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Sample records for range wdr neurons

  1. Fractal characterization of acupuncture-induced spike trains of rat WDR neurons

    International Nuclear Information System (INIS)

    Chen, Yingyuan; Guo, Yi; Wang, Jiang; Hong, Shouhai; Wei, Xile; Yu, Haitao; Deng, Bin

    2015-01-01

    Highlights: •Fractal analysis is a valuable tool for measuring MA-induced neural activities. •In course of the experiments, the spike trains display different fractal properties. •The fractal properties reflect the long-term modulation of MA on WDR neurons. •The results may explain the long-lasting effects induced by acupuncture. -- Abstract: The experimental and the clinical studies have showed manual acupuncture (MA) could evoke multiple responses in various neural regions. Characterising the neuronal activities in these regions may provide more deep insights into acupuncture mechanisms. This paper used fractal analysis to investigate MA-induced spike trains of Wide Dynamic Range (WDR) neurons in rat spinal dorsal horn, an important relay station and integral component in processing acupuncture information. Allan factor and Fano factor were utilized to test whether the spike trains were fractal, and Allan factor were used to evaluate the scaling exponents and Hurst exponents. It was found that these two fractal exponents before and during MA were different significantly. During MA, the scaling exponents of WDR neurons were regulated in a small range, indicating a special fractal pattern. The neuronal activities were long-range correlated over multiple time scales. The scaling exponents during and after MA were similar, suggesting that the long-range correlations not only displayed during MA, but also extended to after withdrawing the needle. Our results showed that fractal analysis is a useful tool for measuring acupuncture effects. MA could modulate neuronal activities of which the fractal properties change as time proceeding. This evolution of fractal dynamics in course of MA experiments may explain at the level of neuron why the effect of MA observed in experiment and in clinic are complex, time-evolutionary, long-range even lasting for some time after stimulation

  2. High Precision Sunphotometer using Wide Dynamic Range (WDR) Camera Tracking

    Science.gov (United States)

    Liss, J.; Dunagan, S. E.; Johnson, R. R.; Chang, C. S.; LeBlanc, S. E.; Shinozuka, Y.; Redemann, J.; Flynn, C. J.; Segal-Rosenhaimer, M.; Pistone, K.; Kacenelenbogen, M. S.; Fahey, L.

    2016-12-01

    High Precision Sunphotometer using Wide Dynamic Range (WDR) Camera TrackingThe NASA Ames Sun-photometer-Satellite Group, DOE, PNNL Atmospheric Sciences and Global Change Division, and NASA Goddard's AERONET (AErosol RObotic NETwork) team recently collaborated on the development of a new airborne sunphotometry instrument that provides information on gases and aerosols extending far beyond what can be derived from discrete-channel direct-beam measurements, while preserving or enhancing many of the desirable AATS features (e.g., compactness, versatility, automation, reliability). The enhanced instrument combines the sun-tracking ability of the current 14-Channel NASA Ames AATS-14 with the sky-scanning ability of the ground-based AERONET Sun/sky photometers, while extending both AATS-14 and AERONET capabilities by providing full spectral information from the UV (350 nm) to the SWIR (1,700 nm). Strengths of this measurement approach include many more wavelengths (isolated from gas absorption features) that may be used to characterize aerosols and detailed (oversampled) measurements of the absorption features of specific gas constituents. The Sky Scanning Sun Tracking Airborne Radiometer (3STAR) replicates the radiometer functionality of the AATS-14 instrument but incorporates modern COTS technologies for all instruments subsystems. A 19-channel radiometer bundle design is borrowed from a commercial water column radiance instrument manufactured by Biospherical Instruments of San Diego California (ref, Morrow and Hooker)) and developed using NASA funds under the Small Business Innovative Research (SBIR) program. The 3STAR design also incorporates the latest in robotic motor technology embodied in Rotary actuators from Oriental motor Corp. having better than 15 arc seconds of positioning accuracy. Control system was designed, tested and simulated using a Hybrid-Dynamical modeling methodology. The design also replaces the classic quadrant detector tracking sensor with a

  3. Neuronal hyperexcitability in the ventral posterior thalamus of neuropathic rats: modality selective effects of pregabalin.

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    Patel, Ryan; Dickenson, Anthony H

    2016-07-01

    Neuropathic pain represents a substantial clinical challenge; understanding the underlying neural mechanisms and back-translation of therapeutics could aid targeting of treatments more effectively. The ventral posterior thalamus (VP) is the major termination site for the spinothalamic tract and relays nociceptive activity to the somatosensory cortex; however, under neuropathic conditions, it is unclear how hyperexcitability of spinal neurons converges onto thalamic relays. This study aimed to identify neural substrates of hypersensitivity and the influence of pregabalin on central processing. In vivo electrophysiology was performed to record from VP wide dynamic range (WDR) and nociceptive-specific (NS) neurons in anesthetized spinal nerve-ligated (SNL), sham-operated, and naive rats. In neuropathic rats, WDR neurons had elevated evoked responses to low- and high-intensity punctate mechanical stimuli, dynamic brushing, and innocuous and noxious cooling, but less so to heat stimulation, of the receptive field. NS neurons in SNL rats also displayed increased responses to noxious punctate mechanical stimulation, dynamic brushing, noxious cooling, and noxious heat. Additionally, WDR, but not NS, neurons in SNL rats exhibited substantially higher rates of spontaneous firing, which may correlate with ongoing pain. The ratio of WDR-to-NS neurons was comparable between SNL and naive/sham groups, suggesting relatively few NS neurons gain sensitivity to low-intensity stimuli leading to a "WDR phenotype." After neuropathy was induced, the proportion of cold-sensitive WDR and NS neurons increased, supporting the suggestion that changes in frequency-dependent firing and population coding underlie cold hypersensitivity. In SNL rats, pregabalin inhibited mechanical and heat responses but not cold-evoked or elevated spontaneous activity. Copyright © 2016 the American Physiological Society.

  4. Modulation of neuronal dynamic range using two different adaptation mechanisms

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    Lei Wang

    2017-01-01

    Full Text Available The capability of neurons to discriminate between intensity of external stimulus is measured by its dynamic range. A larger dynamic range indicates a greater probability of neuronal survival. In this study, the potential roles of adaptation mechanisms (ion currents in modulating neuronal dynamic range were numerically investigated. Based on the adaptive exponential integrate-and-fire model, which includes two different adaptation mechanisms, i.e. subthreshold and suprathreshold (spike-triggered adaptation, our results reveal that the two adaptation mechanisms exhibit rather different roles in regulating neuronal dynamic range. Specifically, subthreshold adaptation acts as a negative factor that observably decreases the neuronal dynamic range, while suprathreshold adaptation has little influence on the neuronal dynamic range. Moreover, when stochastic noise was introduced into the adaptation mechanisms, the dynamic range was apparently enhanced, regardless of what state the neuron was in, e.g. adaptive or non-adaptive. Our model results suggested that the neuronal dynamic range can be differentially modulated by different adaptation mechanisms. Additionally, noise was a non-ignorable factor, which could effectively modulate the neuronal dynamic range.

  5. The conserved Wdr8-hMsd1/SSX2IP complex localises to the centrosome and ensures proper spindle length and orientation

    International Nuclear Information System (INIS)

    Hori, Akiko; Morand, Agathe; Ikebe, Chiho; Frith, David; Snijders, Ambrosius P.; Toda, Takashi

    2015-01-01

    The centrosome plays a pivotal role in a wide range of cellular processes and its dysfunction is causally linked to many human diseases including cancer and developmental and neurological disorders. This organelle contains more than one hundred components, and yet many of them remain uncharacterised. Here we identified a novel centrosome protein Wdr8, based upon the structural conservation of the fission yeast counterpart. We showed that Wdr8 constitutively localises to the centrosome and super resolution microscopy uncovered that this protein is enriched at the proximal end of the mother centriole. Furthermore, we identified hMsd1/SSX2IP, a conserved spindle anchoring protein, as one of Wdr8 interactors by mass spectrometry. Wdr8 formed a complex and partially colocalised with hMsd1/SSX2IP. Intriguingly, knockdown of Wdr8 or hMsd1/SSX2IP displayed very similar mitotic defects, in which spindle microtubules became shortened and misoriented. Indeed, Wdr8 depletion resulted in the reduced recruitment of hMsd1/SSX2IP to the mitotic centrosome, though the converse is not true. Together, we propose that the conserved Wdr8-hMsd1/SSX2IP complex plays a critical role in controlling proper spindle length and orientation. - Highlights: • Human Wdr8 is a centrosomal protein enriched in the proximal end of the centriole. • Wdr8 and hMsd1/SSX2IP form a complex conserved in fungi. • Depletion of Wdr8 results in shorter, tilted spindle microtubules. • Depletion phenotypes of Wdr8 are very similar to those of hMsd1/SSX2IP knockdown.

  6. The conserved Wdr8-hMsd1/SSX2IP complex localises to the centrosome and ensures proper spindle length and orientation

    Energy Technology Data Exchange (ETDEWEB)

    Hori, Akiko; Morand, Agathe; Ikebe, Chiho; Frith, David; Snijders, Ambrosius P.; Toda, Takashi, E-mail: takashi-toda@hiroshima-u.ac.jp

    2015-12-04

    The centrosome plays a pivotal role in a wide range of cellular processes and its dysfunction is causally linked to many human diseases including cancer and developmental and neurological disorders. This organelle contains more than one hundred components, and yet many of them remain uncharacterised. Here we identified a novel centrosome protein Wdr8, based upon the structural conservation of the fission yeast counterpart. We showed that Wdr8 constitutively localises to the centrosome and super resolution microscopy uncovered that this protein is enriched at the proximal end of the mother centriole. Furthermore, we identified hMsd1/SSX2IP, a conserved spindle anchoring protein, as one of Wdr8 interactors by mass spectrometry. Wdr8 formed a complex and partially colocalised with hMsd1/SSX2IP. Intriguingly, knockdown of Wdr8 or hMsd1/SSX2IP displayed very similar mitotic defects, in which spindle microtubules became shortened and misoriented. Indeed, Wdr8 depletion resulted in the reduced recruitment of hMsd1/SSX2IP to the mitotic centrosome, though the converse is not true. Together, we propose that the conserved Wdr8-hMsd1/SSX2IP complex plays a critical role in controlling proper spindle length and orientation. - Highlights: • Human Wdr8 is a centrosomal protein enriched in the proximal end of the centriole. • Wdr8 and hMsd1/SSX2IP form a complex conserved in fungi. • Depletion of Wdr8 results in shorter, tilted spindle microtubules. • Depletion phenotypes of Wdr8 are very similar to those of hMsd1/SSX2IP knockdown.

  7. Short-Rib Polydactyly and Jeune Syndromes Are Caused by Mutations in WDR60

    Science.gov (United States)

    McInerney-Leo, Aideen M.; Schmidts, Miriam; Cortés, Claudio R.; Leo, Paul J.; Gener, Blanca; Courtney, Andrew D.; Gardiner, Brooke; Harris, Jessica A.; Lu, Yeping; Marshall, Mhairi; Scambler, Peter J.; Beales, Philip L.; Brown, Matthew A.; Zankl, Andreas; Mitchison, Hannah M.; Duncan, Emma L.; Wicking, Carol

    2013-01-01

    Short-rib polydactyly syndromes (SRPS I–V) are a group of lethal congenital disorders characterized by shortening of the ribs and long bones, polydactyly, and a range of extraskeletal phenotypes. A number of other disorders in this grouping, including Jeune and Ellis-van Creveld syndromes, have an overlapping but generally milder phenotype. Collectively, these short-rib dysplasias (with or without polydactyly) share a common underlying defect in primary cilium function and form a subset of the ciliopathy disease spectrum. By using whole-exome capture and massive parallel sequencing of DNA from an affected Australian individual with SRPS type III, we detected two novel heterozygous mutations in WDR60, a relatively uncharacterized gene. These mutations segregated appropriately in the unaffected parents and another affected family member, confirming compound heterozygosity, and both were predicted to have a damaging effect on the protein. Analysis of an additional 54 skeletal ciliopathy exomes identified compound heterozygous mutations in WDR60 in a Spanish individual with Jeune syndrome of relatively mild presentation. Of note, these two families share one novel WDR60 missense mutation, although haplotype analysis suggested no shared ancestry. We further show that WDR60 localizes at the base of the primary cilium in wild-type human chondrocytes, and analysis of fibroblasts from affected individuals revealed a defect in ciliogenesis and aberrant accumulation of the GLI2 transcription factor at the centrosome or basal body in the absence of an obvious axoneme. These findings show that WDR60 mutations can cause skeletal ciliopathies and suggest a role for WDR60 in ciliogenesis. PMID:23910462

  8. Short-rib polydactyly and Jeune syndromes are caused by mutations in WDR60.

    Science.gov (United States)

    McInerney-Leo, Aideen M; Schmidts, Miriam; Cortés, Claudio R; Leo, Paul J; Gener, Blanca; Courtney, Andrew D; Gardiner, Brooke; Harris, Jessica A; Lu, Yeping; Marshall, Mhairi; Scambler, Peter J; Beales, Philip L; Brown, Matthew A; Zankl, Andreas; Mitchison, Hannah M; Duncan, Emma L; Wicking, Carol

    2013-09-05

    Short-rib polydactyly syndromes (SRPS I-V) are a group of lethal congenital disorders characterized by shortening of the ribs and long bones, polydactyly, and a range of extraskeletal phenotypes. A number of other disorders in this grouping, including Jeune and Ellis-van Creveld syndromes, have an overlapping but generally milder phenotype. Collectively, these short-rib dysplasias (with or without polydactyly) share a common underlying defect in primary cilium function and form a subset of the ciliopathy disease spectrum. By using whole-exome capture and massive parallel sequencing of DNA from an affected Australian individual with SRPS type III, we detected two novel heterozygous mutations in WDR60, a relatively uncharacterized gene. These mutations segregated appropriately in the unaffected parents and another affected family member, confirming compound heterozygosity, and both were predicted to have a damaging effect on the protein. Analysis of an additional 54 skeletal ciliopathy exomes identified compound heterozygous mutations in WDR60 in a Spanish individual with Jeune syndrome of relatively mild presentation. Of note, these two families share one novel WDR60 missense mutation, although haplotype analysis suggested no shared ancestry. We further show that WDR60 localizes at the base of the primary cilium in wild-type human chondrocytes, and analysis of fibroblasts from affected individuals revealed a defect in ciliogenesis and aberrant accumulation of the GLI2 transcription factor at the centrosome or basal body in the absence of an obvious axoneme. These findings show that WDR60 mutations can cause skeletal ciliopathies and suggest a role for WDR60 in ciliogenesis. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  9. WDR1 Presence in the Songbird Basilar Papilla

    Science.gov (United States)

    Adler, Henry J.; Sanovich, Elena; Brittan-Powell, Elizabeth F.; Yan, Kai; Dooling, Robert J.

    2009-01-01

    WD40 repeat 1 protein (WDR1) was first reported in the acoustically injured chicken inner ear, and bioinformatics revealed that WDR1 has numerous WD40 repeats, important for protein-protein interactions. It has significant homology to actin interacting protein 1 (Aip1) in several lower species such as yeast, roundworm, fruitfly and frog. Several studies have shown that Aip1 binds cofilin/actin depolymerizing factor, and that these interactions are pivotal for actin disassembly via actin filament severing and actin monomer capping. However, the role of WDR1 in auditory function has yet to be determined. WDR1 is typically restricted to hair cells of the normal avian basilar papilla, but is redistributed towards supporting cells after acoustic overstimulation, suggesting that WDR1 may be involved in inner ear response to noise stress. One aim of the present study was to resolve the question as to whether stress factors, other than intense sound, could induce changes in WDR1 presence in the affected avian inner ear. Several techniques were used to assess WDR1 presence in the inner ears of songbird strains, including Belgian Waterslager (BW) canary, an avian strain with degenerative hearing loss thought to have a genetic basis. Reverse transcription, followed by polymerase chain reactions with WDR1-specific primers, confirmed WDR1 presence in the basilar papillae of adult BW, non-BW canaries, and zebra finches. Confocal microscopy examinations, following immunocytochemistry with anti-WDR1 antibody, localized WDR1 to the hair cell cytoplasm along the avian sensory epithelium. In addition, little, if any, staining by anti-WDR1 antibody was observed among supporting cells in the chicken or songbird ear. The present observations confirm and extend the early findings of WDR1 localization in hair cells, but not in supporting cells, in the normal avian basilar papilla. However, unlike supporting cells in the acoustically damaged chicken basilar papilla, the inner ear of the BW

  10. WDR81 mutations cause extreme microcephaly and impair mitotic progression in human fibroblasts and Drosophila neural stem cells.

    Science.gov (United States)

    Cavallin, Mara; Rujano, Maria A; Bednarek, Nathalie; Medina-Cano, Daniel; Bernabe Gelot, Antoinette; Drunat, Severine; Maillard, Camille; Garfa-Traore, Meriem; Bole, Christine; Nitschké, Patrick; Beneteau, Claire; Besnard, Thomas; Cogné, Benjamin; Eveillard, Marion; Kuster, Alice; Poirier, Karine; Verloes, Alain; Martinovic, Jelena; Bidat, Laurent; Rio, Marlene; Lyonnet, Stanislas; Reilly, M Louise; Boddaert, Nathalie; Jenneson-Liver, Melanie; Motte, Jacques; Doco-Fenzy, Martine; Chelly, Jamel; Attie-Bitach, Tania; Simons, Matias; Cantagrel, Vincent; Passemard, Sandrine; Baffet, Alexandre; Thomas, Sophie; Bahi-Buisson, Nadia

    2017-10-01

    Microlissencephaly is a rare brain malformation characterized by congenital microcephaly and lissencephaly. Microlissencephaly is suspected to result from abnormalities in the proliferation or survival of neural progenitors. Despite the recent identification of six genes involved in microlissencephaly, the pathophysiological basis of this condition remains poorly understood. We performed trio-based whole exome sequencing in seven subjects from five non-consanguineous families who presented with either microcephaly or microlissencephaly. This led to the identification of compound heterozygous mutations in WDR81, a gene previously associated with cerebellar ataxia, intellectual disability and quadrupedal locomotion. Patient phenotypes ranged from severe microcephaly with extremely reduced gyration with pontocerebellar hypoplasia to moderate microcephaly with cerebellar atrophy. In patient fibroblast cells, WDR81 mutations were associated with increased mitotic index and delayed prometaphase/metaphase transition. Similarly, in vivo, we showed that knockdown of the WDR81 orthologue in Drosophila led to increased mitotic index of neural stem cells with delayed mitotic progression. In summary, we highlight the broad phenotypic spectrum of WDR81-related brain malformations, which include microcephaly with moderate to extremely reduced gyration and cerebellar anomalies. Our results suggest that WDR81 might have a role in mitosis that is conserved between Drosophila and humans. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Absence of Wdr13 Gene Predisposes Mice to Mild Social Isolation – Chronic Stress, Leading to Depression-Like Phenotype Associated With Differential Expression of Synaptic Proteins

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    Mitra, Shiladitya; Sameer Kumar, Ghantasala S.; Jyothi Lakshmi, B.; Thakur, Suman; Kumar, Satish

    2018-01-01

    We earlier reported that the male mice lacking the Wdr13 gene (Wdr13-/0) showed mild anxiety, better memory retention, and up-regulation of synaptic proteins in the hippocampus. With increasing evidences from parallel studies in our laboratory about the possible role of Wdr13 in stress response, we investigated its role in brain. We observed that Wdr13 transcript gets up-regulated in the hippocampus of the wild-type mice exposed to stress. To further dissect its function, we analyzed the behavioral and molecular phenotypes of Wdr13-/0 mice when subjected to mild chronic psychological stress, namely; mild (attenuated) social isolation. We employed iTRAQ based quantitative proteomics, real time PCR and western blotting to investigate molecular changes. Three weeks of social isolation predisposed Wdr13-/0 mice to anhedonia, heightened anxiety-measured by Open field test (OFT), increased behavior despair- measured by Forced swim test (FST) and reduced dendritic branching along with decreased spine density of hippocampal CA1 neurons as compared to wild-type counterparts. This depression-like-phenotype was however ameliorated when treated with anti-depressant imipramine. Molecular analysis revealed that out of 1002 quantified proteins [1% False discovery rate (FDR), at-least two unique peptides], strikingly, a significant proportion of synaptic proteins including, SYN1, CAMK2A, and RAB3A were down-regulated in the socially isolated Wdr13-/0 mice as compared to its wild-type counterparts. This was in contrast to the elevated levels of these proteins in non-stressed mutants as compared to the controls. We hypothesized that a de-regulated transcription factor upstream of the synaptic genes might be responsible for the observed phenotype. Indeed, in the socially isolated Wdr13-/0 mice, there was an up-regulation of GATA1 – a transcription factor that negatively regulates synaptic genes and has been associated with Major Depression (MD) in humans. The present study

  12. Synergistic effect of SRY and its direct target, WDR5, on Sox9 expression.

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    Zhen Xu

    Full Text Available SRY is a sex-determining gene that encodes a transcription factor, which triggers male development in most mammals. The molecular mechanism of SRY action in testis determination is, however, poorly understood. In this study, we demonstrate that WDR5, which encodes a WD-40 repeat protein, is a direct target of SRY. EMSA experiments and ChIP assays showed that SRY could bind to the WDR5 gene promoter directly. Overexpression of SRY in LNCaP cells significantly increased WDR5 expression concurrent with histone H3K4 methylation on the WDR5 promoter. To specifically address whether SRY contributes to WDR5 regulation, we introduced a 4-hydroxy-tamoxifen-inducible SRY allele into LNCaP cells. Conditional SRY expression triggered enrichment of SRY on the WDR5 promoter resulting in induction of WDR5 transcription. We found that WDR5 was self regulating through a positive feedback loop. WDR5 and SRY interacted and were colocalized in cells. In addition, the interaction of WDR5 with SRY resulted in activation of Sox9 while repressing the expression of β-catenin. These results suggest that, in conjunction with SRY, WDR5 plays an important role in sex determination.

