine hydroxylase, but fewer tyrosine hydroxylase-positive fibers, which were also short, thick and broken. Quantitative analysis using unbiased stereology showed a significant age-related increase in the mean volume of tyrosine hy-droxylase-positive neurons in aged APP/PS1 mice compared with young APP/PS1 mice. Moreover, the mean volume of tyrosine hydroxylase-positive neurons was positively correlated with the total volume of the locus coeruleus. These findings indicate that noradrenergic neurons and fibers in the locus coeruleus are predisposed to degenerative alterations in APP/PS1 double transgenic mice.

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

    Science.gov (United States)

    Sasaki, Kenichi; Makiyama, Takeru; Yoshida, Yoshinori; Wuriyanghai, Yimin; Kamakura, Tsukasa; Nishiuchi, Suguru; Hayano, Mamoru; Harita, Takeshi; Yamamoto, Yuta; Kohjitani, Hirohiko; Hirose, Sayako; Chen, Jiarong; Kawamura, Mihoko; Ohno, Seiko; Itoh, Hideki; Takeuchi, Ayako; Matsuoka, Satoshi; Miura, Masaru; Sumitomo, Naokata; Horie, Minoru; Yamanaka, Shinya; Kimura, Takeshi

    2016-01-01

    Introduction 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. Method and Results 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). Conclusions 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. PMID:27764147

  10. 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

  11. Neuronal Migration Disorders

    Science.gov (United States)

    ... Enhancing Diversity Find People About NINDS NINDS Neuronal Migration Disorders Information Page Table of Contents (click to ... being done? Clinical Trials Organizations What are Neuronal Migration Disorders? Neuronal migration disorders (NMDs) are a group ...

  12. Motor Neuron Diseases

    Science.gov (United States)

    ... Awards Enhancing Diversity Find People About NINDS Motor Neuron Diseases Fact Sheet See a list of all ... can I get more information? What are motor neuron diseases? The motor neuron diseases (MNDs) are a ...

  13. Characteristics of sodium currents in rat geniculate ganglion neurons.

    Science.gov (United States)

    Nakamura, Shiro; Bradley, Robert M

    2011-12-01

    Geniculate ganglion (GG) cell bodies of chorda tympani (CT), greater superficial petrosal (GSP), and posterior auricular (PA) nerves transmit orofacial sensory information to the rostral nucleus of the solitary tract. We have used whole cell recording to investigate the characteristics of the Na(+) channels in isolated Fluorogold-labeled GG neurons that innervate different peripheral receptive fields. GG neurons expressed two classes of Na(+) channels, TTX sensitive (TTX-S) and TTX resistant (TTX-R). The majority of GG neurons expressed TTX-R currents of different amplitudes. TTX-R currents were relatively small in 60% of the neurons but were large in 12% of the sampled population. In a further 28% of the neurons, TTX completely abolished all Na(+) currents. Application of TTX completely inhibited action potential generation in all CT and PA neurons but had little effect on the generation of action potentials in 40% of GSP neurons. Most CT, GSP, and PA neurons stained positively with IB(4), and 27% of the GSP neurons were capsaicin sensitive. The majority of IB(4)-positive GSP neurons with large TTX-R Na(+) currents responded to capsaicin, whereas IB(4)-positive GSP neurons with small TTX-R Na(+) currents were capsaicin insensitive. These data demonstrate the heterogeneity of GG neurons and indicate the existence of a subset of GSP neurons sensitive to capsaicin, usually associated with nociceptors. Since there are no reports of nociceptors in the GSP receptive field, the role of these capsaicin-sensitive neurons is not clear.

  14. Hypothalamic leptin-neurotensin-hypocretin neuronal networks in zebrafish.

    Science.gov (United States)

    Levitas-Djerbi, Talia; Yelin-Bekerman, Laura; Lerer-Goldshtein, Tali; Appelbaum, Lior

    2015-04-01

    Neurotensin (NTS) is a 13 amino acid neuropeptide that is expressed in the hypothalamus. In mammals, NTS-producing neurons that express leptin receptor (LepRb) regulate the function of hypocretin/orexin (HCRT) and dopamine neurons. Thus, the hypothalamic leptin-NTS-HCRT neuronal network orchestrates key homeostatic output, including sleep, feeding, and reward. However, the intricate mechanisms of the circuitry and the unique role of NTS-expressing neurons remain unclear. We studied the NTS neuronal networks in zebrafish and cloned the genes encoding the NTS neuropeptide and receptor (NTSR). Similar to mammals, the ligand is expressed primarily in the hypothalamus, while the receptor is expressed widely throughout the brain in zebrafish. A portion of hypothalamic nts-expressing neurons are inhibitory and some coexpress leptin receptor (lepR1). As in mammals, NTS and HCRT neurons are localized adjacently in the hypothalamus. To track the development and axonal projection of NTS neurons, the NTS promoter was isolated. Transgenesis and double labeling of NTS and HCRT neurons showed that NTS axons project toward HCRT neurons, some of which express ntsr. Moreover, another target of NTS neurons is ntsr-expressing dopaminergeric neurons. These findings suggest structural circuitry between leptin, NTS, and hypocretinergic or dopaminergic neurons and establish the zebrafish as a model to study the role of these neuronal circuits in the regulation of feeding, sleep, and reward.

  15. [Neuronal network].

    Science.gov (United States)

    Langmeier, M; Maresová, D

    2005-01-01

    Function of the central nervous system is based on mutual relations among the nerve cells. Description of nerve cells and their processes, including their contacts was enabled by improvement of optical features of the microscope and by the development of impregnation techniques. It is associated with the name of Antoni van Leeuwenhoek (1632-1723), J. Ev. Purkyne (1787-1869), Camillo Golgi (1843-1926), and Ramón y Cajal (1852-1934). Principal units of the neuronal network are the synapses. The term synapse was introduced into neurophysiology by Charles Scott Sherrington (1857-1952). Majority of the interactions between nerve cells is mediated by neurotransmitters acting at the receptors of the postsynaptic membrane or at the autoreceptors of the presynaptic part of the synapse. Attachment of the vesicles to the presynaptic membrane and the release of the neurotransmitter into the synaptic cleft depend on the intracellular calcium concentration and on the presence of several proteins in the presynaptic element.

  16. Axon guidance and neuronal migration research in China

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Proper migration of neuronal somas and axonal growth cones to designated locations in the developing brain is essential for the assembly of functional neuronal circuits.Rapid progress in research of axon guidance and neuronal migration has been made in the last twenty years.Chinese researchers began their exploration in this field ten years ago and have made significant contributions in clarifying the signal transduction of axon guidance and neuronal migration.Several unique experimental approaches,including the migration assay of single isolated neurons in response to locally delivered guidance cues,have been developed by Chinese neuroscientists to investigate the molecular machinery underlying these guidance events.

  17. The Intracellular Signaling Molecule Darpp-32 Is a Marker for Principal Neurons in the Cerebellum and Cerebellum-Like Circuits of Zebrafish

    Science.gov (United States)

    Robra, Lena; Thirumalai, Vatsala

    2016-01-01

    The dopamine and cAMP regulated phosphoprotein of apparent molecular weight 32 kDa (Darpp-32) is an inhibitory subunit of protein phosphatase-1 (PP-1). Darpp-32 activity is regulated by multiple ligand-activated G-protein coupled receptors (GPCRs). This protein is coded for by the protein phosphatase-1 regulatory subunit 1b (ppp1r1b) gene. Here, we provide experimental evidence for the presence of multiple isoforms of ppp1r1b in zebrafish. We show that these isoforms are differentially expressed during development with the full-length isoform being maternally deposited. Next, with a custom polyclonal antibody generated against the full-length protein, we show that in the adult, Darpp-32 is strongly expressed in principal neurons of the cerebellum and cerebellum-like circuits. These include Purkinje neurons in the cerebellum, Type-I neurons in the optic tectum, and crest cells in the medial octavolateralis nucleus (MON). We confirmed the identity of these neurons through their colocalization with Parvalbumin 7 immunoreactivity. Darpp-32 is seen in the somata and dendrites of these neurons with faint staining in the axons. In all of these regions, Darpp-32-immunoreactive cells were in close proximity to tyrosine hydroxylase (TH) immunoreactive puncta indicating the presence of direct catecholaminergic input to these neurons. Darpp-32 immunoreactivity was seen in Purkinje neurons as early as 3 days post-fertilization (dpf) when Purkinje neurons are first specified. In sum, we show that Darpp-32, a signaling integrator, is a specific marker of principal neurons in the cerebellum and cerebellum-like circuits in zebrafish. PMID:27540357

  18. 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.

  19. Distribution pattern and chemical coding of neurons of the sympathetic chain ganglia supplying the descending colon in the pig.

    Science.gov (United States)

    Skobowiat, Cezary; Calka, Jarosław; Wasowicz, Krzysztof; Majewski, Mariusz

    2010-06-01

    Sympathetic chain ganglia (SChG) neurons projecting to the descending colon of the pig were studied by means of retrograde tracing (Fast Blue, FB) and double-labelling immunofluorescence methods. FB was injected into the gut wall and after three weeks survival time the animals were transcardially perfused with paraformaldehyde and the bilateral sympathetic trunks were collected. The FB-positive neurons were localised only in the lumbar (L(1)-L(5)) ganglia of the sympathetic trunk and appeared either as small (30-50 microm in diameter) round-shaped perikarya forming clusters localised in caudal-ventral area or, rarely, as bigger (50-80 microm) and dispersed solitary irregular perikarya. Immunohistochemical staining revealed the catecholaminergic (tyrosine hydroxylase-/dopamine beta-hydroxylase-immunoreactive) character of the great majority of FB-positive neurons which preferentially co-expressed neuropeptide Y. In addition, none of the FB-positive perikarya was immunopositive to galanin, somatostatin, choline acetyltransferase, vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, leu(5)-enkephalin, nitric oxide synthase, substance P and calcitonin-generelated peptide. PMID:20460218

  20. Cross-talk between sympathetic neurons and adipocytes in coculture

    OpenAIRE

    Turtzo, L. Christine; Marx, Ruth; Lane, M. Daniel

    2001-01-01

    White adipose tissue plays an integral role in energy metabolism and is governed by endocrine, autocrine, and neural signals. Neural control of adipose metabolism is mediated by sympathetic neurons that innervate the tissue. To investigate the effects of this innervation, an ex vivo system was developed in which 3T3-L1 adipocytes are cocultured with sympathetic neurons isolated from the superior cervical ganglia of newborn rats. In coculture, both adipocytes and neurons exhibit appropriate mo...

  1. Neurons controlling Aplysia feeding inhibit themselves by continuous NO production.

    Directory of Open Access Journals (Sweden)

    Nimrod Miller

    Full Text Available BACKGROUND: Neural activity can be affected by nitric oxide (NO produced by spiking neurons. Can neural activity also be affected by NO produced in neurons in the absence of spiking? METHODOLOGY/PRINCIPAL FINDINGS: Applying an NO scavenger to quiescent Aplysia buccal ganglia initiated fictive feeding, indicating that NO production at rest inhibits feeding. The inhibition is in part via effects on neurons B31/B32, neurons initiating food consumption. Applying NO scavengers or nitric oxide synthase (NOS blockers to B31/B32 neurons cultured in isolation caused inactive neurons to depolarize and fire, indicating that B31/B32 produce NO tonically without action potentials, and tonic NO production contributes to the B31/B32 resting potentials. Guanylyl cyclase blockers also caused depolarization and firing, indicating that the cGMP second messenger cascade, presumably activated by the tonic presence of NO, contributes to the B31/B32 resting potential. Blocking NO while voltage-clamping revealed an inward leak current, indicating that NO prevents this current from depolarizing the neuron. Blocking nitrergic transmission had no effect on a number of other cultured, isolated neurons. However, treatment with NO blockers did excite cerebral ganglion neuron C-PR, a command-like neuron initiating food-finding behavior, both in situ, and when the neuron was cultured in isolation, indicating that this neuron also inhibits itself by producing NO at rest. CONCLUSION/SIGNIFICANCE: Self-inhibitory, tonic NO production is a novel mechanism for the modulation of neural activity. Localization of this mechanism to critical neurons in different ganglia controlling different aspects of a behavior provides a mechanism by which a humeral signal affecting background NO production, such as the NO precursor L-arginine, could control multiple aspects of the behavior.

  2. Topology of Central Pattern Generators Selection by Chaotic Neurons

    CERN Document Server

    Huerta, R; Rabinovich, M I; Abarbanel, Henry D I; Abarbanel, Henry D I

    1999-01-01

    Central Pattern Generators (CPGs) in invertebrates are comprised of networks of neurons in which every neuron has reciprocal connections to other members of the CPG. This is a ``closed'' network topology. An ``open'' topology, where one or more neurons receives input but does not send output to other member neurons, is not found in these CPGs. In this paper we investigate a possible reason for this topological structure using the ability to perform a biological functional task as a measure of the efficacy of the network. When the CPG is composed of model neurons which exhibit regular membrane voltage oscillations, open topologies are essentially as able to maximize this functionality as closed topologies. When we replace these models by neurons which exhibit chaotic membrane voltage oscillations, the functional criterion selects closed topologies when the demands of the task are increased, and these are the topologies observed in known CPG networks. As isolated neurons from invertebrate CPGs are known in some...

  3. What causes a neuron to spike?

    CERN Document Server

    Arcas, B A; Arcas, Blaise Aguera y; Fairhall, Adrienne

    2003-01-01

    The computation performed by a neuron can be formulated as a combination of dimensional reduction in stimulus space and the nonlinearity inherent in a spiking output. White noise stimulus and reverse correlation (the spike-triggered average and spike-triggered covariance) are often used in experimental neuroscience to `ask' neurons which dimensions in stimulus space they are sensitive to, and to characterize the nonlinearity of the response. In this paper, we apply reverse correlation to the simplest model neuron with temporal dynamics--the leaky integrate-and-fire model--and find that even for this simple case standard techniques do not recover the known neural computation. To overcome this, we develop novel reverse correlation techniques by selectively analyzing only `isolated' spikes, and taking explicit account of the extended silences that precede these isolated spikes. We discuss the implications of our methods to the characterization of neural adaptation. Although these methods are developed in the con...

  4. Juvenil neuronal ceroid lipofuscinosis

    DEFF Research Database (Denmark)

    Ostergaard, J R; Hertz, Jens Michael

    1998-01-01

    Neuronal ceroid-lipofuscinosis is a group of neurodegenerative diseases which are characterized by an abnormal accumulation of lipopigment in neuronal and extraneuronal cells. The diseases can be differentiated into several subgroups according to age of onset, the clinical picture...

  5. Refractory Neuron Circuits

    OpenAIRE

    Sarpeshkar, Rahul; Watts, Lloyd; Mead, Carver

    1992-01-01

    Neural networks typically use an abstraction of the behaviour of a biological neuron, in which the continuously varying mean firing rate of the neuron is presumed to carry information about the neuron's time-varying state of excitation. However, the detailed timing of action potentials is known to be important in many biological systems. To build electronic models of such systems, one must have well-characterized neuron circuits that capture the essential behaviour of real neur...

  6. NEURON and Python

    OpenAIRE

    Michael Hines; Davison, Andrew P.; Eilif Muller

    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 ...

  7. 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.

  8. S4153R is a gain-of-function mutation in the cardiac Ca(2+) release channel ryanodine receptor associated with catecholaminergic polymorphic ventricular tachycardia and paroxysmal atrial fibrillation.

    Science.gov (United States)

    Zhabyeyev, Pavel; Hiess, Florian; Wang, Ruiwu; Liu, Yingjie; Wayne Chen, S R; Oudit, Gavin Y

    2013-08-01

    Mutations in ryanodine receptor 2 (RYR2) gene can cause catecholaminergic polymorphic ventricular tachycardia (CPVT). The novel RYR2-S4153R mutation has been implicated as a cause of CPVT and atrial fibrillation. The mutation has been functionally characterized via store-overload-induced Ca(2+) release (SOICR) and tritium-labelled ryanodine ([(3)H]ryanodine) binding assays. The S4153R mutation enhanced propensity for spontaneous Ca(2+) release and reduced SOICR threshold but did not alter Ca(2+) activation of [(3)H]ryanodine binding, a common feature of other CPVT gain-of-function RYR2 mutations. We conclude that the S4153R mutation is a gain-of-function RYR2 mutation associated with a clinical phenotype characterized by both CPVT and atrial fibrillation.

  9. A novel mutation in the RYR2 gene leading to catecholaminergic polymorphic ventricular tachycardia and paroxysmal atrial fibrillation: dose-dependent arrhythmia-event suppression by β-blocker therapy.

    Science.gov (United States)

    Kazemian, Pedram; Gollob, Michael H; Pantano, Alfredo; Oudit, Gavin Y

    2011-01-01

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a genetic condition that presents with exercise-induced polymorphic arrhythmias. We describe a case report of a 25-year-old woman who had a cardiac arrest due to ventricular fibrillation. Genetic analysis revealed a novel missense mutation in exon 90 of the ryanodine receptor (RyR2) gene resulting in substitution of arginine for serine at residue 4153 (S4153R). The patient received an implantable cardioverter-defibrillator and low-dose β-blocker therapy. She had recurrent polymorphic ventricular arrhythmias treated with appropriate cardioverter-defibrillator shocks and paroxysmal atrial fibrillation. Titration of β-blocker to a much higher dose suppressed further episodes of ventricular arrhythmia and paroxysmal atrial fibrillation, resulting in reduction in device therapies.

  10. Motor Neurons that Multitask

    OpenAIRE

    Goulding, Martyn

    2012-01-01

    Animals use a form of sensory feedback termed proprioception to monitor their body position and modify the motor programs that control movement. In this issue of Neuron, Wen et al. (2012) provide evidence that a subset of motor neurons function as proprioceptors in C. elegans, where B-type motor neurons sense body curvature to control the bending movements that drive forward locomotion.

  11. Enhanced nigrostriatal neuron-specific, long-term expression by using neural-specific promoters in combination with targeted gene transfer by modified helper virus-free HSV-1 vector particles

    Directory of Open Access Journals (Sweden)

    Kong Lingxin

    2008-04-01

    Full Text Available Abstract Background Direct gene transfer into neurons has potential for developing gene therapy treatments for specific neurological conditions, and for elucidating neuronal physiology. Due to the complex cellular composition of specific brain areas, neuronal type-specific recombinant gene expression is required for many potential applications of neuronal gene transfer. One approach is to target gene transfer to a specific type of neuron. We developed modified Herpes Simplex Virus (HSV-1 particles that contain chimeric glycoprotein C (gC – glial cell line-derived neurotrophic factor (GDNF or brain-derived neurotrophic factor (BDNF proteins. HSV-1 vector particles containing either gC – GDNF or gC – BDNF target gene transfer to nigrostriatal neurons, which contain specific receptors for GDNF or BDNF. A second approach to achieve neuronal type-specific expression is to use a cell type-specific promoter, and we have used the tyrosine hydroxylase (TH promoter to restrict expression to catecholaminergic neurons or a modified neurofilament heavy gene promoter to restrict expression to neurons, and both of these promoters support long-term expression from HSV-1 vectors. To both improve nigrostriatal-neuron specific expression, and to establish that targeted gene transfer can be followed by long-term expression, we performed targeted gene transfer with vectors that support long-term, neuronal-specific expression. Results Helper virus-free HSV-1 vector packaging was performed using either gC – GDNF or gC – BDNF and vectors that contain either the TH promoter or the modified neurofilament heavy gene promoter. Vector stocks were injected into the midbrain proximal to the substantia nigra, and the rats were sacrificed at either 4 days or 1 month after gene transfer. Immunofluorescent costaining was performed to detect both recombinant gene products and nigrostriatal neurons. The combination of targeted gene transfer with neuronal

  12. Somatostatin 2a receptors are not expressed on functionally identified respiratory neurons in the ventral respiratory column of the rat.

    Science.gov (United States)

    Le, Sheng; Turner, Anita J; Parker, Lindsay M; Burke, Peter G; Kumar, Natasha N; Goodchild, Ann K; McMullan, Simon

    2016-05-01

    Microinjection of somatostatin (SST) causes site-specific effects on respiratory phase transition, frequency, and amplitude when microinjected into the ventrolateral medulla (VLM) of the anesthetized rat, suggesting selective expression of SST receptors on different functional classes of respiratory neurons. Of the six subtypes of SST receptor, somatostatin 2a (sst2a ) is the most prevalent in the VLM, and other investigators have suggested that glutamatergic neurons in the preBötzinger Complex (preBötC) that coexpress neurokinin-1 receptor (NK1R), SST, and sst2a are critical for the generation of respiratory rhythm. However, quantitative data describing the distribution of sst2a in respiratory compartments other than preBötC, or on functionally identified respiratory neurons, is absent. Here we examine the medullary expression of sst2a with particular reference to glycinergic/expiratory neurons in the Bötzinger Complex (BötC) and NK1R-immunoreactive/inspiratory neurons in the preBötC. We found robust sst2a expression at all rostrocaudal levels of the VLM, including a large proportion of catecholaminergic neurons, but no colocalization of sst2a and glycine transporter 2 mRNA in the BötC. In the preBötC 54% of sst2a -immunoreactive neurons were also positive for NK1R. sst2a was not observed in any of 52 dye-labeled respiratory interneurons, including seven BötC expiratory-decrementing and 11 preBötC preinspiratory neurons. We conclude that sst2a is not expressed on BötC respiratory neurons and that phasic respiratory activity is a poor predictor of sst2a expression in the preBötC. Therefore, sst2a is unlikely to underlie responses to BötC SST injection, and is sparse or absent on respiratory neurons identified by classical functional criteria. J. Comp. Neurol. 524:1384-1398, 2016. © 2015 Wiley Periodicals, Inc. PMID:26470751

  13. 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.

  14. Process entanglement as a neuronal anchorage mechanism to rough surfaces

    Science.gov (United States)

    Sorkin, Raya; Greenbaum, Alon; David-Pur, Moshe; Anava, Sarit; Ayali, Amir; Ben-Jacob, Eshel; Hanein, Yael

    2009-01-01

    The organization of neurons and glia cells on substrates composed of pristine carbon nanotube islands was investigated using high resolution scanning electron microscopy, immunostaining and confocal microscopy. Neurons were found bound and preferentially anchored to the rough surfaces; moreover, the morphology of the neuronal processes on the small, isolated islands of high density carbon nanotubes was found to be conspicuously curled and entangled. We further demonstrate that the roughness of the surface must match the diameter of the neuronal processes in order to allow them to bind. The results presented here suggest that entanglement, a mechanical effect, may constitute an additional mechanism by which neurons (and possibly other cell types) anchor themselves to rough surfaces. Understanding the nature of the interface between neurons and carbon nanotubes is essential to effectively harness carbon nanotube technology in neurological applications such as neuro-prosthetic and retinal electrodes.

  15. Study of a New Neuron

    OpenAIRE

    Adler, S. L.; Bhanot, G. V.; Weckel, J. D.

    1994-01-01

    We study a modular neuron alternative to the McCulloch-Pitts neuron that arises naturally in analog devices in which the neuron inputs are represented as coherent oscillatory wave signals. Although the modular neuron can compute $XOR$ at the one neuron level, it is still characterized by the same Vapnik-Chervonenkis dimension as the standard neuron. We give the formulas needed for constructing networks using the new neuron and training them using back-propagation. A numerical study of the mod...

  16. 新生大鼠海马源性神经干细胞的分离培养及其向胆碱能神经元定向诱导分化研究%ISOLATION OF NEURAL STEM CELLS FROM NEONATAL RAT HIPPOCAMPUS AND THEIR IN VITRO DIFFERENTIATION INTO CHOLINERGIC NEURONS

    Institute of Scientific and Technical Information of China (English)

    罗湘颖; 杨志敏; 宋晓斌; 刘苏; 赵匡彦; 冯忠堂; 王廷华

    2005-01-01

    The present study aims to isolate neural stem cells from neonatal rat hippocampus and induce them to differentiate into cholinergic neurons. A multipotent cell line derived from the hippocampi of neonatal rats which had the ability to form clones was incubated in serum-free DMEM/F12 medium added with 20ng/ml basic fibroblast growth factor (bFGF) and B27. After differentiation of the neural stem cells, immunocytochemistry was used to detect nestin, the antigen of the cell clone, and β-tubulin (Tuj 1 ), glial fibrillary acidic protein (GFAP) and galactocerebroside (Galc), the markers specific for neurons, astrocytes and oligodendrocytes, respectively. Embryonic chick skeletal muscle extract was used to induce the differentiation of the neural stem cells into cholinergic neurons. The results showed that the cell line isolated from the hippocampi of neonatal rats expressed nestin and had the potential to form clones and differentiate into neurons, astrocytes and oligodendrocytes. Embryonic chick skeletal muscle extract can induce 9.6% of the isolated cell line to differentiate into cholinergic neurons compared with 3.9% in controls. These findings suggested that the cell line, which expressed nestin antigen, was a multipotent cell line capable of self-renewing, and was believed to contain stem cells of the CNS. These neural stem cells can be induced to differentiate into cholinergic neurons by using embryonic chick skeletal muscle extract.%本研究目的是从新生SD大鼠海马分离、培养神经干细胞并诱导其向胆碱能神经元方向分化.利用含b-FGF(20 ng/ml)和B27的无血清DMEM/F12培养基培养新生SD大鼠海马分离的具有自我更新和多向分化能力的细胞群,用免疫细胞化学技术检测巢蛋白(nestin),并于分化后分别检查特异性成熟神经细胞、星形胶质细胞、少突胶质细胞的标记抗原β-微管蛋白(Tuj1)、胶质纤维酸性蛋白(GFAP)和半乳糖脑苷脂(Galc)的表达;用鸡胚骨骼肌提

  17. Noise and Neuronal Heterogeneity

    CERN Document Server

    Barber, Michael J

    2010-01-01

    We consider signal transaction in a simple neuronal model featuring intrinsic noise. The presence of noise limits the precision of neural responses and impacts the quality of neural signal transduction. We assess the signal transduction quality in relation to the level of noise, and show it to be maximized by a non-zero level of noise, analogous to the stochastic resonance effect. The quality enhancement occurs for a finite range of stimuli to a single neuron; we show how to construct networks of neurons that extend the range. The range increases more rapidly with network size when we make use of heterogeneous populations of neurons with a variety of thresholds, rather than homogeneous populations of neurons all with the same threshold. The limited precision of neural responses thus can have a direct effect on the optimal network structure, with diverse functional properties of the constituent neurons supporting an economical information processing strategy that reduces the metabolic costs of handling a broad...

  18. 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.

  19. Kalman Filter Neuron Training

    OpenAIRE

    Murase, Haruhiko; KOYAMA, Shuhei; HONAMI, Nobuo; Kuwabara, Takao

    1991-01-01

    An attempt of implementing Kalman filter algorithm in the procedure for training the neural network was made and evaluated. The Kalman filter neuron training program (KNT) was coded. The performance of Kalman filter in KNT was compared to commonly used neuron training algorithm. The study revealed that KNT requires much less calculation time to accomplish neuron training than commonly used other algorithms do. KNT also gave much smaller final error than any other algorithms tested in this study.

  20. Functional coupling with cardiac muscle promotes maturation of hPSC-derived sympathetic neurons

    Science.gov (United States)

    Oh, Yohan; Cho, Gun-Sik; Li, Zhe; Hong, Ingie; Zhu, Renjun; Kim, Min-Jeong; Kim, Yong Jun; Tampakakis, Emmanouil; Tung, Leslie; Huganir, Richard; Dong, Xinzhong; Kwon, Chulan; Lee, Gabsang

    2016-01-01

    Summary Neurons derived from human pluripotent stem cells (hPSCs) are powerful tools for studying human neural development and diseases. Robust functional coupling of hPSC-derived neurons with target tissues in vitro is essential for modeling intercellular physiology in a dish and to further translational studies, but has proven difficult to achieve. Here, we derive sympathetic neurons from hPSCs and show they can form physical and functional connections with cardiac muscle cells. Using multiple hPSC reporter lines, we recapitulated human autonomic neuron development in vitro and successfully isolated PHOX2B:eGFP+ neurons that exhibit sympathetic marker expression and electrophysiological properties, and norepinephrine secretion. Upon pharmacologic and optogenetic manipulation, PHOX:eGFP+ neurons controlled beating rates of cardiomyocytes, and the physical interactions between these cells increased neuronal maturation. This study provides a foundation for human sympathetic neuron specification and for hPSC-based neuronal control of organs in a dish. PMID:27320040

  1. Energy efficiency of information transmission by electrically coupled neurons

    CERN Document Server

    Torrealdea, Francisco J; d'Anjou, Alicia; Moujahid, Abdelmalik; de Mendizábal, N Vélez; 10.1016/j.biosystems.2009.04.004

    2012-01-01

    The generation of spikes by neurons is energetically a costly process. This paper studies the consumption of energy and the information entropy in the signalling activity of a model neuron both when it is supposed isolated and when it is coupled to another neuron by an electrical synapse. The neuron has been modelled by a four dimensional Hindmarsh-Rose type kinetic model for which an energy function has been deduced. For the isolated neuron values of energy consumption and information entropy at different signalling regimes have been computed. For two neurons coupled by a gap junction we have analyzed the roles of the membrane and synapse in the contribution of the energy that is required for their organized signalling. Computational results are provided for cases of identical and nonidentical neurons coupled by unidirectional and bidirectional gap junctions. One relevant result is that there are values of the coupling strength at which the organized signalling of two neurons induced by the gap junction take...

  2. 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.

  3. 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...

  4. Corticospinal mirror neurons.

    Science.gov (United States)

    Kraskov, A; Philipp, R; Waldert, S; Vigneswaran, G; Quallo, M M; Lemon, R N

    2014-01-01

    Here, we report the properties of neurons with mirror-like characteristics that were identified as pyramidal tract neurons (PTNs) and recorded in the ventral premotor cortex (area F5) and primary motor cortex (M1) of three macaque monkeys. We analysed the neurons' discharge while the monkeys performed active grasp of either food or an object, and also while they observed an experimenter carrying out a similar range of grasps. A considerable proportion of tested PTNs showed clear mirror-like properties (52% F5 and 58% M1). Some PTNs exhibited 'classical' mirror neuron properties, increasing activity for both execution and observation, while others decreased their discharge during observation ('suppression mirror-neurons'). These experiments not only demonstrate the existence of PTNs as mirror neurons in M1, but also reveal some interesting differences between M1 and F5 mirror PTNs. Although observation-related changes in the discharge of PTNs must reach the spinal cord and will include some direct projections to motoneurons supplying grasping muscles, there was no EMG activity in these muscles during action observation. We suggest that the mirror neuron system is involved in the withholding of unwanted movement during action observation. Mirror neurons are differentially recruited in the behaviour that switches rapidly between making your own movements and observing those of others.

  5. 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.

  6. NEURON and Python

    Directory of Open Access Journals (Sweden)

    Michael Hines

    2009-01-01

    Full Text Available 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 GUI 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.

  7. 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.

  8. 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.

  9. 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

    2014-04-01

    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.

  10. Characteristics of sodium currents in rat geniculate ganglion neurons

    OpenAIRE

    NAKAMURA, SHIRO; Bradley, Robert M.

    2011-01-01

    Geniculate ganglion (GG) cell bodies of chorda tympani (CT), greater superficial petrosal (GSP), and posterior auricular (PA) nerves transmit orofacial sensory information to the rostral nucleus of the solitary tract. We have used whole cell recording to investigate the characteristics of the Na+ channels in isolated Fluorogold-labeled GG neurons that innervate different peripheral receptive fields. GG neurons expressed two classes of Na+ channels, TTX sensitive (TTX-S) and TTX resistant (TTX...

  11. 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

  12. Straintronic spin-neuron

    OpenAIRE

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

    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. Here, we propose and analyze a different type of spin-neuron in which t...

  13. Constrained Synaptic Connectivity in Functional Mammalian Neuronal Networks Grown on Patterned Surfaces

    Science.gov (United States)

    Bourdieu, Laurent; Wyart, Claire; Ybert, Christophe; Herr, Catherine; Chatenay, Didier

    2002-03-01

    The use of ordered neuronal networks in vitro is a promising approach to study the development and the activity of neuronal assemblies. However in previous attempts, sufficient growth control and physiological maturation of neurons could not be achieved. We describe an original protocol in which polylysine patterns confine the adhesion of cellular bodies to prescribed spots and the neuritic growth to thin lines. Hippocampal neurons are maintained healthy in serum free medium up to five weeks in vitro. Electrophysiology and immunochemistry show that neurons exhibit mature excitatory and inhibitory synapses and calcium imaging reveals spontaneous bursting activity of neurons in isolated networks. Neurons in these geometrical networks form functional synapses preferentially to their first neighbors. We have therefore established a simple and robust protocol to constrain both the location of neuronal cell bodies and their pattern of connectivity.

  14. An electrophysiological investigation of the effects of cholecystokinin entric neurons.

    OpenAIRE

    Schutte, I.W.M.

    1998-01-01

    Cholecystokinin (CCK) is a peptide, which is present in the gastrointestinat tract in endocrine cells and in the enteric nervous system (ENS). A possible function in the control of motility of the small intestine has been attributed to neuronal CCK. The aim of this thesis was  to obtain a fundamental insight into the action and effects of CCK on enteric neurons. Therefore, intracelluiar recordings were made of myenteric neurons in an isolated preparation of the guinea-pig ileum. Two types of ...

  15. Recent Developments in NEURON

    OpenAIRE

    Hines, Michael L.; Carnevale, Nicholas T.

    2005-01-01

    We describe four recent additions to NEURON's suite of graphical tools that make it easier for users to create and manage models: an enhancement to the Channel Builder that facilitates the specification and efficient simulation of stochastic channel models

  16. Noise and Neuronal Heterogeneity

    OpenAIRE

    Barber, Michael J.; Ristig, Manfred L.

    2010-01-01

    We consider signal transaction in a simple neuronal model featuring intrinsic noise. The presence of noise limits the precision of neural responses and impacts the quality of neural signal transduction. We assess the signal transduction quality in relation to the level of noise, and show it to be maximized by a non-zero level of noise, analogous to the stochastic resonance effect. The quality enhancement occurs for a finite range of stimuli to a single neuron; we show how to construct network...

  17. Josephson junction simulation of neurons

    OpenAIRE

    Crotty, Patrick; Schult, Daniel; Segall, Ken

    2010-01-01

    With the goal of understanding the intricate behavior and dynamics of collections of neurons, we present superconducting circuits containing Josephson junctions that model biologically realistic neurons. These "Josephson junction neurons" reproduce many characteristic behaviors of biological neurons such as action potentials, refractory periods, and firing thresholds. They can be coupled together in ways that mimic electrical and chemical synapses. Using existing fabrication technologies, lar...

  18. 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)

    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

  19. 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.

  20. Rhynchophylline Protects Cultured Rat Neurons against Methamphetamine Cytotoxicity

    Directory of Open Access Journals (Sweden)

    Dan Dan Xu

    2012-01-01

    Full Text Available Rhynchophylline (Rhy is an active component isolated from species of the genus Uncaria which has been used for the treatment of ailments to the central nervous system in traditional Chinese medicine. Besides acting as a calcium channel blocker, Rhy was also reported to be able to protect against glutamate-induced neuronal death. We thus hypothesize that Rhy may have neuroprotective activity against methamphetamine (MA. The primary neurons were cultured directly from the cerebral cortex of neonatal rats, acting as in vitro model in the present study. The neurotoxicity of MA and the protective effect of Rhy were evaluated by MTT assay. The effects of MA, Rhy or their combination on intracellular free calcium concentration ([Ca2+]i were determined in individual neocortical neurons by the Fluo-3/AM tracing method. The MTT assay demonstrated that MA has a dose-dependent neurotoxicity in neuronal cultures. The addition of Rhy prior to the exposure to MA prevented neuronal death. Time course studies with the Fluo-3/AM probe showed that Rhy significantly decreased neuronal [Ca2+]i which was elevated by the exposure to MA. Our results suggested that Rhy can protect the neuronal cultures against MA exposure and promptly attenuate intracellular calcium overload triggered by MA challenge. This is the first report demonstrating an inhibitory effect of Rhy against MA impairment in cultured neurons in vitro.

  1. Neurons of human nucleus accumbens

    Directory of Open Access Journals (Sweden)

    Sazdanović Maja

    2011-01-01

    Full Text Available Background/Aim. Nucleus accumbens is a part of the ventral striatum also known as a drug active brain region, especially related with drug addiction. The aim of the study was to investigate the Golgi morphology of the nucleus accumbens neurons. Methods. The study was performed on the frontal and sagittal sections of 15 human brains by the Golgi Kopsch method. We classified neurons in the human nucleus accumbens according to their morphology and size into four types: type I - fusiform neurons; type II - fusiform neurons with lateral dendrite, arising from a part of the cell body; type III - pyramidal-like neuron; type IV - multipolar neuron. The medium spiny neurons, which are mostly noted regarding to the drug addictive conditions of the brain, correspond to the type IV - multipolar neurons. Results. Two regions of human nucleus accumbens could be clearly recognized on Nissl and Golgi preparations each containing different predominant neuronal types. Central part of nucleus accumbens, core region, has a low density of impregnated neurons with predominant type III, pyramidal-like neurons, with spines on secondary branches and rare type IV, multipolar neurons. Contrary to the core, peripheral region, shell of nucleus, has a high density of impregnated neurons predominantly contained of type I and type IV - multipolar neurons, which all are rich in spines on secondary and tertiary dendritic branches. Conclusion. Our results indicate great morphological variability of human nucleus accumbens neurons. This requires further investigations and clarifying clinical significance of this important brain region.

  2. Synapse-to-neuron ratio is inversely related to neuronal density in mature neuronal cultures

    OpenAIRE

    Cullen, D. Kacy; Gilroy, Meghan; Irons, Hillary R.; LaPlaca, Michelle C.

    2010-01-01

    Synapse formation is a fundamental process in neurons that occurs throughout development, maturity, and aging. Although these stages contain disparate and fluctuating numbers of mature neurons, tactics employed by neuronal networks to modulate synapse number as a function of neuronal density are not well understood. The goal of this study was to utilize an in vitro model to assess the influence of cell density and neuronal maturity on synapse number and distribution. Specifically, cerebral co...

  3. Spine morphology of neurons in the Avian forebrain is affected by rearing conditions

    OpenAIRE

    Rollenhagen, Astrid; Bischof, Hans-Joachim

    1994-01-01

    An area of the caudal forebrain of male zebra finches, the Archi-Neostriatum caudale (ANC), which is active during arousal (Bischof and Herrmann, 1986, 1988), shows rearing-dependent changes in neuron morphology (Rollenhagen and Bischof, 1991). We demonstrate here that rearing conditions also affect the shape of spines of one of the four ANC neuron types. This neuron type was examined in birds reared under five different conditions - in isolation (1), caged (2), in the aviary (3), and with so...

  4. Protoplasmic Astrocytes Enhance the Ability of Neural Stem Cells to Differentiate into Neurons In Vitro

    OpenAIRE

    Yuan Liu; Li Wang; Zaiyun Long; Lin Zeng; Yamin Wu

    2012-01-01

    Protoplasmic astrocytes have been reported to exhibit neuroprotective effects on neurons, but there has been no direct evidence for a functional relationship between protoplasmic astrocytes and neural stem cells (NSCs). In this study, we examined neuronal differentiation of NSCs induced by protoplasmic astrocytes in a co-culture model. Protoplasmic astrocytes were isolated from new-born and NSCs from the E13-15 cortex of rats respectively. The differentiated cells labeled with neuron-specific...

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

    OpenAIRE

    Onesto, Valentina; Cosentino, Carlo; Di Fabrizio, Enzo; 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...

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

    Science.gov (United States)

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

    2014-02-01

    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 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.

  7. 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...

  8. 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

  9. New findings on neuron development

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ A mature neuron receives inputs from multiple dendrites and sends its output to other neurons via a single axon.This polarized morphology requires proper axonal/dendritic differentiation during development.

  10. Exploring neuronal activity with photons

    Science.gov (United States)

    Bourdieu, Laurent; Léger, Jean-François

    2015-10-01

    The following sections are included: * Introduction * Information coding * Optical recordings of neuronal activity * Functional organization of the cortex at the level of a cortical column * Microarchitecture of a cortical column * Dynamics of neuronal populations * Outlook * Bibliography

  11. Neuronal nets in robotics

    International Nuclear Information System (INIS)

    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

  12. Cultures of Cerebellar Granule Neurons

    OpenAIRE

    sprotocols

    2014-01-01

    Authors: Parizad M. Bilimoria and Azad Bonni1 Corresponding author ([]()) ### INTRODUCTION Primary cultures of granule neurons from the post-natal rat cerebellum provide an excellent model system for molecular and cell biological studies of neuronal development and function. The cerebellar cortex, with its highly organized structure and few neuronal subtypes, offers a well-characterized neural circuitry. Many fundamental insight...

  13. Rhythm dynamics of complex neuronal networks with mixed bursting neurons

    Institute of Scientific and Technical Information of China (English)

    Lü Yong-Bing; Shi Xia; Zheng Yan-Hong

    2013-01-01

    The spatiotemporal order and rhythm dynamics of a complex neuronal network with mixed bursting neurons are studied in this paper.A quantitative characteristic,the width factor,is introduced to describe the rhythm dynamics of an individual neuron,and the average width factor is used to characterize the rhythm dynamics of a neuronal network.An r parameter is introduced to denote the ratio of the short bursting neurons in the network.Then we investigate the effect of the ratio on the rhythm dynamics of the neuronal network.The critical value of r is derived,and the neurons in the network always remain short bursting when the r ratio is larger than the critical value.

  14. Electrophysiological evidence of P2X2 receptor expression in the neurons of intracardiac and paratracheal ganglia

    Institute of Scientific and Technical Information of China (English)

    MA Bei; NI Xin; HAN Hong; BURNSTOCK Geoffrey

    2006-01-01

    Objective:To investigate the expression of P2X receptors on rat intracardiac and paratracheal ganglion neurons. Methods: For preparation of intracardiac neurons, hearts were excised, the atria were separated and the medial region containing intracardiac ganglia was isolated and cut into pieces. For preparation of paratracheal neurons, the tracheas were removed and the superficial membranous layer containing paratracheal ganglia was rapidly isolated. Intracardiac and paratracheal ganglion neurons were dissociated after digestion by collagenase and trypsin. Whole-cell patch clamp recording was used to identify the pharmacological properties of P2X receptors in cultured neurons. Results:Neurons from these two ganglia responded to ATP with a rapidly activating, sustained inward current. Αβ-meATP failed to evoke any responses in paratracheal ganglion neurons while a few of intracardiac ganglion neurons responded to αβ-meATP with a tiny sustained inward current. ADP and UTP had no effect on intracardiac neurons. Lowering pH potentiated ATP responses in neurons from these two ganglia whereas increasing pH inhibited ATP responses. Co-application of Zn2+ potentiated ATP responses in intracardiac and paratracheal ganglion neurons. Conclusion: The receptor subtypes involved in intracardiac and paratracheal ganglia appear to be homomeric P2X2, while heteromeric P2X2/3 could not be completely excluded from intracardiac neurons.

  15. The neuron classification problem

    OpenAIRE

    Bota, Mihail; Swanson, Larry W.

    2007-01-01

    A systematic account of neuron cell types is a basic prerequisite for determining the vertebrate nervous system global wiring diagram. With comprehensive lineage and phylogenetic information unavailable, a general ontology based on structure-function taxonomy is proposed and implemented in a knowledge management system, and a prototype analysis of select regions (including retina, cerebellum, and hypothalamus) presented. The supporting Brain Architecture Knowledge Management System (BAMS) Neu...

  16. Motor neurone disease

    OpenAIRE

    Talbot, K.

    2002-01-01

    Motor neurone disease (MND), or amyotrophic lateral sclerosis (ALS), is a neurodegenerative disorder of unknown aetiology. Progressive motor weakness and bulbar dysfunction lead to premature death, usually from respiratory failure. Confirming the diagnosis may initially be difficult until the full clinical features are manifest. For all forms of the disease there is a significant differential diagnosis to consider, including treatable conditions, and therefore specialist neurological opinion ...

  17. Successful elimination of non-neural cells and unachievable elimination of glial cells by means of commonly used cell culture manipulations during differentiation of GFAP and SOX2 positive neural progenitors (NHA to neuronal cells

    Directory of Open Access Journals (Sweden)

    Krynska Barbara

    2008-07-01

    Full Text Available Abstract Background Although extensive research has been performed to control differentiation of neural stem cells – still, the response of those cells to diverse cell culture conditions often appears to be random and difficult to predict. To this end, we strived to obtain stabilized protocol of NHA cells differentiation – allowing for an increase in percentage yield of neuronal cells. Results Uncommitted GFAP and SOX2 positive neural progenitors – so-called, Normal Human Astrocytes (NHA were differentiated in different environmental conditions to: only neural cells consisted of neuronal [MAP2+, GFAP-] and glial [GFAP+, MAP2-] population, non-neural cells [CD44+, VIMENTIN+, FIBRONECTIN+, MAP2-, GFAP-, S100β-, SOX2-], or mixture of neural and non-neural cells. In spite of successfully increasing the percentage yield of glial and neuronal vs. non-neural cells by means of environmental changes, we were not able to increase significantly the percentage of neuronal (GABA-ergic and catecholaminergic over glial cells under several different cell culture testing conditions. Supplementing serum-free medium with several growth factors (SHH, bFGF, GDNF did not radically change the ratio between neuronal and glial cells – i.e., 1,1:1 in medium without growth factors and 1,4:1 in medium with GDNF, respectively. Conclusion We suggest that biotechnologists attempting to enrich in vitro neural cell cultures in one type of cells – such as that required for transplantology purposes, should consider the strong limiting influence of intrinsic factors upon extracellular factors commonly tested in cell culture conditions.

  18. Micropatterning neuronal networks.

    Science.gov (United States)

    Hardelauf, Heike; Waide, Sarah; Sisnaiske, Julia; Jacob, Peter; Hausherr, Vanessa; Schöbel, Nicole; Janasek, Dirk; van Thriel, Christoph; West, Jonathan

    2014-07-01

    Spatially organised neuronal networks have wide reaching applications, including fundamental research, toxicology testing, pharmaceutical screening and the realisation of neuronal implant interfaces. Despite the large number of methods catalogued in the literature there remains the need to identify a method that delivers high pattern compliance, long-term stability and is widely accessible to neuroscientists. In this comparative study, aminated (polylysine/polyornithine and aminosilanes) and cytophobic (poly(ethylene glycol) (PEG) and methylated) material contrasts were evaluated. Backfilling plasma stencilled PEGylated substrates with polylysine does not produce good material contrasts, whereas polylysine patterned on methylated substrates becomes mobilised by agents in the cell culture media which results in rapid pattern decay. Aminosilanes, polylysine substitutes, are prone to hydrolysis and the chemistries prove challenging to master. Instead, the stable coupling between polylysine and PLL-g-PEG can be exploited: Microcontact printing polylysine onto a PLL-g-PEG coated glass substrate provides a simple means to produce microstructured networks of primary neurons that have superior pattern compliance during long term (>1 month) culture.

  19. 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.

  20. Consistent estimation of complete neuronal connectivity in large neuronal populations using sparse "shotgun" neuronal activity sampling.

    Science.gov (United States)

    Mishchenko, Yuriy

    2016-10-01

    We investigate the properties of recently proposed "shotgun" sampling approach for the common inputs problem in the functional estimation of neuronal connectivity. We study the asymptotic correctness, the speed of convergence, and the data size requirements of such an approach. We show that the shotgun approach can be expected to allow the inference of complete connectivity matrix in large neuronal populations under some rather general conditions. However, we find that the posterior error of the shotgun connectivity estimator grows quickly with the size of unobserved neuronal populations, the square of average connectivity strength, and the square of observation sparseness. This implies that the shotgun connectivity estimation will require significantly larger amounts of neuronal activity data whenever the number of neurons in observed neuronal populations remains small. We present a numerical approach for solving the shotgun estimation problem in general settings and use it to demonstrate the shotgun connectivity inference in the examples of simulated synfire and weakly coupled cortical neuronal networks. PMID:27515518

  1. 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. PMID:27058317

  2. Co-culture of astrocytes with neurons from injured brain A time-dependent dichotomy

    Institute of Scientific and Technical Information of China (English)

    Xiaojing Xu; Min Wang; Jing Liu; Jingya Lv; Yanan Hu; Huanxiang Zhang

    2011-01-01

    As supportive cells for neuronal growth and development, much effort has been devoted to the role of astrocytes in the normal state. However, the effect of the astrocytes after injury remains elusive. In the present study, neurons isolated from the subventricular zone of injured neonatal rat brains were co-cultured with astrocytes. After 6 days, these astrocytes showed a mature neuron-like appearance and the number of survivingneurons, primary dendrites and total branches was significantly higher than those at 3 days. The neurons began to shrink at 9 days after co-culture with shorter and thinner processes and the number of primary dendrites and total branches was significantly reduced. These experimental findings indicate that astrocytes in the injured brain promote the development of neurons in the early stages of co-culture while these cells reversely inhibit neuronal growth and development at the later states.

  3. MODULATORY EFFECT OF CAFFEINE ON GABA-ACTIVATED CURRENT FROM ACUTELY ISOLATED RAT DORSAL ROOT GANGLION NEURONS%咖啡因对急性分离大鼠DRG神经元GABA-激活电流的调制作用

    Institute of Scientific and Technical Information of China (English)

    李韶; 孙长凯; 张健; 李爱萍; 朴花; 李之望

    2007-01-01

    应用全细胞膜片钳记录大鼠新鲜分离背根神经节(DRG)神经元GABA-激活电流,观察咖啡因对GABA-激活电流(IGABA)的调制作用.结果显示:大部分受检细胞(97.4%,113/116) 对外加GABA敏感.1-1000 μmol/L GABA引起一剂量依赖性、有明显去敏感作用的内向电流.预加咖啡因(0.01-100 μmol/L)30 s后再加GABA能明显抑制GABA(100 μmol/L )激活电流的幅值.预加咖啡因后GABA量效曲线明显下移;GABA-激活电流的最大值较之对照下降约57%;而Kd值(30 μmol/L)几乎不变.该结果提示此种抑制为非竞争性的.预加氨茶碱(theophylline)亦可明显抑制GABA激活电流,同一浓度(10 μmol/L)下氨茶碱的抑制作用较咖啡因的抑制作用强.预加安定(diazepam, 1 μmol/L)对GABA(10 μmol/L )激活电流有增强作用,而预加咖啡因(10 μmol/L )有拮抗安定增强IGABA的作用.胞内透析H-8后,几乎可以完全消除咖啡因对IGABA的抑制作用.本结果表明咖啡因在初级传入末稍可能产生对抗突触前抑制的效应.%Whole-cell patch clamp technique was performed on acutely isolated rat dorsal root ganglion (DRG) neurons to investigate the modulatory effect of caffeine on γ-aminobutyric acid (GABA)-activated currents (IGABA). The results showed that the majority of the neurons examined (97.4%, 113/116) were sensitive to GABA. 1-1000 μmol/L GABA activated a concentration-dependent inward current which manifested obvious desensitization. After the neurons were treated with caffeine (0.01-100 μmol/L) prior to the application of GABA (100 μmol/L) for 30 s, GABA-activated membrane currents were obviously inhibited. Caffeine shifted the GABA dose-response curve downward and decreased the maximum response to 57% without changing Kd value. These results indicate that the inhibitory effect is non-competitive. Theophylline showed a similar and stronger inhibitory effect on IGABA. The pretreatment with caffeine (10 μmol/L) inhibited IGABA, which was

  4. Differential production of superoxide by neuronal mitochondria

    Directory of Open Access Journals (Sweden)

    Levin Leonard A

    2008-01-01

    Full Text Available Abstract Background Mitochondrial DNA (mtDNA mutations, which are present in all mitochondria-containing cells, paradoxically cause tissue-specific disease. For example, Leber's hereditary optic neuropathy (LHON results from one of three point mutations mtDNA coding for complex I components, but is only manifested in retinal ganglion cells (RGCs, a central neuron contained within the retina. Given that RGCs use superoxide for intracellular signaling after axotomy, and that LHON mutations increase superoxide levels in non-RGC transmitochondrial cybrids, we hypothesized that RGCs regulate superoxide levels differently than other neuronal cells. To study this, we compared superoxide production and mitochondrial electron transport chain (METC components in isolated RGC mitochondria to mitochondria isolated from cerebral cortex and neuroblastoma SK-N-AS cells. Results In the presence of the complex I substrate glutamate/malate or the complex II substrate succinate, the rate of superoxide production in RGC-5 cells was significantly lower than cerebral or neuroblastoma cells. Cerebral but not RGC-5 or neuroblastoma cells increased superoxide production in response to the complex I inhibitor rotenone, while neuroblastoma but not cerebral or RGC-5 cells dramatically decreased superoxide production in response to the complex III inhibitor antimycin A. Immunoblotting and real-time quantitative PCR of METC components demonstrated different patterns of expression among the three different sources of neuronal mitochondria. Conclusion RGC-5 mitochondria produce superoxide at significantly lower rates than cerebral and neuroblastoma mitochondria, most likely as a result of differential expression of complex I components. Diversity in METC component expression and function could explain tissue specificity in diseases associated with inherited mtDNA abnormalities.

  5. Interactions of neurons with topographic nano cues affect branching morphology mimicking neuron-neuron interactions.

    Science.gov (United States)

    Baranes, Koby; Kollmar, Davida; Chejanovsky, Nathan; Sharoni, Amos; Shefi, Orit

    2012-08-01

    We study the effect of topographic nano-cues on neuronal growth-morphology using invertebrate neurons in culture. We use photolithography to fabricate substrates with repeatable line-pattern ridges of nano-scale heights of 10-150 nm. We plate leech neurons atop the patterned-substrates and compare their growth pattern to neurons plated atop non-patterned substrates. The model system allows us the analysis of single neurite-single ridge interactions. The use of high resolution electron microscopy reveals small filopodia processes that attach to the line-pattern ridges. These fine processes, that cannot be detected in light microscopy, add anchoring sites onto the side of the ridges, thus additional physical support. These interactions of the neuronal process dominantly affect the neuronal growth direction. We analyze the response of the entire neuronal branching tree to the patterned substrates and find significant effect on the growth patterns compared to non-patterned substrates. Moreover, interactions with the nano-cues trigger a growth strategy similarly to interactions with other neuronal cells, as reflected in their morphometric parameters. The number of branches and the number of neurites originating from the soma decrease following the interaction demonstrating a tendency to a more simplified neuronal branching tree. The effect of the nano-cues on the neuronal function deserves further investigation and will strengthen our understanding of the interplay between function and form.

  6. The origin of cortical neurons

    OpenAIRE

    Parnavelas J.G.

    2002-01-01

    Neurons of the mammalian cerebral cortex comprise two broad classes: pyramidal neurons, which project to distant targets, and the inhibitory nonpyramidal cells, the cortical interneurons. Pyramidal neurons are generated in the germinal ventricular zone, which lines the lateral ventricles, and migrate along the processes of radial glial cells to their positions in the developing cortex in an `inside-out' sequence. The GABA-containing nonpyramidal cells originate for the most part in the gangli...

  7. The straintronic spin-neuron.

    Science.gov (United States)

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

    2015-07-17

    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.

  8. Microglial control of neuronal activity

    Directory of Open Access Journals (Sweden)

    Catherine eBéchade

    2013-03-01

    Full Text Available Fine-tuning of neuronal activity was thought to be a neuron-autonomous mechanism until the discovery that astrocytes are active players of synaptic transmission. The involvement of astrocytes has changed our understanding of the roles of non-neuronal cells and shed new light on the regulation of neuronal activity. Microglial cells are the macrophages of the brain and they have been mostly investigated as immune cells. However recent data discussed in this review support the notion that, similarly to astrocytes, microglia are involved in the regulation of neuronal activity. For instance, in most, if not all, brain pathologies a strong temporal correlation has long been known to exist between the pathological activation of microglia and dysfunction of neuronal activity. Recent studies have convincingly shown that alteration of microglial function is responsible for pathological neuronal activity. This causal relationship has also been demonstrated in mice bearing loss-of-function mutations in genes specifically expressed by microglia. In addition to these long-term regulations of neuronal activity, recent data show that microglia can also rapidly regulate neuronal activity, thereby acting as partners of neurotransmission.

  9. The biophysics of neuronal growth

    Science.gov (United States)

    Franze, Kristian; Guck, Jochen

    2010-09-01

    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.

  10. STDP in recurrent neuronal networks

    Directory of Open Access Journals (Sweden)

    Matthieu Gilson

    2010-09-01

    Full Text Available Recent results about spike-timing-dependent plasticity (STDP in recurrently connected neurons are reviewed, with a focus on the relationship between the weight dynamics and the emergence of network structure. In particular, the evolution of synaptic weights in the two cases of incoming connections for a single neuron and recurrent connections are compared and contrasted. A theoretical framework is used that is based upon Poisson neurons with a temporally inhomogeneous firing rate and the asymptotic distribution of weights generated by the learning dynamics. Different network configurations examined in recent studies are discussed and an overview of the current understanding of STDP in recurrently connected neuronal networks is presented.

  11. Differentiation of the immortalized adult neuronal progenitor cell line HC2S2 into neurons by regulatable suppression of the v-myc oncogene.

    OpenAIRE

    Hoshimaru, M; Ray, J.; Sah, D W; Gage, F.H.

    1996-01-01

    A regulatable retroviral vector in which the v-myc oncogene is driven by a tetracycline-controlled transactivator and a human cytomegalovirus minimal promoter fused to a tet operator sequence was used for conditional immortalization of adult rat neuronal progenitor cells. A single clone, HC2S2, was isolated and characterized. Two days after the addition of tetracycline, the HC2S2 cells stopped proliferating, began to extend neurites, and expressed the neuronal markers tau, NeuN, neurofilament...

  12. Generation and transplantation of reprogrammed human neurons in the brain using 3D microtopographic scaffolds.

    Science.gov (United States)

    Carlson, Aaron L; Bennett, Neal K; Francis, Nicola L; Halikere, Apoorva; Clarke, Stephen; Moore, Jennifer C; Hart, Ronald P; Paradiso, Kenneth; Wernig, Marius; Kohn, Joachim; Pang, Zhiping P; Moghe, Prabhas V

    2016-01-01

    Cell replacement therapy with human pluripotent stem cell-derived neurons has the potential to ameliorate neurodegenerative dysfunction and central nervous system injuries, but reprogrammed neurons are dissociated and spatially disorganized during transplantation, rendering poor cell survival, functionality and engraftment in vivo. Here, we present the design of three-dimensional (3D) microtopographic scaffolds, using tunable electrospun microfibrous polymeric substrates that promote in situ stem cell neuronal reprogramming, neural network establishment and support neuronal engraftment into the brain. Scaffold-supported, reprogrammed neuronal networks were successfully grafted into organotypic hippocampal brain slices, showing an ∼ 3.5-fold improvement in neurite outgrowth and increased action potential firing relative to injected isolated cells. Transplantation of scaffold-supported neuronal networks into mouse brain striatum improved survival ∼ 38-fold at the injection site relative to injected isolated cells, and allowed delivery of multiple neuronal subtypes. Thus, 3D microscale biomaterials represent a promising platform for the transplantation of therapeutic human neurons with broad neuro-regenerative relevance. PMID:26983594

  13. Nerve growth factor, sphingomyelins, and sensitization in sensory neurons

    Institute of Scientific and Technical Information of China (English)

    Grant D. Nicol

    2008-01-01

    @@ Because nerve growth factor (NGF) is elevated during inflammation, plays a causal role in the initiation of hyperalgesia, and is known to activate the sphingomyelin signalling pathway, we examined whether NGF and its putative second messenger, ceramide, could modulate the excitability of capsaicin-sensitive adult sensory neurons.Using the whole-cell patch-clamp recording technique,exposure of isolated sensory neurons to either 100 ng/mL NGF or 1 mmol/L N-acetyl sphingosine (C2-ceramide) produced a 3-4 fold increase in the number of action po-tentials (APs) evoked by a ramp of depolarizing current in a time-dependent manner. Intracellular perfusion with bac- terial sphingomyelinase (SMase) also increased the num- ber of APs suggesting that the release of native ceramide enhanced neuronal excitability.

  14. Expanding the neuron's calcium signaling repertoire: intracellular calcium release via voltage-induced PLC and IP3R activation.

    Directory of Open Access Journals (Sweden)

    Stefanie Ryglewski

    2007-04-01

    Full Text Available Neuronal calcium acts as a charge carrier during information processing and as a ubiquitous intracellular messenger. Calcium signals are fundamental to numerous aspects of neuronal development and plasticity. Specific and independent regulation of these vital cellular processes is achieved by a rich bouquet of different calcium signaling mechanisms within the neuron, which either can operate independently or may act in concert. This study demonstrates the existence of a novel calcium signaling mechanism by simultaneous patch clamping and calcium imaging from acutely isolated central neurons. These neurons possess a membrane voltage sensor that, independent of calcium influx, causes G-protein activation, which subsequently leads to calcium release from intracellular stores via phospholipase C and inositol 1,4,5-trisphosphate receptor activation. This allows neurons to monitor activity by intracellular calcium release without relying on calcium as the input signal and opens up new insights into intracellular signaling, developmental regulation, and information processing in neuronal compartments lacking calcium channels.

  15. APAF1 is a key transcriptional target for p53 in the regulation of neuronal cell death

    DEFF Research Database (Denmark)

    Fortin, A; Cregan, S P; MacLaurin, J G;

    2001-01-01

    p53 is a transcriptional activator which has been implicated as a key regulator of neuronal cell death after acute injury. We have shown previously that p53-mediated neuronal cell death involves a Bax-dependent activation of caspase 3; however, the transcriptional targets involved in the regulation...... of this process have not been identified. In the present study, we demonstrate that p53 directly upregulates Apaf1 transcription as a critical step in the induction of neuronal cell death. Using DNA microarray analysis of total RNA isolated from neurons undergoing p53-induced apoptosis a 5-6-fold upregulation...... of Apaf1 mRNA was detected. Induction of neuronal cell death by camptothecin, a DNA-damaging agent that functions through a p53-dependent mechanism, resulted in increased Apaf1 mRNA in p53-positive, but not p53-deficient neurons. In both in vitro and in vivo neuronal cell death processes of p53-induced...

  16. 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…

  17. Neurones and neuropeptides in coelenterates

    DEFF Research Database (Denmark)

    Grimmelikhuijzen, C J; Ebbesen, Ditte Graff; McFarlane, I D

    1989-01-01

    The first nervous system probably evolved in coelenterates. Many neurons in coelenterates have morphological characteristics of both sensory and motor neurones, and appear to be multifunctional. Using immunocytochemistry with antisera to the sequence Arg-Phe-NH2 (RFamide), RFamide-like peptides w...... that these neuropeptides play a role in neurotransmission....

  18. Cryopreservation of adherent neuronal networks.

    Science.gov (United States)

    Ma, Wu; O'Shaughnessy, Thomas; Chang, Eddie

    2006-07-31

    Neuronal networks have been widely used for neurophysiology, drug discovery and toxicity testing. An essential prerequisite for future widespread application of neuronal networks is the development of efficient cryopreservation protocols to facilitate their storage and transportation. Here is the first report on cryopreservation of mammalian adherent neuronal networks. Dissociated spinal cord cells were attached to a poly-d-lysine/laminin surface and allowed to form neuronal networks. Adherent neuronal networks were embedded in a thin film of collagen gel and loaded with trehalose prior to transfer to a freezing medium containing DMSO, FBS and culture medium. This was followed by a slow rate of cooling to -80 degrees C for 24 h and then storage for up to 2 months in liquid nitrogen at -196 degrees C. The three components: DMSO, collagen gel entrapment and trehalose loading combined provided the highest post-thaw viability, relative to individual or two component protocols. The post-thaw cells with this protocol demonstrated similar neuronal and astrocytic markers and morphological structure as those detected in unfrozen cells. Fluorescent dye FM1-43 staining revealed active recycling of synaptic vesicles upon depolarizing stimulation in the post-thaw neuronal networks. These results suggest that a combination of DMSO, collagen gel entrapment and trehalose loading can significantly improve conventional slow-cooling methods in cryopreservation of adherent neuronal networks.

  19. More questions for mirror neurons.

    Science.gov (United States)

    Borg, Emma

    2013-09-01

    The mirror neuron system is widely held to provide direct access to the motor goals of others. This paper critically investigates this idea, focusing on the so-called 'intentional worry'. I explore two answers to the intentional worry: first that the worry is premised on too limited an understanding of mirror neuron behaviour (Sections 2 and 3), second that the appeal made to mirror neurons can be refined in such a way as to avoid the worry (Section 4). I argue that the first response requires an account of the mechanism by which small-scale gestures are supposedly mapped to larger chains of actions but that none of the extant accounts of this mechanism are plausible. Section 4 then briefly examines refinements of the mirror neuron-mindreading hypothesis which avoid the intentional worry. I conclude that these refinements may well be plausible but that they undermine many of the claims standardly made for mirror neurons.

  20. Ethanol and neuronal metabolism.

    Science.gov (United States)

    Mandel, P; Ledig, M; M'Paria, J R

    1980-01-01

    The effect of ethanol on membrane enzymes (Na+, K+ and Mg2+ ATPases, 5'-nucleotidase, adenylate cyclase) alcohol dehydrogenase, aldehyde dehydrogenase and superoxide dismutase were studied in nerve cells (established cell lines, primary cultures of chick and rat brain) cultured in the presence of 100 mM ethanol, and in total rat brain, following various ethanol treatments of the rats (20% ethanol as the sole liquid source, intraperitoneal injection). The results show a difference between neuronal and glial cells. Most of the observed changes in enzymatic activities returned rapidly to control values when ethanol was withdrawn from the culture medium or from the diet. Alcohol dehydrogenase was more stimulated by ethanol than aldehyde dehydrogenase; therefore acetaldehyde may be accumulated. The inhibition of superoxide dismutase activity may allow an accumulation of cytotoxic O2- radicals in nervous tissue and may explain the polymorphism of lesions brought about by alcohol intoxication. PMID:6264495

  1. 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.

  2. Disinhibition Bursting of Dopaminergic Neurons

    Directory of Open Access Journals (Sweden)

    Collin J Lobb

    2011-05-01

    Full Text Available Substantia nigra pars compacta (SNpc dopaminergic neurons receive strong tonic inputs from GABAergic neurons in the substantia nigra pars reticulata (SNpr and globus pallidus (GP, and glutamatergic neurons in the subthalamic nucleus. The presence of these tonic inputs raises the possibility that phasic disinhibition may trigger phasic bursts in dopaminergic neurons. We first applied constant NMDA and GABAA conductances onto a two-compartment single cell model of the dopaminergic neuron (Kuznetsov et al., 2006. The model exhibited disinhibition bursting upon stepwise removal of inhibition. A further bifurcation analysis suggests that disinhibition may be more robust than excitation alone in that for most levels of NMDA conductance, the cell remains capable of bursting even after a complete removal of inhibition, whereas too much excitatory input will drive the cell into depolarization block. To investigate the network dynamics of disinhibition, we used a modified version of an integrate-and-fire based model of the basal ganglia (Humphries et al., 2006. Synaptic activity generated in the network was delivered to the two-compartment single cell dopaminergic neuron. Phasic activation of the D1-expressing medium spiny neurons in the striatum (D1STR produced disinhibition bursts in dopaminergic neurons through the direct pathway (D1STR to SNpr to SNpc. Anatomical studies have shown that D1STR neurons have collaterals that terminate in GP. Adding these collaterals to the model, we found that striatal activation increased the intra-burst firing frequency of the disinhibition burst as the weight of this connection was increased. Our studies suggest that striatal activation is a robust means by which disinhibition bursts can be generated by SNpc dopaminergic neurons, and that recruitment of the indirect pathway via collaterals may enhance disinhibition bursting.

  3. Postmitotic specification of Drosophila insulinergic neurons from pioneer neurons.

    Directory of Open Access Journals (Sweden)

    Irene Miguel-Aliaga

    2008-03-01

    Full Text Available Insulin and related peptides play important and conserved functions in growth and metabolism. Although Drosophila has proved useful for the genetic analysis of insulin functions, little is known about the transcription factors and cell lineages involved in insulin production. Within the embryonic central nervous system, the MP2 neuroblast divides once to generate a dMP2 neuron that initially functions as a pioneer, guiding the axons of other later-born embryonic neurons. Later during development, dMP2 neurons in anterior segments undergo apoptosis but their posterior counterparts persist. We show here that surviving posterior dMP2 neurons no longer function in axonal scaffolding but differentiate into neuroendocrine cells that express insulin-like peptide 7 (Ilp7 and innervate the hindgut. We find that the postmitotic transition from pioneer to insulin-producing neuron is a multistep process requiring retrograde bone morphogenetic protein (BMP signalling and four transcription factors: Abdominal-B, Hb9, Fork Head, and Dimmed. These five inputs contribute in a partially overlapping manner to combinatorial codes for dMP2 apoptosis, survival, and insulinergic differentiation. Ectopic reconstitution of this code is sufficient to activate Ilp7 expression in other postmitotic neurons. These studies reveal striking similarities between the transcription factors regulating insulin expression in insect neurons and mammalian pancreatic beta-cells.

  4. Parallel Algorithms for Neuronal Spike Sorting

    OpenAIRE

    Bergheim, Thomas Stian; Skogvold, Arve Aleksander Nymo

    2011-01-01

    Neurons communicate through electrophysiological signals, which may be recorded using electrodes inserted into living tissue.When a neuron emits a signal, it is referred to as a spike, and an electrode can detect these from multiple neurons.Neuronal spike sorting is the process of classifying the spike activity based on which neuron each spike signal is emitted from.Advances in technology have introduced better recording equipment, which allows the recording of many neurons at the same time.H...

  5. Isolated dextrogastria

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Kyung Soo; Kim, Soo Ryun; Lee, Yong Chul; Park, Soo Soung [Chung Ang University College of Medicine, Seoul (Korea, Republic of); Sim, Young Soo [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1982-06-15

    Isolated situs inversus of the stomach with otherwise normal position of the thoracic and abdominal viscera is an extremely rare anomaly occurring in two district forms. Majority of cases are associated with eventration of the diphragm and are reported as being confused with spontaneous pneumothorax or pyopneumothorax at base of the right lung. The right sided stomach may produce interesting and confusing changes in liver scan. We have experienced 2 cases of the isolated dextrogastria.