  13. Network feedback regulates motor output across a range of modulatory neuron activity.

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    Spencer, Robert M; Blitz, Dawn M

    2016-06-01

    Modulatory projection neurons alter network neuron synaptic and intrinsic properties to elicit multiple different outputs. Sensory and other inputs elicit a range of modulatory neuron activity that is further shaped by network feedback, yet little is known regarding how the impact of network feedback on modulatory neurons regulates network output across a physiological range of modulatory neuron activity. Identified network neurons, a fully described connectome, and a well-characterized, identified modulatory projection neuron enabled us to address this issue in the crab (Cancer borealis) stomatogastric nervous system. The modulatory neuron modulatory commissural neuron 1 (MCN1) activates and modulates two networks that generate rhythms via different cellular mechanisms and at distinct frequencies. MCN1 is activated at rates of 5-35 Hz in vivo and in vitro. Additionally, network feedback elicits MCN1 activity time-locked to motor activity. We asked how network activation, rhythm speed, and neuron activity levels are regulated by the presence or absence of network feedback across a physiological range of MCN1 activity rates. There were both similarities and differences in responses of the two networks to MCN1 activity. Many parameters in both networks were sensitive to network feedback effects on MCN1 activity. However, for most parameters, MCN1 activity rate did not determine the extent to which network output was altered by the addition of network feedback. These data demonstrate that the influence of network feedback on modulatory neuron activity is an important determinant of network output and feedback can be effective in shaping network output regardless of the extent of network modulation. Copyright © 2016 the American Physiological Society.

  14. Mechanics of Interrill Erosion with Wind-Driven Rain (WDR)

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    This article provides an evaluation analysis for the performance of the interrill component of the Water Erosion Prediction Project (WEPP) model for Wind-Driven Rain (WDR) events. The interrill delivery rates (Di) were collected in the wind tunnel rainfall simulator facility of the International Cen...

  15. WDR62 overexpression is associated with a poor prognosis in patients with lung adenocarcinoma.

    Science.gov (United States)

    Shinmura, Kazuya; Kato, Hisami; Kawanishi, Yuichi; Igarashi, Hisaki; Inoue, Yusuke; Yoshimura, Katsuhiro; Nakamura, Satoki; Fujita, Hidehiko; Funai, Kazuhito; Tanahashi, Masayuki; Niwa, Hiroshi; Ogawa, Hiroshi; Sugimura, Haruhiko

    2017-08-01

    Human WDR62, which is localized in the cytoplasm including the centrosome, is known to be responsible for primary microcephaly; however, the role of WDR62 abnormality in cancers remains largely unknown. In this study, we aimed to reveal the pathological role of WDR62 abnormality in lung adenocarcinoma (LAC). We first examined the WDR62 mRNA expression level of LAC (n = 64) using a QRT-PCR analysis and found that WDR62 mRNA transcripts were significantly overexpressed in LAC (P = 0.0432, Wilcoxon matched pairs test). An immunohistochemical analysis for LAC (n = 237) showed that WDR62 proteins were also significantly overexpressed in LAC (P overexpression have a short overall survival (P = 0.0378, log-rank test), and a multivariate analysis revealed that WDR62 overexpression was an independent predictor of a poor survival outcome among LAC patients (hazard ratio, 2.032; 95% confidence interval, 1.071-3.777; P = 0.0305). Next, we examined the functional effect of WDR62 overexpression on the lung cancer cell line H1299. WDR62-overexpressing lung cancer cells exhibited an increase in cell growth. Moreover, the concurrent overexpression of WDR62 and TPX2, a WDR62-interacting protein that is also overexpressed in LAC, induced centrosome amplification in the lung cells. Finally, we disclosed that the concurrent overexpression of WDR62 and TPX2 is common in diverse human cancers, using data from the Cancer Genome Atlas. These results suggested that WDR62 overexpression is associated with a poor prognosis in patients with LAC and leads to an increase in the malignant potential of lung cells. © 2017 Wiley Periodicals, Inc.

  16. Enhanced expression of WD repeat-containing protein 35 (WDR35 stimulated by domoic acid in rat hippocampus: involvement of reactive oxygen species generation and p38 mitogen-activated protein kinase activation

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    Tsunekawa Koji

    2013-01-01

    Full Text Available Abstract Background Domoic acid (DA is an excitatory amino acid analogue of kainic acid (KA that acts via activation of glutamate receptors to elicit a rapid and potent excitotoxic response, resulting in neuronal cell death. Recently, DA was shown to elicit reactive oxygen species (ROS production and induce apoptosis accompanied by activation of p38 mitogen-activated protein kinase (MAPK in vitro. We have reported that WDR35, a WD-repeat protein, may mediate apoptosis in several animal models. In the present study, we administered DA to rats intraperitoneally, then used liquid chromatography/ion trap tandem mass spectrometry (LC-MS/MS to identify and quantify DA in the brains of the rats and performed histological examinations of the hippocampus. We further investigated the potential involvement of glutamate receptors, ROS, p38 MAPK, and WDR35 in DA-induced toxicity in vivo. Results Our results showed that intraperitoneally administered DA was present in the brain and induced neurodegenerative changes including apoptosis in the CA1 region of the hippocampus. DA also increased the expression of WDR35 mRNA and protein in a dose- and time-dependent manner in the hippocampus. In experiments using glutamate receptor antagonists, the AMPA/KA receptor antagonist NBQX significantly attenuated the DA-induced increase in WDR35 protein expression, but the NMDA receptor antagonist MK-801 did not. In addition, the radical scavenger edaravone significantly attenuated the DA-induced increase in WDR35 protein expression. Furthermore, NBQX and edaravone significantly attenuated the DA-induced increase in p38 MAPK phosphorylation. Conclusion In summary, our results indicated that DA activated AMPA/KA receptors and induced ROS production and p38 MAPK phosphorylation, resulting in an increase in the expression of WDR35 in vivo.

  17. Phase-coherence transitions and communication in the gamma range between delay-coupled neuronal populations.

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    Alessandro Barardi

    2014-07-01

    Full Text Available Synchronization between neuronal populations plays an important role in information transmission between brain areas. In particular, collective oscillations emerging from the synchronized activity of thousands of neurons can increase the functional connectivity between neural assemblies by coherently coordinating their phases. This synchrony of neuronal activity can take place within a cortical patch or between different cortical regions. While short-range interactions between neurons involve just a few milliseconds, communication through long-range projections between different regions could take up to tens of milliseconds. How these heterogeneous transmission delays affect communication between neuronal populations is not well known. To address this question, we have studied the dynamics of two bidirectionally delayed-coupled neuronal populations using conductance-based spiking models, examining how different synaptic delays give rise to in-phase/anti-phase transitions at particular frequencies within the gamma range, and how this behavior is related to the phase coherence between the two populations at different frequencies. We have used spectral analysis and information theory to quantify the information exchanged between the two networks. For different transmission delays between the two coupled populations, we analyze how the local field potential and multi-unit activity calculated from one population convey information in response to a set of external inputs applied to the other population. The results confirm that zero-lag synchronization maximizes information transmission, although out-of-phase synchronization allows for efficient communication provided the coupling delay, the phase lag between the populations, and the frequency of the oscillations are properly matched.

  18. Organization of Functional Long-Range Circuits Controlling the Activity of Serotonergic Neurons in the Dorsal Raphe Nucleus

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    Li Zhou

    2017-03-01

    Full Text Available Serotonergic neurons play key roles in various biological processes. However, circuit mechanisms underlying tight control of serotonergic neurons remain largely unknown. Here, we systematically investigated the organization of long-range synaptic inputs to serotonergic neurons and GABAergic neurons in the dorsal raphe nucleus (DRN of mice with a combination of viral tracing, slice electrophysiological, and optogenetic techniques. We found that DRN serotonergic neurons and GABAergic neurons receive largely comparable synaptic inputs from six major upstream brain areas. Upon further analysis of the fine functional circuit structures, we found both bilateral and ipsilateral patterns of topographic connectivity in the DRN for the axons from different inputs. Moreover, the upstream brain areas were found to bidirectionally control the activity of DRN serotonergic neurons by recruiting feedforward inhibition or via a push-pull mechanism. Our study provides a framework for further deciphering the functional roles of long-range circuits controlling the activity of serotonergic neurons in the DRN.

  19. Electrophysiological characterization of spinal neurons in different models of diabetes type 1- and type 2-induced neuropathy in rats.

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    Schuelert, N; Gorodetskaya, N; Just, S; Doods, H; Corradini, L

    2015-04-16

    Diabetic polyneuropathy (DPN) is a devastating complication of diabetes. The underlying pathogenesis of DPN is still elusive and an effective treatment devoid of side effects presents a challenge. There is evidence that in type-1 and -2 diabetes, metabolic and morphological changes lead to peripheral nerve damage and altered central nociceptive transmission, which may contribute to neuropathic pain symptoms. We characterized the electrophysiological response properties of spinal wide dynamic range (WDR) neurons in three diabetic models. The streptozotocin (STZ) model was used as a drug-induced model of type-1 diabetes, and the BioBreeding/Worcester (BB/Wor) and Zucker diabetic fatty (ZDF) rat models were used for genetic DPN models. Data were compared to the respective control group (BB/Wor diabetic-resistant, Zucker lean (ZL) and saline-injected Wistar rat). Response properties of WDR neurons to mechanical stimulation and spontaneous activity were assessed. We found abnormal response properties of spinal WDR neurons in all diabetic rats but not controls. Profound differences between models were observed. In BB/Wor diabetic rats evoked responses were increased, while in ZDF rats spontaneous activity was increased and in STZ rats mainly after discharges were increased. The abnormal response properties of neurons might indicate differential pathological, diabetes-induced, changes in spinal neuronal transmission. This study shows for the first time that specific electrophysiological response properties are characteristic for certain models of DPN and that these might reflect the diverse and complex symptomatology of DPN in the clinic. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Bupivacaine-induced apoptosis independently of WDR35 expression in mouse neuroblastoma Neuro2a cells

    Science.gov (United States)

    2012-01-01

    Background Bupivacaine-induced neurotoxicity has been shown to occur through apoptosis. Recently, bupivacaine was shown to elicit reactive oxygen species (ROS) production and induce apoptosis accompanied by activation of p38 mitogen-activated protein kinase (MAPK) in a human neuroblastoma cell line. We have reported that WDR35, a WD40-repeat protein, may mediate apoptosis through caspase-3 activation. The present study was undertaken to test whether bupivacaine induces apoptosis in mouse neuroblastoma Neuro2a cells and to determine whether ROS, p38 MAPK, and WDR35 are involved. Results Our results showed that bupivacaine induced ROS generation and p38 MAPK activation in Neuro2a cells, resulting in apoptosis. Bupivacaine also increased WDR35 expression in a dose- and time-dependent manner. Hydrogen peroxide (H2O2) also increased WDR35 expression in Neuro2a cells. Antioxidant (EUK-8) and p38 MAPK inhibitor (SB202190) treatment attenuated the increase in caspase-3 activity, cell death and WDR35 expression induced by bupivacaine or H2O2. Although transfection of Neuro2a cells with WDR35 siRNA attenuated the bupivacaine- or H2O2-induced increase in expression of WDR35 mRNA and protein, in contrast to our previous studies, it did not inhibit the increase in caspase-3 activity in bupivacaine- or H2O2-treated cells. Conclusions In summary, our results indicated that bupivacaine induced apoptosis in Neuro2a cells. Bupivacaine induced ROS generation and p38 MAPK activation, resulting in an increase in WDR35 expression, in these cells. However, the increase in WDR35 expression may not be essential for the bupivacaine-induced apoptosis in Neuro2a cells. These results may suggest the existence of another mechanism of bupivacaine-induced apoptosis independent from WDR35 expression in Neuro2a cells. PMID:23227925

  1. P44/WDR77 restricts the sensitivity of proliferating cells to TGFβ signaling

    Energy Technology Data Exchange (ETDEWEB)

    Yi, Pengfei [Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, Hubei 430022 (China); Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 (United States); Gao, Shen [Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 (United States); Gu, Zhongping [Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038 (China); Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 (United States); Huang, Tao [Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, Hubei 430022 (China); Wang, Zhengxin, E-mail: zhenwang@mdanderson.org [Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 (United States)

    2014-07-18

    Highlights: • P44/WDR77 causes proliferating cells to become non-responsive to TGFβ signaling. • P44/WDR77 down-regulates TβRII and TβR2 expression. • P44/WDR77 down-regulated TGFβ signaling correlates with lung tumorigenesis. - Abstract: We previously reported that a novel WD-40 domain-containing protein, p44/WDR77, drives quiescent epithelial cells to re-enter the cell cycle and plays an essential role for growth of lung and prostate cancer cells. Transforming growth factor beta (TGFβ) signaling is important in the maintenance of non-transformed cells in the quiescent or slowly cycling stage. However, both non-transformed proliferating cells and human cancer cells are non-responsive to endogenous TGFβ signaling. The mechanism by which proliferating cells become refractory to TGFβ inhibition is not well established. Here, we found that silencing p44/WDR77 increased cellular sensitivity to TGFβ signaling and that this was inversely correlated with decreased cell proliferation. Smad2 or 3 phosphorylation, TGFβ-mediated transcription, and TGFβ2 and TGFβ receptor type II (TβRII) expression were dramatically induced by silencing of p44/WDR77. These data support the hypothesis that p44/WDR77 down-regulates the expression of the TGFβ ligand and its receptor, thereby leading to a cellular non-response to TGFβ signaling. Finally, we found that p44/WDR77 expression was correlated with cell proliferation and decreased TGFβ signaling during lung tumorigenesis. Together, these results suggest that p44/WDR77 expression causes the non-sensitivity of proliferating cells to TGFβ signaling, thereby contributing to cellular proliferation during lung tumorigenesis.

  2. Identification of the first multi-exonic WDR72 deletion in isolated amelogenesis imperfecta, and generation of a WDR72-specific copy number screening tool.

    Science.gov (United States)

    Hentschel, Julia; Tatun, Dana; Parkhomchuk, Dmitri; Kurth, Ingo; Schimmel, Bettina; Heinrich-Weltzien, Roswitha; Bertzbach, Sabine; Peters, Hartmut; Beetz, Christian

    2016-09-15

    Amelogenesis imperfecta (AI) is a clinically and genetically heterogeneous disorder of tooth development which is due to aberrant deposition or composition of enamel. Both syndromic and isolated forms exist; they may be inherited in an X-linked, autosomal recessive, or autosomal dominant manner. WDR72 is one of ten currently known genes for recessive isolated AI; nine WDR72 mutations affecting single nucleotides have been described to date. Based on whole exome sequencing in a large consanguineous AI pedigree, we obtained evidence for presence of a multi-exonic WDR72 deletion. A home-made multiplex ligation-dependent probe amplification assay was used to confirm the aberration, to narrow its extent, and to identify heterozygous carriers. Our study extends the mutational spectrum for WDR72 to include large deletions, and supports a relevance of the previously proposed loss-of-function mechanism. It also introduces an easy-to-use and highly sensitive tool for detecting WDR72 copy number alterations. Copyright © 2016. Published by Elsevier B.V.

  3. WDR73 missense mutation causes infantile onset intellectual disability and cerebellar hypoplasia in a consanguineous family.

    Science.gov (United States)

    Jiang, Chen; Gai, Nan; Zou, Yongyi; Zheng, Yu; Ma, Ruiyu; Wei, Xianda; Liang, Desheng; Wu, Lingqian

    2017-01-01

    Galloway-Mowat syndrome (GMS) is a very rare autosomal-recessive disorder characterized by nephrotic syndrome associated with microcephaly, and various central nervous system abnormalities, mostly cerebral hypoplasia or cerebellar atrophy, intellectual disability and neural-migration defects. WDR73 is the only gene known to cause GMS, and has never been implicated in other disease. Here we present a Chinese consanguineous family with infantile onset intellectual disability and cerebellar hypoplasia but no microcephaly. Whole exome sequencing identified a WDR73 p.W371G missense mutation. The mutation is confirmed to be segregated in this family by Sanger sequencing according to a recessive inheritance pattern. It is predicted to be deleterious by multiple algorithms and affect highly conserved site. Structural modeling revealed conformational differences between the wild type protein and the p.W371G protein. Real-time PCR and Western blotting revealed altered mRNA and protein levels in mutated samples. Our study indicates the novel WDR73 p.W371G missense mutation causes infantile onset intellectual disability and cerebellar hypoplasia in recessive mode of inheritance. Our findings imply that microcephaly is a variable phenotype in WDR73-related disease, suggest WDR73 to be a candidate gene of severe intellectual disability and cerebellar hypoplasia, and expand the molecular spectrum of WDR73-related disease. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Organization of Functional Long-Range Circuits Controlling the Activity of Serotonergic Neurons in the Dorsal Raphe Nucleus.

    Science.gov (United States)

    Zhou, Li; Liu, Ming-Zhe; Li, Qing; Deng, Juan; Mu, Di; Sun, Yan-Gang

    2017-03-21

    Serotonergic neurons play key roles in various biological processes. However, circuit mechanisms underlying tight control of serotonergic neurons remain largely unknown. Here, we systematically investigated the organization of long-range synaptic inputs to serotonergic neurons and GABAergic neurons in the dorsal raphe nucleus (DRN) of mice with a combination of viral tracing, slice electrophysiological, and optogenetic techniques. We found that DRN serotonergic neurons and GABAergic neurons receive largely comparable synaptic inputs from six major upstream brain areas. Upon further analysis of the fine functional circuit structures, we found both bilateral and ipsilateral patterns of topographic connectivity in the DRN for the axons from different inputs. Moreover, the upstream brain areas were found to bidirectionally control the activity of DRN serotonergic neurons by recruiting feedforward inhibition or via a push-pull mechanism. Our study provides a framework for further deciphering the functional roles of long-range circuits controlling the activity of serotonergic neurons in the DRN. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  5. Wdr18 is required for Kupffer's vesicle formation and regulation of body asymmetry in zebrafish.

    Directory of Open Access Journals (Sweden)

    Wei Gao

    Full Text Available Correct specification of the left-right (L-R axis is important for organ morphogenesis. Conserved mechanisms involving cilia rotation inside node-like structures and asymmetric Nodal signaling in the lateral plate mesoderm (LPM, which are important symmetry-breaking events, have been intensively studied. In zebrafish, the clustering and migration of dorsal forerunner cells (DFCs is critical for the formation of the Kuppfer's vesicle (KV. However, molecular events underlying DFC clustering and migration are less understood. The WD-repeat proteins function in a variety of biological processes, including cytoskeleton assembly, intracellular trafficking, mRNA splicing, transcriptional regulation and cell migration. However, little is known about the function of WD-repeat proteins in L-R asymmetry determination. Here, we report the identification and functional analyses of zebrafish wdr18, a novel gene that encodes a WD-repeat protein that is highly conserved among vertebrate species. wdr18 was identified from a Tol2 transposon-mediated enhancer trap screen. Follow-up analysis of wdr18 mRNA expression showed that it was detected in DFCs or the KV progenitor cells and later in the KV at early somitogenesis stages. Morpholino knockdown of wdr18 resulted in laterality defects in the visceral organs, which were preceded by the mis-expression of Nodal-related genes, including spaw and pitx2. Examination of morphants at earlier stages revealed that the KV had fewer and shorter cilia which are immotile and a smaller cavity. We further investigated the organization of DFCs in wdr18 morphant embryos using ntl and sox17 as specific markers and found that the clustering and migration of DFC was altered, leading to a disorganized KV. Finally, through a combination of wdr18 and itgb1b morpholino injections, we provided evidence that wdr18 and itgb1b genetically interact in the laterality determination process. Thus, we reveal a new and essential role for WD

  6. A zebrafish screen for craniofacial mutants identifies wdr68 as a highly conserved gene required for endothelin-1 expression

    Directory of Open Access Journals (Sweden)

    Amsterdam Adam

    2006-06-01

    Full Text Available Abstract Background Craniofacial birth defects result from defects in cranial neural crest (NC patterning and morphogenesis. The vertebrate craniofacial skeleton is derived from cranial NC cells and the patterning of these cells occurs within the pharyngeal arches. Substantial efforts have led to the identification of several genes required for craniofacial skeletal development such as the endothelin-1 (edn1 signaling pathway that is required for lower jaw formation. However, many essential genes required for craniofacial development remain to be identified. Results Through screening a collection of insertional zebrafish mutants containing approximately 25% of the genes essential for embryonic development, we present the identification of 15 essential genes that are required for craniofacial development. We identified 3 genes required for hyomandibular development. We also identified zebrafish models for Campomelic Dysplasia and Ehlers-Danlos syndrome. To further demonstrate the utility of this method, we include a characterization of the wdr68 gene. We show that wdr68 acts upstream of the edn1 pathway and is also required for formation of the upper jaw equivalent, the palatoquadrate. We also present evidence that the level of wdr68 activity required for edn1 pathway function differs between the 1st and 2nd arches. Wdr68 interacts with two minibrain-related kinases, Dyrk1a and Dyrk1b, required for embryonic growth and myotube differentiation, respectively. We show that a GFP-Wdr68 fusion protein localizes to the nucleus with Dyrk1a in contrast to an engineered loss of function mutation Wdr68-T284F that no longer accumulated in the cell nucleus and failed to rescue wdr68 mutant animals. Wdr68 homologs appear to exist in all eukaryotic genomes. Notably, we found that the Drosophila wdr68 homolog CG14614 could substitute for the vertebrate wdr68 gene even though insects lack the NC cell lineage. Conclusion This work represents a systematic

  7. Neurons are sensitive to the magnetic fields applied within the range of MR intensity used for diagnostic purposes

    International Nuclear Information System (INIS)

    Azanza, M.J.

    1997-01-01

    A very high number of data, obtained from molecular and cell biology experimental work, show that living beings are sensitive to either the static magnetic fields (SMF) or the electromagnetic fields in the extremely low frequency (ELF) range (1). Considering the question of the intensity range of the SMF applied for clinical diagnosis, we have made experiments by applying SMF (0,3-0,7 T) directly to neurons. We have shown that there exist a neuron magneto sensitivity explained as a result of the diamagnetism of the phospholipid and protein molecules of the lipid bilayer plasma membrane. This diamagnetism is working together with electric dipolar interactions (a mixed up interaction coined as super diamagnetism) and binded membrane Ca''2+ cooperative coulomb explosion, which in turn operate Ca''2+ -dependent-K''+ membrane channels (2,3). The specific intrinsic metabolic characteristics of the neurons populations explain two types of responses: either a variation in the firing frequency (increases or decreases) or a decrease in the spikes amplitude. This second effect is explained by the inhibition of the Na''+ -K''+-ATP-ase ionic pumps, inactivated by the same superdiamagnetims mechanism. We show in this paper the dependence of the frequency and amplitude changes, of the electrophysiological activity of the neurons, with the intensity of the applied SMF. (Author) 30 refs

  8. Lack of WDR36 leads to preimplantation embryonic lethality in mice and delays the formation of small subunit ribosomal RNA in human cells in vitro.

    Science.gov (United States)

    Gallenberger, Martin; Meinel, Dominik M; Kroeber, Markus; Wegner, Michael; Milkereit, Philipp; Bösl, Michael R; Tamm, Ernst R

    2011-02-01

    Mutations in WD repeat domain 36 gene (WDR36) play a causative role in some forms of primary open-angle glaucoma, a leading cause of blindness worldwide. WDR36 is characterized by the presence of multiple WD40 repeats and shows homology to Utp21, an essential protein component of the yeast small subunit (SSU) processome required for maturation of 18S rRNA. To clarify the functional role of WDR36 in the mammalian organism, we generated and investigated mutant mice with a targeted deletion of Wdr36. In parallel experiments, we used RNA interference to deplete WDR36 mRNA in mouse embryos and cultured human trabecular meshwork (HTM-N) cells. Deletion of Wdr36 in the mouse caused preimplantation embryonic lethality, and essentially similar effects were observed when WDR36 mRNA was depleted in mouse embryos by RNA interference. Depletion of WDR36 mRNA in HTM-N cells caused apoptotic cell death and upregulation of mRNA for BAX, TP53 and CDKN1A. By immunocytochemistry, staining for WDR36 was observed in the nucleolus of cells, which co-localized with that of nucleolar proteins such as nucleophosmin and PWP2. In addition, recombinant and epitope-tagged WDR36 localized to the nucleolus of HTM-N cells. By northern blot analysis, a substantial decrease in 21S rRNA, the precursor of 18S rRNA, was observed following knockdown of WDR36. In addition, metabolic-labeling experiments consistently showed a delay of 18S rRNA maturation in WDR36-depleted cells. Our results provide evidence that WDR36 is an essential protein in mammalian cells which is involved in the nucleolar processing of SSU 18S rRNA.

  9. AAA-ATPase NVL2 acts on MTR4-exosome complex to dissociate the nucleolar protein WDR74

    Energy Technology Data Exchange (ETDEWEB)

    Hiraishi, Nobuhiro; Ishida, Yo-ichi; Nagahama, Masami, E-mail: nagahama@my-pharm.ac.jp

    2015-11-20

    Nuclear VCP-like 2 (NVL2) is a chaperone-like nucleolar ATPase of the AAA (ATPase associated with diverse cellular activities) family, which exhibits a high level of amino acid sequence similarity with the cytosolic AAA-ATPase VCP/p97. These proteins generally act on macromolecular complexes to stimulate energy-dependent release of their constituents. We previously showed that NVL2 interacts with RNA processing/degradation machinery containing an RNA helicase MTR4/DOB1 and an exonuclease complex, nuclear exosome, and involved in the biogenesis of 60S ribosomal subunits. These observations implicate NVL2 as a remodeling factor for the MTR4-exosome complex during the maturation of pre-ribosomal particles. Here, we used a proteomic screen and identified a WD repeat-containing protein 74 (WDR74) as a factor that specifically dissociates from this complex depending on the ATPase activity of NVL2. WDR74 shows weak amino acid sequence similarity with the yeast ribosome biogenesis protein Nsa1 and is co-localized with NVL2 in the nucleolus. Knockdown of WDR74 decreases 60S ribosome levels. Taken together, our results suggest that WDR74 is a novel regulatory protein of the MTR4-exsosome complex whose interaction is regulated by NVL2 and is involved in ribosome biogenesis. - Highlights: • WDR74 accumulates in MTR4-exosome complex upon expression of dominant-negative NVL2. • WDR74 is co-localized with NVL2 in the nucleolus. • WDR74, along with NVL2, is involved in the synthesis of 60S ribosomal subunits.

  10. AAA-ATPase NVL2 acts on MTR4-exosome complex to dissociate the nucleolar protein WDR74

    International Nuclear Information System (INIS)

    Hiraishi, Nobuhiro; Ishida, Yo-ichi; Nagahama, Masami

    2015-01-01

    Nuclear VCP-like 2 (NVL2) is a chaperone-like nucleolar ATPase of the AAA (ATPase associated with diverse cellular activities) family, which exhibits a high level of amino acid sequence similarity with the cytosolic AAA-ATPase VCP/p97. These proteins generally act on macromolecular complexes to stimulate energy-dependent release of their constituents. We previously showed that NVL2 interacts with RNA processing/degradation machinery containing an RNA helicase MTR4/DOB1 and an exonuclease complex, nuclear exosome, and involved in the biogenesis of 60S ribosomal subunits. These observations implicate NVL2 as a remodeling factor for the MTR4-exosome complex during the maturation of pre-ribosomal particles. Here, we used a proteomic screen and identified a WD repeat-containing protein 74 (WDR74) as a factor that specifically dissociates from this complex depending on the ATPase activity of NVL2. WDR74 shows weak amino acid sequence similarity with the yeast ribosome biogenesis protein Nsa1 and is co-localized with NVL2 in the nucleolus. Knockdown of WDR74 decreases 60S ribosome levels. Taken together, our results suggest that WDR74 is a novel regulatory protein of the MTR4-exsosome complex whose interaction is regulated by NVL2 and is involved in ribosome biogenesis. - Highlights: • WDR74 accumulates in MTR4-exosome complex upon expression of dominant-negative NVL2. • WDR74 is co-localized with NVL2 in the nucleolus. • WDR74, along with NVL2, is involved in the synthesis of 60S ribosomal subunits.

  11. Neurofitter: a parameter tuning package for a wide range of electrophysiological neuron models

    Directory of Open Access Journals (Sweden)

    Werner Van Geit

    2007-11-01

    Full Text Available The increase in available computational power and the higher quality of experimental recordings have turned the tuning of neuron model parameters into a problem that can be solved by automatic global optimization algorithms. Neurofitter is a software tool that interfaces existing neural simulation software and sophisticated optimization algorithms with a new way to compute the error measure. This error measure represents how well a given parameter set is able to reproduce the experimental data. It is based on the phase-plane trajectory density method, which is insensitive to small phase differences between model and data. Neurofitter enables the effortless combination of many different time-dependent data traces into the error measure, allowing the neuroscientist to focus on what are the seminal properties of the model. We show results obtained by applying Neurofitter to a simple single compartmental model and a complex multi-compartmental Purkinje cell (PC model. These examples show that the method is able to solve a variety of tuning problems and demonstrate details of its practical application.

  12. Time Delay and Long-Range Connection Induced Synchronization Transitions in Newman-Watts Small-World Neuronal Networks

    Science.gov (United States)

    Qian, Yu

    2014-01-01

    The synchronization transitions in Newman-Watts small-world neuronal networks (SWNNs) induced by time delay and long-range connection (LRC) probability have been investigated by synchronization parameter and space-time plots. Four distinct parameter regions, that is, asynchronous region, transition region, synchronous region, and oscillatory region have been discovered at certain LRC probability as time delay is increased. Interestingly, desynchronization is observed in oscillatory region. More importantly, we consider the spatiotemporal patterns obtained in delayed Newman-Watts SWNNs are the competition results between long-range drivings (LRDs) and neighboring interactions. In addition, for moderate time delay, the synchronization of neuronal network can be enhanced remarkably by increasing LRC probability. Furthermore, lag synchronization has been found between weak synchronization and complete synchronization as LRC probability is a little less than 1.0. Finally, the two necessary conditions, moderate time delay and large numbers of LRCs, are exposed explicitly for synchronization in delayed Newman-Watts SWNNs. PMID:24810595

  13. Analog VLSI Models of Range-Tuned Neurons in the Bat Echolocation System

    Directory of Open Access Journals (Sweden)

    Horiuchi Timothy

    2003-01-01

    Full Text Available Bat echolocation is a fascinating topic of research for both neuroscientists and engineers, due to the complex and extremely time-constrained nature of the problem and its potential for application to engineered systems. In the bat's brainstem and midbrain exist neural circuits that are sensitive to the specific difference in time between the outgoing sonar vocalization and the returning echo. While some of the details of the neural mechanisms are known to be species-specific, a basic model of reafference-triggered, postinhibitory rebound timing is reasonably well supported by available data. We have designed low-power, analog VLSI circuits to mimic this mechanism and have demonstrated range-dependent outputs for use in a real-time sonar system. These circuits are being used to implement range-dependent vocalization amplitude, vocalization rate, and closest target isolation.

  14. Glial-Specific Functions of Microcephaly Protein WDR62 and Interaction with the Mitotic Kinase AURKA Are Essential for Drosophila Brain Growth.

    Science.gov (United States)

    Lim, Nicholas R; Shohayeb, Belal; Zaytseva, Olga; Mitchell, Naomi; Millard, S Sean; Ng, Dominic C H; Quinn, Leonie M

    2017-07-11

    The second most commonly mutated gene in primary microcephaly (MCPH) patients is wd40-repeat protein 62 (wdr62), but the relative contribution of WDR62 function to the growth of major brain lineages is unknown. Here, we use Drosophila models to dissect lineage-specific WDR62 function(s). Interestingly, although neural stem cell (neuroblast)-specific depletion of WDR62 significantly decreased neuroblast number, brain size was unchanged. In contrast, glial lineage-specific WDR62 depletion significantly decreased brain volume. Moreover, loss of function in glia not only decreased the glial population but also non-autonomously caused neuroblast loss. We further demonstrated that WDR62 controls brain growth through lineage-specific interactions with master mitotic signaling kinase, AURKA. Depletion of AURKA in neuroblasts drives brain overgrowth, which was suppressed by WDR62 co-depletion. In contrast, glial-specific depletion of AURKA significantly decreased brain volume, which was further decreased by WDR62 co-depletion. Thus, dissecting relative contributions of MCPH factors to individual neural lineages will be critical for understanding complex diseases such as microcephaly. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  15. Dispersion of the intrinsic neuronal periods affects the relationship of the entrainment range to the coupling strength in the suprachiasmatic nucleus

    Science.gov (United States)

    Gu, Changgui; Yang, Huijie; Wang, Man

    2017-11-01

    Living beings on the Earth are subjected to and entrained (synchronized) to the natural 24-h light-dark cycle. Interestingly, they can also be entrained to an external artificial cycle of non-24-h periods. The range of these periods is called the entrainment range and it differs among species. In mammals, the entrainment range is regulated by a main clock located in the suprachiasmatic nucleus (SCN) which is composed of 10 000 neurons in the brain. Previous works have found that the entrainment range depends on the cellular coupling strength in the SCN. In particular, the entrainment range decreases with the increase of the cellular coupling strength, provided that all the neuronal oscillators are identical. However, the SCN neurons differ in the intrinsic periods that follow a normal distribution in a range from 22 to 28 h. In the present study, taking the dispersion of the intrinsic neuronal periods into account, we examined the relationship between the entrainment range and the coupling strength. Results from numerical simulations and theoretical analyses both show that the relationship is altered to be paraboliclike if the intrinsic neuronal periods are nonidentical, and the maximal entrainment range is obtained with a suitable coupling strength. Our results shed light on the role of the cellular coupling in the entrainment ability of the SCN network.

  16. Upon Infection the Cellular WD Repeat-containing Protein 5 (WDR5) Localizes to Cytoplasmic Inclusion Bodies and Enhances Measles Virus Replication.

    Science.gov (United States)

    Ma, Dzwokai; George, Cyril X; Nomburg, Jason; Pfaller, Christian K; Cattaneo, Roberto; Samuel, Charles E

    2017-12-13

    Replication of negative-strand RNA viruses occurs in association with discrete cytoplasmic foci called inclusion bodies. Whereas inclusion bodies represent a prominent subcellular structure induced by viral infection, our knowledge of the cellular protein components involved in inclusion body formation and function is limited. Using measles virus-infected HeLa cells, we found that the WD repeat-containing protein 5 (WDR5), a subunit of histone H3 lysine 4 methyltransferases, was selectively recruited to virus-induced inclusion bodies. Furthermore, WDR5 was found in complexes containing viral proteins associated with RNA replication. WDR5 was not detected with mitochondria, stress granules, or other known secretory or endocytic compartments of infected cells. WDR5 deficiency decreased both viral protein production and infectious virus yields. Interferon production was modestly increased in WDR5 deficient cells. Thus, our study identifies WDR5 as a novel viral inclusion body-associated cellular protein and suggests a role for WDR5 in promoting viral replication. IMPORTANCE Measles virus is a human pathogen that remains a global concern with more than 100,000 measles-related deaths annually despite the availability of an effective vaccine. As measles continues to cause significant morbidity and mortality, understanding the virus-host interactions at the molecular level that affect virus replication efficiency is important for development and optimization of treatment procedures. Measles virus is an RNA virus that encodes six genes and replicates in the cytoplasm of infected cells in discrete cytoplasmic replication bodies, though little is known of the biochemical nature of these structures. Here we show that the cellular protein WDR5 is enriched in the cytoplasmic viral replication factories and enhances virus growth. WDR5-containing protein complex includes viral proteins responsible for viral RNA replication. Thus, we have identified WDR5 as a host factor that

  17. Digenic Inheritance of PROKR2 and WDR11 Mutations in Pituitary Stalk Interruption Syndrome.

    Science.gov (United States)

    McCormack, Shana E; Li, Dong; Kim, Yeon Joo; Lee, Ji Young; Kim, Soo-Hyun; Rapaport, Robert; Levine, Michael A

    2017-07-01

    Pituitary stalk interruption syndrome (PSIS, ORPHA95496) is a congenital defect of the pituitary gland characterized by the triad of a very thin/interrupted pituitary stalk, an ectopic (or absent) posterior pituitary gland, and hypoplasia or aplasia of the anterior pituitary gland. Complex genetic patterns of inheritance of this disorder are increasingly recognized. The objective of this study was to identify a genetic cause of PSIS in an affected child. Whole exome sequencing (WES) was performed by using standard techniques, with prioritized genetic variants confirmed via Sanger sequencing. To investigate the effects of one candidate variant on mutant WDR11 function, Western blotting and coimmunofluorescence were used to assess binding capacity, and leptomycin B exposure along with immunofluorescence was used to assess nuclear localization. We describe a child who presented in infancy with combined pituitary hormone deficiencies and whose brain imaging demonstrated a small anterior pituitary, ectopic posterior pituitary, and a thin, interrupted stalk. WES demonstrated heterozygous missense mutations in two genes required for pituitary development, a known loss-of-function mutation in PROKR2 (c.253C>T;p.R85C) inherited from an unaffected mother, and a WDR11 (c.1306A>G;p.I436V) mutation inherited from an unaffected father. Mutant WDR11 loses its capacity to bind to its functional partner, EMX1, and to localize to the nucleus. WES in a child with PSIS and his unaffected family implicates a digenic mechanism of inheritance. In cases of hypopituitarism in which there is incomplete segregation of a monogenic genotype with the phenotype, the possibility that a second genetic locus is involved should be considered. Copyright © 2017 Endocrine Society

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

    Science.gov (United States)

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

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Wallace Victoria C

    2009-06-01

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

  20. MLL/WDR5 Complex Regulates Kif2A Localization to Ensure Chromosome Congression and Proper Spindle Assembly during Mitosis.

    Science.gov (United States)

    Ali, Aamir; Veeranki, Sailaja Naga; Chinchole, Akash; Tyagi, Shweta

    2017-06-19

    Mixed-lineage leukemia (MLL), along with multisubunit (WDR5, RbBP5, ASH2L, and DPY30) complex catalyzes the trimethylation of H3K4, leading to gene activation. Here, we characterize a chromatin-independent role for MLL during mitosis. MLL and WDR5 localize to the mitotic spindle apparatus, and loss of function of MLL complex by RNAi results in defects in chromosome congression and compromised spindle formation. We report interaction of MLL complex with several kinesin and dynein motors. We further show that the MLL complex associates with Kif2A, a member of the Kinesin-13 family of microtubule depolymerase, and regulates the spindle localization of Kif2A during mitosis. We have identified a conserved WDR5 interaction (Win) motif, so far unique to the MLL family, in Kif2A. The Win motif of Kif2A engages in direct interactions with WDR5 for its spindle localization. Our findings highlight a non-canonical mitotic function of MLL complex, which may have a direct impact on chromosomal stability, frequently compromised in cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. A prefoldin-associated WD-repeat protein (WDR92) is required for the correct architectural assembly of motile cilia

    Science.gov (United States)

    Patel-King, Ramila S.; King, Stephen M.

    2016-01-01

    WDR92 is a highly conserved WD-repeat protein that has been proposed to be involved in apoptosis and also to be part of a prefoldin-like cochaperone complex. We found that WDR92 has a phylogenetic signature that is generally compatible with it playing a role in the assembly or function of specifically motile cilia. To test this hypothesis, we performed an RNAi-based knockdown of WDR92 gene expression in the planarian Schmidtea mediterranea and were able to achieve a robust reduction in mRNA expression to levels undetectable under our standard RT-PCR conditions. We found that this treatment resulted in a dramatic reduction in the rate of organismal movement that was caused by a switch in the mode of locomotion from smooth, cilia-driven gliding to muscle-based, peristaltic contractions. Although the knockdown animals still assembled cilia of normal length and in similar numbers to controls, these structures had reduced beat frequency and did not maintain hydrodynamic coupling. By transmission electron microscopy we observed that many cilia had pleiomorphic defects in their architecture, including partial loss of dynein arms, incomplete closure of the B-tubule, and occlusion or replacement of the central pair complex by accumulated electron-dense material. These observations suggest that WDR92 is part of a previously unrecognized cytoplasmic chaperone system that is specifically required to fold key components necessary to build motile ciliary axonemes. PMID:26912790

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

    Directory of Open Access Journals (Sweden)

    Lynne Shanley

    2010-12-01

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

  3. Wdr66 is a novel marker for risk stratification and involved in epithelial-mesenchymal transition of esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Wang, Qing; Ma, Chenming; Kemmner, Wolfgang

    2013-01-01

    We attempted to identify novel biomarkers and therapeutic targets for esophageal squamous cell carcinoma by gene expression profiling of frozen esophageal squamous carcinoma specimens and examined the functional relevance of a newly discovered marker gene, WDR66. Laser capture microdissection technique was applied to collect the cells from well-defined tumor areas in collaboration with an experienced pathologist. Whole human gene expression profiling of frozen esophageal squamous carcinoma specimens (n = 10) and normal esophageal squamous tissue (n = 18) was performed using microarray technology. A gene encoding WDR66, WD repeat-containing protein 66 was significantly highly expressed in esophageal squamous carcinoma specimens. Microarray results were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in a second and independent cohort (n = 71) consisting of esophageal squamous cell carcinoma (n = 25), normal esophagus (n = 11), esophageal adenocarcinoma (n = 13), gastric adenocarcinoma (n = 15) and colorectal cancers (n = 7). In order to understand WDR66’s functional relevance siRNA-mediated knockdown was performed in a human esophageal squamous cell carcinoma cell line, KYSE520 and the effects of this treatment were then checked by another microarray analysis. High WDR66 expression was significantly associated with poor overall survival (P = 0.031) of patients suffering from esophageal squamous carcinomas. Multivariate Cox regression analysis revealed that WDR66 expression remained an independent prognostic factor (P = 0.042). WDR66 knockdown by RNA interference resulted particularly in changes of the expression of membrane components. Expression of vimentin was down regulated in WDR66 knockdown cells while that of the tight junction protein occludin was markedly up regulated. Furthermore, siRNA-mediated knockdown of WDR66 resulted in suppression of cell growth and reduced cell motility. WDR66 might be a useful biomarker for risk

  4. Identification of a c.544C>T mutation in WDR34 as a deleterious recessive allele of short rib-polydactyly syndrome

    Directory of Open Access Journals (Sweden)

    Shu-Han You

    2017-12-01

    Conclusion: This study was the first to identify c.544C > T [p.Arg182Trp] mutation in WDR34 in a patient with SRPS. According to the database, the homozygous mutation of c.544C > T in WDR34 was deleterious and the prevalence of heterozygous mutation was relatively higher in Asian population. More studies of this mutation in patients with SRPS are required.

  5. Regulation of mitosis by the NIMA kinase involves TINA and its newly discovered partner, An-WDR8, at spindle pole bodies

    Science.gov (United States)

    Shen, Kuo-Fang; Osmani, Stephen A.