  6. Isolated dextrogastria

    International Nuclear Information System (INIS)

    Isolated situs inversus of the stomach with otherwise normal position of the thoracic and abdominal viscera is an extremely rare anomaly occurring in two district forms. Majority of cases are associated with eventration of the diphragm and are reported as being confused with spontaneous pneumothorax or pyopneumothorax at base of the right lung. The right sided stomach may produce interesting and confusing changes in liver scan. We have experienced 2 cases of the isolated dextrogastria

  7. Behaviorally relevant burst coding in primary sensory neurons.

    Science.gov (United States)

    Sabourin, Patrick; Pollack, Gerald S

    2009-08-01

    Bursts of action potentials in sensory interneurons are believed to signal the occurrence of particularly salient stimulus features. Previous work showed that bursts in an identified, ultrasound-tuned interneuron (AN2) of the cricket Teleogryllus oceanicus code for conspicuous increases in amplitude of an ultrasound stimulus, resulting in behavioral responses that are interpreted as avoidance of echolocating bats. We show that the primary sensory neurons that inform AN2 about high-frequency acoustic stimuli also produce bursts. As is the case for AN2, bursts in sensory neurons perform better as feature detectors than isolated, nonburst, spikes. Bursting is temporally correlated between sensory neurons, suggesting that on occurrence of a salient stimulus feature, AN2 will receive strong synaptic input in the form of coincident bursts, from several sensory neurons, and that this might result in bursting in AN2. Our results show that an important feature of the temporal structure of interneuron spike trains can be established at the earliest possible level of sensory processing, i.e., that of the primary sensory neuron.

  8. Mild hypoxia affects synaptic connectivity in cultured neuronal networks.

    Science.gov (United States)

    Hofmeijer, Jeannette; Mulder, Alex T B; Farinha, Ana C; van Putten, Michel J A M; le Feber, Joost

    2014-04-01

    Eighty percent of patients with chronic mild cerebral ischemia/hypoxia resulting from chronic heart failure or pulmonary disease have cognitive impairment. Overt structural neuronal damage is lacking and the precise cause of neuronal damage is unclear. As almost half of the cerebral energy consumption is used for synaptic transmission, and synaptic failure is the first abrupt consequence of acute complete anoxia, synaptic dysfunction is a candidate mechanism for the cognitive deterioration in chronic mild ischemia/hypoxia. Because measurement of synaptic functioning in patients is problematic, we use cultured networks of cortical neurons from new born rats, grown over a multi-electrode array, as a model system. These were exposed to partial hypoxia (partial oxygen pressure of 150Torr lowered to 40-50Torr) during 3 (n=14) or 6 (n=8) hours. Synaptic functioning was assessed before, during, and after hypoxia by assessment of spontaneous network activity, functional connectivity, and synaptically driven network responses to electrical stimulation. Action potential heights and shapes and non-synaptic stimulus responses were used as measures of individual neuronal integrity. During hypoxia of 3 and 6h, there was a statistically significant decrease of spontaneous network activity, functional connectivity, and synaptically driven network responses, whereas direct responses and action potentials remained unchanged. These changes were largely reversible. Our results indicate that in cultured neuronal networks, partial hypoxia during 3 or 6h causes isolated disturbances of synaptic connectivity.

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

    Institute of Scientific and Technical Information of China (English)

    Qing-quan Li; Guan-qun Qiao; Jun Ma; Hong-wei Fan; Ying-bin Li

    2015-01-01

    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 ifbrillary acidic protein. New neurons were labeled using bromodeoxyuridine and different stages of maturity were identiifed 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 bromode-oxyuridine 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 ifbrillary acidic protein/bromodeoxyuridine double-positive astrocytes were also found in the injured cortex. Our ifndings 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.

  10. Establishment of a mechanical injury model of rat hippocampal neurons in vitro

    Institute of Scientific and Technical Information of China (English)

    YANG Xiao-feng; CAO Fei; PAN De-sheng; LIU Wei-guo; HU Wei-wei; ZHENG Xiu-jue; ZHAO Xue-qun; L(U) Shi-ting

    2006-01-01

    Objective:To establish a simple, reproducible, and practical mechanical injury model of hippocampal neurons of Sprague-Dawley rats in vitro.Methods: Hippocampal neurons isolated from1-2-day old rats were cultured in vitro. Mild, moderate and severe mechanical injuries were delivered to the neurons by syringe needle tearing, respectively. The control neurons were treated identically with the exception of trauma. Cell damage was assessed by measuring the Propidium Iodide(PI) uptaking at different time points (0.5, 1, 6, 12 and24 hours) after injury. The concentration of neuron specific enolase was also measured at some time points.Results: Pathological examination showed that degeneration, degradation and necrosis occurred in the injured cultured neurons. Compared with the control group, the ratio of PI-positive cells in the injured groups increased significantly after 30 minutes of injury (P <0.05). More severe the damage was, more PI-positive neurons were detected. Compared with the control group,the concentration of neuron specific enolase in the injured culture increased significantly after 1 hour of injury (P <0.05).Conclusions: The established model of hippocampal neuron injury in vitro can be repeated easily and can simulate the damage mechanism of traumatic brain injury,which can be used in the future research of traumatic brain injury.

  11. Mutations Affecting the Chemosensory Neurons of Caenorhabditis Elegans

    OpenAIRE

    Starich, T. A.; Herman, R. K.; Kari, C. K.; Yeh, W. H.; Schackwitz, W. S.; Schuyler, M. W.; Collet, J.; Thomas, J. H.; Riddle, D L

    1995-01-01

    We have identified and characterized 95 mutations that reduce or abolish dye filling of amphid and phasmid neurons and that have little effect on viability, fertility or movement. Twenty-seven mutations occurred spontaneously in strains with a high frequency of transposon insertion. Sixty-eight were isolated after treatment with EMS. All of the mutations result in defects in one or more chemosensory responses, such as chemotaxis to ammonium chloride or formation of dauer larvae under conditio...

  12. Murine Mueller cells are progenitor cells for neuronal cells and fibrous tissue cells

    International Nuclear Information System (INIS)

    Mammalian Mueller cells have been reported to possess retinal progenitor cell properties and generate new neurons after injury. This study investigates murine Mueller cells under in vitro conditions for their capability of dedifferentiation into retinal progenitor cells. Mueller cells were isolated from mouse retina, and proliferating cells were expanded in serum-containing medium. For dedifferentiation, the cultured cells were transferred to serum-replacement medium (SRM) at different points in time after their isolation. Interestingly, early cell passages produced fibrous tissue in which extracellular matrix proteins and connective tissue markers were differentially expressed. In contrast, aged Mueller cell cultures formed neurospheres in SRM that are characteristic for neuronal progenitor cells. These neurospheres differentiated into neuron-like cells after cultivation on laminin/ornithine cell culture substrate. Here, we report for the first time that murine Mueller cells can be progenitors for both, fibrous tissue cells and neuronal cells, depending on the age of the cell culture

  13. 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.

  14. A neuron-benign microfluidic gradient generator for studying the response of mammalian neurons towards axon guidance factors.

    Science.gov (United States)

    Bhattacharjee, Nirveek; Li, Nianzhen; Keenan, Thomas M; Folch, Albert

    2010-11-01

    Investigation of biochemical cues in isolation or in combinations in cell culture systems is crucial for unraveling the mechanisms that govern neural development and repair. The most widely used experimental paradigms that elicit axon guidance in vitro utilize as the source of the gradient a pulsatile pipette, transfected cells, or a loaded gel, producing time-varying gradients of poor reproducibility which are not well suited for studying slow-growing mammalian cells. Although microfluidic device design have allowed for generating stable, complex gradients of diffusible molecules, the flow-induced shear forces in a microchannel has made it impossible to maintain viable mammalian neuronal cultures for sufficiently long times. In this paper, we describe axonal responses of mouse cortical neurons in a "neuron-benign" gradient-generator device based on an open chamber that can establish highly stable gradients of diffusible molecules for at least 6 h with negligible shear stress, and also allows the neurons to thrive for at least 2 weeks. Except for the period when the gradient is on, the cells in the gradient are under the same conditions as the cells on the control surfaces, which ensure a consistent set of micro-environmental variables. The gradient stability and uniformity over the cell culture surface achieved by the device, together with our software platform for acquiring, post-processing and quantitatively analyzing the large number of images allowed us to extract valuable information even from small datasets. We report a directed response of primary mammalian neurons (from E14 embryonic mice cortex) to a diffusible gradient of netrin in vitro. We infer from our studies that a large majority (∼73%) of the neurons that extend axons during the gradient application grow towards the netrin source, and our data analysis also indicates that netrin acts as a growth factor for this same population of neurons.

  15. A Neuron Model for FPGA Spiking Neuronal Network Implementation

    Directory of Open Access Journals (Sweden)

    BONTEANU, G.

    2011-11-01

    Full Text Available We propose a neuron model, able to reproduce the basic elements of the neuronal dynamics, optimized for digital implementation of Spiking Neural Networks. Its architecture is structured in two major blocks, a datapath and a control unit. The datapath consists of a membrane potential circuit, which emulates the neuronal dynamics at the soma level, and a synaptic circuit used to update the synaptic weight according to the spike timing dependent plasticity (STDP mechanism. The proposed model is implemented into a Cyclone II-Altera FPGA device. Our results indicate the neuron model can be used to build up 1K Spiking Neural Networks on reconfigurable logic suport, to explore various network topologies.

  16. Highly efficient method for gene delivery in mouse dorsal root ganglia neurons

    OpenAIRE

    Lingli eYu; Florie eReynaud; Julien eFalk; Ambre eSpencer; Yin-Di eDing; Véronique eBaumlé; Ruisheng eLu; Valérie eCastellani; Chonggang eYuan; Rudkin, Brian B.

    2015-01-01

    The development of gene transfection technologies has greatly advanced our understanding of life sciences. While use of viral vectors has clear efficacy, it requires specific expertise and biological containment conditions. Electroporation has become an effective and commonly used method for introducing DNA into neurons and in intact brain tissue. The present study describes the use of the Neon® electroporation system to transfect genes into dorsal root ganglia neurons isolated from embryonic...

  17. Cellular actions of somatostatin on rat periaqueductal grey neurons in vitro

    OpenAIRE

    Connor, Mark; Bagley, Elena E.; Mitchell, Vanessa A; Ingram, Susan L; Christie, MacDonald J.; Humphrey, Patrick P A; Vaughan, Christopher W

    2004-01-01

    Functional studies indicate that the midbrain periaqueductal grey (PAG) is involved in the analgesic actions of somatostatin; however, the cellular actions of somatostatin in this brain region are unknown. In the present study, whole-cell patch clamp recordings were made from rat PAG neurons in vitro. In 93% of acutely isolated neurons, somatostatin inhibited Ca2+-channel currents. This effect was mimicked by the sst-2 selective agonist BIM-23027, but not by the sst-1 and sst-5 selective agon...

  18. Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain.

    Science.gov (United States)

    Lake, Blue B; Ai, Rizi; Kaeser, Gwendolyn E; Salathia, Neeraj S; Yung, Yun C; Liu, Rui; Wildberg, Andre; Gao, Derek; Fung, Ho-Lim; Chen, Song; Vijayaraghavan, Raakhee; Wong, Julian; Chen, Allison; Sheng, Xiaoyan; Kaper, Fiona; Shen, Richard; Ronaghi, Mostafa; Fan, Jian-Bing; Wang, Wei; Chun, Jerold; Zhang, Kun

    2016-06-24

    The human brain has enormously complex cellular diversity and connectivities fundamental to our neural functions, yet difficulties in interrogating individual neurons has impeded understanding of the underlying transcriptional landscape. We developed a scalable approach to sequence and quantify RNA molecules in isolated neuronal nuclei from a postmortem brain, generating 3227 sets of single-neuron data from six distinct regions of the cerebral cortex. Using an iterative clustering and classification approach, we identified 16 neuronal subtypes that were further annotated on the basis of known markers and cortical cytoarchitecture. These data demonstrate a robust and scalable method for identifying and categorizing single nuclear transcriptomes, revealing shared genes sufficient to distinguish previously unknown and orthologous neuronal subtypes as well as regional identity and transcriptomic heterogeneity within the human brain. PMID:27339989

  19. Associative conditioning analog selectively increases cAMP levels of tail sensory neurons in Aplysia.

    Science.gov (United States)

    Ocorr, K A; Walters, E T; Byrne, J H

    1985-04-01

    Bilateral clusters of sensory neurons in the pleural ganglia of Aplysia contain cells involved in a defensive tail withdrawal reflex. These cells exhibit heterosynaptic facilitation in response to noxious skin stimulation that can be mimicked by the application of serotonin. Recently it has been shown that this facilitation can be selectively amplified by the application of a classical conditioning procedure to individual sensory neurons. We now report that an analog of this classical conditioning paradigm produces a selective amplification of the cAMP content of isolated sensory neuron clusters. The enhancement is achieved within a single trial and appears to be localized to the sensory neurons. These results indicate that a pairing-specific enhancement of cAMP levels may be a biochemical mechanism for associative neuronal modifications and perhaps learning.

  20. Single neuron dynamics and computation.

    Science.gov (United States)

    Brunel, Nicolas; Hakim, Vincent; Richardson, Magnus J E

    2014-04-01

    At the single neuron level, information processing involves the transformation of input spike trains into an appropriate output spike train. Building upon the classical view of a neuron as a threshold device, models have been developed in recent years that take into account the diverse electrophysiological make-up of neurons and accurately describe their input-output relations. Here, we review these recent advances and survey the computational roles that they have uncovered for various electrophysiological properties, for dendritic arbor anatomy as well as for short-term synaptic plasticity.

  1. 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...... include changes in the expression of molecules such as transcription factors and microRNAs that regulate stress resistance and adaptation. Moreover, both intrinsic and extrinsic stresses have a tremendous impact on neuronal development and maintenance with implications in many diseases. Here, we review...... the responses of neurons to various physiological stressors at the molecular and cellular level....

  2. Neurofibromatosis: The role of guanosine triphosphatase activating proteins in sensory neuron function

    Institute of Scientific and Technical Information of China (English)

    Cynthia M. Hingtgen

    2008-01-01

    Neurofibromatosis type 1 (NF1) is a common autosomal dominant disease characterized by formation of multiple benign and malignant tumors. People with this disorder also experience chronic pain, which can be disabling. Neurofibromin, the protein product of the Nfl gene, is a gnanosine triphosphatase activating protein (GAP) for p21Ras (Ras). Loss of Nfl results in an increase in activity of the Ras transduction cascade. Because of the growing evidence suggesting involvement of downstream components of the Ras transduction cascade in the sensitization of nociceptive sensory neurons, we examined the stimulus-evoked release of the neuropeptides, substance P (SP) and calcitonin gene-related peptide (CGRP), from primary sensory neurons of mice with a mutation of the Nfl gene (NfI+1-). Measuring the levels of SP and CGRP by radioimmunoassay, we demonstrated that capsaicin-stimulated release of neuropep-tides is 3-5 folds higher in spinal cord slices from Nfl+1-mice than that from wildtype mouse tissue. In addition, the potassium- and capsaicin-stimulated release of CGRP from the culture of sensory neurons isolated from Nfl+1- mice was more than double that from the culture of wildtype neurons. Using patch-clamp electrophysiological techniques, we also examined the excitability of capsaicin-sensitive sensory neurons. It was found that the number of action potentials generated by the neurons from Nfl+1- mice, responsing to a ramp of depolarizing current, was more than three times of that generated by wildtype neurons. Consistent with that observation, neurons from Nfl+1- mice had lower firing thresholds, lower rheobase currents and shorter firing latencies compared with wildtype neurons. These data clearly demonstrate that GAPs, such as neurofihromin, can alter the excitability of nociceptive sensory neurons. The augmented response of sensory neurons with altered Ras signaling may explain the abnormal pain sensations experienced by people with NFI and suggests an important

  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. Neuronal Coding of pacemaker neurons - A random dynamical systems approach

    OpenAIRE

    de Jaeger, T

    2009-01-01

    The behaviour of neurons under the influence of periodic external input has been modelled very successfully by circle maps. The aim of this note is to extend certain aspects of this analysis to a much more general class of forcing processes. We apply results on the fibred rotation number of randomly forced circle maps to show the uniqueness of the asymptotic firing frequency of ergodically forced pacemaker neurons. The details of the analysis are carried out for the forced leaky integrate-and...

  5. Cocaine depresses GABAA current of hippocampal neurons.

    Science.gov (United States)

    Ye, J H; Liu, P L; Wu, W H; McArdle, J J

    1997-10-01

    Although blockade of dopamine re-uptake and the resulting elevation of excitatory agonists is commonly thought the primary mechanism of cocaine-induced seizures, it is possible that other neurotransmitters such as gamma-aminobutyric acid (GABA) are involved. To examine this possibility, the effects of cocaine on the whole cell GABA current (IGABA) of freshly isolated rat hippocampal neurons were investigated with the patch-clamp technique. Preincubation or acute application of cocaine reversibly suppressed IGABA. The IC50 was 127 microM when cocaine was applied before the application of GABA. The concentration-response relations of cocaine in various GABA concentrations revealed that cocaine inhibited IGABA non-competitively. This effect of cocaine appeared to be independent of voltage. The present study suggests that the GABA receptor/channel complex is also a target for cocaine's action. The suppression of IGABA may contribute to cocaine-induced seizures.

  6. The neuronal and actin commitment: Why do neurons need rings?

    Science.gov (United States)

    Leite, Sérgio Carvalho; Sousa, Mónica Mendes

    2016-09-01

    The role of the actin cytoskeleton in neurons has been extensively studied in actin-enriched compartments such as the growth cone and dendritic spines. The recent discovery of actin rings in the axon shaft and in dendrites, together with the identification of axon actin trails, has advanced our understanding on actin organization and dynamics in neurons. However, specifically in the case of actin rings, the mechanisms regulating their nucleation and assembly, and the functions that they may exert in axons and dendrites remain largely unexplored. Here we discuss the possible structural, mechanistic and functional properties of the subcortical neuronal cytoskeleton putting the current knowledge in perspective with the information available on actin rings formed in other biological contexts, and with the organization of actin-spectrin lattices in other cell types. The detailed analysis of these novel neuronal actin ring structures, together with the elucidation of the function of actin-binding proteins in neuron biology, has a large potential to uncover new mechanisms of neuronal function under normal conditions that may have impact in our understanding of axon degeneration and regeneration. © 2016 Wiley Periodicals, Inc.

  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. Neuronal boost to evolutionary dynamics

    Science.gov (United States)

    de Vladar, Harold P.; Szathmáry, Eörs

    2015-01-01

    Standard evolutionary dynamics is limited by the constraints of the genetic system. A central message of evolutionary neurodynamics is that evolutionary dynamics in the brain can happen in a neuronal niche in real time, despite the fact that neurons do not reproduce. We show that Hebbian learning and structural synaptic plasticity broaden the capacity for informational replication and guided variability provided a neuronally plausible mechanism of replication is in place. The synergy between learning and selection is more efficient than the equivalent search by mutation selection. We also consider asymmetric landscapes and show that the learning weights become correlated with the fitness gradient. That is, the neuronal complexes learn the local properties of the fitness landscape, resulting in the generation of variability directed towards the direction of fitness increase, as if mutations in a genetic pool were drawn such that they would increase reproductive success. Evolution might thus be more efficient within evolved brains than among organisms out in the wild. PMID:26640653

  9. Modeling neuronal vulnerability in ALS.

    Science.gov (United States)

    Roselli, Francesco; Caroni, Pico

    2014-08-20

    Using computational models of motor neuron ion fluxes, firing properties, and energy requirements, Le Masson et al. (2014) reveal how local imbalances in energy homeostasis may self-amplify and contribute to neurodegeneration in ALS.

  10. The neuronal infrastructure of speaking

    NARCIS (Netherlands)

    Menenti, L.M.E.; Segaert, K.M.; Hagoort, Peter

    2012-01-01

    Models of speaking distinguish producing meaning, words and syntax as three different linguistic components of speaking. Nevertheless, little is known about the brain's integrated neuronal infrastructure for speech production. We investigated semantic, lexical and syntactic aspects of speaking using

  11. Towards Automatic Classification of Neurons

    OpenAIRE

    Armañanzas, Rubén; Ascoli, Giorgio A.

    2015-01-01

    The classification of neurons into types has been much debated since the inception of modern neuroscience. Recent experimental advances are accelerating the pace of data collection. The resulting information growth of morphological, physiological, and molecular properties encourages efforts to automate neuronal classification by powerful machine learning techniques. We review state-of-the-art analysis approaches and availability of suitable data and resources, highlighting prominent challenge...

  12. Neuronal Classification of Atria Fibrillation

    OpenAIRE

    Mohamed BEN MESSAOUD

    2008-01-01

    Motivation. In medical field, particularly the cardiology, the diagnosis systems constitute the essential domain of research. In some applications, the traditional methods of classification present some limitations. The neuronal technique is considered as one of the promising algorithms to resolve such problem.Method. In this paper, two approaches of the Artificial Neuronal Network (ANN) technique are investigated to classify the heart beats which are Multi Layer Perception (MLP) and Radial B...

  13. A more substantive neuron doctrine

    OpenAIRE

    Lau, JYF

    1999-01-01

    First, it is not clear from Gold and Stoljar's definition of biological neuroscience whether it includes computational and representational concepts. If so, then their evaluation of Kandel's theory is problematic. If not, then a more direct refutation of the radical neuron doctrine is available. Second, objections to the psychological sciences might derive not just from the conflation of the radical and the trivial neuron doctrines. There might also be the implicit belief that, for many menta...

  14. 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...

  15. Novel model of neuronal bioenergetics

    DEFF Research Database (Denmark)

    Bak, Lasse Kristoffer; Obel, Linea Lykke Frimodt; Walls, Anne B;

    2012-01-01

    We have previously investigated the relative roles of extracellular glucose and lactate as fuels for glutamatergic neurons during synaptic activity. The conclusion from these studies was that cultured glutamatergic neurons utilize glucose rather than lactate during NMDA (N-methyl-d-aspartate)-ind......We have previously investigated the relative roles of extracellular glucose and lactate as fuels for glutamatergic neurons during synaptic activity. The conclusion from these studies was that cultured glutamatergic neurons utilize glucose rather than lactate during NMDA (N...... of an ionomycin-induced increase in intracellular Ca2+ (i.e. independent of synaptic activity) on neuronal energy metabolism employing 13C-labelled glucose and lactate and subsequent mass spectrometric analysis of labelling in glutamate, alanine and lactate. The results demonstrate that glucose utilization...... is positively correlated with intracellular Ca2+ whereas lactate utilization is not. This result lends further support for a significant role of glucose in neuronal bioenergetics and that Ca2+ signalling may control the switch between glucose and lactate utilization during synaptic activity. Based...

  16. Network synchronization in hippocampal neurons.

    Science.gov (United States)

    Penn, Yaron; Segal, Menahem; Moses, Elisha

    2016-03-22

    Oscillatory activity is widespread in dynamic neuronal networks. The main paradigm for the origin of periodicity consists of specialized pacemaking elements that synchronize and drive the rest of the network; however, other models exist. Here, we studied the spontaneous emergence of synchronized periodic bursting in a network of cultured dissociated neurons from rat hippocampus and cortex. Surprisingly, about 60% of all active neurons were self-sustained oscillators when disconnected, each with its own natural frequency. The individual neuron's tendency to oscillate and the corresponding oscillation frequency are controlled by its excitability. The single neuron intrinsic oscillations were blocked by riluzole, and are thus dependent on persistent sodium leak currents. Upon a gradual retrieval of connectivity, the synchrony evolves: Loose synchrony appears already at weak connectivity, with the oscillators converging to one common oscillation frequency, yet shifted in phase across the population. Further strengthening of the connectivity causes a reduction in the mean phase shifts until zero-lag is achieved, manifested by synchronous periodic network bursts. Interestingly, the frequency of network bursting matches the average of the intrinsic frequencies. Overall, the network behaves like other universal systems, where order emerges spontaneously by entrainment of independent rhythmic units. Although simplified with respect to circuitry in the brain, our results attribute a basic functional role for intrinsic single neuron excitability mechanisms in driving the network's activity and dynamics, contributing to our understanding of developing neural circuits.

  17. Neuritin 1 promotes neuronal migration.

    Science.gov (United States)

    Zito, Arianna; Cartelli, Daniele; Cappelletti, Graziella; Cariboni, Anna; Andrews, William; Parnavelas, John; Poletti, Angelo; Galbiati, Mariarita

    2014-01-01

    Neuritin 1 (Nrn1 or cpg15-1) is an activity-dependent protein involved in synaptic plasticity during brain development, a process that relies upon neuronal migration. By analyzing Nrn1 expression, we found that it is highly expressed in a mouse model of migrating immortalized neurons (GN11 cells), but not in a mouse model of non-migrating neurons (GT1-7 cells). We thus hypothesized that Nrn1 might control neuronal migration. By using complementary assays, as Boyden's microchemotaxis, scratch-wounding and live cell imaging, we found that GN11 cell migration is enhanced when Nrn1 is overexpressed and decreased when Nrn1 is silenced. The effects of Nrn1 in promoting neuronal migration have been then confirmed ex vivo, on rat cortical interneurons, by Boyden chamber assays and focal electroporation of acute embryonic brain slices. Furthermore, we found that Nrn1 level modulation affects GN11 cell morphology. The process is also paralleled by Nrn1-induced α-tubulin post-translational modifications, a well-recognized marker of microtubule stability. Altogether, the data demonstrate a novel function of Nrn1 in promoting migration of neuronal cells and indicate that Nrn1 levels impact on microtubule stability. PMID:23212301

  18. Cooperative effects of neuronal ensembles.

    Science.gov (United States)

    Rose, G; Siebler, M

    1995-01-01

    Electrophysiological properties of neurons as the basic cellular elements of the central nervous system and their synaptic connections are well characterized down to a molecular level. However, the behavior of complex noisy networks formed by these constituents usually cannot simply be derived from the knowledge of its microscopic parameters. As a consequence, cooperative phenomena based on the interaction of neurons were postulated. This is a report on a study of global network spike activity as a function of synaptic interaction. We performed experiments in dissociated cultured hippocampal neurons and, for comparison, simulations of a mathematical model closely related to electrophysiology. Numeric analyses revealed that at a critical level of synaptic connectivity the firing behavior undergoes a phase transition. This cooperative effect depends crucially on the interaction of numerous cells and cannot be attributed to the spike threshold of individual neurons. In the experiment a drastic increase in the firing level was observed upon increase of synaptic efficacy by lowering of the extracellular magnesium concentration, which is compatible with our theoretical predictions. This "on-off" phenomenon demonstrates that even in small neuronal ensembles collective behavior can emerge which is not explained by the characteristics of single neurons. PMID:8542966

  19. Automated identification of neurons and their locations

    CERN Document Server

    Inglis, Andrew; Roe, Dan L; Stanley, H E; Rosene, Douglas L; Urbanc, Brigita

    2007-01-01

    Individual locations of many neuronal cell bodies (>10^4) are needed to enable statistically significant measurements of spatial organization within the brain such as nearest-neighbor and microcolumnarity measurements. In this paper, we introduce an Automated Neuron Recognition Algorithm (ANRA) which obtains the (x,y) location of individual neurons within digitized images of Nissl-stained, 30 micron thick, frozen sections of the cerebral cortex of the Rhesus monkey. Identification of neurons within such Nissl-stained sections is inherently difficult due to the variability in neuron staining, the overlap of neurons, the presence of partial or damaged neurons at tissue surfaces, and the presence of non-neuron objects, such as glial cells, blood vessels, and random artifacts. To overcome these challenges and identify neurons, ANRA applies a combination of image segmentation and machine learning. The steps involve active contour segmentation to find outlines of potential neuron cell bodies followed by artificial ...

  20. Isoler nu

    DEFF Research Database (Denmark)

    Andersen, N.E.; Ankerstjerne, P.; Jørgensen, B.;

    Omfattende vejledning, der angiver, hvordan energiforbruget i eksisterende huse kan nedbringes ved isolering, tætning og forbedring af varmeanlægget, og hvor meget det koster. Anvisningen indeholder detaljerede eksempler på efterisolering af ydervægge, tage, gulve og vinduer. Henvender sig til ej...

  1. Cognition and behavior in motor neuron disease

    OpenAIRE

    Raaphorst, J.

    2015-01-01

    Motor neuron disease (MND) is a devastating neurodegenerative disorder characterized by progressive motor neuron loss, leading to weakness of the muscles of arms and legs, bulbar and respiratory muscles. Depending on the involvement of the lower and the upper motor neuron, amyotrophic lateral sclerosis (ALS; both lower and upper motor neuron affected) and progressive muscular atrophy (PMA; only lower motor neuron affected) are recognized. There is no cure, despite numerous pharmaceutical tria...

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

    OpenAIRE

    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

    2015-01-01

    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,...

  3. Adhesion to carbon nanotube conductive scaffolds forces action-potential appearance in immature rat spinal neurons.

    Science.gov (United States)

    Fabbro, Alessandra; Sucapane, Antonietta; Toma, Francesca Maria; Calura, Enrica; Rizzetto, Lisa; Carrieri, Claudia; Roncaglia, Paola; Martinelli, Valentina; Scaini, Denis; Masten, Lara; Turco, Antonio; Gustincich, Stefano; Prato, Maurizio; Ballerini, Laura

    2013-01-01

    In the last decade, carbon nanotube growth substrates have been used to investigate neurons and neuronal networks formation in vitro when guided by artificial nano-scaled cues. Besides, nanotube-based interfaces are being developed, such as prosthesis for monitoring brain activity. We recently described how carbon nanotube substrates alter the electrophysiological and synaptic responses of hippocampal neurons in culture. This observation highlighted the exceptional ability of this material in interfering with nerve tissue growth. Here we test the hypothesis that carbon nanotube scaffolds promote the development of immature neurons isolated from the neonatal rat spinal cord, and maintained in vitro. To address this issue we performed electrophysiological studies associated to gene expression analysis. Our results indicate that spinal neurons plated on electro-conductive carbon nanotubes show a facilitated development. Spinal neurons anticipate the expression of functional markers of maturation, such as the generation of voltage dependent currents or action potentials. These changes are accompanied by a selective modulation of gene expression, involving neuronal and non-neuronal components. Our microarray experiments suggest that carbon nanotube platforms trigger reparative activities involving microglia, in the absence of reactive gliosis. Hence, future tissue scaffolds blended with conductive nanotubes may be exploited to promote cell differentiation and reparative pathways in neural regeneration strategies.

  4. Efficient and cost-effective generation of mature neurons from human induced pluripotent stem cells.

    Science.gov (United States)

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

    2014-12-01

    For years, our ability to study pathological changes in neurological diseases has been hampered by the lack of relevant models until the recent groundbreaking work from Yamanaka's group showing that it is feasible to generate induced pluripotent stem cells (iPSCs) from human somatic cells and to redirect the fate of these iPSCs into differentiated cells. In particular, much interest has focused on the ability to differentiate human iPSCs into neuronal progenitors and functional neurons for relevance to a large number of pathologies including mental retardation and behavioral or degenerative syndromes. Current differentiation protocols are time-consuming and generate limited amounts of cells, hindering use on a large scale. We describe a feeder-free method 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. Four days after induction, expression of markers of the neurectoderm lineage is detectable. Between 4 and 7 days, neuronal precursors can be expanded, frozen, and thawed without loss of proliferation and differentiation capacities or further differentiated. Terminal differentiation into the different subtypes of mature neurons found in the human brain were observed. At 6-35 days after induction, cells express typical voltage-gated and ionotrophic receptors for GABA, glycine, and acetylcholine. This specific and efficient single-step strategy in a chemically defined medium allows the production of mature neurons in 20-40 days with multiple applications, especially for modeling human pathologies.

  5. Isoflurane-induced neuronal apoptosis in developing hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    Hongliang Liu; Tijun Dai; Weitao Guo

    2013-01-01

    We hypothesized that the P2X7 receptor may be the target of isoflurane, so we investigated the roles of the P2X7 receptor and inositol triphosphate receptor in calcium overload and neuronal apoptosis induced by isoflurane in cultured embryonic rat hippocampal neurons. Results showed that isoflurane induced widespread neuronal apoptosis and significantly increased cytoplasmic Ca2+. Blockade of P2X7 receptors or removal of extracellular Ca2+ combined with blockade of inositol triphosphate receptors completely inhibited apoptosis or increase in cytoplasmic Ca2+. Removal of extracellular Ca2+ or blockade of inositol triphosphate receptor alone could partly inhibit these effects of isoflurane. Isoflurane could directly activate P2X7-gated channels and induce inward currents, but did not affect the expression of P2X7 receptor protein in neurons. These findings indicate that the mechanism by which isoflurane induced neuronal apoptosis in rat developing brain was mediated by intracellular calcium overload, which was caused by P2X7 receptor mediated calcium influx and inositol triphosphate receptor mediated calcium release.

  6. 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.

  7. Single unit activity of the suprachiasmatic nucleus and surrounding neurons during the wake-sleep cycle in mice.

    Science.gov (United States)

    Sakai, K

    2014-02-28

    The suprachiasmatic nucleus (SCN) of the mammalian hypothalamus contains a circadian clock for timing of diverse neuronal, endocrine, and behavioral rhythms, such as the cycle of sleep and wakefulness. Using extracellular single unit recordings, we have determined, for the first time, the discharge activity of individual SCN neurons during the complete wake-sleep cycle in non-anesthetized, head restrained mice. SCN neurons (n=79) were divided into three types according to their regular (type I; n=38) or irregular (type II; n=19) discharge activity throughout the wake-sleep cycle or their quiescent activity during waking and irregular discharge activity during sleep (type III; n=22). The type I and II neurons displayed a long-duration action potential, while the type III neurons displayed either a short-duration or long-duration action potential. The type I neurons discharged exclusively as single isolated spikes, whereas the type II and III neurons fired as single isolated spikes, clusters, or bursts. The type I and II neurons showed wake-active, wake/paradoxical (or rapid eye movement) sleep-active, or state-unrelated activity profiles and were, respectively, mainly located in the ventral or dorsal region of the SCN. In contrast, the type III neurons displayed sleep-active discharge profiles and were mainly located in the lateral region of the SCN. The majority of type I and II neurons tested showed an increase in discharge rate following application of light to the animal's eyes. Of the 289 extra-SCN neurons recorded, those displaying sleep-active discharge profiles were mainly located dorsal to the SCN, whereas those displaying wake-active discharge profiles were mainly located lateral or dorsolateral to the SCN. This study shows heterogeneity of mouse SCN and surrounding anterior hypothalamic neurons and suggests differences in their topographic organization and roles in mammalian circadian rhythms and the regulation of sleep and wakefulness.

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

    International Nuclear Information System (INIS)

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

  9. Eksistentiel Isolation

    OpenAIRE

    Matikainen, Oliver Albert; Andersen, Kian Alexander; Thorup, Johannes Hoff; Slotsager, Christian Knud; Jensen, Mette Ingersholm; Bachmann, Zenia Gruhl; Razga, Pauline Marie

    2015-01-01

    This study examines whether or not isolation can lead to personal growth. In order to answer this question we distinguish between loneliness and aloneness. We explain the theory of existential psychotherapist Irvin D. Yalom and on the basis of this examination, we analyze a conducted interview through the theory. Based on the theory, interview and analysis, we discuss the validity of Yalom’s theory. Considering the examination, the analysis and the distinction between the two types of isolati...

  10. Stochastic phase-change neurons

    Science.gov (United States)

    Tuma, Tomas; Pantazi, Angeliki; Le Gallo, Manuel; Sebastian, Abu; Eleftheriou, Evangelos

    2016-08-01

    Artificial neuromorphic systems based on populations of spiking neurons are an indispensable tool in understanding the human brain and in constructing neuromimetic computational systems. To reach areal and power efficiencies comparable to those seen in biological systems, electroionics-based and phase-change-based memristive devices have been explored as nanoscale counterparts of synapses. However, progress on scalable realizations of neurons has so far been limited. Here, we show that chalcogenide-based phase-change materials can be used to create an artificial neuron in which the membrane potential is represented by the phase configuration of the nanoscale phase-change device. By exploiting the physics of reversible amorphous-to-crystal phase transitions, we show that the temporal integration of postsynaptic potentials can be achieved on a nanosecond timescale. Moreover, we show that this is inherently stochastic because of the melt-quench-induced reconfiguration of the atomic structure occurring when the neuron is reset. We demonstrate the use of these phase-change neurons, and their populations, in the detection of temporal correlations in parallel data streams and in sub-Nyquist representation of high-bandwidth signals.