    2013-01-01

    The NIMA kinase is required for mitotic nuclear pore complex disassembly and potentially controls other mitotic-specific events. To investigate this possibility, we imaged NIMA–green fluorescent protein (GFP) using four-dimensional spinning disk confocal microscopy. At mitosis NIMA-GFP locates to spindle pole bodies (SPBs), which contain Cdk1/cyclin B, followed by Aurora, TINA, and the BimC kinesin. NIMA promotes NPC disassembly in a spatially regulated manner starting near SPBs. NIMA is also required for TINA, a NIMA-interacting protein, to locate to SPBs during initiation of mitosis, and TINA is then necessary for locating NIMA back to SPBs during mitotic progression. To help expand the NIMA-TINA pathway, we affinity purified TINA and found it to uniquely copurify with An-WDR8, a WD40-domain protein conserved from humans to plants. Like TINA, An-WDR8 accumulates within nuclei during G2 but disperses from nuclei before locating to mitotic SPBs. Without An-WDR8, TINA levels are greatly reduced, whereas TINA is necessary for mitotic targeting of An-WDR8. Finally, we show that TINA is required to anchor mitotic microtubules to SPBs and, in combination with An-WDR8, for successful mitosis. The findings provide new insights into SPB targeting and indicate that the mitotic microtubule-anchoring system at SPBs involves WDR8 in complex with TINA. PMID:24152731

  6. WDR1 and CLNK gene polymorphisms correlate with serum glucose and high-density lipoprotein levels in Tibetan gout patients.

    Science.gov (United States)

    Lan, Bing; Chen, Peng; Jiri, Mutu; He, Na; Feng, Tian; Liu, Kai; Jin, Tianbo; Kang, Longli

    2016-03-01

    Current evidence suggests heredity and metabolic syndrome contributes to gout progression. Specifically, the WDR1 and CLNK genes may play a role in gout progression in European ancestry populations. However, no studies have focused on Chinese populations, especially Tibetan individuals. This study aims to determine whether variations in these two genes correlate with gout-related indices in Chinese-Tibetan gout patients. Eleven single-nucleotide polymorphisms in the WDR1 and CLNK genes were detected in 319 Chinese-Tibetan gout patients and 318 controls. We used one-way analysis of variance to evaluate the polymorphisms' effects on gout based on mean serum levels of metabolism indicators, such as albumin, glucose (GLU), triglycerides, cholesterol, high-density lipoproteins (HDL-C), creatinine, and uric acid, from fasting venous blood samples. All p values were Bonferroni corrected. Polymorphisms of the WDR1 and CLNK genes affected multiple risk factors for gout development. Significant differences in serum GLU levels were detected between different genotypic groups with WDRI polymorphisms rs4604059 (p = 0.005) and rs12498927 (p = 0.005). In addition, significant differences in serum HDL-C levels were detected between different genotypic groups with the CLNK polymorphism rs2041215 (p = 0.001). Polymorphisms of CLNK also affected levels of albumin, triglycerides, and creatinine. This study is the first to investigate and identify positive correlations between WDR1 and CLNK gene polymorphisms in Chinese-Tibetan populations. Our findings provide significant evidence for the effect of genetic polymorphisms on gout-related factors in Chinese-Tibetan populations.

  7. Ciliopathies with Skeletal Anomalies and Renal Insufficiency due to Mutations in the IFT-A Gene WDR19

    Science.gov (United States)

    Bredrup, Cecilie; Saunier, Sophie; Oud, Machteld M.; Fiskerstrand, Torunn; Hoischen, Alexander; Brackman, Damien; Leh, Sabine M.; Midtbø, Marit; Filhol, Emilie; Bole-Feysot, Christine; Nitschké, Patrick; Gilissen, Christian; Haugen, Olav H.; Sanders, Jan-Stephan F.; Stolte-Dijkstra, Irene; Mans, Dorus A.; Steenbergen, Eric J.; Hamel, Ben C.J.; Matignon, Marie; Pfundt, Rolph; Jeanpierre, Cécile; Boman, Helge; Rødahl, Eyvind; Veltman, Joris A.; Knappskog, Per M.; Knoers, Nine V.A.M.; Roepman, Ronald; Arts, Heleen H.

    2011-01-01

    A subset of ciliopathies, including Sensenbrenner, Jeune, and short-rib polydactyly syndromes are characterized by skeletal anomalies accompanied by multiorgan defects such as chronic renal failure and retinitis pigmentosa. Through exome sequencing we identified compound heterozygous mutations in WDR19 in a Norwegian family with Sensenbrenner syndrome. In a Dutch family with the clinically overlapping Jeune syndrome, a homozygous missense mutation in the same gene was found. Both families displayed a nephronophthisis-like nephropathy. Independently, we also identified compound heterozygous WDR19 mutations by exome sequencing in a Moroccan family with isolated nephronophthisis. WDR19 encodes IFT144, a member of the intraflagellar transport (IFT) complex A that drives retrograde ciliary transport. We show that IFT144 is absent from the cilia of fibroblasts from one of the Sensenbrenner patients and that ciliary abundance and morphology is perturbed, demonstrating the ciliary pathogenesis. Our results suggest that isolated nephronophthisis, Jeune, and Sensenbrenner syndromes are clinically overlapping disorders that can result from a similar molecular cause. PMID:22019273

  8. Expression and function of androgen receptor coactivator p44/Mep50/WDR77 in ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Martin Ligr

    Full Text Available Hormones, including estrogen and progesterone, and their receptors play an important role in the development and progression of ovarian carcinoma. Androgen, its receptor and coactivators have also been implicated in these processes. p44/Mep50/WDR77 was identified as a subunit of the methylosome complex and lately characterized as a steroid receptor coactivator that enhances androgen receptor as well as estrogen receptor-mediated transcriptional activity in a ligand-dependent manner. We previously described distinct expression and function of p44 in prostate, testis, and breast cancers. In this report, we examined the expression and function of p44 in ovarian cancer. In contrast to findings in prostate and testicular cancer and similar to breast cancer, p44 shows strong cytoplasmic localization in morphologically normal ovarian surface and fallopian tube epithelia, while nuclear p44 is observed in invasive ovarian carcinoma. We observed that p44 can serve as a coactivator of both androgen receptor (AR and estrogen receptor (ER in ovarian cells. Further, overexpression of nuclear-localized p44 stimulates proliferation and invasion in ovarian cancer cells in the presence of estrogen or androgen. These findings strongly suggest that p44 plays a role in mediating the effects of hormones during ovarian tumorigenesis.

  9. Cellular Protein WDR11 Interacts with Specific Herpes Simplex Virus Proteins at the trans-Golgi Network To Promote Virus Replication

    Science.gov (United States)

    Taylor, Kathryne E.

    2015-01-01

    ABSTRACT It has recently been proposed that the herpes simplex virus (HSV) protein ICP0 has cytoplasmic roles in blocking antiviral signaling and in promoting viral replication in addition to its well-known proteasome-dependent functions in the nucleus. However, the mechanisms through which it produces these effects remain unclear. While investigating this further, we identified a novel cytoplasmic interaction between ICP0 and the poorly characterized cellular protein WDR11. During an HSV infection, WDR11 undergoes a dramatic change in localization at late times in the viral replication cycle, moving from defined perinuclear structures to a dispersed cytoplasmic distribution. While this relocation was not observed during infection with viruses other than HSV-1 and correlated with efficient HSV-1 replication, the redistribution was found to occur independently of ICP0 expression, instead requiring viral late gene expression. We demonstrate for the first time that WDR11 is localized to the trans-Golgi network (TGN), where it interacts specifically with some, but not all, HSV virion components, in addition to ICP0. Knockdown of WDR11 in cultured human cells resulted in a modest but consistent decrease in yields of both wild-type and ICP0-null viruses, in the supernatant and cell-associated fractions, without affecting viral gene expression. Although further study is required, we propose that WDR11 participates in viral assembly and/or secondary envelopment. IMPORTANCE While the TGN has been proposed to be the major site of HSV-1 secondary envelopment, this process is incompletely understood, and in particular, the role of cellular TGN components in this pathway is unknown. Additionally, little is known about the cellular functions of WDR11, although the disruption of this protein has been implicated in multiple human diseases. Therefore, our finding that WDR11 is a TGN-resident protein that interacts with specific viral proteins to enhance viral yields improves both

  10. Cmr1/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control

    DEFF Research Database (Denmark)

    Gallina, Irene; Colding, Camilla Skettrup; Henriksen, Peter

    2015-01-01

    DNA replication stress is a source of genomic instability. Here we identify changed mutation rate 1 (Cmr1) as a factor involved in the response to DNA replication stress in Saccharomyces cerevisiae and show that Cmr1-together with Mrc1/Claspin, Pph3, the chaperonin containing TCP1 (CCT) and 25...... other proteins-define a novel intranuclear quality control compartment (INQ) that sequesters misfolded, ubiquitylated and sumoylated proteins in response to genotoxic stress. The diversity of proteins that localize to INQ indicates that other biological processes such as cell cycle progression...... propose that Cmr1/WDR76 plays a role in the recovery from genotoxic stress through regulation of the turnover of sumoylated and phosphorylated proteins....

  11. Discovery of a Highly Potent, Cell-Permeable Macrocyclic Peptidomimetic (MM-589) Targeting the WD Repeat Domain 5 Protein (WDR5)–Mixed Lineage Leukemia (MLL) Protein–Protein Interaction

    Energy Technology Data Exchange (ETDEWEB)

    Karatas, Hacer; Li, Yangbing; Liu, Liu; Ji, Jiao; Lee, Shirley; Chen, Yong; Yang, Jiuling; Huang, Liyue; Bernard, Denzil; Xu, Jing; Townsend, Elizabeth C.; Cao, Fang; Ran, Xu; Li, Xiaoqin; Wen, Bo; Sun, Duxin; Stuckey, Jeanne A; Lei, Ming; Dou, Yali; Wang, Shaomeng (Michigan)

    2017-06-06

    We report herein the design, synthesis, and evaluation of macrocyclic peptidomimetics that bind to WD repeat domain 5 (WDR5) and block the WDR5–mixed lineage leukemia (MLL) protein–protein interaction. Compound 18 (MM-589) binds to WDR5 with an IC50 value of 0.90 nM (Ki value <1 nM) and inhibits the MLL H3K4 methyltransferase (HMT) activity with an IC50 value of 12.7 nM. Compound 18 potently and selectively inhibits cell growth in human leukemia cell lines harboring MLL translocations and is >40 times better than the previously reported compound MM-401. Cocrystal structures of 16 and 18 complexed with WDR5 provide structural basis for their high affinity binding to WDR5. Additionally, we have developed and optimized a new AlphaLISA-based MLL HMT functional assay to facilitate the functional evaluation of these designed compounds. Compound 18 represents the most potent inhibitor of the WDR5–MLL interaction reported to date, and further optimization of 18 may yield a new therapy for acute leukemia.

  12. Morphological changes in neurons of the central nervous system in response to experimental influence of centimeter-range electromagnetic waves on the body

    Energy Technology Data Exchange (ETDEWEB)

    Belokrinitskiy, V.S.

    1982-08-01

    Experiments on cats and dogs exposed to electromagnetic waves at thermal intensities of 400 to 500 mV/cm/sup 2/ for 1, 10, 20, or 30 days were used to study the effects on brain and spinal cord. Changes occurred in the neurons of animals immediately after irradiation, increasing in magnitude on the 10th, 20th, and 30th day of the study. In the brain, changes were observed in the size and shape of neurons and their components (nuclei, nucleoli, and processes therein), and in the density and location of chromophil and chromatin. The changes varied among neurons located in different regions of the brain. Immediately after irradiation and after prolonged exposure neuron changes were also observed in all sections of the spinal cord. However, each section of the spinal cord was uniquely affected by electromagnetic waves regarding type and number of altered neurons. By the 10th day after irradiation many neurons were in a state of total disintegration, and shadow cells were detected. Beginning with the 7th day after irradiation, the overall condition of the animals gradually worsened. The animals became less active and showed signs of depression. The symptoms were more pronounced in cats than in dogs. None of the animals survived.

  13. Genetic variation in WDR1 is associated with gout risk and gout-related metabolic indices in the Han Chinese population.

    Science.gov (United States)

    Liu, L J; Zhang, X Y; He, N; Liu, K; Shi, X G; Feng, T; Geng, T T; Yuan, D Y; Kang, L L; Jin, T B

    2016-04-28

    Gout is the most common form of inflammatory arthritis affecting men, and current evidence suggests that genetic factors contribute to its progression. As a previous study identified that WD40 repeat protein 1 (WDR1) is associated with gout in populations of European descent, we sought to investigate its relationship with this disease in the Han Chinese population. We genotyped six WDR1 single nucleotide polymorphisms in 143 gout cases and 310 controls using Sequenom MassARRAY technology. The SPSS 16.0 software was used to perform statistical analyses. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression, with adjustments for age and gender. In an analysis using an allelic model, we identified that the minor alleles of rs3756230 (OR = 0.64, 95%CI = 0.450-0.911, P = 0.013) and rs12498927 (OR = 1.377, 95%CI = 1.037-1.831, P = 0.027) were associated with gout risk. In addition, we found that the "A/A" genotype of rs12498927 was associated with increased risk of gout under codominant (OR = 2.22, 95%CI = 1.12- 4.40, P = 0.042) and recessive models (OR = 2.24, 95%CI = 1.20-4.17, P = 0.012). We also determined the "A/G" genotype of rs12498927 to be significantly associated with higher urea levels in gout patients (P = 0.017). Our data shed new light on the association between genetic variations in the WDR1 gene and gout susceptibility in the Han Chinese population.

  14. Mutation in WDR4 impairs tRNA m(7)G46 methylation and causes a distinct form of microcephalic primordial dwarfism.

    Science.gov (United States)

    Shaheen, Ranad; Abdel-Salam, Ghada M H; Guy, Michael P; Alomar, Rana; Abdel-Hamid, Mohamed S; Afifi, Hanan H; Ismail, Samira I; Emam, Bayoumi A; Phizicky, Eric M; Alkuraya, Fowzan S

    2015-09-28

    Primordial dwarfism is a state of extreme prenatal and postnatal growth deficiency, and is characterized by marked clinical and genetic heterogeneity. Two presumably unrelated consanguineous families presented with an apparently novel form of primordial dwarfism in which severe growth deficiency is accompanied by distinct facial dysmorphism, brain malformation (microcephaly, agenesis of corpus callosum, and simplified gyration), and severe encephalopathy with seizures. Combined autozygome/exome analysis revealed a novel missense mutation in WDR4 as the likely causal variant. WDR4 is the human ortholog of the yeast Trm82, an essential component of the Trm8/Trm82 holoenzyme that effects a highly conserved and specific (m(7)G46) methylation of tRNA. The human mutation and the corresponding yeast mutation result in a significant reduction of m(7)G46 methylation of specific tRNA species, which provides a potential mechanism for primordial dwarfism associated with this lesion, since reduced m(7)G46 modification causes a growth deficiency phenotype in yeast. Our study expands the number of biological pathways underlying primordial dwarfism and adds to a growing list of human diseases linked to abnormal tRNA modification.

  15. Interdependence of Pes1, Bop1, and WDR12 controls nucleolar localization and assembly of the PeBoW complex required for maturation of the 60S ribosomal subunit.

    Science.gov (United States)

    Rohrmoser, Michaela; Hölzel, Michael; Grimm, Thomas; Malamoussi, Anastassia; Harasim, Thomas; Orban, Mathias; Pfisterer, Iris; Gruber-Eber, Anita; Kremmer, Elisabeth; Eick, Dirk

    2007-05-01

    The PeBoW complex is essential for cell proliferation and maturation of the large ribosomal subunit in mammalian cells. Here we examined the role of PeBoW-specific proteins Pes1, Bop1, and WDR12 in complex assembly and stability, nucleolar transport, and pre-ribosome association. Recombinant expression of the three subunits is sufficient for complex formation. The stability of all three subunits strongly increases upon incorporation into the complex. Only overexpression of Bop1 inhibits cell proliferation and rRNA processing, and its negative effects could be rescued by coexpression of WDR12, but not Pes1. Elevated levels of Bop1 induce Bop1/WDR12 and Bop1/Pes1 subcomplexes. Knockdown of Bop1 abolishes the copurification of Pes1 with WDR12, demonstrating Bop1 as the integral component of the complex. Overexpressed Bop1 substitutes for endogenous Bop1 in PeBoW complex assembly, leading to the instability of endogenous Bop1. Finally, indirect immunofluorescence, cell fractionation, and sucrose gradient centrifugation experiments indicate that transport of Bop1 from the cytoplasm to the nucleolus is Pes1 dependent, while Pes1 can migrate to the nucleolus and bind to preribosomal particles independently of Bop1. We conclude that the assembly and integrity of the PeBoW complex are highly sensitive to changes in Bop1 protein levels.

  16. Neuromorphic Silicon Neuron Circuits

    Science.gov (United States)

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

    2011-01-01

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

  17. Neuromorphic silicon neuron circuits

    Directory of Open Access Journals (Sweden)

    Giacomo eIndiveri

    2011-05-01

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

  18. Motor Neurons

    DEFF Research Database (Denmark)

    Hounsgaard, Jorn

    2017-01-01

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

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  20. [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.

  1. Neurons other than motor neurons in motor neuron disease.

    Science.gov (United States)

    Ruffoli, Riccardo; Biagioni, Francesca; Busceti, Carla L; Gaglione, Anderson; Ryskalin, Larisa; Gambardella, Stefano; Frati, Alessandro; Fornai, Francesco

    2017-11-01

    Amyotrophic lateral sclerosis (ALS) is typically defined by a loss of motor neurons in the central nervous system. Accordingly, morphological analysis for decades considered motor neurons (in the cortex, brainstem and spinal cord) as the neuronal population selectively involved in ALS. Similarly, this was considered the pathological marker to score disease severity ex vivo both in patients and experimental models. However, the concept of non-autonomous motor neuron death was used recently to indicate the need for additional cell types to produce motor neuron death in ALS. This means that motor neuron loss occurs only when they are connected with other cell types. This concept originally emphasized the need for resident glia as well as non-resident inflammatory cells. Nowadays, the additional role of neurons other than motor neurons emerged in the scenario to induce non-autonomous motor neuron death. In fact, in ALS neurons diverse from motor neurons are involved. These cells play multiple roles in ALS: (i) they participate in the chain of events to produce motor neuron loss; (ii) they may even degenerate more than and before motor neurons. In the present manuscript evidence about multi-neuronal involvement in ALS patients and experimental models is discussed. Specific sub-classes of neurons in the whole spinal cord are reported either to degenerate or to trigger neuronal degeneration, thus portraying ALS as a whole spinal cord disorder rather than a disease affecting motor neurons solely. This is associated with a novel concept in motor neuron disease which recruits abnormal mechanisms of cell to cell communication.

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

    Science.gov (United States)

    Schneider, David M; Woolley, Sarah M N

    2010-06-01

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

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

    International Nuclear Information System (INIS)

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

    2001-01-01

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

  4. WDR-PK-AK-018

    Energy Technology Data Exchange (ETDEWEB)

    Hollister, R

    2009-08-26

    Method - CES SOP-HW-P556 'Field and Bulk Gamma Analysis'. Detector - High-purity germanium, 40% relative efficiency. Calibration - The detector was calibrated on February 8, 2006 using a NIST-traceable sealed source, and the calibration was verified using an independent sealed source. Count Time and Geometry - The sample was counted for 20 minutes at 72 inches from the detector. A lead collimator was used to limit the field-of-view to the region of the sample. The drum was rotated 180 degrees halfway through the count time. Date and Location of Scans - June 1,2006 in Building 235 Room 1136. Spectral Analysis Spectra were analyzed with ORTEC GammaVision software. Matrix and geometry corrections were calculated using OR TEC Isotopic software. A background spectrum was measured at the counting location. No man-made radioactivity was observed in the background. Results were determined from the sample spectra without background subtraction. Minimum detectable activities were calculated by the Nureg 4.16 method. Results - Detected Pu-238, Pu-239, Am-241 and Am-243.

  5. A chimeric path to neuronal synchronization

    Science.gov (United States)

    Essaki Arumugam, Easwara Moorthy; Spano, Mark L.

    2015-01-01

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

  6. 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)

  7. A chimeric path to neuronal synchronization

    International Nuclear Information System (INIS)

    Essaki Arumugam, Easwara Moorthy; Spano, Mark L.

    2015-01-01

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

  8. Loss of C9ORF72 impairs autophagy and synergizes with polyQ Ataxin-2 to induce motor neuron dysfunction and cell death.

    Science.gov (United States)

    Sellier, Chantal; Campanari, Maria-Letizia; Julie Corbier, Camille; Gaucherot, Angeline; Kolb-Cheynel, Isabelle; Oulad-Abdelghani, Mustapha; Ruffenach, Frank; Page, Adeline; Ciura, Sorana; Kabashi, Edor; Charlet-Berguerand, Nicolas

    2016-06-15

    An intronic expansion of GGGGCC repeats within the C9ORF72 gene is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD). Ataxin-2 with intermediate length of polyglutamine expansions (Ataxin-2 Q30x) is a genetic modifier of the disease. Here, we found that C9ORF72 forms a complex with the WDR41 and SMCR8 proteins to act as a GDP/GTP exchange factor for RAB8a and RAB39b and to thereby control autophagic flux. Depletion of C9orf72 in neurons partly impairs autophagy and leads to accumulation of aggregates of TDP-43 and P62 proteins, which are histopathological hallmarks of ALS-FTD SMCR8 is phosphorylated by TBK1 and depletion of TBK1 can be rescued by phosphomimetic mutants of SMCR8 or by constitutively active RAB39b, suggesting that TBK1, SMCR8, C9ORF72, and RAB39b belong to a common pathway regulating autophagy. While depletion of C9ORF72 only has a partial deleterious effect on neuron survival, it synergizes with Ataxin-2 Q30x toxicity to induce motor neuron dysfunction and neuronal cell death. These results indicate that partial loss of function of C9ORF72 is not deleterious by itself but synergizes with Ataxin-2 toxicity, suggesting a double-hit pathological mechanism in ALS-FTD. © 2016 The Authors.