  11. Neuronal factors determining high intelligence.

    Science.gov (United States)

    Dicke, Ursula; Roth, Gerhard

    2016-01-01

    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. PMID:26598734

  12. Peripheral Sensory Neurons Expressing Melanopsin Respond to Light

    Science.gov (United States)

    Matynia, Anna; Nguyen, Eileen; Sun, Xiaoping; Blixt, Frank W.; Parikh, Sachin; Kessler, Jason; Pérez de Sevilla Müller, Luis; Habib, Samer; Kim, Paul; Wang, Zhe Z.; Rodriguez, Allen; Charles, Andrew; Nusinowitz, Steven; Edvinsson, Lars; Barnes, Steven; Brecha, Nicholas C.; Gorin, Michael B.

    2016-01-01

    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. PMID:27559310

  13. Peripheral Sensory Neurons Expressing Melanopsin Respond to Light

    Science.gov (United States)

    Matynia, Anna; Nguyen, Eileen; Sun, Xiaoping; Blixt, Frank W.; Parikh, Sachin; Kessler, Jason; Pérez de Sevilla Müller, Luis; Habib, Samer; Kim, Paul; Wang, Zhe Z.; Rodriguez, Allen; Charles, Andrew; Nusinowitz, Steven; Edvinsson, Lars; Barnes, Steven; Brecha, Nicholas C.; Gorin, Michael B.

    2016-01-01

    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.

  14. Peripheral Sensory Neurons Expressing Melanopsin Respond to Light.

    Science.gov (United States)

    Matynia, Anna; Nguyen, Eileen; Sun, Xiaoping; Blixt, Frank W; Parikh, Sachin; Kessler, Jason; Pérez de Sevilla Müller, Luis; Habib, Samer; Kim, Paul; Wang, Zhe Z; Rodriguez, Allen; Charles, Andrew; Nusinowitz, Steven; Edvinsson, Lars; Barnes, Steven; Brecha, Nicholas C; Gorin, Michael B

    2016-01-01

    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. PMID:27559310

  15. Magnetosensitive neurons mediate geomagnetic orientation in Caenorhabditis elegans

    Science.gov (United States)

    Vidal-Gadea, Andrés; Ward, Kristi; Beron, Celia; Ghorashian, Navid; Gokce, Sertan; Russell, Joshua; Truong, Nicholas; Parikh, Adhishri; Gadea, Otilia; Ben-Yakar, Adela; Pierce-Shimomura, Jonathan

    2015-01-01

    Many organisms spanning from bacteria to mammals orient to the earth's magnetic field. For a few animals, central neurons responsive to earth-strength magnetic fields have been identified; however, magnetosensory neurons have yet to be identified in any animal. We show that the nematode Caenorhabditis elegans orients to the earth's magnetic field during vertical burrowing migrations. Well-fed worms migrated up, while starved worms migrated down. Populations isolated from around the world, migrated at angles to the magnetic vector that would optimize vertical translation in their native soil, with northern- and southern-hemisphere worms displaying opposite migratory preferences. Magnetic orientation and vertical migrations required the TAX-4 cyclic nucleotide-gated ion channel in the AFD sensory neuron pair. Calcium imaging showed that these neurons respond to magnetic fields even without synaptic input. C. elegans may have adapted magnetic orientation to simplify their vertical burrowing migration by reducing the orientation task from three dimensions to one. DOI: http://dx.doi.org/10.7554/eLife.07493.001 PMID:26083711

  16. Correlations and Neuronal Population Information.

    Science.gov (United States)

    Kohn, Adam; Coen-Cagli, Ruben; Kanitscheider, Ingmar; Pouget, Alexandre

    2016-07-01

    Brain function involves the activity of neuronal populations. Much recent effort has been devoted to measuring the activity of neuronal populations in different parts of the brain under various experimental conditions. Population activity patterns contain rich structure, yet many studies have focused on measuring pairwise relationships between members of a larger population-termed noise correlations. Here we review recent progress in understanding how these correlations affect population information, how information should be quantified, and what mechanisms may give rise to correlations. As population coding theory has improved, it has made clear that some forms of correlation are more important for information than others. We argue that this is a critical lesson for those interested in neuronal population responses more generally: Descriptions of population responses should be motivated by and linked to well-specified function. Within this context, we offer suggestions of where current theoretical frameworks fall short.

  17. Chimera states in bursting neurons

    Science.gov (United States)

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

    2016-01-01

    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 the stability function in the incoherent (i.e., disorder), coherent, chimera, and multichimera states. Surprisingly, we find that chimera and multichimera states occur even using local nearest neighbor interaction in a network of identical bursting neurons alone. This is in contrast with the existence of chimera states in populations of nonlocally or globally coupled oscillators. A chemical synaptic coupling function is used which plays a key role in the emergence of chimera states in bursting neurons. The existence of chimera, multichimera, coherent, and disordered states is confirmed by means of the recently introduced statistical measures and mean phase velocity.

  18. The neuronal code for number.

    Science.gov (United States)

    Nieder, Andreas

    2016-06-01

    Humans and non-human primates share an elemental quantification system that resides in a dedicated neural network in the parietal and frontal lobes. In this cortical network, 'number neurons' encode the number of elements in a set, its cardinality or numerosity, irrespective of stimulus appearance across sensory motor systems, and from both spatial and temporal presentation arrays. After numbers have been extracted from sensory input, they need to be processed to support goal-directed behaviour. Studying number neurons provides insights into how information is maintained in working memory and transformed in tasks that require rule-based decisions. Beyond an understanding of how cardinal numbers are encoded, number processing provides a window into the neuronal mechanisms of high-level brain functions.

  19. 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].

  20. 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....

  1. Prospective Coding by Spiking Neurons.

    Directory of Open Access Journals (Sweden)

    Johanni Brea

    2016-06-01

    Full Text Available Animals learn to make predictions, such as associating the sound of a bell with upcoming feeding or predicting a movement that a motor command is eliciting. How predictions are realized on the neuronal level and what plasticity rule underlies their learning is not well understood. Here we propose a biologically plausible synaptic plasticity rule to learn predictions on a single neuron level on a timescale of seconds. The learning rule allows a spiking two-compartment neuron to match its current firing rate to its own expected future discounted firing rate. For instance, if an originally neutral event is repeatedly followed by an event that elevates the firing rate of a neuron, the originally neutral event will eventually also elevate the neuron's firing rate. The plasticity rule is a form of spike timing dependent plasticity in which a presynaptic spike followed by a postsynaptic spike leads to potentiation. Even if the plasticity window has a width of 20 milliseconds, associations on the time scale of seconds can be learned. We illustrate prospective coding with three examples: learning to predict a time varying input, learning to predict the next stimulus in a delayed paired-associate task and learning with a recurrent network to reproduce a temporally compressed version of a sequence. We discuss the potential role of the learning mechanism in classical trace conditioning. In the special case that the signal to be predicted encodes reward, the neuron learns to predict the discounted future reward and learning is closely related to the temporal difference learning algorithm TD(λ.

  2. Intracellular localization of the HCS2 gene products in identified snail neurons in vivo and in vitro.

    Science.gov (United States)

    Ivanova, J L; Leonova, O G; Popenko, V I; Ierusalimsky, V N; Korshunova, T A; Boguslavsky, D V; Malyshev, A Y; Balaban, P M; Belyavsky, A V

    2006-03-01

    1. The HCS2 (Helix command specific 2) gene expressed in giant command neurons for withdrawal behavior of the terrestrial snail Helix lucorum encodes a unique hybrid precursor protein that contains a Ca-binding (EF-hand motif) protein and four small peptides (CNP1-CNP4) with similar Tyr-Pro-Arg-X aminoacid sequence at the C terminus. Previous studies suggest that under conditions of increased intracellular Ca(2+) concentration the HCS2 peptide precursor may be cleaved, and small physiologically active peptides transported to the release sites. In the present paper, intracellular localization of putative peptide products of the HCS2-encoded precursor was studied immunocytochemically by means of light and electron microscopy. 2. Polyclonal antibodies against the CNP3 neuropeptide and a Ca-binding domain of the precursor protein were used for gold labeling of ultrathin sections of identified isolated neurons maintained in culture for several days, and in same identified neurons freshly isolated from the central nervous system. 3. In freshly isolated neurons, the gold particles were mainly localized over the cytoplasmic secretory granules, with the density of labeling for the CNP3 neuropeptide being two-fold higher than for the calcium-binding domain. In cultured neurons, both antibodies mostly labeled clusters of secretory granules in growth cones and neurites of the neuron. The density of labeling for cultured neurons was the same for both antibodies, and was two-fold higher than for the freshly isolated from the central nervous system neurons. 4. The immunogold particles were practically absent in the bodies of cultured neurons. 5. The data obtained conform to the suggestion that the HCS2 gene products are transported from the cell body to the regions of growth or release sites. PMID:16763780

  3. 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 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...

  4. Electrodiagnosis of motor neuron disease.

    Science.gov (United States)

    Duleep, Anuradha; Shefner, Jeremy

    2013-02-01

    Electrodiagnostic testing has proved useful in helping to establish the diagnosis of amyotrophic lateral sclerosis by eliminating possible disease mimics and by demonstrating abnormalities in body areas that are clinically unaffected. Electrodiagnosis begins with an understanding of the clinical features of the disease, because clinical correlation is essential. To improve the sensitivity of the electrophysiologic evaluation, the Awaji criteria have been proposed as a modification to the revised El Escorial criteria. Although techniques to evaluate corticomotor neuron abnormalities and to quantify lower motor neuron loss have been developed, they remain primarily research techniques and have not yet influenced clinical practice.

  5. Intrinsic oscillations of neocortex generated by layer 5 pyramidal neurons.

    Science.gov (United States)

    Silva, L R; Amitai, Y; Connors, B W

    1991-01-25

    Rhythmic activity in the neocortex varies with different behavioral and pathological states and in some cases may encode sensory information. However, the neural mechanisms of these oscillations are largely unknown. Many pyramidal neurons in layer 5 of the neocortex showed prolonged, 5- to 12-hertz rhythmic firing patterns at threshold. Rhythmic firing was due to intrinsic membrane properties, sodium conductances were essential for rhythmicity, and calcium-dependent conductances strongly modified rhythmicity. Isolated slices of neocortex generated epochs of 4- to 10-hertz synchronized activity when N-methyl-D-aspartate receptor-mediated channels were facilitated. Layer 5 was both necessary and sufficient to produce these synchronized oscillations. Thus, synaptic networks of intrinsically rhythmic neurons in layer 5 may generate or promote certain synchronized oscillations of the neocortex.

  6. [What mirror neurons have revealed: revisited].

    Science.gov (United States)

    Murata, Akira; Maeda, Kazutaka

    2014-06-01

    The first paper on mirror neurons was published in 1992. In the span of over two decades since then, much knowledge about the relationship between social cognitive function and the motor control system has been accumulated. Direct matching of visual actions and their corresponding motor representations is the most important functional property of mirror neuron. Many studies have emphasized intrinsic simulation as a core concept for mirror neurons. Mirror neurons are thought to play a role in social cognitive function. However, the function of mirror neurons in the macaque remains unclear, because such cognitive functions are limited or lacking in macaque monkeys. It is therefore important to discuss these neurons in the context of motor function. Rizzolatti and colleagues have stressed that the most important function of mirror neurons in macaques is recognition of actions performed by other individuals. I suggest that mirror neurons in the Macaque inferior pariental lobule might be correlated with body schema. In the parieto-premotor network, matching of corollary discharge and actual sensory feedback is an essential neuronal operation. Recently, neurons showing mirror properties were found in some cortical areas outside the mirror neuron system. The current work would revisit the outcomes of mirror neuron studies to discuss the function of mirror neurons in the monkey.

  7. Bursting neurons and ultrasound avoidance in crickets.

    Science.gov (United States)

    Marsat, Gary; Pollack, Gerald S

    2012-01-01

    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.

  8. 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.

  9. Genetic and pharmacological evidence for low-abundance TRPV3 expression in primary vagal afferent neurons.

    Science.gov (United States)

    Wu, Shaw-Wen; Lindberg, Jonathan E M; Peters, James H

    2016-05-01

    Primary vagal afferent neurons express a multitude of thermosensitive ion channels. Within this family of ion channels, the heat-sensitive capsaicin receptor (TRPV1) greatly influences vagal afferent signaling by determining the threshold for action-potential initiation at the peripheral endings, while controlling temperature-sensitive forms of glutamate release at central vagal terminals. Genetic deletion of TRPV1 does not completely eliminate these temperature-dependent effects, suggesting involvement of additional thermosensitive ion channels. The warm-sensitive, calcium-permeable, ion channel TRPV3 is commonly expressed with TRPV1; however, the extent to which TRPV3 is found in vagal afferent neurons is unknown. Here, we begin to characterize the genetic and functional expression of TRPV3 in vagal afferent neurons using molecular biology (RT-PCR and RT-quantitative PCR) in whole nodose and isolated neurons and fluorescent calcium imaging on primary cultures of nodose ganglia neurons. We confirmed low-level TRPV3 expression in vagal afferent neurons and observed direct activation with putative TRPV3 agonists eugenol, ethyl vanillin (EVA), and farnesyl pyrophosphate (FPP). Agonist activation stimulated neurons also containing TRPV1 and was blocked by ruthenium red. FPP sensitivity overlapped with EVA and eugenol but represented the smallest percentage of vagal afferent neurons, and it was the only agonist that did not stimulate neurons from TRPV3(-/-1) mice, suggesting FPP has the highest selectivity. Further, FPP was predictive of enhanced responses to capsaicin, EVA, and eugenol in rats. From our results, we conclude TRPV3 is expressed in a discrete subpopulation of vagal afferent neurons and may contribute to vagal afferent signaling either directly or in combination with TRPV1. PMID:26843581

  10. Localization of sympathetic postganglionic neurons innervating mesenteric artery and vein in rats.

    Science.gov (United States)

    Hsieh, N K; Liu, J C; Chen, H I

    2000-04-12

    Physiological and histochemical studies have demonstrated the control and innervation of sympathetic nerves to the artery and vein vessels of splanchnic circulation. In our laboratory, we first used the technique of retrograde transport of horseradish peroxidase to identify the origin of sympathetic neurons innervating the mesenteric vein. In this study, double fluorescence staining technique was used for a simultaneous localization of the sympathetic postganglionic neurons supplying the mesenteric artery and vein in rats. First-order branches of mesenteric artery (A) and vein (V) in the vicinity of ileo-cecal junction were isolated for application of fluorescent dyes (Fast Blue, FB and Diamidino Yellow, DY). The application of FB and DY on A and V was alternated in the next animal to minimize the difference in dye uptake. The animal was allowed to recover for 6-7 days assuring a complete uptake of FB and DY into the cytoplasm and nucleus, respectively. The number of FB, DY and double staining neurons in the prevertebral and paravertebral ganglia were counted under a fluorescent microscope after animal fixation and serial frozen section (30 microm) of the sympathetic ganglia. Our study revealed the following findings: (1) Distribution of the fluorescence-staining neurons in the sympathetic ganglia was as follows: right celiac ganglion (39%), superior mesenteric ganglion (30%), left celiac ganglion (26%), inferior mesenteric ganglion (1%) and paravertebral ganglia (4%). (2) Double staining neurons that dually innervate A and V amounted to 54% of total staining neurons. There were 41% neurons singly innervating A and 5% innervating V. (3) The ratio of neurons supplying the A and V ranged from 1.41 to 1.75 (average 1.61). (4) There was no distinct topographical distribution with respect to the neuron location innervating A and V. The distribution of neurons appeared in a scattering pattern.

  11. Widespread Differential Expression of Coding Region and 3' UTR Sequences in Neurons and Other Tissues.

    Science.gov (United States)

    Kocabas, Arif; Duarte, Terence; Kumar, Saranya; Hynes, Mary A

    2015-12-16

    Mature messenger RNAs (mRNAs) consist of coding sequence (CDS) and 5' and 3' UTRs, typically expected to show similar abundance within a given neuron. Examining mRNA from defined neurons, we unexpectedly show extremely common unbalanced expression of cognate 3' UTR and CDS sequences; many genes show high 3' UTR relative to CDS, others show high CDS to 3' UTR. In situ hybridization (19 of 19 genes) shows a broad range of 3' UTR-to-CDS expression ratios across neurons and tissues. Ratios may be spatially graded or change with developmental age but are consistent across animals. Further, for two genes examined, a 3' UTR-to-CDS ratio above a particular threshold in any given neuron correlated with reduced or undetectable protein expression. Our findings raise questions about the role of isolated 3' UTR sequences in regulation of protein expression and highlight the importance of separately examining 3' UTR and CDS sequences in gene expression analyses.

  12. Neurons excitability changes in rat medial vestibular nucleus following vestibular neurectomy

    Institute of Scientific and Technical Information of China (English)

    金麟毅

    2008-01-01

    Intrinsic excitabilities of acutely isolated medial vestibular nucleus (MVN) neurons of rats with normal labyrinth and with undergoingvestibular compensation from 30 min to 24 h after unilateral vestibular deafferentation (UVD) were compared. In control rats, proportions of type A andB cells were 30 and 70%, respectively, however, the proportion of type A cells increased following UVD. Bursting discharge and irregular firingpatterns were recorded from 2 to 12 h post UVD. The spontaneous discharge rate of neurons in the ipsilesional MVN increased significantly at 2 hpost-UVD and remained high until 12 h post-UVD in both type A and type B cells. Mter-hyperpolarization (AHP) of the MVN neurons decreasedsignificantly from 2 h post-UVD in both types of cells. These results suggest that the early stage of vestibular compensation after peripheralneurectomy is associated with an increase in intrinsic excitability due to reduction of AHP in MVN neurons.

  13. [The ontogeny of the mirror neuron system].

    Science.gov (United States)

    Myowa-Yamakoshi, Masako

    2014-06-01

    Abstract Humans utilize the mirror neuron system to understand and predict others' actions. However, the ontogeny of the mirror neuron system remains unknown. Whether mirror neuron function is an innate trait or whether mirror neurons acquire their sensorimotor matching properties ontogenetically remains to be clarified. In this paper, I review the ontogenetic theory of the mirror neuron system. I then discuss the functioning of the mirror neuron system in the context of social cognitive abilities, which are unique to humans. Recently, some researchers argue that it is too early to interpret the function of mirror neurons as an understanding of the underlying psychological states of others. They imply that such functioning would require inferential cognitive processes that are known to involve areas outside the mirror neuron system. Filling in this missing link may be the key to elucidating the unique ability of humans to understand others' actions.

  14. Performance of a Single Quantum Neuron

    Institute of Scientific and Technical Information of China (English)

    LIFei; ZHAOShengmei; ZHENGBaoyu

    2005-01-01

    Quantum neural network (QNN) is a promising area in the field of quantum computing and quantum information processing. A novel model for quantum neuron is described, a quantum learning algorithm is proposed and its convergence property is investigated. It has been shown, Quantum neuron (QN) has the same convergence property as Conventional neuron (CN) but can attain faster training than Conventional neuron. The computational power of the quantum neuron is also explored.Numerical and graphical results show that this single quantum neuron can implement the Walsh-Hadamard transformation, perform the XOR function unrealizable with a classical neuron and can eliminate the necessity of building a network of neurons to obtain nonlinear mapping.

  15. 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 acquire

  16. The neuronal infrastructure of speaking

    NARCIS (Netherlands)

    Menenti, L.M.E.; Segaert, K.M.; Hagoort, P.

    2012-01-01

    Models of speaking distinguish producing meaning, words and syntax as three different linguistic components of speaking. Nevertheless, little is known about the brain’s integrated neuronal infrastructure for speech production. We investigated semantic, lexical and syntactic aspects of speaking using

  17. 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.

  18. Cellular pathways of energy metabolism in the brain: is glucose used by neurons or astrocytes?

    Science.gov (United States)

    Nehlig, Astrid; Coles, Jonathan A

    2007-09-01

    Most techniques presently available to measure cerebral activity in humans and animals, i.e. positron emission tomography (PET), autoradiography, and functional magnetic resonance imaging, do not record the activity of neurons directly. Furthermore, they do not allow the investigator to discriminate which cell type is using glucose, the predominant fuel provided to the brain by the blood. Here, we review the experimental approaches aimed at determining the percentage of glucose that is taken up by neurons and by astrocytes. This review is integrated in an overview of the current concepts on compartmentation and substrate trafficking between astrocytes and neurons. In the brain in vivo, about half of the glucose leaving the capillaries crosses the extracellular space and directly enters neurons. The other half is taken up by astrocytes. Calculations suggest that neurons consume more energy than do astrocytes, implying that astrocytes transfer an intermediate substrate to neurons. Experimental approaches in vitro on the honeybee drone retina and on the isolated vagus nerve also point to a continuous transfer of intermediate metabolites from glial cells to neurons in these tissues. Solid direct evidence of such transfer in the mammalian brain in vivo is still lacking. PET using [(18)F]fluorodeoxyglucose reflects in part glucose uptake by astrocytes but does not indicate to which step the glucose taken up is metabolized within this cell type. Finally, the sequence of metabolic changes occurring during a transient increase of electrical activity in specific regions of the brain remains to be clarified. PMID:17659529

  19. Nicotine modulates GABAergic transmission to dopaminergic neurons in substantia nigra pars compacta

    Institute of Scientific and Technical Information of China (English)

    Cheng XIAO; Ke-chun YANG; Chun-yi ZHOU; Guo-zhang JIN; Jie WU; Jiang-hong YE

    2009-01-01

    Aim: Dopaminergic neurons in the substantia nigra pars compacta (SNc) play important roles in motor control and drug addiction. As the major afferent, GABAergic innervation controls the activity of SNc dopaminergic neurons. Although it is clear that nicotine modulates SNc dopaminergic neurons by activating subtypes of somatodendritic nicotinic acetylcholine receptors (nAChRs), the detailed mechanisms of this activation remain to be addressed.Methods: In the current study, we recorded GABAA receptor-mediated spontaneous inhibitory postsynaptic currents (sIP-SCs) from dissociated SNc dopaminergic neurons that were obtained using an enzyme-free procedure. These neurons preserved some functional terminals after isolation, including those that release GABA.Results: We found that both extra- and intra-cellular calcium modulates sIPSCs in these neurons. Furthermore, both nicotine and endogenous acetylcholine enhance the frequency of sIPSCs. Moreover, endogenous acetylcholine tonically facilitates sIPSC frequency, primarily by activating the a4B2* nAChRs on the GABAergic terminals.Conclusion: Nicotine facilitates GABA release onto SNc dopaminergic neurons mainly via the activation of presynaptic a4B2* nAChRs.

  20. Responses of medullary reticular formation neurons to input from the male genitalia.

    Science.gov (United States)

    Hubscher, C H; Johnson, R D

    1996-10-01

    1. The medullary reticular formation (MRF) is known to be involved in the modulation of certain reproductive behaviors. Ejaculation in the male, disrupted after spinal transection, may depend on a spinal-bulbo-spinal connection. To determine whether single neurons in the MRF receive sensory input from the male genitalia, the present study was undertaken using electrophysiological techniques. 2. The MRF of 14 urethan-anesthetized mature male rats was searched for single neurons responsive to bilateral electrical stimulation of the dorsal nerve of the penis (DNP). In addition, each DNP-responsive neuron was tested for responsiveness to bilateral electrical stimulation of the pelvic nerve (PN) and to mechanical stimulation (gentle touch, pressure, pinch) of the external genitalia, anus, urethra, and skin over most regions of the body. 3. A total of 165 single neurons responsive to bilateral electrical stimulation of the DNP were isolated and characterized throughout the MRF. All neurons responded to both ipsilateral and contralateral DNP stimulation. The majority of responses were excitatory, and most neurons had no background activity. Some neurons required wind-up with bilateral electrical stimulation of the DNP to respond. 4. About half of the neurons were located in the nucleus reticularis gigantocellularis (Gi); the remainder were located in surrounding (dorsal, ventral, lateral) regions of the MRF. Variations in response properties were found among neurons located in different MRF regions. 5. Eighty-eight DNP-responsive neurons were additionally responsive to bilateral electrical stimulation of the PN. None of the responses to bilateral PN were stronger than those for bilateral DNP and many (48%) were weaker. 6. Of the 165 DNP-responsive neurons, all were responsive to pressure/pinching of the penis; 16% responded to gentle stroking of the glans. Most of these neurons were additionally responsive (bilaterally) to pinching more than one (often all) of the

  1. Mechanisms of neuronal chloride accumulation in intact mouse olfactory epithelium.

    Science.gov (United States)

    Nickell, William T; Kleene, Nancy K; Kleene, Steven J

    2007-09-15

    When olfactory receptor neurons respond to odours, a depolarizing Cl(-) efflux is a substantial part of the response. This requires that the resting neuron accumulate Cl(-) against an electrochemical gradient. In isolated olfactory receptor neurons, the Na(+)-K(+)-2Cl(-) cotransporter NKCC1 is essential for Cl(-) accumulation. However, in intact epithelium, a robust electrical olfactory response persists in mice lacking NKCC1. This response is largely due to a neuronal Cl(-) efflux. It thus appears that NKCC1 is an important part of a more complex system of Cl(-) accumulation. To identify the remaining transport proteins, we first screened by RT-PCR for 21 Cl(-) transporters in mouse nasal tissue containing olfactory mucosa. For most of the Cl(-) transporters, the presence of mRNA was demonstrated. We also investigated the effects of pharmacological block or genetic ablation of Cl(-) transporters on the olfactory field potential, the electroolfactogram (EOG). Mice lacking the common Cl(-)/HCO(3)(-) exchanger AE2 had normal EOGs. Block of NKCC cotransport with bumetanide reduced the EOG in epithelia from wild-type mice but had no effect in mice lacking NKCC1. Hydrochlorothiazide, a blocker of the Na(+)-Cl(-) cotransporter, had only a small effect. DIDS, a blocker of some KCC cotransporters and Cl(-)/HCO(3)(-) exchangers, reduced the EOG in epithelia from both wild-type and NKCC1 knockout mice. A combination of bumetanide and DIDS decreased the response more than either drug alone. However, no combination of drugs completely abolished the Cl(-) component of the response. These results support the involvement of both NKCC1 and one or more DIDS-sensitive transporters in Cl(-) accumulation in olfactory receptor neurons.

  2. Automated identification of neurons and their locations

    OpenAIRE

    Inglis, A.; Cruz, L; Roe, D L; H. E. Stanley; Rosene, D.L.; Urbanc, B.

    2008-01-01

    Individual locations of many neuronal cell bodies (>10^4) are needed to enable statistically significant measurements of spatial organization within the brain such as nearest-neighbor and microcolumnarity measurements. In this paper, we introduce an Automated Neuron Recognition Algorithm (ANRA) which obtains the (x,y) location of individual neurons within digitized images of Nissl-stained, 30 micron thick, frozen sections of the cerebral cortex of the Rhesus monkey. Identification of neurons ...

  3. Signal Propagation in Drosophila Central Neurons

    OpenAIRE

    Gouwens, Nathan W.; Wilson, Rachel I.

    2009-01-01

    Drosophila is an important model organism for investigating neural development, neural morphology, neurophysiology, and neural correlates of behaviors. However, almost nothing is known about how electrical signals propagate in Drosophila neurons. Here we address these issues in antennal lobe projection neurons (PNs), one of the most well-studied classes of Drosophila neurons. We use morphological and electrophysiological data to deduce the passive membrane properties of these neurons and to b...

  4. Artificial Neurons with Arbitrarily Complex Internal Structures

    OpenAIRE

    Kohring, G. A.

    2001-01-01

    Artificial neurons with arbitrarily complex internal structure are introduced. The neurons can be described in terms of a set of internal variables, a set activation functions which describe the time evolution of these variables and a set of characteristic functions which control how the neurons interact with one another. The information capacity of attractor networks composed of these generalized neurons is shown to reach the maximum allowed bound. A simple example taken from the domain of p...

  5. Characterization of cutaneous and articular sensory neurons

    OpenAIRE

    da Silva Serra, I.; Husson, Z.; Bartlett, J.D.; Smith, E.S.J.

    2016-01-01

    Background A wide range of stimuli can activate sensory neurons and neurons innervating specific tissues often have distinct properties. Here, we used retrograde tracing to identify sensory neurons innervating the hind paw skin (cutaneous) and ankle/knee joints (articular), and combined immunohistochemistry and electrophysiology analysis to determine the neurochemical phenotype of cutaneous and articular neurons, as well as their electrical and chemical excitability. Results Immunohistoche...

  6. Convergent cortical innervation of striatal projection neurons

    OpenAIRE

    Kress, Geraldine J.; Yamawaki, Naoki; Wokosin, David L.; Wickersham, Ian R.; Gordon M. G Shepherd; Surmeier, D. James

    2013-01-01

    Anatomical studies have led to the assertion that intratelencephalic (IT) and pyramidal tract (PT) cortical neurons innervate different striatal projection neurons. To test this hypothesis, the responses of mouse striatal neurons to optogenetic activation of IT and PT axons were measured. Contrary to expectation, direct and indirect pathway striatal spiny projection neurons (SPNs) responded to both IT and PT activation, arguing that these cortical networks innervate both striatal projection n...

  7. A Method for Neuronal Source Identification

    OpenAIRE

    Lee, Chang Won; Szymanska, Agnieszka A.; Wu, Shun Chi; Swindlehurst, A. Lee; Nenadic, Zoran

    2013-01-01

    Multi-sensor microelectrodes for extracellular action potential recording have significantly improved the quality of in vivo recorded neuronal signals. These microelectrodes have also been instrumental in the localization of neuronal signal sources. However, existing neuron localization methods have been mostly utilized in vivo, where the true neuron location remains unknown. Therefore, these methods could not be experimentally validated. This article presents experimental validation of a met...

  8. Adaptation to visual stimulation modifies the burst firing property of V1 neurons%Adaptation to visual stimulation modifies the burst firing property of V1neurons

    Institute of Scientific and Technical Information of China (English)

    Rui-Long LIU; Ke WANG; Jian-Jun MENG; Tian-Miao HUA; Zhen LIANG; Min-Min XI

    2013-01-01

    The mean firing rate of visual cortical neurons is reduced after prolonged visual stimulation,but the underlying process by which this occurs as well as the biological significance of this phenomenon remains unknown.Computational neuroscience studies indicate that high-frequency bursts in stimulus-driven responses can be transmitted across synapses more reliably than isolated spikes,and thus may carry accurate stimulus-related information.Our research examined whether or not adaptation affects the burst firing property of visual cortical neurons by examining changes in the burst firing changes of V1 neurons during adaptation to the preferred visual stimulus.The results show that adaptation to prolonged visual stimulation significantly decreased burst frequency (bursts/s) and burst length (spikes/burst),but increased burst duration and the interspike interval within bursts.These results suggest that the adaptation of V1 neurons to visual stimulation may result in a decrease of feedforward response gain but an increase of functional activities from lateral and/or feedback connections,which could lead to a reduction in the effectiveness of adapted neurons in transmitting information to its driven neurons.

  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. Studies Gain Insight into Neuronal Polarity

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ A typical matured nerve cell (or neuron) has one axon and multiple dendrites. It receives information at the dendrites and sending signals to other neurons via the axon. Although scientists have discovered that this axon-dendrite polarity is a cardinal feature of neuronal morphology essential for information flow, they are still in the dark about the cause of this polarization.

  11. Information processing at single neuron level

    OpenAIRE

    Vidybida, A. K.

    2007-01-01

    Based on numerical simulation of Hodgkin and Huxley type neuron stimulated from many synaptic inputs, an abstract concept of signal processing in individual neuron is proposed. In the concept proposed, neuron performs binding of synaptic inputs into a single output event, based on the degree of temporal coherence between the inputs. Inhibition serves as controlling factor of this type of binding.

  12. NEURONAL PHOSPHOPROTEINS: PHYSIOLOGICAL AND CLINICAL IMPLICATIONS

    Science.gov (United States)

    The presence of a great variety of neuron-specific phosproteins in nervous tissue supports the view that protein phosphorylation plays many roles in neuronal function. The physiological significance of several of these phosphoproteins has already been established. Some neuronal p...

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

    Institute of Scientific and Technical Information of China (English)

    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/cm2) is sufficient to induce the maximal spiking coherence and the best sub-threshold signal encoding.

  14. P2Y1 receptors expressed by C1 neurons determine peripheral chemoreceptor modulation of breathing, sympathetic activity, and blood pressure.

    Science.gov (United States)

    Wenker, Ian C; Sobrinho, Cleyton R; Takakura, Ana C; Mulkey, Daniel K; Moreira, Thiago S

    2013-08-01

    Catecholaminergic C1 cells of the rostral ventrolateral medulla (RVLM) are key determinants of the sympathoexcitatory response to peripheral chemoreceptor activation. Overactivation of this reflex is thought to contribute to increased sympathetic activity and hypertension; however, molecular mechanisms linking peripheral chemoreceptor drive to hypertension remain poorly understood. We have recently determined that activation of P2Y1 receptors in the RVLM mimicked effects of peripheral chemoreceptor activation. Therefore, we hypothesize that P2Y1 receptors regulate peripheral chemoreceptor drive in this region. Here, we determine whether P2Y1 receptors are expressed by C1 neurons in the RVLM and contribute to peripheral chemoreceptor control of breathing, sympathetic activity, and blood pressure. We found that injection of a specific P2Y1 receptor agonist (MRS2365) into the RVLM of anesthetized adult rats increased phrenic nerve activity (≈55%), sympathetic nerve activity (38 ± 6%), and blood pressure (23 ± 1 mm Hg), whereas application of a specific P2Y1 receptor antagonist (MRS2179) decreased peripheral chemoreceptor-mediated activation of phrenic nerve activity, sympathetic nerve activity, and blood pressure. To establish that P2Y1 receptors are expressed by C1 cells, we determine in the brain slice preparation using cell-attached recording techniques that cells responsive to MRS2365 are immunoreactive for tyrosine hydroxylase (a marker of C1 cells), and we determine in vivo that C1-lesioned animals do not respond to RVLM injection of MRS2365. These data identify P2Y1 receptors as key determinants of peripheral chemoreceptor regulation of breathing, sympathetic nerve activity, and blood pressure.

  15. 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.

  16. Serotonin released from amacrine neurons is scavenged and degraded in bipolar neurons in the retina

    OpenAIRE

    Ghai, Kanika; Zelinka, Christopher; Fischer, Andy J.

    2009-01-01

    The neurotransmitter serotonin is synthesized in the retina by one type of amacrine neuron but accumulates in bipolar neurons in many vertebrates. The mechanisms, functions and purpose underlying of serotonin in bipolar cells remain unknown. Here, we demonstrate that exogenous serotonin transiently accumulates in a distinct type of bipolar neuron. KCl-mediated depolarization causes the depletion of serotonin from amacrine neurons and, subsequently, serotonin is taken-up by bipolar neurons. Th...

  17. Neural Networks for Template Matching: Application to Real-Time Classification of the Action Potentials of Real Neurons

    OpenAIRE

    Wong, Yiu-fai; Banik, Jashojiban; Bower, James M.

    1988-01-01

    Much experimental study of real neural networks relies on the proper classification of extracellulary sampled neural signals (i .e. action potentials) recorded from the brains of experimental animals. In most neurophysiology laboratories this classification task is simplified by limiting investigations to single, electrically well-isolated neurons recorded one at a time. However, for those interested in sampling the activities of many single neurons simultaneously, waveform cla...