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

    Science.gov (United States)

    Pamphlett, Roger; Kum Jew, Stephen

    2013-12-12

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

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

    Science.gov (United States)

    2013-01-01

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

  11. Synchronization of motor neurons during locomotion in the neonatal rat

    DEFF Research Database (Denmark)

    Tresch, Matthew C.; Kiehn, Ole

    2002-01-01

    We describe here the robust synchronization of motor neurons at a millisecond time scale during locomotor activity in the neonatal rat. Action potential activity of motor neuron pairs was recorded extracellularly using tetrodes during locomotor activity in the in vitro neonatal rat spinal cord....... Approximately 40% of motor neuron pairs recorded in the same spinal segment showed significant synchronization, with the duration of the central peak in cross-correlograms between motor neurons typically ranging between ∼ 30 and 100 msec. The percentage of synchronized motor neuron pairs was considerably higher...... between motor neurons persisted. On the other hand, both local and distant coupling between motor neurons were preserved after antagonism of gap junction coupling between motor neurons. These results demonstrate that motor neuron activity is strongly synchronized at a millisecond time scale during...

  12. Population coding in sparsely connected networks of noisy neurons

    OpenAIRE

    Tripp, Bryan P.; Orchard, Jeff

    2012-01-01

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

  13. Glutamate mediated astrocytic filtering of neuronal activity.

    Directory of Open Access Journals (Sweden)

    Gilad Wallach

    2014-12-01

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

  14. Glutamate Mediated Astrocytic Filtering of Neuronal Activity

    Science.gov (United States)

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

    2014-01-01

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

  15. Neuronal Migration Disorders

    Science.gov (United States)

    ... Understanding Sleep The Life and Death of a Neuron Genes At Work In The Brain Order Publications ... birth defects caused by the abnormal migration of neurons in the developing brain and nervous system. In ...

  16. Motor Neuron Diseases

    Science.gov (United States)

    ... and other neurodegenerative diseases to better understand the function of neurons and other support cells and identify candidate therapeutic ... and other neurodegenerative diseases to better understand the function of neurons and other support cells and identify candidate therapeutic ...

  17. Combinatorial analysis of lupulin gland transcription factors from R2R3Myb, bHLH and WDR families indicates a complex regulation of chs_H1 genes essential for prenylflavonoid biosynthesis in hop (Humulus Lupulus L.

    Directory of Open Access Journals (Sweden)

    Matoušek Jaroslav

    2012-02-01

    Full Text Available Abstract Background Lupulin glands of hop produce a specific metabolome including hop bitter acids valuable for the brewing process and prenylflavonoids with promising health-beneficial activities. The detailed analysis of the transcription factor (TF-mediated regulation of the oligofamily of one of the key enzymes, i.e., chalcone synthase CHS_H1 that efficiently catalyzes the production of naringenin chalcone, a direct precursor of prenylflavonoids in hop, constitutes an important part of the dissection of the biosynthetic pathways leading to the accumulation of these compounds. Results Homologues of flavonoid-regulating TFs HlMyb2 (M2, HlbHLH2 (B2 and HlWDR1 (W1 from hop were cloned using a lupulin gland-specific cDNA library from the hop variety Osvald's 72. Using a "combinatorial" transient GUS expression system it was shown that these unique lupulin-gland-associated TFs significantly activated the promoter (P of chs_H1 in ternary combinations of B2, W1 and either M2 or the previously characterized HlMyb3 (M3. The promoter activation was strongly dependent on the Myb-P binding box TCCTACC having a core sequence CCWACC positioned on its 5' end region and it seems that the complexity of the promoter plays an important role. M2B2W1-mediated activation significantly exceeded the strength of expression of native chs_H1 gene driven by the 35S promoter of CaMV, while M3B2W1 resulted in 30% of the 35S:chs_H1 expression level, as quantified by real-time PCR. Another newly cloned hop TF, HlMyb7, containing a transcriptional repressor-like motif pdLNLD/ELxiG/S (PDLNLELRIS, was identified as an efficient inhibitor of chs_H1-activating TFs. Comparative analyses of hop and A. thaliana TFs revealed a complex activation of Pchs_H1 and Pchs4 in combinatorial or independent manners. Conclusions This study on the sequences and functions of various lupulin gland-specific transcription factors provides insight into the complex character of the regulation of the

  18. Where do mirror neurons come from?

    Science.gov (United States)

    Heyes, Cecilia

    2010-03-01

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

  19. Underwater Ranging

    OpenAIRE

    S. P. Gaba

    1984-01-01

    The paper deals with underwater laser ranging system, its principle of operation and maximum depth capability. The sources of external noise and methods to improve signal-to-noise ratio are also discussed.

  20. Evoking prescribed spike times in stochastic neurons

    Science.gov (United States)

    Doose, Jens; Lindner, Benjamin

    2017-09-01

    Single cell stimulation in vivo is a powerful tool to investigate the properties of single neurons and their functionality in neural networks. We present a method to determine a cell-specific stimulus that reliably evokes a prescribed spike train with high temporal precision of action potentials. We test the performance of this stimulus in simulations for two different stochastic neuron models. For a broad range of parameters and a neuron firing with intermediate firing rates (20-40 Hz) the reliability in evoking the prescribed spike train is close to its theoretical maximum that is mainly determined by the level of intrinsic noise.

  1. Mirror neurons: from origin to function.

    Science.gov (United States)

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

    2014-04-01

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

  2. First-spike latency in Hodgkin's three classes of neurons.

    Science.gov (United States)

    Wang, Hengtong; Chen, Yueling; Chen, Yong

    2013-07-07

    We study the first-spike latency (FSL) in Hodgkin's three classes of neurons with the Morris-Lecar neuron model. It is found that all the three classes of neurons can encode an external stimulus into FSLs. With DC inputs, the FSLs of all of the neurons decrease with input intensity. With input current decreased to the threshold, class 1 neurons show an arbitrary long FSL whereas class 2 and 3 neurons exhibit the short-limit FSLs. When the input current is sinusoidal, the amplitude, frequency and initial phase can be encoded by all the three classes of neurons. The FSLs of all of the neurons decrease with the input amplitude and frequency. When the input frequency is too high, all of the neurons respond with infinite FSLs. When the initial phase increases, the FSL decreases and then jumps to a maximal value and finally decreases linearly. With changes in the input parameters, the FSLs of the class 1 and 2 neurons exhibit similar properties. However, the FSL of the class 3 neurons became slightly longer and only produces responses for a narrow range of initial phase if input frequencies are low. Moreover, our results also show that the FSL and firing rate responses are mutually independent processes and that neurons can encode an external stimulus into different FSLs and firing rates simultaneously. This finding is consistent with the current theory of dual or multiple complementary coding mechanisms. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2017-06-15

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

  4. Oscillatory integration windows in neurons

    Science.gov (United States)

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

    2016-01-01

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

  5. 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...

  6. Response sensitivity of barrel neuron subpopulations to simulated thalamic input.

    Science.gov (United States)

    Pesavento, Michael J; Rittenhouse, Cynthia D; Pinto, David J

    2010-06-01

    Our goal is to examine the relationship between neuron- and network-level processing in the context of a well-studied cortical function, the processing of thalamic input by whisker-barrel circuits in rodent neocortex. Here we focus on neuron-level processing and investigate the responses of excitatory and inhibitory barrel neurons to simulated thalamic inputs applied using the dynamic clamp method in brain slices. Simulated inputs are modeled after real thalamic inputs recorded in vivo in response to brief whisker deflections. Our results suggest that inhibitory neurons require more input to reach firing threshold, but then fire earlier, with less variability, and respond to a broader range of inputs than do excitatory neurons. Differences in the responses of barrel neuron subtypes depend on their intrinsic membrane properties. Neurons with a low input resistance require more input to reach threshold but then fire earlier than neurons with a higher input resistance, regardless of the neuron's classification. Our results also suggest that the response properties of excitatory versus inhibitory barrel neurons are consistent with the response sensitivities of the ensemble barrel network. The short response latency of inhibitory neurons may serve to suppress ensemble barrel responses to asynchronous thalamic input. Correspondingly, whereas neurons acting as part of the barrel circuit in vivo are highly selective for temporally correlated thalamic input, excitatory barrel neurons acting alone in vitro are less so. These data suggest that network-level processing of thalamic input in barrel cortex depends on neuron-level processing of the same input by excitatory and inhibitory barrel neurons.

  7. 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.

  8. Relating normalization to neuronal populations across cortical areas.

    Science.gov (United States)

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

    2016-09-01

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

  9. Spinal cord: motor neuron diseases.

    Science.gov (United States)

    Rezania, Kourosh; Roos, Raymond P

    2013-02-01

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

  10. Neuronal-glial trafficking

    International Nuclear Information System (INIS)

    Bachelard, H.S.

    2001-01-01

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

  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. Mesmerising mirror neurons.

    Science.gov (United States)

    Heyes, Cecilia

    2010-06-01

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

  13. The mirror neuron system.

    Science.gov (United States)

    Cattaneo, Luigi; Rizzolatti, Giacomo

    2009-05-01

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

  14. Energy-efficient neural information processing in individual neurons and neuronal networks.

    Science.gov (United States)

    Yu, Lianchun; Yu, Yuguo

    2017-11-01

    Brains are composed of networks of an enormous number of neurons interconnected with synapses. Neural information is carried by the electrical signals within neurons and the chemical signals among neurons. Generating these electrical and chemical signals is metabolically expensive. The fundamental issue raised here is whether brains have evolved efficient ways of developing an energy-efficient neural code from the molecular level to the circuit level. Here, we summarize the factors and biophysical mechanisms that could contribute to the energy-efficient neural code for processing input signals. The factors range from ion channel kinetics, body temperature, axonal propagation of action potentials, low-probability release of synaptic neurotransmitters, optimal input and noise, the size of neurons and neuronal clusters, excitation/inhibition balance, coding strategy, cortical wiring, and the organization of functional connectivity. Both experimental and computational evidence suggests that neural systems may use these factors to maximize the efficiency of energy consumption in processing neural signals. Studies indicate that efficient energy utilization may be universal in neuronal systems as an evolutionary consequence of the pressure of limited energy. As a result, neuronal connections may be wired in a highly economical manner to lower energy costs and space. Individual neurons within a network may encode independent stimulus components to allow a minimal number of neurons to represent whole stimulus characteristics efficiently. This basic principle may fundamentally change our view of how billions of neurons organize themselves into complex circuits to operate and generate the most powerful intelligent cognition in nature. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. 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.

  16. NeuronBank: a tool for cataloging neuronal circuitry

    Directory of Open Access Journals (Sweden)

    Paul S Katz

    2010-04-01

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

  17. Direct Neuronal Reprogramming for Disease Modeling Studies Using Patient-Derived Neurons: What Have We Learned?

    Directory of Open Access Journals (Sweden)

    Janelle Drouin-Ouellet

    2017-09-01

    Full Text Available Direct neuronal reprogramming, by which a neuron is formed via direct conversion from a somatic cell without going through a pluripotent intermediate stage, allows for the possibility of generating patient-derived neurons. A unique feature of these so-called induced neurons (iNs is the potential to maintain aging and epigenetic signatures of the donor, which is critical given that many diseases of the CNS are age related. Here, we review the published literature on the work that has been undertaken using iNs to model human brain disorders. Furthermore, as disease-modeling studies using this direct neuronal reprogramming approach are becoming more widely adopted, it is important to assess the criteria that are used to characterize the iNs, especially in relation to the extent to which they are mature adult neurons. In particular: i what constitutes an iN cell, ii which stages of conversion offer the earliest/optimal time to assess features that are specific to neurons and/or a disorder and iii whether generating subtype-specific iNs is critical to the disease-related features that iNs express. Finally, we discuss the range of potential biomedical applications that can be explored using patient-specific models of neurological disorders with iNs, and the challenges that will need to be overcome in order to realize these applications.

  18. Direct projections from hypothalamic orexin neurons to brainstem cardiac vagal neurons.

    Science.gov (United States)

    Dergacheva, Olga; Yamanaka, Akihiro; Schwartz, Alan R; Polotsky, Vsevolod Y; Mendelowitz, David

    2016-12-17

    Orexin neurons are known to augment the sympathetic control of cardiovascular function, however the role of orexin neurons in parasympathetic cardiac regulation remains unclear. To test the hypothesis that orexin neurons contribute to parasympathetic control we selectively expressed channelrhodopsin-2 (ChR2) in orexin neurons in orexin-Cre transgenic rats and examined postsynaptic currents in cardiac vagal neurons (CVNs) in the dorsal motor nucleus of the vagus (DMV). Simultaneous photostimulation and recording in ChR2-expressing orexin neurons in the lateral hypothalamus resulted in reliable action potential firing as well as large whole-cell currents suggesting a strong expression of ChR2 and reliable optogenetic excitation. Photostimulation of ChR2-expressing fibers in the DMV elicited short-latency (ranging from 3.2ms to 8.5ms) postsynaptic currents in 16 out of 44 CVNs tested. These responses were heterogeneous and included excitatory glutamatergic (63%) and inhibitory GABAergic (37%) postsynaptic currents. The results from this study suggest different sub-population of orexin neurons may exert diverse influences on brainstem CVNs and therefore may play distinct functional roles in parasympathetic control of the heart. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2014-04-08

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

  20. Neuronal avalanches and learning

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-05-01

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

  1. Neuronal avalanches and learning

    International Nuclear Information System (INIS)

    Arcangelis, Lucilla de

    2011-01-01

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

  2. Insights into the role of neuronal glucokinase.

    Science.gov (United States)

    De Backer, Ivan; Hussain, Sufyan S; Bloom, Stephen R; Gardiner, James V

    2016-07-01

    Glucokinase is a key component of the neuronal glucose-sensing mechanism and is expressed in brain regions that control a range of homeostatic processes. In this review, we detail recently identified roles for neuronal glucokinase in glucose homeostasis and counterregulatory responses to hypoglycemia and in regulating appetite. We describe clinical implications from these advances in our knowledge, especially for developing novel treatments for diabetes and obesity. Further research required to extend our knowledge and help our efforts to tackle the diabetes and obesity epidemics is suggested. Copyright © 2016 the American Physiological Society.

  3. Insights into the role of neuronal glucokinase

    Science.gov (United States)

    De Backer, Ivan; Hussain, Sufyan S.; Gardiner, James V.

    2016-01-01

    Glucokinase is a key component of the neuronal glucose-sensing mechanism and is expressed in brain regions that control a range of homeostatic processes. In this review, we detail recently identified roles for neuronal glucokinase in glucose homeostasis and counterregulatory responses to hypoglycemia and in regulating appetite. We describe clinical implications from these advances in our knowledge, especially for developing novel treatments for diabetes and obesity. Further research required to extend our knowledge and help our efforts to tackle the diabetes and obesity epidemics is suggested. PMID:27189932

  4. Evidence for a persistent sodium conductance in neurons from the nucleus prepositus hypoglossi

    DEFF Research Database (Denmark)

    Rekling, J C; Laursen, A M

    1989-01-01

    Intracellular recordings were made from 39 neurons in a slice preparation of the prepositus hypoglossi nucleus from guinea pigs. Morphological characteristics were confirmed by dying neurons with Lucifer yellow. The neurons were spontaneously active, firing in the range of 8-50 spikes/s. Spike...

  5. HCS-Neurons: identifying phenotypic changes in multi-neuron images upon drug treatments of high-content screening.

    Science.gov (United States)

    Charoenkwan, Phasit; Hwang, Eric; Cutler, Robert W; Lee, Hua-Chin; Ko, Li-Wei; Huang, Hui-Ling; Ho, Shinn-Ying

    2013-01-01

    High-content screening (HCS) has become a powerful tool for drug discovery. However, the discovery of drugs targeting neurons is still hampered by the inability to accurately identify and quantify the phenotypic changes of multiple neurons in a single image (named multi-neuron image) of a high-content screen. Therefore, it is desirable to develop an automated image analysis method for analyzing multi-neuron images. We propose an automated analysis method with novel descriptors of neuromorphology features for analyzing HCS-based multi-neuron images, called HCS-neurons. To observe multiple phenotypic changes of neurons, we propose two kinds of descriptors which are neuron feature descriptor (NFD) of 13 neuromorphology features, e.g., neurite length, and generic feature descriptors (GFDs), e.g., Haralick texture. HCS-neurons can 1) automatically extract all quantitative phenotype features in both NFD and GFDs, 2) identify statistically significant phenotypic changes upon drug treatments using ANOVA and regression analysis, and 3) generate an accurate classifier to group neurons treated by different drug concentrations using support vector machine and an intelligent feature selection method. To evaluate HCS-neurons, we treated P19 neurons with nocodazole (a microtubule depolymerizing drug which has been shown to impair neurite development) at six concentrations ranging from 0 to 1000 ng/mL. The experimental results show that all the 13 features of NFD have statistically significant difference with respect to changes in various levels of nocodazole drug concentrations (NDC) and the phenotypic changes of neurites were consistent to the known effect of nocodazole in promoting neurite retraction. Three identified features, total neurite length, average neurite length, and average neurite area were able to achieve an independent test accuracy of 90.28% for the six-dosage classification problem. This NFD module and neuron image datasets are provided as a freely downloadable

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

    Science.gov (United States)

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

    2014-02-10

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons are identified by their Go-like immunoreactivity, and show a distinct spatial distribution within the olfactory epithelium, similar to, but significantly different from that of crypt neurons. Furthermore, kappe neurons project to a single identified target glomerulus within the olfactory bulb, mdg5 of the mediodorsal cluster, whereas crypt neurons are known to project exclusively to the mdg2 glomerulus. Kappe neurons are negative for established markers of ciliated, microvillous and crypt neurons, but appear to have microvilli. Kappe neurons constitute the fourth type of olfactory sensory neurons reported in teleost fishes and their existence suggests that encoding of olfactory stimuli may require a higher complexity than hitherto assumed already in the peripheral olfactory system.

  7. Dynamics of a structured neuron population

    International Nuclear Information System (INIS)

    Pakdaman, Khashayar; Salort, Delphine; Perthame, Benoît

    2010-01-01

    We study the dynamics of assemblies of interacting neurons. For large fully connected networks, the dynamics of the system can be described by a partial differential equation reminiscent of age-structure models used in mathematical ecology, where the 'age' of a neuron represents the time elapsed since its last discharge. The nonlinearity arises from the connectivity J of the network. We prove some mathematical properties of the model that are directly related to qualitative properties. On the one hand, we prove that it is well-posed and that it admits stationary states which, depending upon the connectivity, can be unique or not. On the other hand, we study the long time behaviour of solutions; both for small and large J, we prove the relaxation to the steady state describing asynchronous firing of the neurons. In the middle range, numerical experiments show that periodic solutions appear expressing re-synchronization of the network and asynchronous firing

  8. 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...

  9. Measure of synchrony in the activity of intrinsic cardiac neurons

    International Nuclear Information System (INIS)

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

    2014-01-01

    Recent multielectrode array recordings in ganglionated plexi of canine atria have opened the way to the study of population dynamics of intrinsic cardiac neurons. These data provide critical insights into the role of local processing that these ganglia play in the regulation of cardiac function. Low firing rates, marked non-stationarity, interplay with the cardiovascular and pulmonary systems and artifacts generated by myocardial activity create new constraints not present in brain recordings for which almost all neuronal analysis techniques have been developed. We adapted and extended the jitter-based synchrony index (SI) to (1) provide a robust and computationally efficient tool for assessing the level and statistical significance of SI between cardiac neurons, (2) estimate the bias on SI resulting from neuronal activity possibly hidden in myocardial artifacts, (3) quantify the synchrony or anti-synchrony between neuronal activity and the phase in the cardiac and respiratory cycles. The method was validated on firing time series from a total of 98 individual neurons identified in 8 dog experiments. SI ranged from −0.14 to 0.66, with 23 pairs of neurons with SI > 0.1. The estimated bias due to artifacts was typically <1%. Strongly cardiovascular- and pulmonary-related neurons (SI > 0.5) were found. Results support the use of jitter-based SI in the context of intrinsic cardiac neurons. (paper)

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

    Science.gov (United States)

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

    2015-05-28

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

  11. Doubly stochastic coherence in complex neuronal networks

    Science.gov (United States)

    Gao, Yang; Wang, Jianjun

    2012-11-01

    A system composed of coupled FitzHugh-Nagumo neurons with various topological structures is investigated under the co-presence of two independently additive and multiplicative Gaussian white noises, in which particular attention is paid to the neuronal networks spiking regularity. As the additive noise intensity and the multiplicative noise intensity are simultaneously adjusted to optimal values, the temporal periodicity of the output of the system reaches the maximum, indicating the occurrence of doubly stochastic coherence. The network topology randomness exerts different influences on the temporal coherence of the spiking oscillation for dissimilar coupling strength regimes. At a small coupling strength, the spiking regularity shows nearly no difference in the regular, small-world, and completely random networks. At an intermediate coupling strength, the temporal periodicity in a small-world neuronal network can be improved slightly by adding a small fraction of long-range connections. At a large coupling strength, the dynamical behavior of the neurons completely loses the resonance property with regard to the additive noise intensity or the multiplicative noise intensity, and the spiking regularity decreases considerably with the increase of the network topology randomness. The network topology randomness plays more of a depressed role than a favorable role in improving the temporal coherence of the spiking oscillation in the neuronal network research study.