  18. Isolation and Cannulation of Cerebral Parenchymal Arterioles.

    Science.gov (United States)

    Pires, Paulo W; Dabertrand, Fabrice; Earley, Scott

    2016-01-01

    Intracerebral parenchymal arterioles (PAs), which include parenchymal arterioles, penetrating arterioles and pre-capillary arterioles, are high resistance blood vessels branching out from pial arteries and arterioles and diving into the brain parenchyma. Individual PA perfuse a discrete cylindrical territory of the parenchyma and the neurons contained within. These arterioles are a central player in the regulation of cerebral blood flow both globally (cerebrovascular autoregulation) and locally (functional hyperemia). PAs are part of the neurovascular unit, a structure that matches regional blood flow to metabolic activity within the brain and also includes neurons, interneurons, and astrocytes. Perfusion through PAs is directly linked to the activity of neurons in that particular territory and increases in neuronal metabolism lead to an augmentation in local perfusion caused by dilation of the feed PA. Regulation of PAs differs from that of better-characterized pial arteries. Pressure-induced vasoconstriction is greater in PAs and vasodilatory mechanisms vary. In addition, PAs do not receive extrinsic innervation from perivascular nerves - innervation is intrinsic and indirect in nature through contact with astrocytic endfeet. Thus, data regarding contractile regulation accumulated by studies using pial arteries does not directly translate to understanding PA function. Further, it remains undetermined how pathological states, such as hypertension and diabetes, affect PA structure and reactivity. This knowledge gap is in part a consequence of the technical difficulties pertaining to PA isolation and cannulation. In this manuscript we present a protocol for isolation and cannulation of rodent PAs. Further, we show examples of experiments that can be performed with these arterioles, including agonist-induced constriction and myogenic reactivity. Although the focus of this manuscript is on PA cannulation and pressure myography, isolated PAs can also be used for

  19. What we know currently about mirror neurons.

    Science.gov (United States)

    Kilner, J M; Lemon, R N

    2013-12-01

    Mirror neurons were discovered over twenty years ago in the ventral premotor region F5 of the macaque monkey. Since their discovery much has been written about these neurons, both in the scientific literature and in the popular press. They have been proposed to be the neuronal substrate underlying a vast array of different functions. Indeed so much has been written about mirror neurons that last year they were referred to, rightly or wrongly, as "The most hyped concept in neuroscience". Here we try to cut through some of this hyperbole and review what is currently known (and not known) about mirror neurons.

  20. Spatially selective photoconductive stimulation of live neurons

    Directory of Open Access Journals (Sweden)

    Jacob eCampbell

    2014-05-01

    Full Text Available Synaptic activity is intimately linked to neuronal structure and function. Stimulation of live cultured primary neurons, coupled with fluorescent indicator imaging, is a powerful technique to assess the impact of synaptic activity on neuronal protein trafficking and function. Current technology for neuronal stimulation in culture include chemical techniques or microelectrode or optogenetic based techniques. While technically powerful, chemical stimulation has limited spatial resolution and microelectrode and optogenetic techniques require specialized equipment and expertise. We report an optimized and improved technique for laser based photoconductive stimulation of live neurons using an inverted confocal microscope that overcomes these limitations. The advantages of this approach include its non-invasive nature and adaptability to temporal and spatial manipulation. We demonstrate that the technique can be manipulated to achieve spatially selective stimulation of live neurons. Coupled with live imaging of fluorescent indicators, this simple and efficient technique should allow for significant advances in neuronal cell biology.

  1. Neuronal avalanches and brain plasticity

    Science.gov (United States)

    de Arcangelis, L.; Herrmann, H. J.; Perrone-Capano, C.

    2007-12-01

    Networks of living neurons exhibit an avalanche mode of activity, experimentally found in organotypic cultures. Moreover, experimental studies of morphology indicate that neurons develop a network of small-world-like connections, with the possibility of a very high connectivity degree. Here we discuss a recent model based on self-organized criticality, which consists of an electrical network with threshold firing and activity-dependent synapse strengths. The model is implemented on regular and small world lattices and on a scale-free network, the Apollonian network. The system exhibits an avalanche activity with a power law distribution of sizes and durations. The analysis of the power spectra of the electrical signal reproduces very robustly the power law behaviour with the exponent 0.8, experimentally measured in electroencephalogram (EEG) spectra. The exponents are found to be quite stable with respect to initial configurations and strength of plastic remodelling, indicating that universality holds for a wide class of neural network models.

  2. Neuronal autophagy in cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Feng Xu; Jin-Hua Gu; Zheng-Hong Qin

    2012-01-01

    Autophagy has evolved as a conserved process for the bulk degradation and recycling of cytosolic components,such as long-lived proteins and organelles.In neurons,autophagy is important for homeostasis and protein quality control and is maintained at relatively low levels under normal conditions,while it is upregulated in response to pathophysiological conditions,such as cerebral ischemic injury.However,the role of autophagy is more complex.It depends on age or brain maturity,region,severity of insult,and the stage of ischemia.Whether autophagy plays a beneficial or a detrimental role in cerebral ischemia depends on various pathological conditions.In this review,we elucidate the role of neuronal autophagy in cerebral ischemia.

  3. Differentiation of fetal pancreatic stem cells into neuron-like and islet-like cells in vitro ★

    OpenAIRE

    Hua, Xiufeng; Wang, Yanwei; Lian, Peiwen; Zhang, Shouxin; Li, Jianyuan; Wang, Haiyan; Chen, Shulin; Gao, Wei

    2012-01-01

    Pancreatic stem cells were isolated and cultured from aborted human fetal pancreases of gestational age 14–20 weeks. They were seeded at a density of 1 × 104 in serum-free media for differentiation into neuron-like cells, expressing β-tubulin III and glial fibrillary acidic protein. These neuron-like cells displayed a synapse-like morphology and appeared to form a neuronal network. Pancreatic stem cells were also seeded at a density of 1 × 105 for differentiation into islet-like cells, expres...

  4. 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.

  5. Neuronal responses to physiological stress.

    Science.gov (United States)

    Kagias, Konstantinos; Nehammer, Camilla; Pocock, Roger

    2012-01-01

    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 chemistry during normal development. For example, conditions such as intrinsic hypoxia and oxidative stress, due to an increase in tissue mass, have to be confronted by developing embryos in order to complete their development. Finally, organisms face the challenge of stochastic accumulation of molecular 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 include changes in the expression of molecules such as transcription factors and microRNAs that regulate stress resistance and adaptation. Moreover, both intrinsic and extrinsic stresses have a tremendous impact on neuronal development and maintenance with implications in many diseases. Here, we review the responses of neurons to various physiological stressors at the molecular and cellular level. PMID:23112806

  6. Neuronal responses to physiological stress

    Directory of Open Access Journals (Sweden)

    Konstantinos eKagias

    2012-10-01

    Full Text Available Physiological stress can be defined as any external or internal condition that challenges the homeostasis of a cell or an organism. Physiological stress 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 chemistry during normal development. For example, conditions such as intrinsic hypoxia and oxidative stress, which result from an increase in tissue mass, have to be confronted by developing embryos in order to complete their development. Finally, organisms face the challenge of stochastic accumulation of molecular 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 include changes in the expression of molecules such as transcription factors and microRNAs that regulate stress resistance and adaptation. Moreover, both intrinsic and extrinsic stresses have a tremendous impact on neuronal development and maintenance with implications in many diseases. Here, we review the responses of neurons to various physiological stressors at the molecular and cellular level.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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. PMID:27373836

  9. 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.

  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). PMID:21347547

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  13. Multiple isolated cutaneous plexiform schwannomas

    Directory of Open Access Journals (Sweden)

    Enas A. S. Attia

    2011-01-01

    Full Text Available Plexiform schwannoma is a rare neurogenic tumor, arising from skin and subcutaneous tissue. The presence of multiple schwannomas suggests a possible association with neurofibromatosis type 2 (NF2. A 50-year old male patient presented with multiple papulo-nodular cutaneous lesions on both arms and forearms. Histopathological examination revealed a dermal multinodular pattern of well-circumscribed masses of closely packed cells, with peripheral myxoid tissue, well-encapsulated in a thin collagenous capsule. S-100 immunohistochemical staining was diffusely and strongly positive. Neuron-specific enolase was positive, confirming a neural tissue tumor. An audiogram and Magnetic Resonance Imaging (MRI of cerebro-pontine angle showed no detected abnormality, excluding acoustic neuroma. Thus, we present a case of multiple bilateral isolated cutaneous plexiform schwannomas, not associated with NF2. Multiple plexiform schwannomas is a very rare entity, distinct from neurofibromatosis (NF, and being confined to the dermis is even more rarely reported.

  14. Chronic excitotoxin-induced axon degeneration in a compartmented neuronal culture model

    Directory of Open Access Journals (Sweden)

    Katherine A Hosie

    2012-02-01

    Full Text Available Glutamate excitotoxicity is a major pathogenic process implicated in many neurodegenerative conditions, including AD (Alzheimer's disease and following traumatic brain injury. Occurring predominantly from over-stimulation of ionotropic glutamate receptors located along dendrites, excitotoxic axonal degeneration may also occur in white matter tracts. Recent identification of axonal glutamate receptor subunits within axonal nanocomplexes raises the possibility of direct excitotoxic effects on axons. Individual neuronal responses to excitotoxicity are highly dependent on the complement of glutamate receptors expressed by the cell, and the localization of the functional receptors. To enable isolation of distal axons and targeted excitotoxicity, murine cortical neuron cultures were prepared in compartmented microfluidic devices, such that distal axons were isolated from neuronal cell bodies. Within the compartmented culture system, cortical neurons developed to relative maturity at 11 DIV (days in vitro as demonstrated by the formation of dendritic spines and clustering of the presynaptic protein synaptophysin. The isolated distal axons retained growth cone structures in the absence of synaptic targets, and expressed glutamate receptor subunits. Glutamate treatment (100 μM to the cell body chamber resulted in widespread degeneration within this chamber and degeneration of distal axons in the other chamber. Glutamate application to the distal axon chamber triggered a lesser degree of axonal degeneration without degenerative changes in the untreated somal chamber. These data indicate that in addition to current mechanisms of indirect axonal excitotoxicity, the distal axon may be a primary target for excitotoxicity in neurodegenerative conditions.

  15. tPA promotes cortical neuron survival via mTOR-dependent mechanisms.

    Science.gov (United States)

    Grummisch, Julia A; Jadavji, Nafisa M; Smith, Patrice D

    2016-07-01

    Tissue plasminogen activator (tPA) is a thrombolytic agent commonly used in the treatment of ischemic stroke. While the thrombolytic effects of tPA have been well established, the impact of this blood-brain barrier (BBB) crossing drug on neurons is not known. Given the widespread use of tPA in the clinical setting and the strict therapeutic window established for effective use of the drug, we examined the molecular mechanisms mediating the impact of tPA on postnatal cortical neurons isolated from the mouse brain. Dissociated postnatal primary cortical neurons were treated with tPA and the effects on neuron survival were evaluated. Pharmacological inhibitors of several signaling pathways previously implicated in neuroprotection (mTOR, JAK/STAT, MAPK and PKA-dependent mechanisms) were used to pinpoint the mechanistic effectors of tPA on neuron survival in vitro. We report here that tPA treatment results in a time-dependent neuroprotective effect on postnatal cortical neurons that relies predominantly on Janus kinase (JAK) and mammalian target of rapamycin (mTOR) signaling mechanisms. Taken together, these data suggest that tPA promotes neuroprotection in a temporally-regulated manner and that both JAK and mTOR signaling effectors are critical mediators of this neuroprotective effect. The results suggest the possibility of targeting these defined mechanisms to potentially expand the therapeutic window for tPA. PMID:26995507

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Rapid and efficient generation of neurons from human pluripotent stem cells in a multititre plate format.

    Science.gov (United States)

    Zhang, Miao; Schöler, Hans R; Greber, Boris

    2013-01-01

    Existing protocols for the generation of neurons from human pluripotent stem cells (hPSCs) are often tedious in that they are multistep procedures involving the isolation and expansion of neural precursor cells, prior to terminal differentiation. In comparison to these time-consuming approaches, we have recently found that combined inhibition of three signaling pathways, TGFβ/SMAD2, BMP/SMAD1, and FGF/ERK, promotes rapid induction of neuroectoderm from hPSCs, followed by immediate differentiation into functional neurons. Here, we have adapted our procedure to a novel multititre plate format, to further enhance its reproducibility and to make it compatible with mid-throughput applications. It comprises four days of neuroectoderm formation in floating spheres (embryoid bodies), followed by a further four days of differentiation into neurons under adherent conditions. Most cells obtained with this protocol appear to be bipolar sensory neurons. Moreover, the procedure is highly efficient, does not require particular expert skills, and is based on a simple chemically defined medium with cost-efficient small molecules. Due to these features, the procedure may serve as a useful platform for further functional investigation as well as for cell-based screening approaches requiring human sensory neurons or neurons of any type. PMID:23486189

  18. Preliminary evidence for human globus pallidus pars interna neurons signaling reward and sensory stimuli.

    Science.gov (United States)

    Howell, Nicholas A; Prescott, Ian A; Lozano, Andres M; Hodaie, Mojgan; Voon, Valerie; Hutchison, William D

    2016-07-22

    The globus pallidus pars interna (GPi) is a component of the basal ganglia, a network of subcortical nuclei that process motor, associative, and limbic information. While non-human primate studies have suggested a role for the GPi in non-motor functions, there have been no single-unit studies of non-motor electrophysiological behavior of human GPi neurons. We therefore sought to extend these findings by collecting single-unit recordings from awake patients during functional stereotactic neurosurgery targeting the GPi for deep brain stimulation. To assess cellular responses to non-motor information, patients performed a reward task where virtual money could be won, lost, or neither, depending on their performance while cellular activity was monitored. Changes in the firing rates of isolated GPi neurons after the presentation of reward-related stimuli were compared between different reward contingencies (win, loss, null). We observed neurons that modulated their firing rate significantly to the presentation of reward-related stimuli. We furthermore found neurons that responded to visual-stimuli more broadly. This is the first single-unit evidence of human GPi neurons carrying non-motor information. These results are broadly consistent with previous findings in the animal literature and suggest non-motor information may be represented in the single-unit activity of human GPi neurons. PMID:27109924

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

    Science.gov (United States)

    Jiang, Zhiwu; Gu, Liming; Chen, Yanxia

    2016-01-01

    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. PMID:27525278

  20. 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.

  1. Directing astroglia from the cerebral cortex into subtype specific functional neurons.

    Directory of Open Access Journals (Sweden)

    Christophe Heinrich

    2010-05-01

    Full Text Available Astroglia from the postnatal cerebral cortex can be reprogrammed in vitro to generate neurons following forced expression of neurogenic transcription factors, thus opening new avenues towards a potential use of endogenous astroglia for brain repair. However, in previous attempts astroglia-derived neurons failed to establish functional synapses, a severe limitation towards functional neurogenesis. It remained therefore also unknown whether neurons derived from reprogrammed astroglia could be directed towards distinct neuronal subtype identities by selective expression of distinct neurogenic fate determinants. Here we show that strong and persistent expression of neurogenic fate determinants driven by silencing-resistant retroviral vectors instructs astroglia from the postnatal cortex in vitro to mature into fully functional, synapse-forming neurons. Importantly, the neurotransmitter fate choice of astroglia-derived neurons can be controlled by selective expression of distinct neurogenic transcription factors: forced expression of the dorsal telencephalic fate determinant neurogenin-2 (Neurog2 directs cortical astroglia to generate synapse-forming glutamatergic neurons; in contrast, the ventral telencephalic fate determinant Dlx2 induces a GABAergic identity, although the overall efficiency of Dlx2-mediated neuronal reprogramming is much lower compared to Neurog2, suggesting that cortical astroglia possess a higher competence to respond to the dorsal telencephalic fate determinant. Interestingly, however, reprogramming of astroglia towards the generation of GABAergic neurons was greatly facilitated when the astroglial cells were first expanded as neurosphere cells prior to transduction with Dlx2. Importantly, this approach of expansion under neurosphere conditions and subsequent reprogramming with distinct neurogenic transcription factors can also be extended to reactive astroglia isolated from the adult injured cerebral cortex, allowing for the

  2. Isolation of dorsal unpaired median (DUM) neurons from the central nervous system of the cockroach Periplaneta americana and patch-clamp recording of their voltage-gated sodium current%美洲大蠊中枢DUM神经元的分离和电压门控Na+电流的记录

    Institute of Scientific and Technical Information of China (English)

    许鹏; 孙芹; 陈超; 程洁; 高蓉; 姜志宽; 肖杭

    2009-01-01

    [目的]建立美洲大蠊Periplaneta americana中枢神经系统背侧不成对中间神经元(dorsal unpaired median neurons,DUM neurons)的分离方法和DUM神经元电生理实验模型.[方法]IA型胶原酶法消化美洲大蠊末端腹神经节,机械吹打得到DUM神经元细胞,运用膜片钳技术记录DUM神经元细胞电压门控Na+电流.[结果]分离得到的DUM神经元细胞状态良好,具有DUN神经元典型的梨状形态和表面特征.以膜片钳全细胞方式记录到的Na+电流符合钠通道电流特征.[结论]IA型胶原酶消化得到美洲大蠊DUM神经元细胞的方法可靠,能稳定地记录到Na+电流.本文描述的方法为昆虫神经细胞的电生理机制研究提供一个可用的实验模型.

  3. Characterization of NCAM diversity in cultured neurons

    DEFF Research Database (Denmark)

    Gegelashvili, George; Andersson, A M; Schousboe, Arne;

    1993-01-01

    A single transcript of the NCAM gene undergoes differential processing resulting in a multiplicity of mRNAs and their translation products. In this study, the diversity of NCAM in rat primary neuronal cultures was investigated utilizing immuno- and Northern blot analyses. NCAM polypeptides of 190 k......Da (NCAM-A) and 135 kDa (NCAM-B) were shown to be associated with the neuronal phenotype. These data were confirmed by Northern blotting, which in both neocortical neurons and cerebellar granule neurons revealed mRNA classes of 7.4 kb and 6.7 kb encoding for NCAM-A and -B, respectively. However......, oligonucleotide probes, specific for selected exons or exon combinations, revealed special features of cerebellar granule neurons as compared to neocortical neurons: expression of 4.3 kb NCAM mRNA, a relatively low amount of VASE-containing variants, and an apparent lack of mRNA species containing exons alpha...

  4. 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)

  5. 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. PMID:26398224

  6. 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.

  7. Effective stimuli for constructing reliable neuron models.

    OpenAIRE

    Shaul Druckmann; Berger, Thomas K.; Felix Schürmann; Sean Hill; Henry Markram; Idan Segev

    2011-01-01

    Author Summary Neurons perform complicated non-linear transformations on their input before producing their output - a train of action potentials. This input-output transformation is shaped by the specific composition of ion channels, out of the many possible types, that are embedded in the neuron's membrane. Experimentally, characterizing this transformation relies on injecting different stimuli to the neuron while recording its output; but which of the many possible stimuli should one apply...

  8. Neuronal degeneration in spinal multiple sclerosis

    OpenAIRE

    Bernhardt, Lydia

    2010-01-01

    To elucidate neuronal degeneration in spinal multiple sclerosis the spinal cord of 27 post mortem patients of the years 1997 to 2000 was investigated in comparison to 29 controls matched for sex, age and year of death. In addition to immunohistochemical examinations and demonstration of pathological cell changes, we also quantified the neurons of the cervical and thoracic spinal cord. In comparison to controls, MS-patients show a significant loss of 43% of the cervical neurons and a signif...

  9. Neuronal organization of olfactory bulb circuits

    OpenAIRE

    Shin eNagayama; Ryota eHomma; Fumiaki eImamura

    2014-01-01

    Olfactory sensory neurons extend their axons solely to the olfactory bulb, which is dedicated to odor information processing. The olfactory bulb is divided into multiple layers, with different types of neurons found in each of the layers. Therefore, neurons in the olfactory bulb have conventionally been categorized based on the layers in which their cell bodies are found; namely, juxtaglomerular cells in the glomerular layer, tufted cells in the external plexiform layer, mitral cells in the...

  10. Towards functional classification of neuronal types

    OpenAIRE

    Sharpee, Tatyana O.

    2014-01-01

    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 th...

  11. The genealogy of genealogy of neurons.

    Science.gov (United States)

    Moroz, Leonid L

    2014-12-01

    Two scenarios of neuronal evolution (monophyly and polyphyly) are discussed in the historical timeline starting from the 19th century. The recent genomic studies on Ctenophores re-initiated a broad interest in the hypotheses of independent origins of neurons. However, even earlier work on ctenophores suggested that their nervous systems are unique in many aspects of their organization and a possibility of the independent origin of neurons and synapses was introduced well before modern advances in genomic biology.

  12. Neuron model-free PID control

    Science.gov (United States)

    Wang, Ning; Zhang, Li; Wang, Shuqing

    2001-09-01

    Based on the neuron model and learning strategy, the neuron intelligent PID control system is set up in this paper. The neuron model-free PID control method is posed. The simulation tests with an example of a hydraulic turbine generator unit are made. The result show that god control performances are obtained. This new intelligent controller is very simple and has very strong adaptability and robustness. It can be used directly in practice.

  13. Tracing lineages to uncover neuronal identity

    OpenAIRE

    Perlmann Thomas; Panman Lia

    2011-01-01

    Abstract Many previous studies have focused on understanding how midbrain dopamine neurons, which are implicated in many neurological conditions, are generated during embryogenesis. One of the remaining questions concerns how different dopamine neuron subtypes are specified. A recent paper in Neural Development has revealed features of a spatial and temporal lineage map that, together with other studies, begins to elucidate the developmental origin of distinct neuronal subtypes within the dev...

  14. Reflections on mirror neurons and speech perception

    OpenAIRE

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

    2009-01-01

    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 theoreti...

  15. Cold-inducible RNA-binding protein inhibits neuron apoptosis through the suppression of mitochondrial apoptosis.

    Science.gov (United States)

    Zhang, Hai-Tao; Xue, Jing-Hui; Zhang, Zhi-Wen; Kong, Hai-Bo; Liu, Ai-Jun; Li, Shou-Chun; Xu, Dong-Gang

    2015-10-01

    Cold-inducible RNA-binding protein (CIRP) is induced by mild hypothermia in several mammals, but the precise mechanism by which CIRP mediates hypothermia-induced neuroprotection remains unknown. We aimed to investigate the molecular mechanisms by which CIRP protects the nervous system during mild hypothermia. Rat cortical neurons were isolated and cultured in vitro under mild hypothermia (32°C). Apoptosis was measured by annexin V and propidium iodide staining, visualized by flow cytometry. Neuron ultrastructure was visualized by transmission electron microscopy. CIRP overexpression and knockdown were achieved via infection with pL/IRES/GFP-CIRP and pL/shRNA/F-CIRP-A lentivirus. RT(2) Profiler PCR Array Pathway Analysis and western blotting were used to evaluate the effects of CIRP overexpresion/knockdown on the neurons׳ transcriptome. Neuron late apoptosis was significantly reduced at day 7 of culture by 12h hypothermia, but neuron ultrastructure remained relatively intact. RT(2) Profiler PCR Array Pathway Analysis of 84 apoptosis pathway-associated factors revealed that mild hypothermia and CIRP overexpression induce similar gene expression profiles, specifically alterations of genes implicated in the mitochondrial apoptosis pathway. Mild hypothermia-treated neurons up-regulated 12 and down-regulated 38 apoptosis pathway-associated genes. CIRP-overexpressing neurons up-regulated 15 and down-regulated 46 genes. CIRP-knocked-down hypothermia-treated cells up-regulated 9 and down-regulated 40 genes. Similar results were obtained at the protein level. In conclusion, CIRP may inhibit neuron apoptosis through the suppression of the mitochondria apoptosis pathway during mild hypothermia.

  16. 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.

  17. Correction: Understanding metal homeostasis in primary cultured neurons. Studies using single neuron subcellular and quantitative metallomics.

    Science.gov (United States)

    Colvin, Robert A; Lai, Barry; Holmes, William R; Lee, Daewoo

    2015-09-01

    Correction for 'Understanding metal homeostasis in primary cultured neurons. Studies using single neuron subcellular and quantitative metallomics' by Robert A. Colvin et al., Metallomics, 2015, 7, 1111-1123.

  18. Brain state-dependent neuronal computation

    Directory of Open Access Journals (Sweden)

    Pascale eQuilichini

    2012-10-01

    Full Text Available Neuronal firing pattern, which includes both the frequency and the timing of action potentials, is a key component of information processing in the brain. Although the relationship between neuronal output (the firing pattern and function (during a task/behavior is not fully understood, there is now considerable evidence that a given neuron can show very different firing patterns according to brain state. Thus, such neurons assembled into neuronal networks generate different rhythms (e.g. theta, gamma, sharp wave ripples, which sign specific brain states (e.g. learning, sleep. This implies that a given neuronal network, defined by its hard-wired physical connectivity, can support different brain state-dependent activities through the modulation of its functional connectivity. Here, we review data demonstrating that not only the firing pattern, but also the functional connections between neurons, can change dynamically. We then explore the possible mechanisms of such versatility, focusing on the intrinsic properties of neurons and the properties of the synapses they establish, and how they can be modified by neuromodulators, i.e. the different ways that neurons can use to switch from one mode of communication to the other.

  19. Macroscopic Description for Networks of Spiking Neurons

    Science.gov (United States)

    Montbrió, Ernest; Pazó, Diego; Roxin, Alex

    2015-04-01

    A major goal of neuroscience, statistical physics, and nonlinear dynamics is to understand how brain function arises from the collective dynamics of networks of spiking neurons. This challenge has been chiefly addressed through large-scale numerical simulations. Alternatively, researchers have formulated mean-field theories to gain insight into macroscopic states of large neuronal networks in terms of the collective firing activity of the neurons, or the firing rate. However, these theories have not succeeded in establishing an exact correspondence between the firing rate of the network and the underlying microscopic state of the spiking neurons. This has largely constrained the range of applicability of such macroscopic descriptions, particularly when trying to describe neuronal synchronization. Here, we provide the derivation of a set of exact macroscopic equations for a network of spiking neurons. Our results reveal that the spike generation mechanism of individual neurons introduces an effective coupling between two biophysically relevant macroscopic quantities, the firing rate and the mean membrane potential, which together govern the evolution of the neuronal network. The resulting equations exactly describe all possible macroscopic dynamical states of the network, including states of synchronous spiking activity. Finally, we show that the firing-rate description is related, via a conformal map, to a low-dimensional description in terms of the Kuramoto order parameter, called Ott-Antonsen theory. We anticipate that our results will be an important tool in investigating how large networks of spiking neurons self-organize in time to process and encode information in the brain.

  20. 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.

  1. Effective stimuli for constructing reliable neuron models.

    Directory of Open Access Journals (Sweden)

    Shaul Druckmann

    2011-08-01

    Full Text Available The rich dynamical nature of neurons poses major conceptual and technical challenges for unraveling their nonlinear membrane properties. Traditionally, various current waveforms have been injected at the soma to probe neuron dynamics, but the rationale for selecting specific stimuli has never been rigorously justified. The present experimental and theoretical study proposes a novel framework, inspired by learning theory, for objectively selecting the stimuli that best unravel the neuron's dynamics. The efficacy of stimuli is assessed in terms of their ability to constrain the parameter space of biophysically detailed conductance-based models that faithfully replicate the neuron's dynamics as attested by their ability to generalize well to the neuron's response to novel experimental stimuli. We used this framework to evaluate a variety of stimuli in different types of cortical neurons, ages and animals. Despite their simplicity, a set of stimuli consisting of step and ramp current pulses outperforms synaptic-like noisy stimuli in revealing the dynamics of these neurons. The general framework that we propose paves a new way for defining, evaluating and standardizing effective electrical probing of neurons and will thus lay the foundation for a much deeper understanding of the electrical nature of these highly sophisticated and non-linear devices and of the neuronal networks that they compose.

  2. Shaping Neuronal Network Activity by Presynaptic Mechanisms.

    Directory of Open Access Journals (Sweden)

    Ayal Lavi

    2015-09-01

    Full Text Available Neuronal microcircuits generate oscillatory activity, which has been linked to basic functions such as sleep, learning and sensorimotor gating. Although synaptic release processes are well known for their ability to shape the interaction between neurons in microcircuits, most computational models do not simulate the synaptic transmission process directly and hence cannot explain how changes in synaptic parameters alter neuronal network activity. In this paper, we present a novel neuronal network model that incorporates presynaptic release mechanisms, such as vesicle pool dynamics and calcium-dependent release probability, to model the spontaneous activity of neuronal networks. The model, which is based on modified leaky integrate-and-fire neurons, generates spontaneous network activity patterns, which are similar to experimental data and robust under changes in the model's primary gain parameters such as excitatory postsynaptic potential and connectivity ratio. Furthermore, it reliably recreates experimental findings and provides mechanistic explanations for data obtained from microelectrode array recordings, such as network burst termination and the effects of pharmacological and genetic manipulations. The model demonstrates how elevated asynchronous release, but not spontaneous release, synchronizes neuronal network activity and reveals that asynchronous release enhances utilization of the recycling vesicle pool to induce the network effect. The model further predicts a positive correlation between vesicle priming at the single-neuron level and burst frequency at the network level; this prediction is supported by experimental findings. Thus, the model is utilized to reveal how synaptic release processes at the neuronal level govern activity patterns and synchronization at the network level.

  3. 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

  4. 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...

  5. Not Just for Bimodal Neurons Anymore: The Contribution of Unimodal Neurons to Cortical Multisensory Processing

    OpenAIRE

    Allman, Brian L.; Keniston, Leslie P.; Meredith, M. Alex

    2009-01-01

    Traditionally, neuronal studies of multisensory processing proceeded by first identifying neurons that were overtly multisensory (e.g., bimodal, trimodal) and then testing them. In contrast, the present study examined, without precondition, neurons in an extrastriate visual area of the cat for their responses to separate (visual, auditory) and combined-modality (visual and auditory) stimulation. As expected, traditional bimodal forms of multisensory neurons were identified. In addition, howev...

  6. Neuronal Classification of Atria Fibrillation

    Directory of Open Access Journals (Sweden)

    Mohamed BEN MESSAOUD

    2008-06-01

    Full Text Available Motivation. In medical field, particularly the cardiology, the diagnosis systems constitute the essential domain of research. In some applications, the traditional methods of classification present some limitations. The neuronal technique is considered as one of the promising algorithms to resolve such problem.Method. In this paper, two approaches of the Artificial Neuronal Network (ANN technique are investigated to classify the heart beats which are Multi Layer Perception (MLP and Radial Basis Function (RBF. A calculation algorithm of the RBF centers is proposed. For the Atria Fibrillation anomalies, an artificial neural network was used as a pattern classifier to distinguish three classes of the cardiac arrhythmias. The different classes consist of the normal beats (N, the Arrhythmia (AFA and Tachycardia (TFA Atria Fibrillation cases. The global and the partition classifier are performed. The arrhythmias of MIT-BIH database are analyzed. The ANN inputs are the temporal and morphological parameters deduced from the electrocardiograph.Results. The simulation results illustrate the performances of the studied versions of the neural network and give the fault detection rate of the tested data, a rate of classification reaching the 3.7%.Conclusion. This system can constitute a mesh in a chain of automated diagnosis and can be a tool for assistance for the classification of the cardiac anomalies in the services of urgencies before the arrival of a qualified personal person.

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

    Science.gov (United States)

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

    2015-07-15

    Understanding 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.

  8. 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.

  9. 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.

  10. Neuron Mid-Infrared Absorption Study for Direct Optical Excitation of Neurons

    OpenAIRE

    Guo, Dingkai; Chen, Xing; Vadala, Shilpa; Leach, Jennie; Choa, Fow-Sen

    2011-01-01

    Neuron optical excitations are important for brain-circuitry explorations and sensory-neuron-stimulation applications. To optimize the stimulation, we identify neuron mid-IR absorption peaks in this study and discuss their meanings and delivery methods of mid-IR photons.

  11. Human Motor Neuron Progenitor Transplantation Leads to Endogenous Neuronal Sparing in 3 Models of Motor Neuron Loss

    Directory of Open Access Journals (Sweden)

    Tanya J. Wyatt

    2011-01-01

    Full Text Available Motor neuron loss is characteristic of many neurodegenerative disorders and results in rapid loss of muscle control, paralysis, and eventual death in severe cases. In order to investigate the neurotrophic effects of a motor neuron lineage graft, we transplanted human embryonic stem cell-derived motor neuron progenitors (hMNPs and examined their histopathological effect in three animal models of motor neuron loss. Specifically, we transplanted hMNPs into rodent models of SMA (Δ7SMN, ALS (SOD1 G93A, and spinal cord injury (SCI. The transplanted cells survived and differentiated in all models. In addition, we have also found that hMNPs secrete physiologically active growth factors in vivo, including NGF and NT-3, which significantly enhanced the number of spared endogenous neurons in all three animal models. The ability to maintain dying motor neurons by delivering motor neuron-specific neurotrophic support represents a powerful treatment strategy for diseases characterized by motor neuron loss.

  12. Nitric oxide damages neuronal mitochondria and induces apoptosis in neurons

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The cytotoxic effect of nitric oxide on primarily cultured rat cerebellar granule cells was studied,and the mechanisms were discussed.The results showed that nitric oxide donor S-nitroso-N-acetyl-penicillamine (SNAP; 500 μmol/L) could induce apoptosis in immature cultures of cerebellar granule cells.Flow cytometry and HPLC analyses revealed that after treatment with SNAP,the mitochondrial transmembrane potential and the cellular ATP content decreased significantly.Nitric oxide scavenger hemoglobin could effectively prevent the neuronal mitochondria from dysfunction and attenuate apoptosis.The results suggested that nitric oxide activated the apoptotic program by inhibiting the activity of mitochondrial respiratory chain and thus decreasing the cellular ATP content.

  13. GABA(A) receptors on calbindin-immunoreactive myenteric neurons of guinea pig intestine.

    Science.gov (United States)

    Zhou, X; Galligan, J J

    2000-01-14

    These studies were carried out to characterize the properties of gamma-aminobutyric acidA (GABA(A)) receptors on guinea pig intestinal myenteric neurons maintained in primary culture. In addition, the type of neuron expressing GABA(A) receptors was identified using immunohistochemical methods. Whole-cell patch clamp recordings of currents elicited by GABA and acetylcholine (ACh) were obtained using pipettes containing Neurobiotin. After electrophysiological studies, neurons were processed for localization of calbindin-D28K-immunoreactivity (calbindin-ir). GABA (1 mM) and ACh (3 mM) caused inward currents in most cells tested. GABA currents were mimicked by muscimol (1-300 microM) and were blocked by bicuculline (10 microM) indicating that GABA was acting at GABA(A) receptors. GABA currents were associated with a conductance increase and a linear current/voltage relationship with a reversal potential of 1 +/- 1 mV (n = 5). Pentobarbital (PB, 3-1000 microM) and diazepam (DZP, 0.01-10 microM) potentiated GABA-induced currents. A maximum concentration of DZP (1 microM) increased GABA-induced currents 3.1 +/- 0.3 times while PB (1000 microM) increased GABA currents by 11 +/- 2 times. In outside-out patches, the amplitude of GABA-activated single-channel currents was linearly related to membrane potential with a single-channel conductance of 28.5 + 0.5 pS (n = 10). PB and DZP increased the open probability of GABA-induced single-channel currents. Neurons containing calbindin-ir were large, were isolated from other neurons and had GABA current amplitudes of -3.4 +/- 0.3 nA (n = 48). Neurons with weak or absent calbindin-ir were smaller, were localized in clusters of cells and had GABA-induced current amplitudes of -0.6 +/- 0.1 nA (n = 20). ACh-induced currents were smaller in calbindin-ir neurons (-0.7 +/- 0.1 nA) compared to weakly calbindin-ir neurons (-1.4 +/- 0.1 nA). These results indicate that myenteric calbindin-ir neurons express a high density of GABA

  14. Protection of neuronal cells against reactive oxygen species by carnosine and related compounds.

    Science.gov (United States)

    Boldyrev, Alexander; Bulygina, Elena; Leinsoo, Toomas; Petrushanko, Irina; Tsubone, Shiori; Abe, Hiroki

    2004-01-01

    Carnosine and related compounds were compared in terms of their abilities to decrease the levels of reactive oxygen species (ROS) in suspensions of isolated neurons activated by N-methyl-D-aspartic acid (NMDA) using both stationary fluorescence measurements and flow cytometry. Carnosine was found to suppress the fluorescent signal induced by ROS production and decreased the proportion of highly fluorescent neurons, while histidine showed opposite effects. N-Acetylated derivatives of both carnosine and histidine demonstrated weak (statistically indistinguishable) suppressive effects on the ROS signal. N-Methylated derivatives of carnosine suppressed intracellular ROS generation to the same extent as carnosine. This rank of effectiveness is distinct from that previously obtained for the anti-radical ability of CRCs (anserine>carnosine>ophidine). These differences suggest that the similar ability of carnosine and its N-methylated derivatives to protect neuronal cells against the excitotoxic effect of NMDA is not solely related to the antioxidant properties of these compounds. PMID:14698913

  15. Isolated lingual involvement in Wilson's disease.

    Science.gov (United States)

    Choudhary, Neera; Joshi, Laxmikant; Duggal, Ashish; Puri, Vinod; Khwaja, Geeta Anjum

    2015-01-01

    Lingual involvement can occur in a variety of neurological disorders including pyramidal, extrapyramidal and lower motor neuron disorders. It can be seen in the form of tremor, bradykinesia, dystonia, atrophy and weakness of tongue movements and can clinically present as difficulty in swallowing and dysarthria which can be a source of great discomfort to the patient. We describe a patient who presented with isolated lingual involvement and was diagnosed to have Wilsons's disease. This case emphasizes the clinical variability in presentation of Wilson's disease and importance of early clinical diagnosis.

  16. Neuronal 'On' and 'Off' signals control microglia

    NARCIS (Netherlands)

    Biber, Knut; Neumann, Harald; Inoue, Kazuhide; Boddeke, Hendrikus W. G. M.

    2007-01-01

    Recent findings indicate that neurons are not merely passive targets of microglia but rather control microglial activity. The variety of different signals that neurons use to control microglia can be divided into two categories: 'Off' signals constitutively keep microglia in their resting state and

  17. Neuronal Development: SAD Kinases Make Happy Axons

    OpenAIRE

    Xing, Lei; Newbern, Jason M.; Snider, William D

    2013-01-01

    The polarity proteins LKB1 and SAD-A/B are key regulators of axon specification in the developing cerebral cortex. Recent studies now show that this mechanism cannot be generalized to other classes of neurons: instead, SAD-A/B functions downstream of neurotrophin signaling in sensory neurons to mediate a later stage of axon development — arborization in the target field.

  18. Adaptive Neurons For Artificial Neural Networks

    Science.gov (United States)

    Tawel, Raoul

    1990-01-01

    Training time decreases dramatically. In improved mathematical model of neural-network processor, temperature of neurons (in addition to connection strengths, also called weights, of synapses) varied during supervised-learning phase of operation according to mathematical formalism and not heuristic rule. Evidence that biological neural networks also process information at neuronal level.

  19. Polarity and intracellular compartmentalization of Drosophila neurons

    Directory of Open Access Journals (Sweden)

    Henner Astra L

    2007-04-01

    Full Text Available Abstract Background Proper neuronal function depends on forming three primary subcellular compartments: axons, dendrites, and soma. Each compartment has a specialized function (the axon to send information, dendrites to receive information, and the soma is where most cellular components are produced. In mammalian neurons, each primary compartment has distinctive molecular and morphological features, as well as smaller domains, such as the axon initial segment, that have more specialized functions. How neuronal subcellular compartments are established and maintained is not well understood. Genetic studies in Drosophila have provided insight into other areas of neurobiology, but it is not known whether flies are a good system in which to study neuronal polarity as a comprehensive analysis of Drosophila neuronal subcellular organization has not been performed. Results Here we use new and previously characterized markers to examine Drosophila neuronal compartments. We find that: axons and dendrites can accumulate different microtubule-binding proteins; protein synthesis machinery is concentrated in the cell body; pre- and post-synaptic sites localize to distinct regions of the neuron; and specializations similar to the initial segment are present. In addition, we track EB1-GFP dynamics and determine microtubules in axons and dendrites have opposite polarity. Conclusion We conclude that Drosophila will be a powerful system to study the establishment and maintenance of neuronal compartments.

  20. Social neuroscience: mirror neurons recorded in humans.

    Science.gov (United States)

    Keysers, Christian; Gazzola, Valeria

    2010-04-27

    New single-cell recordings show that humans do have mirror neurons, and in more brain regions than previously suspected. Some action-execution neurons were seen to be inhibited during observation, possibly preventing imitation and helping self/other discrimination.

  1. Do mirror neurons subserve action understanding?

    Science.gov (United States)

    Hickok, Gregory

    2013-04-12

    Mirror neurons were once widely believed to support action understanding via motor simulation of the observed actions. Recent evidence regarding the functional properties of mirror neurons in monkeys as well as much neuropsychological evidence in humans has shown that this is not the case.

  2. 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.

  3. 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.

  4. 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…

  5. SnapShot: Neuronal Regulation of Aging.

    Science.gov (United States)

    Weir, Heather J; Mair, William B

    2016-07-28

    Aging is characterized by loss of homeostasis across multiple tissues. The nervous system governs whole-body homeostasis by communicating external and internal signals to peripheral tissues. Here, we highlight neuronal mechanisms and downstream outputs that regulate aging and longevity. Targeting these neuronal pathways may be a novel strategy to promote healthy aging. To view this SnapShot, open or download the PDF.

  6. Power laws from linear neuronal cable theory

    DEFF Research Database (Denmark)

    Pettersen, Klas H; Lindén, Henrik Anders; Tetzlaff, Tom;

    2014-01-01

    expressions for the PSD transfer functions for a set of measures of neuronal activity: the soma membrane current, the current-dipole moment (corresponding to the single-neuron EEG contribution), and the soma membrane potential. These PSD transfer functions relate the PSDs of the respective measurements...

  7. The Neuronal Network Orchestration behind Motor Behaviors

    DEFF Research Database (Denmark)

    Petersen, Peter Christian

    with the balanced model proposed by van Vreeswijk and Sompolinsky (1996) and Roxin et al. (2011). The studied spinal neuronal network is predominantly operating in the irregular subthreshold regime, yet neurons are pushed towards the regular superthreshold regime with increased synaptic input....

  8. Neuron-glia cell adhesion molecule interacts with neurons and astroglia via different binding mechanisms

    OpenAIRE

    1988-01-01

    The neuron-glia cell adhesion molecule (Ng-CAM) is present in the central nervous system on postmitotic neurons and in the periphery on neurons and Schwann cells. It has been implicated in binding between neurons and between neurons and glia. To understand the molecular mechanisms of Ng-CAM binding, we analyzed the aggregation of chick Ng- CAM either immobilized on 0.5-micron beads (Covaspheres) or reconstituted into liposomes. The results were correlated with the binding of these particles t...

  9. 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.

  10. Vestibular efferent neurons project to the flocculus

    Science.gov (United States)

    Shinder, M. E.; Purcell, I. M.; Kaufman, G. D.; Perachio, A. A.

    2001-01-01

    A bilateral projection from the vestibular efferent neurons, located dorsal to the genu of the facial nerve, to the cerebellar flocculus and ventral paraflocculus was demonstrated. Efferent neurons were double-labeled by the unilateral injections of separate retrograde tracers into the labyrinth and into the floccular and ventral parafloccular lobules. Efferent neurons were found with double retrograde tracer labeling both ipsilateral and contralateral to the sites of injection. No double labeling was found when using a fluorescent tracer with non-fluorescent tracers such as horseradish peroxidase (HRP) or biotinylated dextran amine (BDA), but large percentages of efferent neurons were found to be double labeled when using two fluorescent substances including: fluorogold, microruby dextran amine, or rhodamine labeled latex beads. These data suggest a potential role for vestibular efferent neurons in modulating the dynamics of the vestibulo-ocular reflex (VOR) during normal and adaptive conditions.

  11. An overview of the neuron ring model

    Science.gov (United States)

    Taber, Rod

    1991-01-01

    The Neuron Ring model employs an avalanche structure with two important distinctions at the neuron level. Each neuron has two memory latches; one traps maximum neuronal activation during pattern presentation, and the other records the time of latch content change. The latches filter short term memory. In the process, they preserve length 1 snapshots of activation theory history. The model finds utility in pattern classification. Its synaptic weights are first conditioned with sample spectra. The model then receives a test or unknown signal. The objective is to identify the sample closest to the test signal. Class decision follows complete presentation of the test data. The decision maker relies exclusively on the latch contents. Presented here is an overview of the Neuron Ring at the seminar level.

  12. A hybrid bioorganic interface for neuronal photoactivation.

    Science.gov (United States)

    Ghezzi, Diego; Antognazza, Maria Rosa; Dal Maschio, Marco; Lanzarini, Erica; Benfenati, Fabio; Lanzani, Guglielmo

    2011-01-25

    A key issue in the realization of retinal prosthetic devices is reliable transduction of information carried by light into specific patterns of electrical activity in visual information processing networks. Soft organic materials can be used to couple artificial sensors with neuronal tissues. Here, we interface a network of primary neurons with an organic blend. We show that primary neurons can be successfully grown onto the polymer layer without affecting the optoelectronic properties of the active material or the biological functionality of neuronal network. Moreover, action potentials can be triggered in a temporally reliable and spatially selective manner with short pulses of visible light. Our results may lead to new neuronal communication and photo manipulation techniques, thus paving way to the development of artificial retinas and other neuroprosthetic interfaces based on organic photodetectors.

  13. Mirror neurons: their implications for group psychotherapy.

    Science.gov (United States)

    Schermer, Victor L

    2010-10-01

    Recently discovered mirror neurons in the motor cortex of the brain register the actions and intentions of both the organism and others in the environment. As such, they may play a significant role in social behavior and groups. This paper considers the potential implications of mirror neurons and related neural networks for group therapists, proposing that mirror neurons and mirror systems provide "hard-wired" support for the group therapist's belief in the centrality of relationships in the treatment process and exploring their value in accounting for group-as-a-whole phenomena. Mirror neurons further confirm the holistic, social nature of perception, action, and intention as distinct from a stimulus-response behaviorism. The implications of mirror neurons and mirroring processes for the group therapist role, interventions, and training are also discussed.

  14. Mirror neurons through the lens of epigenetics.

    Science.gov (United States)

    Ferrari, Pier F; Tramacere, Antonella; Simpson, Elizabeth A; Iriki, Atsushi

    2013-09-01

    The consensus view in mirror neuron research is that mirror neurons comprise a uniform, stable execution-observation matching system. In this opinion article, we argue that, in light of recent evidence, this is at best an incomplete and oversimplified view of mirror neurons, where activity is actually variable and more plastic than previously theorized. We propose an epigenetic account for understanding developmental changes in sensorimotor systems, including variations in mirror neuron activity. Although associative and genetic accounts fail to consider the complexity of genetic and nongenetic interactions, we propose a new evolutionary developmental biology (evo-devo) perspective, which predicts that environmental differences early in development should produce variations in mirror neuron response patterns, tuning them to the social environment.

  15. Reflections on mirror neurons and speech perception.

    Science.gov (United States)

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

    2009-03-01

    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.

  16. 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.

  17. Central auditory neurons have composite receptive fields.

    Science.gov (United States)

    Kozlov, Andrei S; Gentner, Timothy Q

    2016-02-01

    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. PMID:26787894

  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. 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.

  20. 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.

  1. Ionic currents of morphologically distinct peptidergic neurons in defined culture.

    Science.gov (United States)

    Meyers, D E; Graf, R A; Cooke, I M

    1992-05-01

    1. The X-organ sinus gland is a major peptidergic neurosecretory system in Crustacea, analogous to the vertebrate hypothalamoneurohypophyseal system. Neuronal somata isolated from the crab (Cardisoma carnifex) X-organ and maintained in primary culture in unconditioned, fully defined medium show immediate regenerative outgrowth. Outgrowth occurring as broad lamellipodia ("veiled") distinguishes neurons consistently showing crustacean hyperglycemic hormone immunoreactivity. Neurons that are immunoreactive against molt-inhibiting hormone and red pigment concentrating hormone antisera give rise to branched neurites ("branched"). 2. The whole-cell variation of the patch-clamp technique was used to study the electrophysiology of these two cell types 24-48 h after plating. Under current clamp, only veiled neurons fired overshooting action potentials either spontaneously or in response to depolarization. 3. Under voltage clamp, net current was predominantly outward. When solutions that suppressed outward current were used, only veiled neurons showed significant inward current. These included a tetrodotoxin (TTX)-sensitive Na current and a slow (time to peak 6-10 ms at 0 mV) Cd-sensitive Ca current (ICa) that was activated at potentials less than -30 mV, was maximal at 0 to +20 mV, and did not reverse at potentials up to +60 mV. 4. In TTX, the form of the Ca current I(V) curve was unchanged by changes of holding potential between -40 and -80 mV, and 75-100% of ICa was available from -40 mV. 5. ICa inactivated slowly and incompletely. Analysis with two-pulse regimes suggested that both inactivation and facilitation mechanisms were present. 6. Outward current was examined in the presence and absence of 0.5 mM Cd2+ (1 microM TTX was always present in the external medium). Cd2+ ions slightly reduced the peak outward current, usually by less than 10% (Vc = -10 to +20 mV; Vh = -80 mV). All additional observations were in the presence of TTX and Cd2+. 7. Both cell types expressed

  2. Parallel network simulations with NEURON.

    Science.gov (United States)

    Migliore, M; Cannia, C; Lytton, W W; Markram, Henry; Hines, M L

    2006-10-01

    The NEURON simulation environment has been extended to support parallel network simulations. Each processor integrates the equations for its subnet over an interval equal to the minimum (interprocessor) presynaptic spike generation to postsynaptic spike delivery connection delay. The performance of three published network models with very different spike patterns exhibits superlinear speedup on Beowulf clusters and demonstrates that spike communication overhead is often less than the benefit of an increased fraction of the entire problem fitting into high speed cache. On the EPFL IBM Blue Gene, almost linear speedup was obtained up to 100 processors. Increasing one model from 500 to 40,000 realistic cells exhibited almost linear speedup on 2,000 processors, with an integration time of 9.8 seconds and communication time of 1.3 seconds. The potential for speed-ups of several orders of magnitude makes practical the running of large network simulations that could otherwise not be explored.

  3. Pathological Changes of von Economo Neuron and Fork Neuron in Neuropsychiatric Diseases.

    Science.gov (United States)

    Liu, Jia; Wang, Lu-ning; Arzberger, Thomas; Zhu, Ming-wei

    2016-02-01

    von Economo neuron (VEN) is a bipolar neuron characterized by a large spindle-shaped soma. VEN is generally distributed in the layer V of anterior insular lobe and anterior cingulate cortex. Fork neuron is another featured bipolar neuron. In recent years,many studies have illustrated that VEN and fork neurons are correlated with complicated cognition such as self-consciousness and social emotion. Studies in the development and morpholigies of these two neurons as well as their pathological changes in various neurological and psychiatric disorders have found that the abnormal number and functions of VEN can cause corresponding dysfunctions in social recognition and emotions both during the neuro-developmental stages of childhood and during the nerve degeneration in old age stage. Therefore, more attentions should be paid on the research of VEN and fork neurons in neuropsychiatric diseases.

  4. 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...

  5. Differentiation of fetal pancreatic stem cells into neuron-like and islet-like cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Xiufeng Hua; Yanwei Wang; Peiwen Lian; Shouxin Zhang; Jianyuan Li; Haiyan Wang; Shulin Chen; Wei Gao

    2012-01-01

    Pancreatic stem cells were isolated and cultured from aborted human fetal pancreases of gestational age 14-20 weeks.They were seeded at a density of 1 × 104 in serum-free media for differentiation into neuron-like cells, expressing β-tubulin III and glial fibrillary acidic protein.These neuron-like cells displayed a synapse-like morphology and appeared to form a neuronal network.Pancreatic stem cells were also seeded at a density of 1 × 105 for differentiation into islet-like cells, expressing insulin and glucagon, with an islet-like morphology.These cells had glucose-stimulated secretion of human insulin and C-peptide.Results suggest that pancreatic stem cells can be differentiated into neuron-like and islet-like cells.

  6. 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.

  7. Effect of cholecystokinin on experimental neuronal aging

    Institute of Scientific and Technical Information of China (English)

    Xiao-Jiang Sun; Qin-Chi Lu; Yan Cai

    2005-01-01

    AIM: To observe the effect of cholecystokinin (CCK) on lipofusin value, neuronal dendrite and spine ultrastructure, and total cellular protein during the process of experimental neuronal aging.METHODS: Experimental neuronal aging study model was established by NBA2cellular serum-free culture method. By using single irtracellular lipofusin value from microspectrophotometry,morphology of neuronal dendrites and spines from the scanner electron microscopy, and total cellular protein as the indexes of experimental neuronal aging, we observed the effect of CCK8 on the process of experimental neuronal aging.RESULTS: Under the condition of serum-free culture,intracellular fluorescence value (%) increased with the extension of culture time (1 d 8.51±3.43; 5 d 10.12±3.03;10 d 20.54±10.3; 15 d 36.88±10.49; bP<0.01). When CCK was added to serum-free culture medium, intracellular lipofusin value (%) decreased remarkably after consecutive CCK reaction for 10 and 15 d (control 36.88±10.49; 5 d 32.03±10.01; 10 d 14.37±5.55; 15 d 17.31±4.80; bP<0.01).As the time of serum-free culturing was prolonged, the number of neuronal dendrite and spine cells decreased.The later increased in number when CCK8 was added. CCK8 could improve the total cellular protein in the process of experimental neuronal aging.CONCLUSION: CCK8 may prolong the process of experimental neuronal aging by maintaining the structure and the number of neuronal dendrite and spine cells and changing the total cellular protein.

  8. Evidence for homologous peptidergic neurons in the buccal ganglia of diverse nudibranch mollusks.

    Science.gov (United States)

    Watson, W H; Willows, A O

    1992-03-01

    The buccal ganglia of seven nudibranches (Aeolidia papillosa, Armina californica, Dirona albolineata, D. picta, Hermissenda crassicornis, Melibe leonina, and Tritonia diomedea) were examined to explore possible homologies between large cells that reacted with antibodies directed against small cardioactive peptide B (SCPB). The buccal ganglion of each species possessed a pair of large, dorsal-lateral, whitish neurons that contained an SCPB-like peptide. We refer to these neurons as the SLB (SCPB-immunoreactive Large Buccal) cells. In all species examined, the SLB cells project out the gastroesophageal nerves and appear to innervate the esophagus. In each species, an apparent rhythmic feeding motor program (FMP) was observed by intracellular recording from both SLB neurons and other neurons in isolated preparations of the buccal ganglia. SLB cells often fire at a high frequency, and usually burst in a specific phase relation to the FMP activity. Stimulation of SLB cells enhances expression of the feeding motor program, either by potentiating existing activity or eliciting the FMP in quiescent preparations. Finally, perfusion of isolated buccal ganglia with SCPB excites the SLB cells and activates FMPs. Thus, both the immunohistochemical and electrophysiological data suggest that the SLB cells within three suborders of the opisthobranchia (Dendronotacea, Arminacea, and Aeolidacea) are homologous. A comparison of our data with previously published studies indicates that SLB cell homologs may exist in other gastropods as well. PMID:1527526

  9. Cloned myogenic cells can transdifferentiate in vivo into neuron-like cells.

    Directory of Open Access Journals (Sweden)

    Rachel Sarig

    Full Text Available BACKGROUND: The question of whether intact somatic cells committed to a specific differentiation fate, can be reprogrammed in vivo by exposing them to a different host microenvironment is a matter of controversy. Many reports on transdifferentiation could be explained by fusion with host cells or reflect intrinsic heterogeneity of the donor cell population. METHODOLOGY/PRINCIPAL FINDINGS: We have tested the capacity of cloned populations of mouse and human muscle progenitor cells, committed to the myogenic pathway, to transdifferentiate to neurons, following their inoculation into the developing brain of newborn mice. Both cell types migrated into various brain regions, and a fraction of them gained a neuronal morphology and expressed neuronal or glial markers. Likewise, inoculated cloned human myogenic cells expressed a human specific neurofilament protein. Brain injected donor cells that expressed a YFP transgene controlled by a neuronal specific promoter, were isolated by FACS. The isolated cells had a wild-type diploid DNA content. CONCLUSIONS: These and other results indicate a genuine transdifferentiation phenomenon induced by the host brain microenvironment and not by fusion with host cells. The results may potentially be relevant to the prospect of autologous cell therapy approach for CNS diseases.

  10. The role of NO synthase isoforms in PDT-induced injury of neurons and glial cells

    Science.gov (United States)

    Kovaleva, V. D.; Berezhnaya, E. V.; Uzdensky, A. B.

    2015-03-01

    Nitric oxide (NO) is an important second messenger, involved in the implementation of various cell functions. It regulates various physiological and pathological processes such as neurotransmission, cell responses to stress, and neurodegeneration. NO synthase is a family of enzymes that synthesize NO from L-arginine. The activity of different NOS isoforms depends both on endogenous and exogenous factors. In particular, it is modulated by oxidative stress, induced by photodynamic therapy (PDT). We have studied the possible role of NOS in the regulation of survival and death of neurons and surrounding glial cells under photo-oxidative stress induced by photodynamic treatment (PDT). The crayfish stretch receptor consisting of a single identified sensory neuron enveloped by glial cells is a simple but informative model object. It was photosensitized with alumophthalocyanine photosens (10 nM) and irradiated with a laser diode (670 nm, 0.4 W/cm2). Antinecrotic and proapoptotic effects of NO on the glial cells were found using inhibitory analysis. We have shown the role of inducible NO synthase in photoinduced apoptosis and involvement of neuronal NO synthase in photoinduced necrosis of glial cells in the isolated crayfish stretch receptor. The activation of NO synthase was evaluated using NADPH-diaphorase histochemistry, a marker of neurons expressing the enzyme. The activation of NO synthase in the isolated crayfish stretch receptor was evaluated as a function of time after PDT. Photodynamic treatment induced transient increase in NO synthase activity and then slowly inhibited this enzyme.

  11. Investigation of mitochondrial dysfunction by sequential microplate-based respiration measurements from intact and permeabilized neurons.

    Directory of Open Access Journals (Sweden)

    Pascaline Clerc

    Full Text Available 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.

  12. Generation of sensory neurons is stimulated by leukemia inhibitory factor.

    OpenAIRE

    M. Murphy; Reid, K.; Hilton, D J; Bartlett, P F

    1991-01-01

    The processes that regulate the development of peripheral neurons from their precursors in the embryonic neural crest are essentially unknown. In this report, we show that leukemia inhibitory factor stimulates the generation of neurons in cultures of mouse neural crest. These neurons have the morphology of sensory neurons and contain neuropeptides found in mammalian sensory neurons. Consistent with these neurons being of the sensory lineage is the finding that they arise from nondividing prec...

  13. A proposal for the morphological classification and nomenclature of neurons

    Institute of Scientific and Technical Information of China (English)

    Rong Jiang; Qiang Liu; Quan Liu; Shenquan Liu

    2011-01-01

    The morphological and functional characteristics of neurons are quite varied and complex. There is a need for a comprehensive approach for distinguishing and classifying neurons. Similar to the biological species classification system, this study proposes a morphological classification system for neurons based on principal component analysis. Based on four principal components of neuronal morphology derived from principal component analysis, a nomenclature system for neurons was obtained. This system can accurately distinguish between the same type of neuron from different species.

  14. Bursting and Synchrony in Networks of Model Neurons

    CERN Document Server

    Geier, Christian; Elger, Christian E; Lehnertz, Klaus

    2016-01-01

    Bursting neurons are considered to be a potential cause of over-excitability and seizure susceptibility. The functional influence of these neurons in extended epileptic networks is still poorly understood. There is mounting evidence that the dynamics of neuronal networks is influenced not only by neuronal and synaptic properties but also by network topology. We investigate numerically the influence of different neuron dynamics on global synchrony in neuronal networks with complex connection topologies.

  15. The release of glutamate from cortical neurons regulated by BDNF via the TrkB/Src/PLC-γ1 pathway.

    Science.gov (United States)

    Zhang, Zitao; Fan, Jin; Ren, Yongxin; Zhou, Wei; Yin, Guoyong

    2013-01-01

    The brain-derived neurotrophic factor (BDNF) participates in the regulation of cortical neurons by influencing the release of glutamate. However, the specific mechanisms are unclear. Hence, we isolated and cultured the cortical neurons of Sprague Dawley rats. Specific inhibitors of TrkB, Src, PLC-γ1, Akt, and MEK1/2 (i.e., K252a, PP2, U73122, LY294002, and PD98059, respectively) were used to treat cortical neurons and to detect the glutamate release from cortical neurons stimulated with BDNF. BDNF significantly increased glutamate release, and simultaneously enhanced phosphorylation levels of TrkB, Src, PLC-γ, Akt, and Erk1/2. For BDNF-stimulated cortical neurons, K252a inhibited glutamate release and inhibited the phosphorylation levels of TrkB, Src, PLC-γ, Erk1/2, and Akt (P PLC-γ1 (P 0.05). U73122 inhibited the glutamate release from BDNF-stimulated cortical neurons, but had no influence on the phosphorylation levels of TrkB, Src, Erk1/2, or Akt (P > 0.05). LY294002 and PD98059 did not affect the BDNF-stimulated glutamate release and did not inhibit the phosphorylation levels of TrkB, Src, or PLC-γ1. In summary, BDNF stimulated the glutamate release from cortical neurons via the TrkB/Src/PLC-γ1 signaling pathway.

  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. 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...

  18. Enhanced excitability of small dorsal root ganglion neurons in rats with bone cancer pain

    Directory of Open Access Journals (Sweden)

    Zheng Qin

    2012-04-01

    cancer rats. In addiotion, immunofluorescent staining and single-cell reverse-transcriptase PCR revealed that in isolated small DRG neurons, most neurons were IB4-positive, or expressed TRPV1 or CGRP, indicating that most recorded small DRG neurons were nociceptive neurons. Finally, using in vivo behavioral test, we found that blockade of DRG neurons activity by TTX inhibited the tumor-evoked mechanical allodynia and thermal hyperalgesia in bone cancer rats, implicating that the enhanced excitability of primary sensory neurons underlied the development of bone cancer pain. Conclusions Our present results suggest that implantation of tumor cells into the tibial canal in rats induces an enhanced excitability of small-sized DRG neurons that is probably as results of alterations in intrinsic electrogenic properties of these neurons. Therefore, alterations in intrinsic membrane properties associated with the hyperexcitability of primary sensory neurons likely contribute to the peripheral sensitization and tumor-induced hyperalgesia under cancer condition.

  19. Independent complexity patterns in single neuron activity induced by static magnetic field.

    Science.gov (United States)

    Spasić, S; Nikolić, Lj; Mutavdžić, D; Saponjić, J

    2011-11-01

    We applied a combination of fractal analysis and Independent Component Analysis (ICA) method to detect the sources of fractal complexity in snail Br neuron activity induced by static magnetic field of 2.7 mT. The fractal complexity of Br neuron activity was analyzed before (Control), during (MF), and after (AMF) exposure to the static magnetic field in six experimental animals. We estimated the fractal dimension (FD) of electrophysiological signals using Higuchi's algorithm, and empirical FD distributions. By using the Principal Component Analysis (PCA) and FastICA algorithm we determined the number of components, and defined the statistically independent components (ICs) in the fractal complexity of signal waveforms. We have isolated two independent components of the empirical FD distributions for each of three groups of data by using FastICA algorithm. ICs represent the sources of fractal waveforms complexity of Br neuron activity in particular experimental conditions. Our main results have shown that there could be two opposite intrinsic mechanisms in single snail Br neuron response to static magnetic field stimulation. We named identified ICs that correspond to those mechanisms - the component of plasticity and the component of elasticity. We have shown that combination of fractal analysis with ICA method could be very useful for the decomposition and identification of the sources of fractal complexity of bursting neuronal activity waveforms.

  20. 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.

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

    Science.gov (United States)

    Sümbül, Uygar; Zlateski, Aleksandar; Vishwanathan, Ashwin; Masland, Richard H; Seung, H Sebastian

    2014-01-01

    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.

  2. Lymphocytes with cytotoxic activity induce rapid microtubule axonal destabilization independently and before signs of neuronal death

    Directory of Open Access Journals (Sweden)

    Arundhati Jana

    2013-02-01

    Full Text Available MS (multiple sclerosis is the most prevalent autoimmune disease of the CNS (central nervous system historically characterized as an inflammatory and demyelinating disease. More recently, extensive neuronal pathology has lead to its classification as a neurodegenerative disease as well. While the immune system initiates the autoimmune response it remains unclear how it orchestrates neuronal damage. In our previous studies, using in vitro cultured embryonic neurons, we demonstrated that MBP (myelin basic protein-specific encephalitogenic CD4 T-cells induce early neuronal damage. In an extension of those studies, here we show that polarized CD4 Th1 and Th17 cells as wells as CD8 T-cells and NK (natural killer cells induce microtubule destabilization within neurites in a contact-independent manner. Owing to the cytotoxic potential of these immune cells, we isolated the luminal components of lytic granules and determined that they were sufficient to drive microtubule destabilization. Since lytic granules contain cytolytic proteins, we determined that the induction of microtubule destabilization occurred prior to signs of apoptosis. Furthermore, we determined that microtubule destabilization was largely restricted to axons, sparing dendrites. This study demonstrated that lymphocytes with cytolytic activity have the capacity to directly drive MAD (microtubule axonal destabilization in a bystander manner that is independent of neuronal death.

  3. 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.

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

    Science.gov (United States)

    Onesto, Valentina; Cosentino, Carlo; Di Fabrizio, Enzo; 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.

  5. 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.

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

    Science.gov (United States)

    Onesto, Valentina; Cosentino, Carlo; Di Fabrizio, Enzo; 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. PMID:27403421

  7. Akt1 mediates neuronal differentiation in zebrafish via a reciprocal interaction with notch signaling.

    Directory of Open Access Journals (Sweden)

    Yi-Chuan Cheng

    Full Text Available Akt1 is well known for its role in regulating cell proliferation, differentiation, and apoptosis and is implicated in tumors and several neurological disorders. However, the role of Akt1 in neural development has not been well defined. We have isolated zebrafish akt1 and shown that this gene is primarily transcribed in the developing nervous system, and its spatiotemporal expression pattern suggests a role in neural differentiation. Injection of akt1 morpholinos resulted in loss of neuronal precursors with a concomitant increase in post-mitotic neurons, indicating that knockdown of Akt1 is sufficient to cause premature differentiation of neurons. A similar phenotype was observed in embryos deficient for Notch signaling. Both the ligand (deltaA and the downstream target of Notch (her8a were downregulated in akt1 morphants, indicating that Akt1 is required for Delta-Notch signaling. Furthermore, akt1 expression was downregulated in Delta-Notch signaling-deficient embryos and could be induced by constitutive activation of Notch signaling. In addition, knockdown of Akt1 was able to nullify the inhibition of neuronal differentiation caused by constitutive activation of Notch signaling. Taken together, these results provide in vivo evidence that Akt1 interacts with Notch signaling reciprocally and provide an explanation of why Akt1 is essential for the inhibition of neuronal differentiation.

  8. 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.

  9. 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.

  10. Acute stress increases interstitial fluid amyloid-β via corticotropin-releasing factor and neuronal activity

    OpenAIRE

    Kang, Jae-Eun; Cirrito, John R.; Dong, Hongxin; John G. Csernansky; Holtzman, David M.

    2007-01-01

    Aggregation of the amyloid-β (Aβ) peptide in the extracellular space of the brain is critical in the pathogenesis of Alzheimer's disease. Aβ is produced by neurons and released into the brain interstitial fluid (ISF), a process regulated by synaptic activity. To determine whether behavioral stressors can regulate ISF Aβ levels, we assessed the effects of chronic and acute stress paradigms in amyloid precursor protein transgenic mice. Isolation stress over 3 months increased Aβ levels by 84%. ...

  11. Mirror neurons are central for a second-person neuroscience: insights from developmental studies.

    Science.gov (United States)

    Simpson, Elizabeth Ann; Ferrari, Pier Francesco

    2013-08-01

    Based on mirror neurons' properties, viewers are emotionally engaged when observing others - even when not actively interacting; therefore, characterizing non-participatory action-viewing as isolated may be misleading. Instead, we propose a continuum of socio-emotional engagement. We also highlight recent developmental work that uses a second-person perspective, investigating behavioral, physiological, and neural activity during caregiver-infant interactions.

  12. SNAP-29-mediated Modulation of Synaptic Transmission in Cultured Hippocampal Neurons*

    OpenAIRE

    Pan, Ping-Yue; Cai, Qian; Lin, Lin; Lu, Pei-Hua; Duan, Shumin; Sheng, Zu-Hang

    2005-01-01

    Identifying the molecules that regulate both the recycling of synaptic vesicles and the SNARE components required for fusion is critical for elucidating the molecular mechanisms underlying synaptic plasticity. SNAP-29 was initially isolated as a syntaxin-binding and ubiquitously expressed protein. Previous studies have suggested that SNAP-29 inhibits SNARE complex disassembly, thereby reducing synaptic transmission in cultured superior cervical ganglion neurons in an activity-dependent manner...

  13. Attachment to an endogenous laminin-like protein initiates sprouting by leech neurons

    OpenAIRE

    1988-01-01

    Leech neurons in culture sprout rapidly when attached to extracts from connective tissue surrounding the nervous system. Laminin-like molecules that promote sprouting have now been isolated from this extracellular matrix. Two mAbs have been prepared that react on immunoblots with a approximately equal to 220- and a approximately equal to 340-kD polypeptide, respectively. These antibodies have been used to purify molecules with cross-shaped structures in the electron microscope. The molecules,...

  14. Firing dynamics of an autaptic neuron

    Science.gov (United States)

    Wang, Heng-Tong; Chen, Yong

    2015-12-01

    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. Project supported by the National Natural Science Foundation of China (Grant Nos. 11275084 and 11447027) and the Fundamental Research Funds for the Central Universities, China (Grant No. GK201503025).

  15. Sloppiness in spontaneously active neuronal networks.

    Science.gov (United States)

    Panas, Dagmara; Amin, Hayder; Maccione, Alessandro; Muthmann, Oliver; van Rossum, Mark; Berdondini, Luca; Hennig, Matthias H

    2015-06-01

    Various plasticity mechanisms, including experience-dependent, spontaneous, as well as homeostatic ones, continuously remodel neural circuits. Yet, despite fluctuations in the properties of single neurons and synapses, the behavior and function of neuronal assemblies are generally found to be very stable over time. This raises the important question of how plasticity is coordinated across the network. To address this, we investigated the stability of network activity in cultured rat hippocampal neurons recorded with high-density multielectrode arrays over several days. We used parametric models to characterize multineuron activity patterns and analyzed their sensitivity to changes. We found that the models exhibited sloppiness, a property where the model behavior is insensitive to changes in many parameter combinations, but very sensitive to a few. The activity of neurons with sloppy parameters showed faster and larger fluctuations than the activity of a small subset of neurons associated with sensitive parameters. Furthermore, parameter sensitivity was highly correlated with firing rates. Finally, we tested our observations from cell cultures on an in vivo recording from monkey visual cortex and we confirm that spontaneous cortical activity also shows hallmarks of sloppy behavior and firing rate dependence. Our findings suggest that a small subnetwork of highly active and stable neurons supports group stability, and that this endows neuronal networks with the flexibility to continuously remodel without compromising stability and function.