  12. Neuronal Migration and Neuronal Migration Disorder in Cerebral Cortex

    OpenAIRE

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

    2002-01-01

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

  13. Neuronal nets in robotics

    International Nuclear Information System (INIS)

    Jimenez Sanchez, Raul

    1999-01-01

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

  14. A Neuron Model Based Ultralow Current Sensor System for Bioapplications

    Directory of Open Access Journals (Sweden)

    A. K. M. Arifuzzman

    2016-01-01

    Full Text Available An ultralow current sensor system based on the Izhikevich neuron model is presented in this paper. The Izhikevich neuron model has been used for its superior computational efficiency and greater biological plausibility over other well-known neuron spiking models. Of the many biological neuron spiking features, regular spiking, chattering, and neostriatal spiny projection spiking have been reproduced by adjusting the parameters associated with the model at hand. This paper also presents a modified interpretation of the regular spiking feature in which the firing pattern is similar to that of the regular spiking but with improved dynamic range offering. The sensor current ranges between 2 pA and 8 nA and exhibits linearity in the range of 0.9665 to 0.9989 for different spiking features. The efficacy of the sensor system in detecting low amount of current along with its high linearity attribute makes it very suitable for biomedical applications.

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

    Science.gov (United States)

    Ni, Amy M; Maunsell, John H R

    2017-09-01

    area can be largely explained by between-neuron differences in normalization strength. Here we demonstrate that attention modulation size varies within neurons as well and that this variance is largely explained by within-neuron differences in normalization strength. We provide a new spatially tuned normalization model that explains this broad range of observed normalization and attention effects. Copyright © 2017 the American Physiological Society.

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

    Science.gov (United States)

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

    2016-12-14

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

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

    DEFF Research Database (Denmark)

    Pfisterer, Ulrich Gottfried; Khodosevich, Konstantin

    2017-01-01

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

  18. Review Essay: Mirror Neurons in the Discourse of Social Sciences

    Directory of Open Access Journals (Sweden)

    Henning Pätzold

    2010-08-01

    Full Text Available Since their discovery in the mid-1990s, mirror neurons have been the subject of continuous discussions in neurosciences as well as in the social sciences. The interest of scientists outside the life sciences in mirror neurons is primarily based on the fact that mirror neurons not only have epistemological meaning, but also seem to play an important role in processes of social insights and emotions, like empathy. With her book, Nadia ZABOURA provides a new contribution from a social and cultural sciences point of view, which critically reflects the discussion on mirror neurons and its consequences on the social sciences and humanities. Starting off from philosophical approaches to the mind-matter-dualism and the question of intersubjectivity, she explores the meaning of mirror neurons for the debate on empathy and communication. By discussing concepts of philosophy and communication sciences as well as current knowledge on mirror neurons, she concludes that they do not provide a stable basis for any material reductionism, which would explain phenomena like intersubjectivity only by recordable neuronal processes. The book refers to a variety of related theories (ranging from DESCARTES through to MEAD and TOMASELLO; these references are inspiring, yet they stay cursory for the most part. All in all the book offers avenues for further inquiry on the issues in focus, and can rather be taken as "tour of suggestions" through the topical field of mirror neurons and the related research. URN: urn:nbn:de:0114-fqs1003245

  19. Neuronal synchrony: peculiarity and generality.

    Science.gov (United States)

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

    2008-09-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  1. From Neurons to Newtons

    DEFF Research Database (Denmark)

    Nielsen, Bjørn Gilbert

    2001-01-01

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

  2. Criticality in Neuronal Networks

    Science.gov (United States)

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

    2012-02-01

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

  3. Dipeptide Piracetam Analogue Noopept Improves Viability of Hippocampal HT-22 Neurons in the Glutamate Toxicity Model.

    Science.gov (United States)

    Antipova, T A; Nikolaev, S V; Ostrovskaya, P U; Gudasheva, T A; Seredenin, S B

    2016-05-01

    Effect of noopept (N-phenylacetyl-prolylglycine ethyl ester) on viability of neurons exposed to neurotoxic action of glutamic acid (5 mM) was studied in vitro in immortalized mouse hippocampal HT-22 neurons. Noopept added to the medium before or after glutamic acid improved neuronal survival in a concentration range of 10-11-10-5 M. Comparison of the effective noopept concentrations determined in previous studies on cultured cortical and cerebellar neurons showed that hippocampal neurons are more sensitive to the protective effect of noopept.

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

    Science.gov (United States)

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

    2015-08-26

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

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

    Science.gov (United States)

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

    2015-01-01

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

  6. 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.

  7. Connectivity and dynamics of neuronal networks as defined by the shape of individual neurons

    International Nuclear Information System (INIS)

    Ahnert, Sebastian E; A N Travencolo, Bruno; Costa, Luciano da Fontoura

    2009-01-01

    Biological neuronal networks constitute a special class of dynamical systems, as they are formed by individual geometrical components, namely the neurons. In the existing literature, relatively little attention has been given to the influence of neuron shape on the overall connectivity and dynamics of the emerging networks. The current work addresses this issue by considering simplified neuronal shapes consisting of circular regions (soma/axons) with spokes (dendrites). Networks are grown by placing these patterns randomly in the two-dimensional (2D) plane and establishing connections whenever a piece of dendrite falls inside an axon. Several topological and dynamical properties of the resulting graph are measured, including the degree distribution, clustering coefficients, symmetry of connections, size of the largest connected component, as well as three hierarchical measurements of the local topology. By varying the number of processes of the individual basic patterns, we can quantify relationships between the individual neuronal shape and the topological and dynamical features of the networks. Integrate-and-fire dynamics on these networks is also investigated with respect to transient activation from a source node, indicating that long-range connections play an important role in the propagation of avalanches.

  8. Multifunctional role of astrocytes as gatekeepers of neuronal energy supply

    Directory of Open Access Journals (Sweden)

    Jillian L Stobart

    2013-04-01

    Full Text Available Dynamic adjustments to neuronal energy supply in response to synaptic activity are critical for neuronal function. Glial cells known as astrocytes have processes that ensheath most central synapses and express G-protein-coupled neurotransmitter receptors and transporters that respond to neuronal activity. Astrocytes also release substrates for neuronal oxidative phosphorylation and have processes that terminate on the surface of brain arterioles and can influence vascular smooth muscle tone and local blood flow. Membrane receptor or transporter-mediated effects of glutamate represent a convergence point of astrocyte influence on neuronal bioenergetics. Astrocytic glutamate uptake drives glycolysis and subsequent shuttling of lactate from astrocytes to neurons for oxidative metabolism. Astrocytes also convert synaptically reclaimed glutamate to glutamine, which is returned to neurons for glutamate salvage or oxidation. Finally, astrocytes store brain energy currency in the form of glycogen, which can be mobilized to produce lactate for neuronal oxidative phosphorylation in response to glutamatergic neurotransmission. These mechanisms couple synaptically-driven astrocytic responses to glutamate with release of energy substrates back to neurons to match demand with supply. In addition, astrocytes directly influence the tone of penetrating brain arterioles in response to glutamatergic neurotransmission, coordinating dynamic regulation of local blood flow. We will describe the role of astrocytes in neurometabolic and neurovascular coupling in detail and discuss, in turn, how astrocyte dysfunction may contribute to neuronal bioenergetic deficit and neurodegeneration. Understanding the role of astrocytes as a hub for neurometabolic and neurovascular coupling mechanisms is a critical underpinning for therapeutic development in a broad range of neurodegenerative disorders characterized by chronic generalized brain ischemia and brain microvascular

  9. Imitation, mirror neurons and autism

    OpenAIRE

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

    2001-01-01

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

  10. The biophysics of neuronal growth

    International Nuclear Information System (INIS)

    Franze, Kristian; Guck, Jochen

    2010-01-01

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

  11. How neurons migrate: a dynamic in-silico model of neuronal migration in the developing cortex

    LENUS (Irish Health Repository)

    Setty, Yaki

    2011-09-30

    , testable framework. Our model accounts for a range of observable behaviors and affords a computational framework to study aspects of neuronal migration as a complex process that is driven by a relatively simple molecular program. Analysis of the model generated new hypotheses and yet unobserved phenomena that may guide future experimental studies. This paper thus reports a first step toward a comprehensive in-silico model of neuronal migration.

  12. How neurons migrate: a dynamic in-silico model of neuronal migration in the developing cortex

    Directory of Open Access Journals (Sweden)

    Skoblov Nikita

    2011-09-01

    precise, testable framework. Our model accounts for a range of observable behaviors and affords a computational framework to study aspects of neuronal migration as a complex process that is driven by a relatively simple molecular program. Analysis of the model generated new hypotheses and yet unobserved phenomena that may guide future experimental studies. This paper thus reports a first step toward a comprehensive in-silico model of neuronal migration.

  13. Population coding in sparsely connected networks of noisy neurons.

    Science.gov (United States)

    Tripp, Bryan P; Orchard, Jeff

    2012-01-01

    This study examines the relationship between population coding and spatial connection statistics in networks of noisy neurons. Encoding of sensory information in the neocortex is thought to require coordinated neural populations, because individual cortical neurons respond to a wide range of stimuli, and exhibit highly variable spiking in response to repeated stimuli. Population coding is rooted in network structure, because cortical neurons receive information only from other neurons, and because the information they encode must be decoded by other neurons, if it is to affect behavior. However, population coding theory has often ignored network structure, or assumed discrete, fully connected populations (in contrast with the sparsely connected, continuous sheet of the cortex). In this study, we modeled a sheet of cortical neurons with sparse, primarily local connections, and found that a network with this structure could encode multiple internal state variables with high signal-to-noise ratio. However, we were unable to create high-fidelity networks by instantiating connections at random according to spatial connection probabilities. In our models, high-fidelity networks required additional structure, with higher cluster factors and correlations between the inputs to nearby neurons.

  14. Population Coding in Sparsely Connected Networks of Noisy Neurons

    Directory of Open Access Journals (Sweden)

    Bryan Patrick Tripp

    2012-05-01

    Full Text Available This study examines the relationship between population coding and spatial connection statistics in networks of noisy neurons. Encoding of sensory information in the neocortex is thought to require coordinated neural populations, because individual cortical neurons respond to a wide range of stimuli, and exhibit highly variable spiking in response to repeated stimuli. Population coding is rooted in network structure, because cortical neurons receive information only from other neurons, and because the information they encode must be decoded by other neurons, if it is to affect behaviour. However, population coding theory has often ignored network structure, or assumed discrete, fully-connected populations (in contrast with the sparsely connected, continuous sheet of the cortex. In this study, we model a sheet of cortical neurons with sparse, primarily local connections, and find that a network with this structure can encode multiple internal state variables with high signal-to-noise ratio. However, in our model, although connection probability varies with the distance between neurons, we find that the connections cannot be instantiated at random according to these probabilities, but must have additional structure if information is to be encoded with high fidelity.

  15. The mirror neuron system: new frontiers.

    Science.gov (United States)

    Keysers, Christian; Fadiga, Luciano

    2008-01-01

    Since the discovery of mirror neurons, much effort has been invested into studying their location and properties in the human brain. Here we review these original findings and introduce the main topics of this special issue of Social Neuroscience. What does the mirror system code? How is the mirror system embedded into the mosaic of circuits that compose our brain? How does the mirror system contribute to communication, language and social interaction? Can the principle of mirror neurons be extended to emotions, sensations and thoughts? Papers using a wide range of methods, including single cell recordings, fMRI, TMS, EEG and psychophysics, collected in this special issue, start to give us some impressive answers.

  16. Transistor analogs of emergent iono-neuronal dynamics.

    Science.gov (United States)

    Rachmuth, Guy; Poon, Chi-Sang

    2008-06-01

    Neuromorphic analog metal-oxide-silicon (MOS) transistor circuits promise compact, low-power, and high-speed emulations of iono-neuronal dynamics orders-of-magnitude faster than digital simulation. However, their inherently limited input voltage dynamic range vs power consumption and silicon die area tradeoffs makes them highly sensitive to transistor mismatch due to fabrication inaccuracy, device noise, and other nonidealities. This limitation precludes robust analog very-large-scale-integration (aVLSI) circuits implementation of emergent iono-neuronal dynamics computations beyond simple spiking with limited ion channel dynamics. Here we present versatile neuromorphic analog building-block circuits that afford near-maximum voltage dynamic range operating within the low-power MOS transistor weak-inversion regime which is ideal for aVLSI implementation or implantable biomimetic device applications. The fabricated microchip allowed robust realization of dynamic iono-neuronal computations such as coincidence detection of presynaptic spikes or pre- and postsynaptic activities. As a critical performance benchmark, the high-speed and highly interactive iono-neuronal simulation capability on-chip enabled our prompt discovery of a minimal model of chaotic pacemaker bursting, an emergent iono-neuronal behavior of fundamental biological significance which has hitherto defied experimental testing or computational exploration via conventional digital or analog simulations. These compact and power-efficient transistor analogs of emergent iono-neuronal dynamics open new avenues for next-generation neuromorphic, neuroprosthetic, and brain-machine interface applications.

  17. Study of ATM Phosphorylation by Cdk5 in Neuronal Cells.

    Science.gov (United States)

    She, Hua; Mao, Zixu

    2017-01-01

    The phosphatidylinositol-3-kinase-like kinase ATM (ataxia-telangiectasia mutated) plays a central role in coordinating the DNA damage responses including cell cycle checkpoint control, DNA repair, and apoptosis. Mutations of ATM cause a spectrum of defects ranging from neurodegeneration to cancer predisposition. We previously showed that Cdk5 (cyclin-dependent kinase 5) is activated by DNA damage and directly phosphorylates ATM at serine 794 in postmitotic neurons. Phosphorylation at serine 794 precedes and is required for ATM autophosphorylation at serine 1981, and activates ATM kinase activity. Cdk5-ATM pathway plays a crucial role in DNA damage-induced neuronal injury. This chapter describes protocols used in analyzing ATM phosphorylation by Cdk5 in CGNs (cerebellar granule neurons) and its effects on neuronal survival.

  18. Proton- and ammonium- sensing by histaminergic neurons controlling wakefulness.

    Directory of Open Access Journals (Sweden)

    Yvgenij eYanovsky

    2012-04-01

    Full Text Available Orexinergic and histaminergic neurons in the posterior hypothalamus are involved in the control of arousal. Extracellular levels of acid /CO2 are fundamental physicochemical signals controlling wakefulness and breathing. Acidification excites orexinergic neurons like the chemosensory neurons in the brain stem. Hypercapnia induces c-Fos expression, a marker for increased neuronal activity, in the rat histaminergic tuberomamillary nucleus (TMN, but the mechanisms of this excitation are unknown. Acid-sensing ion channels (ASICs are gated by protons and also by ammonium. Recordings in rat brain slices revealed now that acidification within the physiological range (pH from 7.3 to 7.0 as well as ammonium chloride (5mM excite histaminergic neurons. We detected variable combinations of 4 known types of ASICs in single TMN neurons, along with the pharmacological properties of pH-induced current. At pH 7.0 however, activation of ASICs in TMN neurons was negligible. Block of type I metabotropic glutamate receptors abolished proton- but not ammonium- induced excitation. Mouse TMN neurons were identified within a novel HDC-Cre transgenic reporter mouse line. In contrast to the rat these lacked pH 7.0-induced excitation and showed only a minimal response to the mGluR I agonist DHPG (0.5µM. Ammonium-induced excitation was similar in mouse and rat. Thus glutamate, which is released by glial cells and orexinergic axons amplifies CO2/acid-induced arousal through the recruitment of the histaminergic system in rat but not in mouse. These results are relevant for the understanding of neuronal mechanisms controlling H+/CO2-induced arousal in hepatic encephalopathy and obstructive sleep apnoea. The new HDC-Cre mouse model will be a useful tool for studying the physiological and pathophysiological roles of the histaminergic system.

  19. Distribution of glycinergic neuronal somata in the rat spinal cord.

    Science.gov (United States)

    Hossaini, Mehdi; French, Pim J; Holstege, Jan C

    2007-04-20

    Glycine transporter 2 (GlyT2) mRNA is exclusively expressed in glycinergic neurons, and is presently considered a reliable marker for glycinergic neuronal somata. In this study, we have performed non-radioactive in situ hybridization to localize GlyT2 mRNA in fixed free-floating sections of cervical (C2 and C6), thoracic (T5), lumbar (L2 and L5) and sacral (S1) segments of the rat spinal cord. The results showed that in all segments the majority of the GlyT2 mRNA labeled (glycinergic) neuronal somata was present in the deep dorsal horn and the intermediate zone (laminae III-VIII), with around 50% (range 43.7-70.9%) in laminae VII&VIII. In contrast, the superficial dorsal horn, the motoneuronal cell groups and the area around the central canal contained only few glycinergic neuronal somata. The density (number of glycinergic neuronal somata per mm(2)) was also low in these areas, while the highest densities were found in laminae V to VIII. The lateral spinal nucleus and the lateral cervical nucleus also contained a limited number of glycinergic neurons. Our findings showed that the distribution pattern of the glycinergic neuronal somata is similar in all the examined segments. The few differences that were found in the relative laminar distribution between some of the segments, are most likely due to technical reasons. We therefore conclude that the observed distribution pattern of glycinergic neuronal somata is present throughout the spinal cord. Our findings further showed that the non-radioactive in situ hybridization technique for identifying GlyT2 mRNA in fixed free-floating sections is a highly efficient tool for identifying glycinergic neurons in the spinal cord.

  20. 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…

  1. The straintronic spin-neuron

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  2. Metabolism of Mannose in Cultured Primary Rat Neurons.

    Science.gov (United States)

    Rastedt, Wiebke; Blumrich, Eva-Maria; Dringen, Ralf

    2017-08-01

    Glucose is the main peripheral substrate for energy production in the brain. However, as other hexoses are present in blood and cerebrospinal fluid, we have investigated whether neurons have the potential to metabolize, in addition to glucose, also the hexoses mannose, fructose or galactose. Incubation of primary cerebellar granule neurons in the absence of glucose caused severe cell toxicity within 24 h, which could not be prevented by application of galactose or fructose, while the cells remained viable during incubation in the presence of either mannose or glucose. In addition, cultured neurons produced substantial and almost identical amounts of lactate after exposure to either glucose or mannose, while lactate production was low in the presence of fructose and hardly detectable during incubations without hexoses or with galactose as carbon source. Determination of the K M values of hexokinase in lysates of cultured neurons for the hexoses revealed values in the micromolar range for mannose (32 ± 2 µM) and glucose (59 ± 10 µM) and in the millimolar range for fructose (4.4 ± 2.3 mM), demonstrating that mannose is efficiently phosphorylated by neuronal hexokinase. Finally, cultured neurons contained reasonable specific activity of the enzyme phosphomannose isomerase, which is required for isomerization of the hexokinase product mannose-6-phosphate into the glycolysis intermediate fructose-6-phosphate. These data demonstrate that cultured cerebellar granule neurons have the potential and express the required enzymes to efficiently metabolize mannose, while galactose and fructose serve at best poorly as extracellular carbon sources for neurons.

  3. Differential Receptive Field Properties of Parvalbumin and Somatostatin Inhibitory Neurons in Mouse Auditory Cortex.

    Science.gov (United States)

    Li, Ling-Yun; Xiong, Xiaorui R; Ibrahim, Leena A; Yuan, Wei; Tao, Huizhong W; Zhang, Li I

    2015-07-01

    Cortical inhibitory circuits play important roles in shaping sensory processing. In auditory cortex, however, functional properties of genetically identified inhibitory neurons are poorly characterized. By two-photon imaging-guided recordings, we specifically targeted 2 major types of cortical inhibitory neuron, parvalbumin (PV) and somatostatin (SOM) expressing neurons, in superficial layers of mouse auditory cortex. We found that PV cells exhibited broader tonal receptive fields with lower intensity thresholds and stronger tone-evoked spike responses compared with SOM neurons. The latter exhibited similar frequency selectivity as excitatory neurons. The broader/weaker frequency tuning of PV neurons was attributed to a broader range of synaptic inputs and stronger subthreshold responses elicited, which resulted in a higher efficiency in the conversion of input to output. In addition, onsets of both the input and spike responses of SOM neurons were significantly delayed compared with PV and excitatory cells. Our results suggest that PV and SOM neurons engage in auditory cortical circuits in different manners: while PV neurons may provide broadly tuned feedforward inhibition for a rapid control of ascending inputs to excitatory neurons, the delayed and more selective inhibition from SOM neurons may provide a specific modulation of feedback inputs on their distal dendrites. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Auditory DUM neurons in a bush-cricket: A filter bank for carrier frequency.

    Science.gov (United States)

    Lefebvre, Paule Chloé; Seifert, Marvin; Stumpner, Andreas

    2018-05-01

    In bush-crickets the first stage of central auditory processing occurs in the prothoracic ganglion. About 15 to 50 different auditory dorsal unpaired median neurons (DUM neurons) exist but they have not been studied in any detail. These DUM neurons may be classified into seven different morphological types, although, there is only limited correlation between morphology and physiological responses. Ninety seven percent of the stained neurons were local, 3% were intersegmental. About 90% project nearly exclusively into the auditory neuropile, and 45% into restricted areas therein. Lateral extensions overlap with the axons of primary auditory sensory neurons close to their branching point. DUM neurons are typically tuned to frequencies covering the range between 2 and 50 kHz and thereby may establish a filter bank for carrier frequency. Less than 10% of DUM neurons have their branches in adjacent and more posterior regions of the auditory neuropile and are mostly tuned to low frequencies, less sensitive than the other types and respond to vibration. Thirty five percent of DUM show indications of inhibition, either through reduced responses at higher intensities, or by hyperpolarizing responses to sound. Most DUM neurons produce phasic spike responses preferably at higher intensities. Spikes may be elicited by intracellular current injection. Preliminary data suggest that auditory DUM neurons have GABA as transmitter and therefore may inhibit other auditory interneurons. From all known local auditory neurons, only DUM neurons have frequency specific responses which appear suited for local processing relevant for acoustic communication in bush crickets. © 2018 Wiley Periodicals, Inc.

  5. Neuronal discrimination capacity

    International Nuclear Information System (INIS)

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

    2003-01-01

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

  6. Neuronal discrimination capacity

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-12-19

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

  7. 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.

  8. Beta-band intermuscular coherence: a novel biomarker of upper motor neuron dysfunction in motor neuron disease

    Science.gov (United States)

    Fisher, Karen M.; Zaaimi, Boubker; Williams, Timothy L.; Baker, Stuart N.

    2012-01-01

    In motor neuron disease, the focus of therapy is to prevent or slow neuronal degeneration with neuroprotective pharmacological agents; early diagnosis and treatment are thus essential. Incorporation of needle electromyographic evidence of lower motor neuron degeneration into diagnostic criteria has undoubtedly advanced diagnosis, but even earlier diagnosis might be possible by including tests of subclinical upper motor neuron disease. We hypothesized that beta-band (15–30 Hz) intermuscular coherence could be used as an electrophysiological marker of upper motor neuron integrity in such patients. We measured intermuscular coherence in eight patients who conformed to established diagnostic criteria for primary lateral sclerosis and six patients with progressive muscular atrophy, together with 16 age-matched controls. In the primary lateral sclerosis variant of motor neuron disease, there is selective destruction of motor cortical layer V pyramidal neurons and degeneration of the corticospinal tract, without involvement of anterior horn cells. In progressive muscular atrophy, there is selective degeneration of anterior horn cells but a normal corticospinal tract. All patients with primary lateral sclerosis had abnormal motor-evoked potentials as assessed using transcranial magnetic stimulation, whereas these were similar to controls in progressive muscular atrophy. Upper and lower limb intermuscular coherence was measured during a precision grip and an ankle dorsiflexion task, respectively. Significant beta-band coherence was observed in all control subjects and all patients with progressive muscular atrophy tested, but not in the patients with primary lateral sclerosis. We conclude that intermuscular coherence in the 15–30 Hz range is dependent on an intact corticospinal tract but persists in the face of selective anterior horn cell destruction. Based on the distributions of coherence values measured from patients with primary lateral sclerosis and control

  9. Tunneling nanotube (TNT)-mediated neuron-to neuron transfer of pathological Tau protein assemblies

    OpenAIRE

    TARDIVEL , Meryem; Bégard , Séverine; Bousset , Luc; Dujardin , Simon; Coens , Audrey; Melki , Ronald; Buée , Luc; Colin , Morvane

    2016-01-01

    A given cell makes exchanges with its neighbors through a variety of means ranging from diffusible factors to vesicles. Cells use also tunneling nanotubes (TNTs), filamentous-actin-containing membranous structures that bridge and connect cells. First described in immune cells, TNTs facilitate HIV-1 transfer and are found in various cell types, including neurons. We show that the microtubule-associated protein Tau, a key player in Alzheimer?s disease, is a bona fide constituent of TNTs. This i...

  10. Proton- and ammonium-sensing by histaminergic neurons controlling wakefulness.

    Science.gov (United States)

    Yanovsky, Yevgenij; Zigman, Jeffrey M; Kernder, Anna; Bein, Alisa; Sakata, Ichiro; Osborne-Lawrence, Sherri; Haas, Helmut L; Sergeeva, Olga A

    2012-01-01

    The histaminergic neurons in the tuberomamillary nucleus (TMN) of the posterior hypothalamus are involved in the control of arousal. These neurons are sensitive to hypercapnia as has been shown in experiments examining c-Fos expression, a marker for increased neuronal activity. We investigated the mechanisms through which TMN neurons respond to changes in extracellular levels of acid/CO(2). Recordings in rat brain slices revealed that acidification within the physiological range (pH from 7.4 to 7.0), as well as ammonium chloride (5 mM), excite histaminergic neurons. This excitation is significantly reduced by antagonists of type I metabotropic glutamate receptors and abolished by benzamil, an antagonist of acid-sensing ion channels (ASICs) and Na(+)/Ca(2+) exchanger, or by ouabain which blocks Na(+)/K(+) ATPase. We detected variable combinations of 4 known types of ASICs in single TMN neurons, and observed activation of ASICs in single dissociated TMN neurons only at pH lower than 7.0. Thus, glutamate, which is known to be released by glial cells and orexinergic neurons, amplifies the acid/CO(2)-induced activation of TMN neurons. This amplification demands the coordinated function of metabotropic glutamate receptors, Na(+)/Ca(2+) exchanger and Na(+)/K(+) ATPase. We also developed a novel HDC-Cre transgenic reporter mouse line in which histaminergic TMN neurons can be visualized. In contrast to the rat, the mouse histaminergic neurons lacked the pH 7.0-induced excitation and displayed only a minimal response to the mGluR I agonist DHPG (0.5 μM). On the other hand, ammonium-induced excitation was similar in mouse and rat. These results are relevant for the understanding of the neuronal mechanisms controlling acid/CO(2)-induced arousal in hepatic encephalopathy and obstructive sleep apnoea. Moreover, the new HDC-Cre mouse model will be a useful tool for studying the physiological and pathophysiological roles of the histaminergic system.

  11. Topographical distribution and morphology of NADPH-diaphorase-stained neurons in the human claustrum

    Science.gov (United States)

    Hinova-Palova, Dimka V.; Edelstein, Lawrence; Landzhov, Boycho; Minkov, Minko; Malinova, Lina; Hristov, Stanislav; Denaro, Frank J.; Alexandrov, Alexandar; Kiriakova, Teodora; Brainova, Ilina; Paloff, Adrian; Ovtscharoff, Wladimir

    2014-01-01

    We studied the topographical distribution and morphological characteristics of NADPH-diaphorase-positive neurons and fibers in the human claustrum. These neurons were seen to be heterogeneously distributed throughout the claustrum. Taking into account the size and shape of stained perikarya as well as dendritic and axonal characteristics, Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPHd)-positive neurons were categorized by diameter into three types: large, medium and small. Large neurons ranged from 25 to 35 μm in diameter and typically displayed elliptical or multipolar cell bodies. Medium neurons ranged from 20 to 25 μm in diameter and displayed multipolar, bipolar and irregular cell bodies. Small neurons ranged from 14 to 20 μm in diameter and most often displayed oval or elliptical cell bodies. Based on dendritic characteristics, these neurons were divided into spiny and aspiny subtypes. Our findings reveal two populations of NADPHd-positive neurons in the human claustrum—one comprised of large and medium cells consistent with a projection neuron phenotype, the other represented by small cells resembling the interneuron phenotype as defined by previous Golgi impregnation studies. PMID:24904317

  12. Functional Connectome Analysis of Dopamine Neuron Glutamatergic Connections in Forebrain Regions.

    Science.gov (United States)

    Mingote, Susana; Chuhma, Nao; Kusnoor, Sheila V; Field, Bianca; Deutch, Ariel Y; Rayport, Stephen

    2015-12-09

    capable of glutamate cotransmission. With conditional expression of channelrhodopsin in dopamine neurons, we systematically explored dopamine neuron connections in the forebrain and identified regionally specific dopamine neuron excitatory connections. Establishing that only a subset of forebrain regions receive excitatory connections from dopamine neurons will help to determine the function of dopamine neuron glutamate cotransmission, which likely involves transmission of precise temporal signals and enhancement of the dynamic range of dopamine neuron signals. Copyright © 2015 the authors 0270-6474/15/3516259-13$15.00/0.

  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. Long-range GABAergic connections distributed throughout the neocortex and their possible function

    Directory of Open Access Journals (Sweden)

    Nobuaki eTamamaki

    2010-12-01

    Full Text Available Features and functions of long range GABAergic projection neurons in the developing cerebral cortex have been reported previously, although until now their significance in the adult cerebral cortex has remained uncertain. The septo-hippocampal circuit is one exception – in this system, long range mature GABAergic projection neurons have been well analyzed and their contribution to the generation of theta-oscillatory behavior in the hippocampus has been documented. To have a clue to the function of the GABAergic projection neurons in the neocortex, we view the long range GABAergic projections those participating in the cortico-cortical, cortico-fugal, and afferent projections in the cerebral cortex. Then, we consider the possibility that the GABAergic projection neurons are involved in the generation, modification, and/or synchronization of oscillations in mature neocortical neuron activity. When markers that identify the GABAergic projection neurons are examined in anatomical and developmental studies, it is clear that neuronal NO synthetase (nNOS-immunoreactivity can readily identify GABAergic projection fibers (i.e. those longer than 1.5 mm. To elucidate the role of the GABAergic projection neurons in the neocortex, it will be necessary to clarify the network constructed by nNOS-positive GABAergic projection neurons and their postsynaptic targets. Thus, our long-range goals will be to label and manipulate (including deleting the GABAergic projection neurons using genetic tools driven by a nNOS promoter. We recognize that this may be a complex endeavor, as most excitatory neurons in the murine neocortex express nNOS transiently. Nevertheless, additional studies characterizing long range GABAergic projection neurons will have great value to the overall understanding of mature cortical function.

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

    Science.gov (United States)

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

    2014-05-01

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

  16. Simulating synchronization in neuronal networks

    Science.gov (United States)

    Fink, Christian G.

    2016-06-01

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

  17. Glial tumors with neuronal differentiation.

    Science.gov (United States)

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

    2015-01-01

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

  18. Mechanosensing in hypothalamic osmosensory neurons.

    Science.gov (United States)

    Prager-Khoutorsky, Masha

    2017-11-01

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

  19. Species and Sex Differences in the Morphogenic Response of Primary Rodent Neurons to 3,3'-Dichlorobiphenyl (PCB 11).

    Science.gov (United States)

    Sethi, Sunjay; Keil, Kimberly P; Lein, Pamela J

    2017-12-23

    PCB 11 is an emerging global pollutant that we recently showed promotes axonal and dendritic growth in primary rat neuronal cell cultures. Here, we address the influence of sex and species on neuronal responses to PCB 11. Neuronal morphology was quantified in sex-specific primary hippocampal and cortical neuron-glia co-cultures derived from neonatal C57BL/6J mice and Sprague Dawley rats exposed for 48 h to vehicle (0.1% DMSO) or PCB 11 at concentrations ranging from 1 fM to 1 nM. Total axonal length was quantified in tau-1 immunoreactive neurons at day in vitro (DIV) 2; dendritic arborization was assessed by Sholl analysis at DIV 9 in neurons transfected with MAP2B-FusRed. In mouse cultures, PCB 11 enhanced dendritic arborization in female, but not male, hippocampal neurons and male, but not female, cortical neurons. In rat cultures, PCB 11 promoted dendritic arborization in male and female hippocampal and cortical neurons. PCB 11 also increased axonal growth in mouse and rat neurons of both sexes and neuronal cell types. These data demonstrate that PCB 11 exerts sex-specific effects on neuronal morphogenesis that vary depending on species, neurite type, and neuronal cell type. These findings have significant implications for risk assessment of this emerging developmental neurotoxicant.

  20. 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 ...

  1. Dendrites Enable a Robust Mechanism for Neuronal Stimulus Selectivity.

    Science.gov (United States)

    Cazé, Romain D; Jarvis, Sarah; Foust, Amanda J; Schultz, Simon R

    2017-09-01

    Hearing, vision, touch: underlying all of these senses is stimulus selectivity, a robust information processing operation in which cortical neurons respond more to some stimuli than to others. Previous models assume that these neurons receive the highest weighted input from an ensemble encoding the preferred stimulus, but dendrites enable other possibilities. Nonlinear dendritic processing can produce stimulus selectivity based on the spatial distribution of synapses, even if the total preferred stimulus weight does not exceed that of nonpreferred stimuli. Using a multi-subunit nonlinear model, we demonstrate that stimulus selectivity can arise from the spatial distribution of synapses. We propose this as a general mechanism for information processing by neurons possessing dendritic trees. Moreover, we show that this implementation of stimulus selectivity increases the neuron's robustness to synaptic and dendritic failure. Importantly, our model can maintain stimulus selectivity for a larger range of loss of synapses or dendrites than an equivalent linear model. We then use a layer 2/3 biophysical neuron model to show that our implementation is consistent with two recent experimental observations: (1) one can observe a mixture of selectivities in dendrites that can differ from the somatic selectivity, and (2) hyperpolarization can broaden somatic tuning without affecting dendritic tuning. Our model predicts that an initially nonselective neuron can become selective when depolarized. In addition to motivating new experiments, the model's increased robustness to synapses and dendrites loss provides a starting point for fault-resistant neuromorphic chip development.

  2. Fluorescence imaging of glutamate release in neurons

    International Nuclear Information System (INIS)

    Wang, Ziqiang; Yeung, Edward S.

    1999-01-01

    A noninvasive detection scheme based on glutamate dehydrogenase (GDH) enzymatic assay combined with microscopy was developed to measure the glutamate release in cultured cells from the central nervous system (CNS). The enzyme reaction is very specific and sensitive. The detection limit with charge-coupled device (CCD) imaging is down to μM levels of glutamate with reasonable response time (∼30 s). The standard glutamate test shows a linear response over 3 orders of magnitude, from μM to 0.1 mM range. The in vitro monitoring of glutamate release from cultured neuron cells demonstrated excellent spatial and temporal resolution. (c) 1999 Society for Applied Spectroscopy

  3. Mechanisms for multiple activity modes of VTA dopamine neurons

    Directory of Open Access Journals (Sweden)

    Andrew eOster

    2015-07-01

    Full Text Available Midbrain ventral segmental area (VTA dopaminergic neurons send numerous projections to cortical and sub-cortical areas, and diffusely release dopamine (DA to their targets. DA neurons display a range of activity modes that vary in frequency and degree of burst firing. Importantly, DA neuronal bursting is associated with a significantly greater degree of DA release than an equivalent tonic activity pattern. Here, we introduce a single compartmental, conductance-based computational model for DA cell activity that captures the behavior of DA neuronal dynamics and examine the multiple factors that underlie DA firing modes: the strength of the SK conductance, the amount of drive, and GABA inhibition. Our results suggest that neurons with low SK conductance fire in a fast firing mode, are correlated with burst firing, and require higher levels of applied current before undergoing depolarization block. We go on to consider the role of GABAergic inhibition on an ensemble of dynamical classes of DA neurons and find that strong GABA inhibition suppresses burst firing. Our studies suggest differences in the distribution of the SK conductance and GABA inhibition levels may indicate subclasses of DA neurons within the VTA. We further identify, that by considering alternate potassium dynamics, the dynamics display burst patterns that terminate via depolarization block, akin to those observed in vivo in VTA DA neurons and in substantia nigra pars compacta DA cell preparations under apamin application. In addition, we consider the generation of transient burst firing events that are NMDA-initiated or elicited by a sudden decrease of GABA inhibition, that is, disinhibition.

  4. Serotonin neuron development: shaping molecular and structural identities.

    Science.gov (United States)

    Deneris, Evan; Gaspar, Patricia

    2018-01-01

    The continuing fascination with serotonin (5-hydroxytryptamine, 5-HT) as a nervous system chemical messenger began with its discovery in the brains of mammals in 1953. Among the many reasons for this decades-long interest is that the small numbers of neurons that make 5-HT influence the excitability of neural circuits in nearly every region of the brain and spinal cord. A further reason is that 5-HT dysfunction has been linked to a range of psychiatric and neurological disorders many of which have a neurodevelopmental component. This has led to intense interest in understanding 5-HT neuron development with the aim of determining whether early alterations in their generation lead to brain disease susceptibility. Here, we present an overview of the neuroanatomical organization of vertebrate 5-HT neurons, their neurogenesis, and prodigious axonal architectures, which enables the expansive reach of 5-HT neuromodulation in the central nervous system. We review recent findings that have revealed the molecular basis for the tremendous diversity of 5-HT neuron subtypes, the impact of environmental factors on 5-HT neuron development, and how 5-HT axons are topographically organized through disparate signaling pathways. We summarize studies of the gene regulatory networks that control the differentiation, maturation, and maintenance of 5-HT neurons. These studies show that the regulatory factors controlling acquisition of 5-HT-type transmitter identity continue to play critical roles in the functional maturation and the maintenance of 5-HT neurons. New insights are presented into how continuously expressed 5-HT regulatory factors control 5-HT neurons at different stages of life and how the regulatory networks themselves are maintained. WIREs Dev Biol 2018, 7:e301. doi: 10.1002/wdev.301 This article is categorized under: Nervous System Development > Vertebrates: General Principles Gene Expression and Transcriptional Hierarchies > Gene Networks and Genomics Gene Expression and

  5. Associative learning is necessary but not sufficient for mirror neuron development

    OpenAIRE

    Bonaiuto, James

    2014-01-01

    Existing computational models of the mirror system demonstrate the additional circuitry needed for mirror neurons to display the range of properties that they exhibit. Such models emphasize the need for existing connectivity to form visuomotor associations, processing to reduce the space of possible inputs, and demonstrate the role neurons with mirror properties might play in monitoring one's own actions.

  6. Associative learning is necessary but not sufficient for mirror neuron development.

    Science.gov (United States)

    Bonaiuto, James

    2014-04-01

    Existing computational models of the mirror system demonstrate the additional circuitry needed for mirror neurons to display the range of properties that they exhibit. Such models emphasize the need for existing connectivity to form visuomotor associations, processing to reduce the space of possible inputs, and demonstrate the role neurons with mirror properties might play in monitoring one's own actions.

  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. PMID:24778376

  8. Neurons on the couch.

    Science.gov (United States)

    Marić, Nadja P; Jašović-Gašić, Miroslava

    2010-12-01

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

  9. 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.

  10. Understanding Neuronal Mechanisms of Epilepsy ...

    Indian Academy of Sciences (India)

    Admin

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

  11. Imitation, mirror neurons and autism.

    Science.gov (United States)

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

    2001-06-01

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

  12. Information processing by neuronal populations

    National Research Council Canada - National Science Library

    Hölscher, Christian; Munk, Matthias

    2009-01-01

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

  13. Orexin receptor activation generates gamma band input to cholinergic and serotonergic arousal system neurons and drives an intrinsic Ca2+-dependent resonance in LDT and PPT cholinergic neurons.

    Directory of Open Access Journals (Sweden)

    Masaru eIshibashi

    2015-06-01

    Full Text Available A hallmark of the waking state is a shift in EEG power to higher frequencies with epochs of synchronized intracortical gamma activity (30-60 Hz - a process associated with high-level cognitive functions. The ascending arousal system, including cholinergic laterodorsal (LDT and pedunculopontine (PPT tegmental neurons and serotonergic dorsal raphe (DR neurons, promotes this state. Recently, this system has been proposed as a gamma wave generator, in part, because some neurons produce high-threshold, Ca2+-dependent oscillations at gamma frequencies. However, it is not known whether arousal-related inputs to these neurons generate such oscillations, or whether such oscillations are ever transmitted to neuronal targets. Since key arousal input arises from hypothalamic orexin (hypocretin neurons, we investigated whether the unusually noisy, depolarizing orexin current could provide significant gamma input to cholinergic and serotonergic neurons, and whether such input could drive Ca2+-dependent oscillations. Whole-cell recordings in brain slices were obtained from mice expressing Cre-induced fluorescence in cholinergic LDT and PPT, and serotonergic DR neurons. After first quantifying reporter expression accuracy in cholinergic and serotonergic neurons, we found that the orexin current produced significant high frequency, including gamma, input to both cholinergic and serotonergic neurons. Then, by using a dynamic clamp, we found that adding a noisy orexin conductance to cholinergic neurons induced a Ca2+-dependent resonance that peaked in the theta and alpha frequency range (4 - 14 Hz and extended up to 100 Hz. We propose that this orexin current noise and the Ca2+ dependent resonance work synergistically to boost the encoding of high-frequency synaptic inputs into action potentials and to help ensure cholinergic neurons fire during EEG activation. This activity could reinforce thalamocortical states supporting arousal, REM sleep and intracortical

  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. Imaging Action Potential in Single Mammalian Neurons by Tracking the Accompanying Sub-Nanometer Mechanical Motion.

    Science.gov (United States)

    Yang, Yunze; Liu, Xian-Wei; Wang, Hui; Yu, Hui; Guan, Yan; Wang, Shaopeng; Tao, Nongjian

    2018-03-28

    Action potentials in neurons have been studied traditionally by intracellular electrophysiological recordings and more recently by the fluorescence detection methods. Here we describe a label-free optical imaging method that can measure mechanical motion in single cells with a sub-nanometer detection limit. Using the method, we have observed sub-nanometer mechanical motion accompanying the action potential in single mammalian neurons by averaging the repeated action potential spikes. The shape and width of the transient displacement are similar to those of the electrically recorded action potential, but the amplitude varies from neuron to neuron, and from one region of a neuron to another, ranging from 0.2-0.4 nm. The work indicates that action potentials may be studied noninvasively in single mammalian neurons by label-free imaging of the accompanying sub-nanometer mechanical motion.