  16. 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.

  17. Human embryonic stem cell-derived neuronal cells form spontaneously active neuronal networks in vitro.

    Science.gov (United States)

    Heikkilä, Teemu J; Ylä-Outinen, Laura; Tanskanen, Jarno M A; Lappalainen, Riikka S; Skottman, Heli; Suuronen, Riitta; Mikkonen, Jarno E; Hyttinen, Jari A K; Narkilahti, Susanna

    2009-07-01

    The production of functional human embryonic stem cell (hESC)-derived neuronal cells is critical for the application of hESCs in treating neurodegenerative disorders. To study the potential functionality of hESC-derived neurons, we cultured and monitored the development of hESC-derived neuronal networks on microelectrode arrays. Immunocytochemical studies revealed that these networks were positive for the neuronal marker proteins beta-tubulin(III) and microtubule-associated protein 2 (MAP-2). The hESC-derived neuronal networks were spontaneously active and exhibited a multitude of electrical impulse firing patterns. Synchronous bursts of electrical activity similar to those reported for hippocampal neurons and rodent embryonic stem cell-derived neuronal networks were recorded from the differentiated cultures until up to 4 months. The dependence of the observed neuronal network activity on sodium ion channels was examined using tetrodotoxin (TTX). Antagonists for the glutamate receptors NMDA [D(-)-2-amino-5-phosphonopentanoic acid] and AMPA/kainate [6-cyano-7-nitroquinoxaline-2,3-dione], and for GABAA receptors [(-)-bicuculline methiodide] modulated the spontaneous electrical activity, indicating that pharmacologically susceptible neuronal networks with functional synapses had been generated. The findings indicate that hESC-derived neuronal cells can generate spontaneously active networks with synchronous communication in vitro, and are therefore suitable for use in developmental and drug screening studies, as well as for regenerative medicine.

  18. Neurons controlling jumping in froghopper insects.

    Science.gov (United States)

    Bräunig, Peter; Burrows, Malcolm

    2008-03-01

    The neurons innervating muscles that deliver the enormous power enabling froghopper insects to excel at jumping were revealed by backfilling the nerves from those muscles. The huge trochanteral depressor muscle (M133) of a hind leg consists of four parts. The two largest parts (M133b,c) occupy most of the metathorax and are innervated by the same two motor neurons that have small, laterally placed somata in the metathoracic ganglion and axons in nerve N3C(2). They are also supplied by three dorsal unpaired median (DUM) neurons with the largest diameter somata in the central nervous system. A small metathoracic part of the muscle (M133d) is supplied by two motor neurons with lateral somata and by common inhibitory motor neuron CI(1), all with axons in nerve N3C(3) The motor neuron with the larger soma has a thick primary neurite that projects across the midline of the ganglion so that its branches overlap those of its symmetrical counterpart,innervating the same muscle of the other hind leg. The fourth coxal part of the muscle (M133a) is innervated by two motor neurons (one with a ventral and the other with a dorsal and lateral soma), by CI(1), and by a DUM neuron with a small soma. All have axons in nerve N5A. The two trochanteral levator muscles of a hind leg are contained within the coxa and are separately innervated by nerves N3B and N4, respectively. The properties of the different motor neurons are discussed in the context of the neural patterns that generate jumping. PMID:18095320

  19. Statistical Mechanics Characterization of Neuronal Mosaics

    CERN Document Server

    Costa, Luciano da Fontoura; de Lima, Silene Maria Araujo

    2005-01-01

    The spatial distribution of neuronal cells is an important requirement for achieving proper neuronal function in several parts of the nervous system of most animals. For instance, specific distribution of photoreceptors and related neuronal cells, particularly the ganglion cells, in mammal's retina is required in order to properly sample the projected scene. This work presents how two concepts from the areas of statistical mechanics and complex systems, namely the \\emph{lacunarity} and the \\emph{multiscale entropy} (i.e. the entropy calculated over progressively diffused representations of the cell mosaic), have allowed effective characterization of the spatial distribution of retinal cells.

  20. Associative memory - An optimum binary neuron representation

    Science.gov (United States)

    Awwal, A. A.; Karim, M. A.; Liu, H. K.

    1989-01-01

    Convergence mechanism of vectors in the Hopfield's neural network is studied in terms of both weights (i.e., inner products) and Hamming distance. It is shown that Hamming distance should not always be used in determining the convergence of vectors. Instead, weights (which in turn depend on the neuron representation) are found to play a more dominant role in the convergence mechanism. Consequently, a new binary neuron representation for associative memory is proposed. With the new neuron representation, the associative memory responds unambiguously to the partial input in retrieving the stored information.

  1. Towards the automatic classification of neurons.

    Science.gov (United States)

    Armañanzas, Rubén; Ascoli, Giorgio A

    2015-05-01

    The classification of neurons into types has been much debated since the inception of modern neuroscience. Recent experimental advances are accelerating the pace of data collection. The resulting growth of information about morphological, physiological, and molecular properties encourages efforts to automate neuronal classification by powerful machine learning techniques. We review state-of-the-art analysis approaches and the availability of suitable data and resources, highlighting prominent challenges and opportunities. The effective solution of the neuronal classification problem will require continuous development of computational methods, high-throughput data production, and systematic metadata organization to enable cross-laboratory integration. PMID:25765323

  2. Reverberatory activity in neuronal networks in vitro

    Institute of Scientific and Technical Information of China (English)

    LAU PakMing; BI GuoQiang

    2009-01-01

    It has been proposed that during cognitive processes, "online" memory traces in the brain are carried by reverberatory activity in neuronal circuits. However, the nature of such reverberation has remained elusive from experimental studies, largely due to the enormous complexity of intact circuits. Recent works have attempted to address this issue using cultured neuronal network and have revealed new dynamic properties of network reverberation as well as the underlying cellular mechanisms. These results demonstrate the effectiveness of in vitro networks as a useful tool for mechanistic dissection of neuronal circuit dynamics.

  3. Neuronal Alignment On Asymmetric Textured Surfaces

    CERN Document Server

    Beighley, Ross; Sekeroglu, Koray; Atherton, Timothy; Demirel, Melik C; Staii, Cristian

    2013-01-01

    Axonal growth and the formation of synaptic connections are key steps in the development of the nervous system. Here we present experimental and theoretical results on axonal growth and interconnectivity in order to elucidate some of the basic rules that neuronal cells use for functional connections with one another. We demonstrate that a unidirectional nanotextured surface can bias axonal growth. We perform a systematic investigation of neuronal processes on asymmetric surfaces and quantify the role that biomechanical surface cues play in neuronal growth. These results represent an important step towards engineering directed axonal growth for neuro-regeneration studies.

  4. Tracing lineages to uncover neuronal identity

    Directory of Open Access Journals (Sweden)

    Perlmann Thomas

    2011-07-01

    Full Text Available Abstract Many previous studies have focused on understanding how midbrain dopamine neurons, which are implicated in many neurological conditions, are generated during embryogenesis. One of the remaining questions concerns how different dopamine neuron subtypes are specified. A recent paper in Neural Development has revealed features of a spatial and temporal lineage map that, together with other studies, begins to elucidate the developmental origin of distinct neuronal subtypes within the developing midbrain. See research article http://www.neuraldevelopment.com/content/6/1/29

  5. Somatostatin-expressing neurons in cortical networks.

    Science.gov (United States)

    Urban-Ciecko, Joanna; Barth, Alison L

    2016-07-01

    Somatostatin-expressing GABAergic neurons constitute a major class of inhibitory neurons in the mammalian cortex and are characterized by dense wiring into the local network and high basal firing activity that persists in the absence of synaptic input. This firing provides both GABA type A receptor (GABAAR)- and GABABR-mediated inhibition that operates at fast and slow timescales. The activity of somatostatin-expressing neurons is regulated by brain state, during learning and in rewarded behaviour. Here, we review recent advances in our understanding of how this class of cells can control network activity, with specific reference to how this is constrained by their anatomical and electrophysiological properties. PMID:27225074

  6. Neuroserpin, a brain-associated inhibitor of tissue plasminogen activator is localized primarily in neurons. Implications for the regulation of motor learning and neuronal survival.

    Science.gov (United States)

    Hastings, G A; Coleman, T A; Haudenschild, C C; Stefansson, S; Smith, E P; Barthlow, R; Cherry, S; Sandkvist, M; Lawrence, D A

    1997-12-26

    A cDNA clone for the serine proteinase inhibitor (serpin), neuroserpin, was isolated from a human whole brain cDNA library, and recombinant protein was expressed in insect cells. The purified protein is an efficient inhibitor of tissue type plasminogen activator (tPA), having an apparent second-order rate constant of 6. 2 x 10(5) M-1 s-1 for the two-chain form. However, unlike other known plasminogen activator inhibitors, neuroserpin is a more effective inactivator of tPA than of urokinase-type plasminogen activator. Neuroserpin also effectively inhibited trypsin and nerve growth factor-gamma but reacted only slowly with plasmin and thrombin. Northern blot analysis showed a 1.8 kilobase messenger RNA expressed predominantly in adult human brain and spinal cord, and immunohistochemical studies of normal mouse tissue detected strong staining primarily in neuronal cells with occasionally positive microglial cells. Staining was most prominent in the ependymal cells of the choroid plexus, Purkinje cells of the cerebellum, select neurons of the hypothalamus and hippocampus, and in the myelinated axons of the commissura. Expression of tPA within these regions is reported to be high and has previously been correlated with both motor learning and neuronal survival. Taken together, these data suggest that neuroserpin is likely to be a critical regulator of tPA activity in the central nervous system, and as such may play an important role in neuronal plasticity and/or maintenance.

  7. Estradiol rapidly modulates odor responses in mouse vomeronasal sensory neurons.

    Science.gov (United States)

    Cherian, S; Wai Lam, Y; McDaniels, I; Struziak, M; Delay, R J

    2014-06-01

    In rodents, many social behaviors are driven by the sense of smell. The vomeronasal organ (VNO), part of the accessory olfactory system mediates many of these chemically driven behaviors. The VNO is heavily vascularized, and is readily accessible to circulating peptide or steroid hormones. Potentially, this allows circulating hormones to alter behavior through modulating the output of the primary sensory neurons in the VNO, the vomeronasal sensory neurons (VSNs). Based on this, we hypothesized that steroid hormones, in particular 17β-estradiol, would modulate activity of VSNs. In this paper, we show that the estrogen receptors, GPR30 and ERα, were present in VSNs and that estradiol may be synthesized locally in the VNO. Our results also showed that 17β-estradiol decreased responses of isolated VSNs to dilute urine, a potent natural stimulus, with respect to current amplitudes and depolarization. Further, 17β-estradiol increased the latency of the first action potential (AP) and the AP amplitude. Additionally, calcium responses to sulfated steroids (present in the low molecular weight fraction of urine) that act as ligands for apical vomeronasal receptors were decreased by 17β-estradiol. In conclusion, we show that estradiol modulates odorant responses mediated by VSNs and hence paves the way for future studies to better understand the mechanisms by which odorant mediated behavior is altered by endocrine status of the animal. PMID:24680884

  8. Mutations affecting the chemosensory neurons of Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Starich, T.A.; Herman, R.K.; Kari, C.K. [Univ. of Minnesota, St. Paul, MN (United States)] [and others

    1995-01-01

    We have identified and characterized 95 mutations that reduce or abolish dye filling of amphid and phasmid neurons and that have little effect on viability, fertility or movement. Twenty-seven mutations occurred spontaneously in strains with a high frequency of transposon insertion. Sixty-eight were isolated after treatment with EMS. All of the mutations result in defects in one or more chemosensory responses, such as chemotaxis to ammonium chloride or formation of dauer larvae under conditions of starvation and overcrowding. Seventy-five of the mutations are alleles of 12 previously defined genes, mutations which were previously shown to lead to defects in amphid ultrastructure. We have assigned 20 mutations to 13 new genes, called dyf-1 through dyf-13. We expect that the genes represented by dye-filling defective mutants are important for the differentiation of amphid and phasmid chemosensilla. 58 refs., 3 figs., 6 tabs.

  9. Mutations affecting the chemosensory neurons of Caenorhabditis elegans.

    Science.gov (United States)

    Starich, T A; Herman, R K; Kari, C K; Yeh, W H; Schackwitz, W S; Schuyler, M W; Collet, J; Thomas, J H; Riddle, D L

    1995-01-01

    We have identified and characterized 95 mutations that reduce or abolish dye filling of amphid and phasmid neurons and that have little effect on viability, fertility or movement. Twenty-seven mutations occurred spontaneously in strains with a high frequency of transposon insertion. Sixty-eight were isolated after treatment with EMS. All of the mutations result in defects in one or more chemosensory responses, such as chemotaxis to ammonium chloride or formation of dauer larvae under conditions of starvation and overcrowding. Seventy-five of the mutations are alleles of 12 previously defined genes, mutations which were previously shown to lead to defects in amphid ultrastructure. We have assigned 20 mutations to 13 new genes, called dyf-1 through dyf-13. We expect that the genes represented by dye-filing defective mutants are important for the differentiation of amphid and phasmid chemosensilla. PMID:7705621

  10. 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.

  11. Understand Quarantine and Isolation

    Science.gov (United States)

    ... Social Media What CDC is Doing Blog: Public Health Matters What's New Preparation & Planning Emergency Preparedness and Response Understand Quarantine and Isolation Recommend on Facebook Tweet Share Compartir Isolation and quarantine help protect the public by ...

  12. The ontogenetic origins of mirror neurons: evidence from 'tool-use' and 'audiovisual' mirror neurons.

    Science.gov (United States)

    Cook, Richard

    2012-10-23

    Since their discovery, mirror neurons--units in the macaque brain that discharge both during action observation and execution--have attracted considerable interest. Whether mirror neurons are an innate endowment or acquire their sensorimotor matching properties ontogenetically has been the subject of intense debate. It is widely believed that these units are an innate trait; that we are born with a set of mature mirror neurons because their matching properties conveyed upon our ancestors an evolutionary advantage. However, an alternative view is that mirror neurons acquire their matching properties during ontogeny, through correlated experience of observing and performing actions. The present article re-examines frequently overlooked neurophysiological reports of 'tool-use' and 'audiovisual' mirror neurons within the context of this debate. It is argued that these findings represent compelling evidence that mirror neurons are a product of sensorimotor experience, and not an innate endowment.

  13. Epibranchial placode-derived neurons produce BDNF required for early sensory neuron development.

    Science.gov (United States)

    Harlow, Danielle E; Yang, Hui; Williams, Trevor; Barlow, Linda A

    2011-02-01

    In mice, BDNF provided by the developing taste epithelium is required for gustatory neuron survival following target innervation. However, we find that expression of BDNF, as detected by BDNF-driven β-galactosidase, begins in the cranial ganglia before its expression in the central (hindbrain) or peripheral (taste papillae) targets of these sensory neurons, and before gustatory ganglion cells innervate either target. To test early BDNF function, we examined the ganglia of bdnf null mice before target innervation, and found that while initial neuron survival is unaltered, early neuron development is disrupted. In addition, fate mapping analysis in mice demonstrates that murine cranial ganglia arise from two embryonic populations, i.e., epibranchial placodes and neural crest, as has been described for these ganglia in non-mammalian vertebrates. Only placodal neurons produce BDNF, however, which indicates that prior to innervation, early ganglionic BDNF produced by placode-derived cells promotes gustatory neuron development.

  14. Regulation of neuronal axon specification by glia-neuron gap junctions in C. elegans

    Science.gov (United States)

    Meng, Lingfeng; Zhang, Albert; Jin, Yishi; Yan, Dong

    2016-01-01

    Axon specification is a critical step in neuronal development, and the function of glial cells in this process is not fully understood. Here, we show that C. elegans GLR glial cells regulate axon specification of their nearby GABAergic RME neurons through GLR-RME gap junctions. Disruption of GLR-RME gap junctions causes misaccumulation of axonal markers in non-axonal neurites of RME neurons and converts microtubules in those neurites to form an axon-like assembly. We further uncover that GLR-RME gap junctions regulate RME axon specification through activation of the CDK-5 pathway in a calcium-dependent manner, involving a calpain clp-4. Therefore, our study reveals the function of glia-neuron gap junctions in neuronal axon specification and shows that calcium originated from glial cells can regulate neuronal intracellular pathways through gap junctions. DOI: http://dx.doi.org/10.7554/eLife.19510.001 PMID:27767956

  15. Genetic strategies to investigate neuronal circuit properties using stem cell-derived neurons

    Directory of Open Access Journals (Sweden)

    Isabella eGarcia

    2012-12-01

    Full Text Available The mammalian brain is anatomically and functionally complex, and prone to diverse forms of injury and neuropathology. Scientists have long strived to develop cell replacement therapies to repair damaged and diseased nervous tissue. However, this goal has remained unrealized for various reasons, including nascent knowledge of neuronal development, the inability to track and manipulate transplanted cells within complex neuronal networks, and host graft rejection. Recent advances in embryonic stem cell (ESC and induced pluripotent stem cell (iPSC technology, alongside novel genetic strategies to mark and manipulate stem cell-derived neurons now provide unprecedented opportunities to investigate complex neuronal circuits in both healthy and diseased brains. Here, we review current technologies aimed at generating and manipulating neurons derived from ESCs and iPSCs towards investigation and manipulation of complex neuronal circuits, ultimately leading to the design and development of novel cell-based therapeutic approaches.

  16. Leptin transiently antagonizes ghrelin and long-lastingly orexin in regulation of Ca2+ signaling in neuropeptide Y neurons of the arcuate nucleus

    Institute of Scientific and Technical Information of China (English)

    Daisuke Kohno; Shigetomo Suyama; Toshihiko Yada

    2008-01-01

    AIM: To explore the mechanism for interactions of leptin with ghrelin and orexin in the arcuate nucleus (ARC) activating neuropeptide Y (NPY) neurons during physiological regulation of feeding. METHODS: Single neurons from ARC of adult rats with matured feeding function were isolated. [Ca2+]I was measured to monitore their activities. The time course of leptin effects on ghrelin-induced versus orexin-induced [Ca2+]I increases in NPY neurons was studied. RESULTS: Administration of ghrelin or orexin-A at 10-10 mol/L increased cytosolic Ca2+ concentration ([Ca2+I) in NPY neurons isolated from the ARC of adult rats. Upon administration of leptin at 10-14-1012 mol/L, ghrelin-induced [Ca2+]I increases were initially (<10 min) inhibited but later restored, exhibiting a transient pattern of inhibition. In contrast, orexin-induced [Ca2+]I increases were inhibited by leptin in a long-lasting manner. Furthermore, a prior administration of leptin inhibited orexin action but not ghrelin action to increase [Ca2+]I. CONCLUSION: Leptin counteracted ghrelin effects transiently and orexin effects long-lastingly in NPY neurons. The transient property with which leptin counteracts ghrelin action in NPY neurons may allow the fasting-associated increase in ghrelin levels to activate NPY neurons in the presence of physiological leptin and to stimulate feeding.

  17. Mrgprd-expressing polymodal nociceptive neurons innervate most known classes of substantia gelatinosa neurons

    OpenAIRE

    Wang, Hong; Zylka, Mark J.

    2009-01-01

    The Mas-related G protein-coupled receptor D (Mrgprd) marks a distinct subset of sensory neurons that transmit polymodal nociceptive information from the skin epidermis to the substantia gelatinosa (SG, lamina II) of the spinal cord. Moreover, Mrgprd-expressing (Mrgprd+) neurons are required for the full expression of mechanical but not thermal nociception. While such anatomical and functional specificity suggests Mrgprd+ neurons might synapse with specific postsynaptic targets in the SG, pre...

  18. GABAergic Neurons in the Preoptic Area Send Direct Inhibitory Projections to Orexin Neurons

    OpenAIRE

    Yuki eSaito; Natsuko eTsujino; Emi eHasegawa; Kaoru eAkashi; Manabu eAbe; Michihiro eMieda; Kenji eSakimura; Takeshi eSakurai

    2013-01-01

    Populations of neurons in the hypothalamic preoptic area (POA) fire rapidly during sleep, exhibiting sleep/waking state-dependent firing patterns that are the reciprocal of those observed in the arousal system. The majority of these preoptic “sleep-active” neurons contain the inhibitory neurotransmitter GABA. On the other hand, a population of neurons in the lateral hypothalamic area (LHA) contains orexins, which play an important role in the maintenance of wakefulness, and exhibit an excitat...

  19. GABAergic neurons in the preoptic area send direct inhibitory projections to orexin neurons

    OpenAIRE

    Saito, Yuki C.; Tsujino, Natsuko; Hasegawa, Emi; Akashi, Kaori; Abe, Manabu; Mieda, Michihiro; Sakimura, Kenji; Sakurai, Takeshi

    2013-01-01

    Populations of neurons in the hypothalamic preoptic area (POA) fire rapidly during sleep, exhibiting sleep/waking state-dependent firing patterns that are the reciprocal of those observed in the arousal system. The majority of these preoptic "sleep-active" neurons contain the inhibitory neurotransmitter GABA. On the other hand, a population of neurons in the lateral hypothalamic area (LHA) contains orexins, which play an important role in the maintenance of wakefulness, and exhibit an excitat...

  20. 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.

  1. Neuronal Differentiation of Human Mesenchymal Stem Cells Using Exosomes Derived from Differentiating Neuronal Cells

    OpenAIRE

    Takeda, Yuji S.; Qiaobing Xu

    2015-01-01

    Exosomes deliver functional proteins and genetic materials to neighboring cells, and have potential applications for tissue regeneration. One possible mechanism of exosome-promoted tissue regeneration is through the delivery of microRNA (miRNA). In this study, we hypothesized that exosomes derived from neuronal progenitor cells contain miRNAs that promote neuronal differentiation. We treated mesenchymal stem cells (MSCs) daily with exosomes derived from PC12 cells, a neuronal cell line, for 1...

  2. Control and Synchronization of Neuron Ensembles

    CERN Document Server

    Li, Jr-Shin; Ruths, Justin

    2011-01-01

    Synchronization of oscillations is a phenomenon prevalent in natural, social, and engineering systems. Controlling synchronization of oscillating systems is motivated by a wide range of applications from neurological treatment of Parkinson's disease to the design of neurocomputers. In this article, we study the control of an ensemble of uncoupled neuron oscillators described by phase models. We examine controllability of such a neuron ensemble for various phase models and, furthermore, study the related optimal control problems. In particular, by employing Pontryagin's maximum principle, we analytically derive optimal controls for spiking single- and two-neuron systems, and analyze the applicability of the latter to an ensemble system. Finally, we present a robust computational method for optimal control of spiking neurons based on pseudospectral approximations. The methodology developed here is universal to the control of general nonlinear phase oscillators.

  3. How Might New Neurons Buffer Against Stress?

    Science.gov (United States)

    ... 99 items) How Might New Neurons Buffer Against Stress? Clues Emerging from Studies in New Porter Neuroscience ... role in the action of antidepressants , resilience to stress , the benefits of exercise and enriched environments , and ...

  4. The Age of Human Cerebral Cortex Neurons

    Energy Technology Data Exchange (ETDEWEB)

    Bhardwaj, R D; Curtis, M A; Spalding, K L; Buchholz, B A; Fink, D; Bjork-Eriksson, T; Nordborg, C; Gage, F H; Druid, H; Eriksson, P S; Frisen, J

    2006-04-06

    The traditional static view of the adult mammalian brain has been challenged by the realization of continuous generation of neurons from stem cells. Based mainly on studies in experimental animals, adult neurogenesis may contribute to recovery after brain insults and decreased neurogenesis has been implicated in the pathogenesis of neurological and psychiatric diseases in man. The extent of neurogenesis in the adult human brain has, however, been difficult to establish. We have taken advantage of the integration of {sup 14}C, generated by nuclear bomb tests during the Cold War, in DNA to establish the age of neurons in the major areas of the human cerebral cortex. Together with the analysis of the cortex from patients who received BrdU, which integrates in the DNA of dividing cells, our results demonstrate that whereas non-neuronal cells turn over, neurons in the human cerebral cortex are not generated postnatally at detectable levels, but are as old as the individual.

  5. Physiology and pharmacology of striatal neurons.

    Science.gov (United States)

    Kreitzer, Anatol C

    2009-01-01

    The basal ganglia occupy the core of the forebrain and consist of evolutionarily conserved motor nuclei that form recurrent circuits critical for motivation and motor planning. The striatum is the main input nucleus of the basal ganglia and a key neural substrate for procedural learning and memory. The vast majority of striatal neurons are spiny GABAergic projection neurons, which exhibit slow but temporally precise spiking in vivo. Contributing to this precision are several different types of interneurons that constitute only a small fraction of total neuron number but play a critical role in regulating striatal output. This review examines the cellular physiology and modulation of striatal neurons that give rise to their unique properties and function. PMID:19400717

  6. 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.

  7. Fitting Neuron Models to Spike Trains

    Science.gov (United States)

    Rossant, Cyrille; Goodman, Dan F. M.; Fontaine, Bertrand; Platkiewicz, Jonathan; Magnusson, Anna K.; Brette, Romain

    2011-01-01

    Computational modeling is increasingly used to understand the function of neural circuits in systems neuroscience. These studies require models of individual neurons with realistic input–output properties. Recently, it was found that spiking models can accurately predict the precisely timed spike trains produced by cortical neurons in response to somatically injected currents, if properly fitted. This requires fitting techniques that are efficient and 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 allows the user to define and fit arbitrary neuron models to electrophysiological recordings. It relies on vectorization and parallel computing techniques to achieve efficiency. We demonstrate its use on neural recordings in the barrel cortex and in the auditory brainstem, and confirm that simple adaptive spiking models can accurately predict the response of cortical neurons. Finally, we show how a complex multicompartmental model can be reduced to a simple effective spiking model. PMID:21415925

  8. Controlling neuronal noise using chaos control

    CERN Document Server

    Christini, D J; Christini, David J; Collins, James J

    1995-01-01

    Chaos control techniques have been applied to a wide variety of experimental systems, including magneto-elastic ribbons, lasers, chemical reactions, arrhythmic cardiac tissue, and spontaneously bursting neuronal networks. An underlying assumption in all of these studies is that the system being controlled is chaotic. However, the identification of chaos in experimental systems, particularly physiological systems, is a difficult and often misleading task. Here we demonstrate that the chaos criteria used in a recent study can falsely classify a noise-driven, non-chaotic neuronal model as being chaotic. We apply chaos control, periodic pacing, and anticontrol to the non-chaotic model and obtain results which are similar to those reported for apparently chaotic, {\\em in vitro} neuronal networks. We also obtain similar results when we apply chaos control to a simple stochastic system. These novel findings challenge the claim that the aforementioned neuronal networks were chaotic and suggest that chaos control tech...

  9. Transient Synchronization in Complex Neuronal Networks

    CERN Document Server

    Costa, Luciano da Fontoura

    2008-01-01

    Transient synchronization in complex neuronal networks as a consequence of activation-conserved dynamics induced by having sources placed at specific neurons is investigated. The basic integrate-and-fire neuron is adopted, and the dynamics is estimated computationally so as to obtain the activation at each node along each instant of time. The dynamics is implemented so as to conserve the total activation entering the system, which is a distinctive feature of the current work. The synchronization of the activation of the network is then quantified along time in terms of its normalized instantaneous entropy. The potential of such concepts and measurements is explored with respect to 6 theoretical models, as well as for the neuronal network of \\emph{C. elegans}. A series of interesting results are obtained and discussed, including the fact that all models led to a transient period of synchronization, whose specific features depend heavily on the topological features of the networks.

  10. Integrated microfluidic platforms for investigating neuronal networks

    Science.gov (United States)

    Kim, Hyung Joon

    This dissertation describes the development and application of integrated microfluidics-based assay platforms to study neuronal activities in the nervous system in-vitro. The assay platforms were fabricated using soft lithography and micro/nano fabrication including microfluidics, surface patterning, and nanomaterial synthesis. The use of integrated microfluidics-based assay platform allows culturing and manipulating many types of neuronal tissues in precisely controlled microenvironment. Furthermore, they provide organized multi-cellular in-vitro model, long-term monitoring with live cell imaging, and compatibility with molecular biology techniques and electrophysiology experiment. In this dissertation, the integrated microfluidics-based assay platforms are developed for investigation of neuronal activities such as local protein synthesis, impairment of axonal transport by chemical/physical variants, growth cone path finding under chemical/physical cues, and synaptic transmission in neuronal circuit. Chapter 1 describes the motivation, objectives, and scope for developing in-vitro platform to study various neuronal activities. Chapter 2 introduces microfluidic culture platform for biochemical assay with large-scale neuronal tissues that are utilized as model system in neuroscience research. Chapter 3 focuses on the investigation of impaired axonal transport by beta-Amyloid and oxidative stress. The platform allows to control neuronal processes and to quantify mitochondrial movement in various regions of axons away from applied drugs. Chapter 4 demonstrates the development of microfluidics-based growth cone turning assay to elucidate the mechanism underlying axon guidance under soluble factors and shear flow. Using this platform, the behaviors of growth cone of mammalian neurons are verified under the gradient of inhibitory molecules and also shear flow in well-controlled manner. In Chapter 5, I combine in-vitro multicellular model with microfabricated MEA

  11. Neuronal dysfunction with aging and its amelioration

    OpenAIRE

    Ando, Susumu

    2012-01-01

    The author focused on the functional decline of synapses in the brain with aging to understand the underlying mechanisms and to ameliorate the deficits. The first attempt was to unravel the neuronal functions of gangliosides so that gangliosides could be used for enhancing synaptic activity. The second attempt was to elicit the neuronal plasticity in aged animals through enriched environmental stimulation and nutritional intervention. Environmental stimuli were revealed neurochemically and mo...

  12. Inside the brain of a neuron

    OpenAIRE

    Sidiropoulou, Kyriaki; Pissadaki, Eleftheria Kyriaki; Poirazi, Panayiota

    2006-01-01

    For many decades, neurons were considered to be the elementary computational units of the brain and were assumed to summate incoming signals and elicit action potentials only in response to suprathreshold stimuli. Although modelling studies predicted that single neurons constitute a much more powerful computational entity, able to perform an array of nonlinear calculations, this possibility was not explored experimentally until the discovery of active mechanisms in the dendrites of most neuro...

  13. Neural network with dynamically adaptable neurons

    Science.gov (United States)

    Tawel, Raoul (Inventor)

    1994-01-01

    This invention is an adaptive neuron for use in neural network processors. The adaptive neuron participates in the supervised learning phase of operation on a co-equal basis with the synapse matrix elements by adaptively changing its gain in a similar manner to the change of weights in the synapse IO elements. In this manner, training time is decreased by as much as three orders of magnitude.

  14. Beyond the frontiers of neuronal types

    OpenAIRE

    Demian eBattaglia; Anastassios eKaragiannis; Thierry eGallopin; Gutch, Harold W; Bruno eCauli

    2013-01-01

    Cortical neurons and, particularly, inhibitory interneurons display a large diversity of morphological, synaptic, electrophysiological, and molecular properties, as well as diverse embryonic origins. Various authors have proposed alternative classification schemes that rely on the concomitant observation of several multimodal features. However, a broad variability is generally observed even among cells that are grouped into a same class. Furthermore, the attribution of specific neurons to a s...

  15. Authors’ response: mirror neurons: tests and testability.

    Science.gov (United States)

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

    2014-04-01

    Commentators have tended to focus on the conceptual framework of our article, the contrast between genetic and associative accounts of mirror neurons, and to challenge it with additional possibilities rather than empirical data. This makes the empirically focused comments especially valuable. The mirror neuron debate is replete with ideas; what it needs now are system-level theories and careful experiments – tests and testability.

  16. 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....

  17. Synchronized Firing in Coupled Inhomogeneous Excitable Neurons

    Institute of Scientific and Technical Information of China (English)

    ZHENG Zhi-Gang; WANG Fu-Zhong

    2002-01-01

    We study the firing synchronization behavior of the inhomogeneous excitable media. Phase synchronizationof neuron firings is observed with increasing the coupling, while the phases of neurons are different (out-of-phase synchronization). We found the synchronization of bursts can be greatly enhanced by applying an external forcing (in-phasesynchronization). The external forcing can be either a periodic or just homogeneous thermal noise. The mechanismresponsible for this enhancement is discussed.PACS numbers: 05.45.-a, 87.10.+e

  18. Studies on metals in motor neuron disease

    OpenAIRE

    Roos, Per M.

    2013-01-01

    A slow but steady increase in neurodegenerative disorders has been noted in recent decades. Degenerations in the nervous system are found in Alzheimer´s disease, Parkinson´s disease and motor neuron diseases. Amyotrophic lateral sclerosis (ALS) is the most common of the motor neuron diseases. It is often considered a model disorder of neurodegeneration. Early symptoms of ALS are limb weakness or weakness in muscles of speech and swallowing. Muscle atrophy follow and a slowly progressing paral...

  19. Waveform sample method of excitable sensory neuron

    OpenAIRE

    Wang, Sheng-Jun; Xu, Xin-Jian; Wang, Ying-Hai

    2006-01-01

    We present a new interpretation for encoding information of the period of input signals into spike-trains in individual sensory neuronal systems. The spike-train could be described as the waveform sample of the input signal which locks sample points to wave crests with randomness. Based on simulations of the Hodgkin-Huxley (HH) neuron responding to periodic inputs, we demonstrate that the random sampling is a proper encoding method in medium frequency region since power spectra of the reconst...

  20. Neuronal alignment on asymmetric textured surfaces

    OpenAIRE

    Beighley, Ross; Spedden, Elise; Sekeroglu, Koray; Atherton, Timothy; Demirel, Melik C.; Staii, Cristian

    2012-01-01

    Axonal growth and the formation of synaptic connections are key steps in the development of the nervous system. Here, we present experimental and theoretical results on axonal growth and interconnectivity in order to elucidate some of the basic rules that neuronal cells use for functional connections with one another. We demonstrate that a unidirectional nanotextured surface can bias axonal growth. We perform a systematic investigation of neuronal processes on asymmetric surfaces and quantify...

  1. 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

  2. SnapShot: Neuronal Regulation of Aging.

    Science.gov (United States)

    Weir, Heather J; Mair, William B

    2016-07-28

    Aging is characterized by loss of homeostasis across multiple tissues. The nervous system governs whole-body homeostasis by communicating external and internal signals to peripheral tissues. Here, we highlight neuronal mechanisms and downstream outputs that regulate aging and longevity. Targeting these neuronal pathways may be a novel strategy to promote healthy aging. To view this SnapShot, open or download the PDF. PMID:27471972

  3. Neuronal organization of olfactory bulb circuits

    Directory of Open Access Journals (Sweden)

    Shin eNagayama

    2014-09-01

    Full Text Available Olfactory sensory neurons extend their axons solely to the olfactory bulb, which is dedicated to odor information processing. The olfactory bulb is divided into multiple layers, with different types of neurons found in each of the layers. Therefore, neurons in the olfactory bulb have conventionally been categorized based on the layers in which their cell bodies are found; namely, juxtaglomerular cells in the glomerular layer, tufted cells in the external plexiform layer, mitral cells in the mitral cell layer, and granule cells in the granule cell layer. More recently, numerous studies have revealed the heterogeneous nature of each of these cell types, allowing them to be further divided into subclasses based on differences in morphological, molecular, and electrophysiological properties. In addition, technical developments and advances have resulted in an increasing number of studies regarding cell types other than the conventionally categorized ones described above, including short-axon cells and adult-generated interneurons. Thus, the expanding diversity of cells in the olfactory bulb is now being acknowledged. However, our current understanding of olfactory bulb neuronal circuits is mostly based on the conventional and simplest classification of cell types. Few studies have taken neuronal diversity into account for understanding the function of the neuronal circuits in this region of the brain. This oversight may contribute to the roadblocks in developing more precise and accurate models of olfactory neuronal networks. The purpose of this review is therefore to discuss the expanse of existing work on neuronal diversity in the olfactory bulb up to this point, so as to provide an overall picture of the olfactory bulb circuit.

  4. Background activity drives criticality of neuronal avalanches

    Energy Technology Data Exchange (ETDEWEB)

    Juanico, D E; Monterola, C [National Institute of Physics, University of the Philippines, Diliman, Quezon City 1101 (Philippines)

    2007-08-03

    We establish a general framework that explains how leaky, dissipative systems, such as neuronal networks (NN), can exhibit robust self-organized criticality (SOC). Consistent with recent experiments, we propose that persistent membrane potential fluctuations allow NNs to transform from a sub-critical to a critical state. Our results also account for the tendency in small networks to tip towards an epileptiform state (the case of largely synchronized neurons) when background activity is strong.

  5. 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.

  6. Effects of weak electric fields on the activity of neurons and neuronal networks

    Energy Technology Data Exchange (ETDEWEB)

    Jeffreys, J.G.R.; Deans, J.; Bikson, M.; Fox, J

    2003-07-01

    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{sup -1}. (author)

  7. Effect of the heterogeneous neuron and information transmission delay on stochastic resonance of neuronal networks.

    Science.gov (United States)

    Wang, Qingyun; Zhang, Honghui; Chen, Guanrong

    2012-12-01

    We study the effect of heterogeneous neuron and information transmission delay on stochastic resonance of scale-free neuronal networks. For this purpose, we introduce the heterogeneity to the specified neuron with the highest degree. It is shown that in the absence of delay, an intermediate noise level can optimally assist spike firings of collective neurons so as to achieve stochastic resonance on scale-free neuronal networks for small and intermediate α(h), which plays a heterogeneous role. Maxima of stochastic resonance measure are enhanced as α(h) increases, which implies that the heterogeneity can improve stochastic resonance. However, as α(h) is beyond a certain large value, no obvious stochastic resonance can be observed. If the information transmission delay is introduced to neuronal networks, stochastic resonance is dramatically affected. In particular, the tuned information transmission delay can induce multiple stochastic resonance, which can be manifested as well-expressed maximum in the measure for stochastic resonance, appearing every multiple of one half of the subthreshold stimulus period. Furthermore, we can observe that stochastic resonance at odd multiple of one half of the subthreshold stimulus period is subharmonic, as opposed to the case of even multiple of one half of the subthreshold stimulus period. More interestingly, multiple stochastic resonance can also be improved by the suitable heterogeneous neuron. Presented results can provide good insights into the understanding of the heterogeneous neuron and information transmission delay on realistic neuronal networks.

  8. Double-Wavelet Neuron Based on Analytical Activation Functions

    OpenAIRE

    Bodyanskiy, Yevgeniy; Lamonova, Nataliya; Vynokurova, Olena

    2007-01-01

    In this paper a new double-wavelet neuron architecture obtained by modification of standard wavelet neuron, and its learning algorithm are proposed. The offered architecture allows to improve the approximation properties of wavelet neuron. Double-wavelet neuron and its learning algorithm are examined for forecasting non-stationary chaotic time series.

  9. Vibrational resonance in excitable neuronal systems.

    Science.gov (United States)

    Yu, Haitao; Wang, Jiang; Liu, Chen; Deng, Bin; Wei, Xile

    2011-12-01

    In this paper, we investigate the effect of a high-frequency driving on the dynamical response of excitable neuronal systems to a subthreshold low-frequency signal by numerical simulation. We demonstrate the occurrence of vibrational resonance in spatially extended neuronal networks. Different network topologies from single small-world networks to modular networks of small-world subnetworks are considered. It is shown that an optimal amplitude of high-frequency driving enhances the response of neuron populations to a low-frequency signal. This effect of vibrational resonance of neuronal systems depends extensively on the network structure and parameters, such as the coupling strength between neurons, network size, and rewiring probability of single small-world networks, as well as the number of links between different subnetworks and the number of subnetworks in the modular networks. All these parameters play a key role in determining the ability of the network to enhance the outreach of the localized subthreshold low-frequency signal. Considering that two-frequency signals are ubiquity in brain dynamics, we expect the presented results could have important implications for the weak signal detection and information propagation across neuronal systems. PMID:22225338

  10. A fly's view of neuronal remodeling.

    Science.gov (United States)

    Yaniv, Shiri P; Schuldiner, Oren

    2016-09-01

    Developmental neuronal remodeling is a crucial step in sculpting the final and mature brain connectivity in both vertebrates and invertebrates. Remodeling includes degenerative events, such as neurite pruning, that may be followed by regeneration to form novel connections during normal development. Drosophila provides an excellent model to study both steps of remodeling since its nervous system undergoes massive and stereotypic remodeling during metamorphosis. Although pruning has been widely studied, our knowledge of the molecular and cellular mechanisms is far from complete. Our understanding of the processes underlying regrowth is even more fragmentary. In this review, we discuss recent progress by focusing on three groups of neurons that undergo stereotypic pruning and regrowth during metamorphosis, the mushroom body γ neurons, the dendritic arborization neurons and the crustacean cardioactive peptide peptidergic neurons. By comparing and contrasting the mechanisms involved in remodeling of these three neuronal types, we highlight the common themes and differences as well as raise key questions for future investigation in the field. WIREs Dev Biol 2016, 5:618-635. doi: 10.1002/wdev.241 For further resources related to this article, please visit the WIREs website. PMID:27351747

  11. Oscillatorylike behavior in feedforward neuronal networks

    Science.gov (United States)

    Payeur, Alexandre; Maler, Leonard; Longtin, André

    2015-07-01

    We demonstrate how rhythmic activity can arise in neural networks from feedforward rather than recurrent circuitry and, in so doing, we provide a mechanism capable of explaining the temporal decorrelation of γ -band oscillations. We compare the spiking activity of a delayed recurrent network of inhibitory neurons with that of a feedforward network with the same neural properties and axonal delays. Paradoxically, these very different connectivities can yield very similar spike-train statistics in response to correlated input. This happens when neurons are noisy and axonal delays are short. A Taylor expansion of the feedback network's susceptibility—or frequency-dependent gain function—can then be stopped at first order to a good approximation, thus matching the feedforward net's susceptibility. The feedback network is known to display oscillations; these oscillations imply that the spiking activity of the population is felt by all neurons within the network, leading to direct spike correlations in a given neuron. On the other hand, in the output layer of the feedforward net, the interaction between the external drive and the delayed feedforward projection of this drive by the input layer causes indirect spike correlations: spikes fired by a given output layer neuron are correlated only through the activity of the input layer neurons. High noise and short delays partially bridge the gap between these two types of correlation, yielding similar spike-train statistics for both networks. This similarity is even stronger when the delay is distributed, as confirmed by linear response theory.

  12. How to make a midbrain dopaminergic neuron.

    Science.gov (United States)

    Arenas, Ernest; Denham, Mark; Villaescusa, J Carlos

    2015-06-01

    Midbrain dopaminergic (mDA) neuron development has been an intense area of research during recent years. This is due in part to a growing interest in regenerative medicine and the hope that treatment for diseases affecting mDA neurons, such as Parkinson's disease (PD), might be facilitated by a better understanding of how these neurons are specified, differentiated and maintained in vivo. This knowledge might help to instruct efforts to generate mDA neurons in vitro, which holds promise not only for cell replacement therapy, but also for disease modeling and drug discovery. In this Primer, we will focus on recent developments in understanding the molecular mechanisms that regulate the development of mDA neurons in vivo, and how they have been used to generate human mDA neurons in vitro from pluripotent stem cells or from somatic cells via direct reprogramming. Current challenges and future avenues in the development of a regenerative medicine for PD will be identified and discussed.

  13. Cultured neuronal networks as environmental biosensors.

    Science.gov (United States)

    O'Shaughnessy, Thomas J; Gray, Samuel A; Pancrazio, Joseph J

    2004-01-01

    Contamination of water by toxins, either intentionally or unintentionally, is a growing concern for both military and civilian agencies and thus there is a need for systems capable of monitoring a wide range of natural and industrial toxicants. The EILATox-Oregon Workshop held in September 2002 provided an opportunity to test the capabilities of a prototype neuronal network-based biosensor with unknown contaminants in water samples. The biosensor is a portable device capable of recording the action potential activity from a network of mammalian neurons grown on glass microelectrode arrays. Changes in the action potential fi ring rate across the network are monitored to determine exposure to toxicants. A series of three neuronal networks derived from mice was used to test seven unknown samples. Two of these unknowns later were revealed to be blanks, to which the neuronal networks did not respond. Of the five remaining unknowns, a significant change in network activity was detected for four of the compounds at concentrations below a lethal level for humans: mercuric chloride, sodium arsenite, phosdrin and chlordimeform. These compounds--two heavy metals, an organophosphate and an insecticide--demonstrate the breadth of detection possible with neuronal networks. The results generated at the workshop show the promise of the neuronal network biosensor as an environmental detector but there is still considerable effort needed to produce a device suitable for routine environmental threat monitoring. PMID:15478174

  14. Selective attention in an insect auditory neuron.

    Science.gov (United States)

    Pollack, G S

    1988-07-01

    Previous work (Pollack, 1986) showed that an identified auditory neuron of crickets, the omega neuron, selectively encodes the temporal structure of an ipsilateral sound stimulus when a contralateral stimulus is presented simultaneously, even though the contralateral stimulus is clearly encoded when it is presented alone. The present paper investigates the physiological basis for this selective response. The selectivity for the ipsilateral stimulus is a result of the apparent intensity difference of ipsi- and contralateral stimuli, which is imposed by auditory directionality; when simultaneous presentation of stimuli from the 2 sides is mimicked by presenting low- and high-intensity stimuli simultaneously from the ipsilateral side, the neuron responds selectively to the high-intensity stimulus, even though the low-intensity stimulus is effective when it is presented alone. The selective encoding of the more intense (= ipsilateral) stimulus is due to intensity-dependent inhibition, which is superimposed on the cell's excitatory response to sound. Because of the inhibition, the stimulus with lower intensity (i.e., the contralateral stimulus) is rendered subthreshold, while the stimulus with higher intensity (the ipsilateral stimulus) remains above threshold. Consequently, the temporal structure of the low-intensity stimulus is filtered out of the neuron's spike train. The source of the inhibition is not known. It is not a consequence of activation of the omega neuron. Its characteristics are not consistent with those of known inhibitory inputs to the omega neuron.

  15. Optimal stimulus shapes for neuronal excitation.

    Directory of Open Access Journals (Sweden)

    Daniel B Forger

    2011-07-01

    Full Text Available An important problem in neuronal computation is to discern how features of stimuli control the timing of action potentials. One aspect of this problem is to determine how an action potential, or spike, can be elicited with the least energy cost, e.g., a minimal amount of applied current. Here we show in the Hodgkin & Huxley model of the action potential and in experiments on squid giant axons that: 1 spike generation in a neuron can be highly discriminatory for stimulus shape and 2 the optimal stimulus shape is dependent upon inputs to the neuron. We show how polarity and time course of post-synaptic currents determine which of these optimal stimulus shapes best excites the neuron. These results are obtained mathematically using the calculus of variations and experimentally using a stochastic search methodology. Our findings reveal a surprising complexity of computation at the single cell level that may be relevant for understanding optimization of signaling in neurons and neuronal networks.

  16. Frequency-Domain Analysis of Intrinsic Neuronal Properties using High-Resistant Electrodes.

    Science.gov (United States)

    Rössert, Christian; Straka, Hans; Glasauer, Stefan; Moore, Lee E

    2009-01-01

    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. PMID:20582288

  17. 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.

  18. Protective effects of Humanin on hypoxia-induced neuronal death

    Institute of Scientific and Technical Information of China (English)

    Yunqi Zhu; Yanli Li; Jingyi Liu; Xiaorong Yang; Ce Zhang

    2009-01-01

    BACKGROUND: Humanin is a 24-amino acid peptide isolated from the brain of an Alzheimer's disease patient. Several studies have indicated that Humanin can protect cells against cytotoxicity induced by various insults.OBJECTIVE: To investigate the protective role of Humanin on hypoxia-induced neuronal death, and to determine the most appropriate therapeutic concentration of Humanin.DESIGN, TIME AND SETTING: Neuropathophysiological, randomized, controlled experiment, conducted at the Department of Physiology and Neurobiology, Shanxi Medical University, between March 2007 and October 2007.MATERIALS: Newborn Wistar rats, 5,5',6,6' tetrachloro-1,1',3,3'-tetraethyl- benzimidazolylcarbocyanine iodide (JC-1, USA), calcein-acetoxymethylester (calcein-AM, USA), and Humanin (Shanghai, China) were used in this study. METHODS: Primary cortical neurons were cultured with dulbecco's modified eagle's medium containing 15% fetal bovine serum. Cultures were divided into three groups: control, hypoxia, and hypoxia + Humanin. Various concentrations of Humanin (1, 10, and 20 μmol/L) were added to the cultures 16 hours prior to hypoxia induction. For hypoxic conditions, cells were maintained at 37 ℃ within an incubator chamber filled with 95% N2 and 5% CO2 for 24 hours. Cells in the control group were cultured in normal oxygen. MAIN OUTCOME MEASURES: Cell viability was determined through the use of the vital dye calcein-AM, and the number of live cells was determined. Mitochondrial membrane potential (ΔΨm) was assessed using the fluorescent probe JC-1. Mitochondrial permeability transition pore (mPTP) opening was determined with calcein-AM in the presence of cobalt chloride.RESULTS: (1) Cell viability: Hypoxia for 24 hours induced death in a large number of neurons. Pretreatment with 10 μmol/L and 20 μmol/L Humanin, 16 hours prior to hypoxia, protected cells against hypoxia. However, 1 μmol/L Humanin provided little protection. (2) ΔΨm: ΔΨm was reduced after 24-hour hypoxia

  19. Sustained Exposure to the Widely Used Herbicide Atrazine: Altered Function and Loss of Neurons in Brain Monoamine Systems

    OpenAIRE

    Rodriguez, Veronica M.; Thiruchelvam, Mona; Cory-Slechta, Deborah A.

    2005-01-01

    The widespread use of atrazine (ATR) and its persistence in the environment have resulted in documented human exposure. Alterations in hypothalamic catecholamines have been suggested as the mechanistic basis of the toxicity of ATR to hormonal systems in females and the reproductive tract in males. Because multiple catecholamine systems are present in the brain, however, ATR could have far broader effects than are currently understood. Catecholaminergic systems such as the two major long-lengt...

  20. Silicon neuron: digital hardware implementation of the quartic model

    OpenAIRE

    Grassia, Filippo; Levi, Timothée; Kohno, Takashi; Saïghi, Sylvain

    2014-01-01

    International audience This paper presents an FPGA implementation of the quartic neuron model. This approach uses digital computation to emulate individual neuron behavior. We implemented the neuron model using fixed point arithmetic operation. The neuron model's computations are performed in arithmetic pipelines. It was designed in VHDL language and simulated prior to mapping in the FPGA. We show that the proposed FPGA implementation of the quartic neuron model can emulate the electrophys...

  1. Lineage origins of GABAergic versus glutamatergic neurons in the neocortex

    OpenAIRE

    Marín, Oscar; Müller, Ulrich

    2014-01-01

    Neocortical circuits are assembled from subtypes of glutamatergic excitatory and GABAergic inhibitory neurons with divergent anatomical and molecular signatures and unique physiological properties. Excitatory neurons derive from progenitors in the pallium, whereas inhibitory neurons originate from progenitors in the subpallium. Both classes of neurons subsequently migrate along well-defined routes to their final target area, where they integrate into common neuronal circuits. Recent findings ...

  2. Regeneration of New Neurons is Preserved in Aged Vomeronasal Epithelia

    OpenAIRE

    Brann, Jessica H.; Firestein, Stuart

    2010-01-01

    During normal and diseased aging, it is thought the capacity for tissue regeneration and repair in neuronal tissues diminishes. In the peripheral olfactory system, stem cell reservoirs permit regeneration of olfactory and vomeronasal sensory neurons, a unique capacity among neurons. Following injury a large number of new neurons can be regenerated in a young animal. However, it is unknown whether this capacity for renewal exists in aged proliferative populations. Here we report that neuronal ...

  3. Revisiting the concept of identifiable neurons.

    Science.gov (United States)

    Bullock, T H

    2000-05-01

    Although eutely in nematodes was known, giant neurons in several taxa and unique motor neurons to leg muscles in decapod crustaceans, the idea that many animals have many identifiable neurons with relatively consistent dynamical properties and connections was only slowly established in the late 1960s and early 1970s. This has to be one of the important quiet revolutions in neurobiology. It stimulated a vast acquisition of specific information and led to some euphoria in the degree and pace of understanding activity of nervous systems and consequent behavior in terms of neuronal connections and properties. Some implications, problems and opportunities for new discovery are developed. The distribution of identifiable neurons among taxa and parts of the nervous system is not yet satisfactorily known. Their evolution may have been a case of several independent inventions. The degree of consistency has been quantified only in a few examples and the plasticity is little known. Identified neurons imply identifiable circuits but whether this extends to discrete systems, functionally definable, seems likely to have several answers in different animals or sites. Very limited attempts have been made to extend the concept to cases of two or ten or a hundred fully equivalent neurons, on all kinds of criteria. These attempts suggest a much smaller redundancy and vaster number of types of neurons than hitherto believed. Theory as well as empirical information has not yet interpreted the range of systems from those with small sets of relatively reliable neurons to those with large numbers of parallel, partially redundant units. The now classical notion of local circuits has to be extended to take account of and find roles for the plethora of integrative variables, of evidence for neural processing independent of spikes and classical synapses, of spatial configurations of terminal arbors and dendritic geometry, of modulators and transmitters, degrees of rhythmicity (regularity

  4. Viral transduction of the neonatal brain delivers controllable genetic mosaicism for visualising and manipulating neuronal circuits in vivo.

    Science.gov (United States)

    Kim, Ji-Yoen; Ash, Ryan T; Ceballos-Diaz, Carolina; Levites, Yona; Golde, Todd E; Smirnakis, Stelios M; Jankowsky, Joanna L

    2013-04-01

    The neonatal intraventricular injection of adeno-associated virus has been shown to transduce neurons widely throughout the brain, but its full potential for experimental neuroscience has not been adequately explored. We report a detailed analysis of the method's versatility with an emphasis on experimental applications where tools for genetic manipulation are currently lacking. Viral injection into the neonatal mouse brain is fast, easy, and accesses regions of the brain including the cerebellum and brainstem that have been difficult to target with other techniques such as electroporation. We show that viral transduction produces an inherently mosaic expression pattern that can be exploited by varying the titer to transduce isolated neurons or densely-packed populations. We demonstrate that the expression of virally-encoded proteins is active much sooner than previously believed, allowing genetic perturbation during critical periods of neuronal plasticity, but is also long-lasting and stable, allowing chronic studies of aging. We harness these features to visualise and manipulate neurons in the hindbrain that have been recalcitrant to approaches commonly applied in the cortex. We show that viral labeling aids the analysis of postnatal dendritic maturation in cerebellar Purkinje neurons by allowing individual cells to be readily distinguished, and then demonstrate that the same sparse labeling allows live in vivo imaging of mature Purkinje neurons at a resolution sufficient for complete analytical reconstruction. Given the rising availability of viral constructs, packaging services, and genetically modified animals, these techniques should facilitate a wide range of experiments into brain development, function, and degeneration. PMID:23347239

  5. Abelson tyrosine kinase links PDGFbeta receptor activation to cytoskeletal regulation of NMDA receptors in CA1 hippocampal neurons

    Directory of Open Access Journals (Sweden)

    Beazely Michael A

    2008-12-01

    Full Text Available Abstract Background We have previously demonstrated that PDGF receptor activation indirectly inhibits N-methyl-D-aspartate (NMDA currents by modifying the cytoskeleton. PDGF receptor ligand is also neuroprotective in hippocampal slices and cultured neurons. PDGF receptors are tyrosine kinases that control a variety of signal transduction pathways including those mediated by PLCγ. In fibroblasts Src and another non-receptor tyrosine kinase, Abelson kinase (Abl, control PDGF receptor regulation of cytoskeletal dynamics. The mechanism whereby PDGF receptor regulates cytoskeletal dynamics in central neurons remains poorly understood. Results Intracellular applications of active Abl, but not heat-inactivated Abl, decreased NMDA-evoked currents in isolated hippocampal neurons. This mimics the effects of PDGF receptor activation in these neurons. The Abl kinase inhibitor, STI571, blocked the inhibition of NMDA currents by Abl. We demonstrate that PDGF receptors can activate Abl kinase in hippocampal neurons via mechanisms similar to those observed previously in fibroblasts. Furthermore, PDGFβ receptor activation alters the subcellular localization of Abl. Abl kinase is linked to actin cytoskeletal dynamics in many systems. We show that the inhibition of NMDA receptor currents by Abl kinase is blocked by the inclusion of the Rho kinase inhibitor, Y-27632, and that activation of Abl correlates with an increase in ROCK tyrosine phosphorylation. Conclusion This study demonstrates that PDGFβ receptors act via an interaction with Abl kinase and Rho kinase to regulated cytoskeletal regulation of NMDA receptor channels in CA1 pyramidal neurons.

  6. Erratum to "Noise-induced changes of neuronal spontaneous activity in mice inferior colliculus brain slices".

    Science.gov (United States)

    Basta, Dietmar; Ernst, Arne

    2005-02-01

    The inferior colliculus (IC) in vivo is reportedly subject to a noise-induced decrease of GABA-related inhibitory synaptic transmission accompanied by an amplitude increase of auditory evoked responses, a widening of tuning curves and a higher neuronal discharge rate at suprathreshold levels. However, other in vivo experiments which demonstrated constant neuronal auditory thresholds or unchanged spontaneous activity in the IC after noise exposure did not confirm those findings. Perhaps this can be the result of complex noise-induced interactions between different central auditory structures. It was, therefore, the aim of the present study to investigate the effects of noise exposure on the spontaneous electrical activity of single neurons in a slice preparation of the isolated mouse IC. Normal hearing mice were exposed to noise (10 kHz center frequency at 115 dB SPL for 3 h) at the age of 21 days under anesthesia (Ketamin/Rompun 10:1). After one week, auditory brainstem response (ABR) recordings and extracellular single-unit recordings from spontaneously active neurons within the IC slice were performed in noise-exposed and in normal hearing control mice. Noise-exposed animals showed a significant ABR threshold shift in the whole tested frequency range and a significant lower neuronal spontaneous activity in all investigated isofrequency laminae compared to controls. In both groups, the firing rate of 80% of IC neurons (approximately) increased significantly during the application of the GABA(A) receptor antagonist Bicucullin (10 microM). The present findings demonstrate a noise-related modulation of spontaneous activity in the IC, which possibly contribute to the generation of noise-induced tinnitus and hearing loss.

  7. Noise-induced changes of neuronal spontaneous activity in mice inferior colliculus brain slices.

    Science.gov (United States)

    Basta, Dietmar; Ernest, Arne

    2004-09-30

    The inferior colliculus (IC) in vivo is reportedly subject to a noise-induced decrease of GABA-related inhibitory synaptic transmission accompanied by an amplitude increase of auditory evoked responses, a widening of tuning curves and a higher neuronal discharge rate at suprathreshold levels. However, other in vivo experiments which demonstrated constant neuronal auditory thresholds or unchanged spontaneous activity in the IC after noise exposure did not confirm those findings. Perhaps this can be the result of complex noise-induced interactions between different central auditory structures. It was, therefore, the aim of the present study to investigate the effects of noise exposure on the spontaneous electrical activity of single neurons in a slice preparation of the isolated mouse IC. Normal hearing mice were exposed to noise (10 kHz center frequency at 115 dB SPL for 3 h) at the age of 21 days under anesthesia (Ketamin/Rompun 10:1). After one week, auditory brainstem response (ABR) recordings and extracellular single-unit recordings from spontaneously active neurons within the IC slice were performed in noise-exposed and in normal hearing control mice. Noise-exposed animals showed a significant ABR threshold shift in the whole tested frequency range and a significant lower neuronal spontaneous activity in all investigated isofrequency laminae compared to controls. In both groups, the firing rate of 80% of IC neurons (approximately) increased significantly during the application of the GABA(A) receptor antagonist Bicucullin (10 microM). The present findings demonstrate a noise-related modulation of spontaneous activity in the IC, which possibly contribute to the generation of noise-induced tinnitus and hearing loss.

  8. Activity-dependent structural plasticity after aversive experiences in amygdala and auditory cortex pyramidal neurons.

    Science.gov (United States)

    Gruene, Tina; Flick, Katelyn; Rendall, Sam; Cho, Jin Hyung; Gray, Jesse; Shansky, Rebecca

    2016-07-22

    The brain is highly plastic and undergoes changes in response to many experiences. Learning especially can induce structural remodeling of dendritic spines, which is thought to relate to memory formation. Classical Pavlovian fear conditioning (FC) traditionally pairs an auditory cue with an aversive footshock, and has been widely used to study neural processes underlying associative learning and memory. Past research has found dendritic spine changes after FC in several structures. But, due to heterogeneity of cells within brain structures and limitations of traditional neuroanatomical techniques, it is unclear if all cells included in analyses were actually active during learning processes, even if known circuits are isolated. In this study, we employed a novel approach to analyze structural plasticity explicitly in neurons activated by exposure to either cued or uncued footshocks. We used male and female Arc-dVenus transgenic mice, which express the Venus fluorophore driven by the activity-related Arc promoter, to identify neurons that were active during either scenario. We then targeted fluorescent microinjections to Arc+ and neighboring Arc- neurons in the basolateral area of the amygdala (BLA) and auditory association cortex (TeA). In both BLA and TeA, Arc+ neurons had reduced thin and mushroom spine densities compared to Arc- neurons. This effect was present in males and females alike and also in both cued and uncued shock groups. Overall, this study adds to our understanding of how neuronal activity affects structural plasticity, and represents a methodological advance in the ways we can directly relate structural changes to experience-related neural activity.

  9. Activity-dependent structural plasticity after aversive experiences in amygdala and auditory cortex pyramidal neurons.

    Science.gov (United States)

    Gruene, Tina; Flick, Katelyn; Rendall, Sam; Cho, Jin Hyung; Gray, Jesse; Shansky, Rebecca

    2016-07-22

    The brain is highly plastic and undergoes changes in response to many experiences. Learning especially can induce structural remodeling of dendritic spines, which is thought to relate to memory formation. Classical Pavlovian fear conditioning (FC) traditionally pairs an auditory cue with an aversive footshock, and has been widely used to study neural processes underlying associative learning and memory. Past research has found dendritic spine changes after FC in several structures. But, due to heterogeneity of cells within brain structures and limitations of traditional neuroanatomical techniques, it is unclear if all cells included in analyses were actually active during learning processes, even if known circuits are isolated. In this study, we employed a novel approach to analyze structural plasticity explicitly in neurons activated by exposure to either cued or uncued footshocks. We used male and female Arc-dVenus transgenic mice, which express the Venus fluorophore driven by the activity-related Arc promoter, to identify neurons that were active during either scenario. We then targeted fluorescent microinjections to Arc+ and neighboring Arc- neurons in the basolateral area of the amygdala (BLA) and auditory association cortex (TeA). In both BLA and TeA, Arc+ neurons had reduced thin and mushroom spine densities compared to Arc- neurons. This effect was present in males and females alike and also in both cued and uncued shock groups. Overall, this study adds to our understanding of how neuronal activity affects structural plasticity, and represents a methodological advance in the ways we can directly relate structural changes to experience-related neural activity. PMID:27155146

  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. Endogenous GLP-1 acts on paraventricular nucleus to suppress feeding: projection from nucleus tractus solitarius and activation of corticotropin-releasing hormone, nesfatin-1 and oxytocin neurons.

    Science.gov (United States)

    Katsurada, Kenichi; Maejima, Yuko; Nakata, Masanori; Kodaira, Misato; Suyama, Shigetomo; Iwasaki, Yusaku; Kario, Kazuomi; Yada, Toshihiko

    2014-08-22

    Glucagon-like peptide-1 (GLP-1) receptor agonists have been used to treat type 2 diabetic patients and shown to reduce food intake and body weight. The anorexigenic effects of GLP-1 and GLP-1 receptor agonists are thought to be mediated primarily via the hypothalamic paraventricular nucleus (PVN). GLP-1, an intestinal hormone, is also localized in the nucleus tractus solitarius (NTS) of the brain stem. However, the role of endogenous GLP-1, particularly that in the NTS neurons, in feeding regulation remains to be established. The present study examined whether the NTS GLP-1 neurons project to PVN and whether the endogenous GLP-1 acts on PVN to restrict feeding. Intra-PVN injection of GLP-1 receptor antagonist exendin (9-39) increased food intake. Injection of retrograde tracer into PVN combined with immunohistochemistry for GLP-1 in NTS revealed direct projection of NTS GLP-1 neurons to PVN. Moreover, GLP-1 evoked Ca(2+) signaling in single neurons isolated from PVN. The majority of GLP-1-responsive neurons were immunoreactive predominantly to corticotropin-releasing hormone (CRH) and nesfatin-1, and less frequently to oxytocin. These results indicate that endogenous GLP-1 targets PVN to restrict feeding behavior, in which the projection from NTS GLP-1 neurons and activation of CRH and nesfatin-1 neurons might be implicated. This study reveals a neuronal basis for the anorexigenic effect of endogenous GLP-1 in the brain.

  12. 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.

  13. 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.

  14. Hyperexcitable neurons and altered non-neuronal cells in the compressed spinal ganglion

    Institute of Scientific and Technical Information of China (English)

    Robert H. LaMotte; Chao MA

    2008-01-01

    The cell body or soma in the dosal root ganglion (DRG) is normally excitable and this excitability can increase and persist after an injury of peripheral sensory neurons. In a rat model of radicular pain, an intraforaminal implantation of a rod that chronically compressed the lumbar DRG ("CCD" model) resulted in neuronal somal hyperexcitability and spontaneous activity that was accom-panied by hyperalgesia in the ipsilateral hind paw. By the 5th day after onset of CCD, there was a novel upregulation in neuronal expression of the chemokine, monocyte chemoattractant protein-1 (MCP- 1 or CCL2) and also its receptor, CCR2. The neurons developed, in response to topically applied MCP-1, an excitatory response that they normally do not have. CCD also activated non-neuronal cells including, for example, the endothelial cells as evidenced by angiogenesis in the form of an increased number of capillaries in the DRG after 7 days. A working hypothesis is that the CCD induced changes in neurons and non-neuronal cells that may act together to promote the survival of the injured tissue. The release of ligands such as CCL2, in addition to possibly activating nociceptive neurons (maintaining the pain), may also act to preserve injured cells in the face of ischemia and hypoxia, for example, by promoting angiogenesis. Thus, somal hyperexcitability, as often said of inflammation, may represent a double edged sword.

  15. 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.

  16. Neuron Image Analyzer: Automated and Accurate Extraction of Neuronal Data from Low Quality Images.

    Science.gov (United States)

    Kim, Kwang-Min; Son, Kilho; Palmore, G Tayhas R

    2015-01-01

    Image analysis software is an essential tool used in neuroscience and neural engineering to evaluate changes in neuronal structure following extracellular stimuli. Both manual and automated methods in current use are severely inadequate at detecting and quantifying changes in neuronal morphology when the images analyzed have a low signal-to-noise ratio (SNR). This inadequacy derives from the fact that these methods often include data from non-neuronal structures or artifacts by simply tracing pixels with high intensity. In this paper, we describe Neuron Image Analyzer (NIA), a novel algorithm that overcomes these inadequacies by employing Laplacian of Gaussian filter and graphical models (i.e., Hidden Markov Model, Fully Connected Chain Model) to specifically extract relational pixel information corresponding to neuronal structures (i.e., soma, neurite). As such, NIA that is based on vector representation is less likely to detect false signals (i.e., non-neuronal structures) or generate artifact signals (i.e., deformation of original structures) than current image analysis algorithms that are based on raster representation. We demonstrate that NIA enables precise quantification of neuronal processes (e.g., length and orientation of neurites) in low quality images with a significant increase in the accuracy of detecting neuronal changes post-stimulation. PMID:26593337

  17. ACQUISITION AND LOSS OF NEURONAL CA2+/CALMODULIN-DEPENDENT PROTEIN KINASE DURING NEURONAL DIFFERENTIATION

    Science.gov (United States)

    Neurons display characteristic schedules by which they acquire and lose the neuron-specific Ca2+/calmodulin-dependent protein Kinase-Gr (CaM Kinase-Gr) during differentiation. uch schedules are exemplified by patterns of expression of this kinase in the developing cerebellum and ...

  18. Closing the Phenotypic Gap between Transformed Neuronal Cell Lines in Culture and Untransformed Neurons

    Science.gov (United States)

    Myers, Tereance A.; Nickerson, Cheryl A.; Kaushal, Deepak; Ott, C. Mark; HonerzuBentrup, Kerstin; Ramamurthy, Rajee; Nelman-Gonzales, Mayra; Pierson, Duane L.; Philipp, Mario T.

    2008-01-01

    Studies of neuronal dysfunction in the central nervous system (CNS) are frequently limited by the failure of primary neurons to propagate in vitro. Neuronal cell lines can be substituted for primary cells but they often misrepresent normal conditions. We hypothesized that a dimensional (3-D) cell culture system would drive the phenotype of transformed neurons closer to that of untransformed cells. In our studies comparing 3-D versus 2-dimensional (2-D) culture, neuronal SH-SY5Y (SY) cells underwent distinct morphological changes combined with a significant drop in their rate of cell division. Expression of the proto-oncogene N-myc and the RNA binding protein HuD was decreased in 3-D culture as compared to standard 2-D conditions. We observed a decline in the anti-apoptotic protein Bcl-2 in 3-D culture, coupled with increased expression of the pro-apoptotic proteins Bax and Bak. Moreover, thapsigargin (TG)-induced apoptosis was enhanced in the 3-D cells. Microarray analysis demonstrated significantly differing mRNA levels for over 700 genes in the cells of each culture type. These results indicate that a 3-D culture approach narrows the phenotypic gap between neuronal cell lines and primary neurons. The resulting cells may readily be used for in vitro research of neuronal pathogenesis.

  19. Human von Economo neurons express transcription factors associated with Layer V subcerebral projection neurons.

    Science.gov (United States)

    Cobos, Inma; Seeley, William W

    2015-01-01

    The von Economo neurons (VENs) are large bipolar Layer V projection neurons found chiefly in the anterior cingulate and frontoinsular cortices. Although VENs have been linked to prevalent illnesses such as frontotemporal dementia, autism, and schizophrenia, little is known about VEN identity, including their major projection targets. Here, we undertook a developmental transcription factor expression study, focusing on markers associated with specific classes of Layer V projection neurons. Using mRNA in situ hybridization, we found that VENs prominently express FEZF2 and CTIP2, transcription factors that regulate the fate and differentiation of subcerebral projection neurons, in humans aged 3 months to 65 years. In contrast, few VENs expressed markers associated with callosal or corticothalamic projections. These findings suggest that VENs may represent a specialized Layer V projection neuron for linking cortical autonomic control sites to brainstem or spinal cord regions. PMID:23960210

  20. Mutation and premating isolation.

    Science.gov (United States)

    Woodruff, R C; Thompson, J N

    2002-11-01

    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.