  16. Tonopah Test Range - Index

    Science.gov (United States)

    Capabilities Test Operations Center Test Director Range Control Track Control Communications Tracking Radars Photos Header Facebook Twitter YouTube Flickr RSS Tonopah Test Range Top TTR_TOC Tonopah is the testing range of choice for all national security missions. Tonopah Test Range (TTR) provides research and

  17. Communication among neurons.

    Science.gov (United States)

    Marner, Lisbeth

    2012-04-01

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

  18. Spectral components of cytosolic [Ca2+] spiking in neurons

    DEFF Research Database (Denmark)

    Kardos, J; Szilágyi, N; Juhász, G

    1998-01-01

    . Delayed complex responses of large [Ca2+]c spiking observed in cells from a different set of cultures were synthesized by a set of frequencies within the range 0.018-0.117 Hz. Differential frequency patterns are suggested as characteristics of the [Ca2+]c spiking responses of neurons under different...

  19. How adaptation shapes spike rate oscillations in recurrent neuronal networks

    Directory of Open Access Journals (Sweden)

    Moritz eAugustin

    2013-02-01

    Full Text Available Neural mass signals from in-vivo recordings often show oscillations with frequencies ranging from <1 Hz to 100 Hz. Fast rhythmic activity in the beta and gamma range can be generated by network based mechanisms such as recurrent synaptic excitation-inhibition loops. Slower oscillations might instead depend on neuronal adaptation currents whose timescales range from tens of milliseconds to seconds. Here we investigate how the dynamics of such adaptation currents contribute to spike rate oscillations and resonance properties in recurrent networks of excitatory and inhibitory neurons. Based on a network of sparsely coupled spiking model neurons with two types of adaptation current and conductance based synapses with heterogeneous strengths and delays we use a mean-field approach to analyze oscillatory network activity. For constant external input, we find that spike-triggered adaptation currents provide a mechanism to generate slow oscillations over a wide range of adaptation timescales as long as recurrent synaptic excitation is sufficiently strong. Faster rhythms occur when recurrent inhibition is slower than excitation and oscillation frequency increases with the strength of inhibition. Adaptation facilitates such network based oscillations for fast synaptic inhibition and leads to decreased frequencies. For oscillatory external input, adaptation currents amplify a narrow band of frequencies and cause phase advances for low frequencies in addition to phase delays at higher frequencies. Our results therefore identify the different key roles of neuronal adaptation dynamics for rhythmogenesis and selective signal propagation in recurrent networks.

  20. Tunneling nanotube (TNT)-mediated neuron-to neuron transfer of pathological Tau protein assemblies.

    Science.gov (United States)

    Tardivel, Meryem; Bégard, Séverine; Bousset, Luc; Dujardin, Simon; Coens, Audrey; Melki, Ronald; Buée, Luc; Colin, Morvane

    2016-11-04

    A given cell makes exchanges with its neighbors through a variety of means ranging from diffusible factors to vesicles. Cells use also tunneling nanotubes (TNTs), filamentous-actin-containing membranous structures that bridge and connect cells. First described in immune cells, TNTs facilitate HIV-1 transfer and are found in various cell types, including neurons. We show that the microtubule-associated protein Tau, a key player in Alzheimer's disease, is a bona fide constituent of TNTs. This is important because Tau appears beside filamentous actin and myosin 10 as a specific marker of these fine protrusions of membranes and cytosol that are difficult to visualize. Furthermore, we observed that exogenous Tau species increase the number of TNTs established between primary neurons, thereby facilitating the intercellular transfer of Tau fibrils. In conclusion, Tau may contribute to the formation and function of the highly dynamic TNTs that may be involved in the prion-like propagation of Tau assemblies.

  1. NADPH- Diaphorase positive cardiac neurons in the atria of mice. A morphoquantitative study

    Directory of Open Access Journals (Sweden)

    Castelucci Patrícia

    2006-02-01

    Full Text Available Abstract Background The present study was conducted to determine the location, the morphology and distribution of NADPH-diaphorase positive neurons in the cardiac nerve plexus of the atria of mice (ASn. This plexus lies over the muscular layer of the atria, dorsal to the muscle itself, in the connective tissue of the subepicardium. NADPH- diaphorase staining was performed on whole-mount preparations of the atria mice. For descriptive purposes, all data are presented as means ± SEM. Results The majority of the NADPH-diaphorase positive neurons were observed in the ganglia of the plexus. A few single neurons were also observed. The number of NADPH-d positive neurons was 57 ± 4 (ranging from 39 to 79 neurons. The ganglion neurons were located in 3 distinct groups: (1 in the region situated cranial to the pulmonary veins, (2 caudally to the pulmonary veins, and (3 in the atrial groove. The largest group of neurons was located cranially to the pulmonary veins (66.7%. Three morphological types of NADPH-diaphorase neurons could be distinguished on the basis of their shape: unipolar cells, bipolar cells and cells with three processes (multipolar cells. The unipolar neurons predominated (78.9%, whereas the multipolar were encountered less frequently (5,3%. The sizes (area of maximal cell profile of the neurons ranged from about 90 μm2to about 220 μm2. Morphometrically, the three types of neurons were similar and there were no significant differences in their sizes. The total number of cardiac neurons (obtained by staining the neurons with NADH-diaphorase method was 530 ± 23. Therefore, the NADPH-diaphorase positive neurons of the heart represent 10% of the number of cardiac neurons stained by NADH. Conclusion The obtained data have shown that the NADPH-d positive neurons in the cardiac plexus of the atria of mice are morphologically different, and therefore, it is possible that the function of the neurons may also be different.

  2. Physiological Characterization of Vestibular Efferent Brainstem Neurons Using a Transgenic Mouse Model

    Science.gov (United States)

    Leijon, Sara; Magnusson, Anna K.

    2014-01-01

    The functional role of efferent innervation of the vestibular end-organs in the inner ear remains elusive. This study provides the first physiological characterization of the cholinergic vestibular efferent (VE) neurons in the brainstem by utilizing a transgenic mouse model, expressing eGFP under a choline-acetyltransferase (ChAT)-locus spanning promoter in combination with targeted patch clamp recordings. The intrinsic electrical properties of the eGFP-positive VE neurons were compared to the properties of the lateral olivocochlear (LOC) brainstem neurons, which gives rise to efferent innervation of the cochlea. Both VE and the LOC neurons were marked by their negative resting membrane potential neurons differed significantly in the depolarizing range. When injected with positive currents, VE neurons fired action potentials faithfully to the onset of depolarization followed by sparse firing with long inter-spike intervals. This response gave rise to a low response gain. The LOC neurons, conversely, responded with a characteristic delayed tonic firing upon depolarizing stimuli, giving rise to higher response gain than the VE neurons. Depolarization triggered large TEA insensitive outward currents with fast inactivation kinetics, indicating A-type potassium currents, in both the inner ear-projecting neuronal types. Immunohistochemistry confirmed expression of Kv4.3 and 4.2 ion channel subunits in both the VE and LOC neurons. The difference in spiking responses to depolarization is related to a two-fold impact of these transient outward currents on somatic integration in the LOC neurons compared to in VE neurons. It is speculated that the physiological properties of the VE neurons might be compatible with a wide-spread control over motion and gravity sensation in the inner ear, providing likewise feed-back amplification of abrupt and strong phasic signals from the semi-circular canals and of tonic signals from the gravito-sensitive macular organs. PMID:24867596

  3. Analysis of laser-induced heating in optical neuronal guidance

    DEFF Research Database (Denmark)

    Ebbesen, Christian L.; Bruus, Henrik

    2012-01-01

    Recently, it has been shown that it is possible to control the growth direction of neuronal growth cones by stimulation with weak laser light; an effect dubbed optical neuronal guidance. The effect exists for a broad range of laser wavelengths, spot sizes, spot intensities, optical intensity...... profiles and beam modulations, but it is unknown which biophysical mechanisms govern it. Based on thermodynamic modeling and simulation using published experimental parameters as input, we argue that the guidance is linked to heating. Until now, temperature effects due to laser-induced heating...

  4. Temporally selective processing of communication signals by auditory midbrain neurons

    DEFF Research Database (Denmark)

    Elliott, Taffeta M; Christensen-Dalsgaard, Jakob; Kelley, Darcy B

    2011-01-01

    click rates ranged from 4 to 50 Hz, the rate at which the clicks begin to overlap. Frequency selectivity and temporal processing were characterized using response-intensity curves, temporal-discharge patterns, and autocorrelations of reduplicated responses to click trains. Characteristic frequencies...... of the rate of clicks in calls. The majority of neurons (85%) were selective for click rates, and this selectivity remained unchanged over sound levels 10 to 20 dB above threshold. Selective neurons give phasic, tonic, or adapting responses to tone bursts and click trains. Some algorithms that could compute...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-02-07

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

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

    International Nuclear Information System (INIS)

    Miyazaki, Y; Kinzel, W; Shinomoto, S

    2003-01-01

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

  7. The mirror-neuron system.

    Science.gov (United States)

    Rizzolatti, Giacomo; Craighero, Laila

    2004-01-01

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

  8. Neuronal factors determining high intelligence.

    Science.gov (United States)

    Dicke, Ursula; Roth, Gerhard

    2016-01-05

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

  9. Energy Model of Neuron Activation.

    Science.gov (United States)

    Romanyshyn, Yuriy; Smerdov, Andriy; Petrytska, Svitlana

    2017-02-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

  11. p38 phosphorylation in medullary microglia mediates ectopic orofacial inflammatory pain in rats.

    Science.gov (United States)

    Kiyomoto, Masaaki; Shinoda, Masamichi; Honda, Kuniya; Nakaya, Yuka; Dezawa, Ko; Katagiri, Ayano; Kamakura, Satoshi; Inoue, Tomio; Iwata, Koichi

    2015-08-12

    Orofacial inflammatory pain is likely to accompany referred pain in uninflamed orofacial structures. The ectopic pain precludes precise diagnosis and makes treatment problematic, because the underlying mechanism is not well understood. Using the established ectopic orofacial pain model induced by complete Freund's adjuvant (CFA) injection into trapezius muscle, we analyzed the possible role of p38 phosphorylation in activated microglia in ectopic orofacial pain. Mechanical allodynia in the lateral facial skin was induced following trapezius muscle inflammation, which accompanied microglial activation with p38 phosphorylation and hyperexcitability of wide dynamic range (WDR) neurons in the trigeminal spinal subnucleus caudalis (Vc). Intra-cisterna successive administration of a p38 mitogen-activated protein kinase selective inhibitor, SB203580, suppressed microglial activation and its phosphorylation of p38. Moreover, SB203580 administration completely suppressed mechanical allodynia in the lateral facial skin and enhanced WDR neuronal excitability in Vc. Microglial interleukin-1β over-expression in Vc was induced by trapezius muscle inflammation, which was significantly suppressed by SB203580 administration. These findings indicate that microglia, activated via p38 phosphorylation, play a pivotal role in WDR neuronal hyperexcitability, which accounts for the mechanical hypersensitivity in the lateral facial skin associated with trapezius muscle inflammation.

  12. 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].

  13. Differential effects of synthetic progestagens on neuron survival and estrogen neuroprotection in cultured neurons.

    Science.gov (United States)

    Jayaraman, Anusha; Pike, Christian J

    2014-03-25

    Progesterone and other progestagens are used in combination with estrogens for clinical purposes, including contraception and postmenopausal hormone therapy. Progesterone and estrogens have interactive effects in brain, however interactions between synthetic progestagens and 17β-estradiol (E2) in neurons are not well understood. In this study, we investigated the effects of seven clinically relevant progestagens on estrogen receptor (ER) mRNA expression, E2-induced neuroprotection, and E2-induced BDNF mRNA expression. We found that medroxyprogesterone acetate decreased both ERα and ERβ expression and blocked E2-mediated neuroprotection and BDNF expression. Conversely, levonorgestrel and nesterone increased ERα and or ERβ expression, were neuroprotective, and failed to attenuate E2-mediated increases in neuron survival and BDNF expression. Other progestagens tested, including norethindrone, norethindrone acetate, norethynodrel, and norgestimate, had variable effects on the measured endpoints. Our results demonstrate a range of qualitatively different actions of progestagens in cultured neurons, suggesting significant variability in the neural effects of clinically utilized progestagens. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Integrated workflows for spiking neuronal network simulations

    Directory of Open Access Journals (Sweden)

    Ján eAntolík

    2013-12-01

    Full Text Available The increasing availability of computational resources is enabling more detailed, realistic modelling in computational neuroscience, resulting in a shift towards more heterogeneous models of neuronal circuits, and employment of complex experimental protocols. This poses a challenge for existing tool chains, as the set of tools involved in a typical modeller's workflow is expanding concomitantly, with growing complexity in the metadata flowing between them. For many parts of the workflow, a range of tools is available; however, numerous areas lack dedicated tools, while integration of existing tools is limited. This forces modellers to either handle the workflow manually, leading to errors, or to write substantial amounts of code to automate parts of the workflow, in both cases reducing their productivity.To address these issues, we have developed Mozaik: a workflow system for spiking neuronal network simulations written in Python. Mozaik integrates model, experiment and stimulation specification, simulation execution, data storage, data analysis and visualisation into a single automated workflow, ensuring that all relevant metadata are available to all workflow components. It is based on several existing tools, including PyNN, Neo and Matplotlib. It offers a declarative way to specify models and recording configurations using hierarchically organised configuration files. Mozaik automatically records all data together with all relevant metadata about the experimental context, allowing automation of the analysis and visualisation stages. Mozaik has a modular architecture, and the existing modules are designed to be extensible with minimal programming effort. Mozaik increases the productivity of running virtual experiments on highly structured neuronal networks by automating the entire experimental cycle, while increasing the reliability of modelling studies by relieving the user from manual handling of the flow of metadata between the individual

  15. Neuronal involvement in cisplatin neuropathy

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  16. Calcium signals in olfactory neurons.

    Science.gov (United States)

    Tareilus, E; Noé, J; Breer, H

    1995-11-09

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

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

    Directory of Open Access Journals (Sweden)

    Grammas Paula

    2009-03-01

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

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

    NARCIS (Netherlands)

    Zeitler-Geurds, M.

    2010-01-01

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

  19. Compressive laser ranging.

    Science.gov (United States)

    Babbitt, Wm Randall; Barber, Zeb W; Renner, Christoffer

    2011-12-15

    Compressive sampling has been previously proposed as a technique for sampling radar returns and determining sparse range profiles with a reduced number of measurements compared to conventional techniques. By employing modulation on both transmission and reception, compressive sensing in ranging is extended to the direct measurement of range profiles without intermediate measurement of the return waveform. This compressive ranging approach enables the use of pseudorandom binary transmit waveforms and return modulation, along with low-bandwidth optical detectors to yield high-resolution ranging information. A proof-of-concept experiment is presented. With currently available compact, off-the-shelf electronics and photonics, such as high data rate binary pattern generators and high-bandwidth digital optical modulators, compressive laser ranging can readily achieve subcentimeter resolution in a compact, lightweight package.

  20. Dryden Aeronautical Test Range

    Data.gov (United States)

    Federal Laboratory Consortium — Recently redesignated to honor Dr. Hugh L. Dryden, NASA's Dryden Aeronautical Test Range (DATR) supports aerospace flight research and technology integration, space...

  1. Compact Antenna Range

    Data.gov (United States)

    Federal Laboratory Consortium — Facility consists of a folded compact antenna range including a computer controlled three axis position table, parabolic reflector and RF sources for the measurement...

  2. Inhibitory effects of aspirin-triggered resolvin D1 on spinal nociceptive processing in rat pain models.

    Science.gov (United States)

    Meesawatsom, Pongsatorn; Burston, James; Hathway, Gareth; Bennett, Andrew; Chapman, Victoria

    2016-09-02

    Harnessing the actions of the resolvin pathways has the potential for the treatment of a wide range of conditions associated with overt inflammatory signalling. Aspirin-triggered resolvin D1 (AT-RvD1) has robust analgesic effects in behavioural models of pain; however, the potential underlying spinal neurophysiological mechanisms contributing to these inhibitory effects in vivo are yet to be determined. This study investigated the acute effects of spinal AT-RvD1 on evoked responses of spinal neurones in vivo in a model of acute inflammatory pain and chronic osteoarthritic (OA) pain and the relevance of alterations in spinal gene expression to these neurophysiological effects. Pain behaviour was assessed in rats with established carrageenan-induced inflammatory or monosodium iodoacetate (MIA)-induced OA pain, and changes in spinal gene expression of resolvin receptors and relevant enzymatic pathways were examined. At timepoints of established pain behaviour, responses of deep dorsal horn wide dynamic range (WDR) neurones to transcutaneous electrical stimulation of the hind paw were recorded pre- and post direct spinal administration of AT-RvD1 (15 and 150 ng/50 μl). AT-RvD1 (15 ng/50 μl) significantly inhibited WDR neurone responses to electrical stimuli at C- (29 % inhibition) and Aδ-fibre (27 % inhibition) intensities. Both wind-up (53 %) and post-discharge (46 %) responses of WDR neurones in carrageenan-treated animals were significantly inhibited by AT-RvD1, compared to pre-drug response (p < 0.05). These effects were abolished by spinal pre-administration of a formyl peptide receptor 2 (FPR2/ALX) antagonist, butoxy carbonyl-Phe-Leu-Phe-Leu-Phe (BOC-2) (50 μg/50 μl). AT-RvD1 did not alter evoked WDR neurone responses in non-inflamed or MIA-treated rats. Electrophysiological effects in carrageenan-inflamed rats were accompanied by a significant increase in messenger RNA (mRNA) for chemerin (ChemR23) receptor and 5-lipoxygenase

  3. Models of the stochastic activity of neurones

    CERN Document Server

    Holden, Arun Vivian

    1976-01-01

    These notes have grown from a series of seminars given at Leeds between 1972 and 1975. They represent an attempt to gather together the different kinds of model which have been proposed to account for the stochastic activity of neurones, and to provide an introduction to this area of mathematical biology. A striking feature of the electrical activity of the nervous system is that it appears stochastic: this is apparent at all levels of recording, ranging from intracellular recordings to the electroencephalogram. The chapters start with fluctuations in membrane potential, proceed through single unit and synaptic activity and end with the behaviour of large aggregates of neurones: L have chgaen this seque~~e\\/~~';uggest that the interesting behaviourr~f :the nervous system - its individuality, variability and dynamic forms - may in part result from the stochastic behaviour of its components. I would like to thank Dr. Julio Rubio for reading and commenting on the drafts, Mrs. Doris Beighton for producing the fin...

  4. Range Scheduling Aid (RSA)

    Science.gov (United States)

    Logan, J. R.; Pulvermacher, M. K.

    1991-01-01

    Range Scheduling Aid (RSA) is presented in the form of the viewgraphs. The following subject areas are covered: satellite control network; current and new approaches to range scheduling; MITRE tasking; RSA features; RSA display; constraint based analytic capability; RSA architecture; and RSA benefits.

  5. On Range of Skill

    DEFF Research Database (Denmark)

    Hansen, Thomas Dueholm; Miltersen, Peter Bro; Sørensen, Troels Bjerre

    2008-01-01

    size (and doubly exponential in its depth). We also provide techniques that yield concrete bounds for unbalanced game trees and apply these to estimate the Range of Skill of Tic-Tac-Toe and Heads-Up Limit Texas Hold'em Poker. In particular, we show that the Range of Skill of Tic-Tac-Toe is more than...

  6. Home range and travels

    Science.gov (United States)

    Stickel, L.F.; King, John A.

    1968-01-01

    The concept of home range was expressed by Seton (1909) in the term 'home region,' which Burr (1940, 1943) clarified with a definition of home range and exemplified in a definitive study of Peromyscus in the field. Burt pointed out the ever-changing characteristics of home-range area and the consequent absence of boundaries in the usual sense--a finding verified by investigators thereafter. In the studies summarized in this paper, sizes of home ranges of Peromyscus varied within two magnitudes, approximately from 0.1 acre to ten acres, in 34 studies conducted in a variety of habitats from the seaside dunes of Florida to the Alaskan forests. Variation in sizes of home ranges was correlated with both environmental and physiological factors; with habitat it was conspicuous, both in the same and different regions. Food supply also was related to size of home range, both seasonally and in relation to habitat. Home ranges generally were smallest in winter and largest in spring, at the onset of the breeding season. Activity and size also were affected by changes in weather. Activity was least when temperatures were low and nights were bright. Effects of rainfall were variable. Sizes varied according to sex and age; young mice remained in the parents' range until they approached maturity, when they began to travel more widely. Adult males commonly had larger home ranges than females, although there were a number of exceptions. An inverse relationship between population density and size of home range was shown in several studies and probably is the usual relationship. A basic need for activity and exploration also appeared to influence size of home range. Behavior within the home range was discussed in terms of travel patterns, travels in relation to home sites and refuges, territory, and stability of size of home range. Travels within the home range consisted of repeated use of well-worn trails to sites of food, shelter, and refuge, plus more random exploratory travels

  7. Autonomous Target Ranging Techniques

    DEFF Research Database (Denmark)

    Jørgensen, Peter Siegbjørn; Jørgensen, John Leif; Denver, Troelz

    2003-01-01

    of this telescope, a fast determination of the range to and the motion of the detected targets are important. This is needed in order to prepare the future observation strategy for each target, i.e. when is the closest approach where imaging will be optimal. In order to quickly obtain such a determination two...... ranging strategies are presented. One is an improved laser ranger with an effective range with non-cooperative targets of at least 10,000 km, demonstrated in ground tests. The accuracy of the laser ranging will be approximately 1 m. The laser ranger may furthermore be used for trajectory determination...... of nano-gravity probes, which will perform direct mass measurements of selected targets. The other is triangulation from two spacecraft. For this method it is important to distinguish between detection and tracking range, which will be different for Bering since different instruments are used...

  8. Soliton microcomb range measurement

    Science.gov (United States)

    Suh, Myoung-Gyun; Vahala, Kerry J.

    2018-02-01

    Laser-based range measurement systems are important in many application areas, including autonomous vehicles, robotics, manufacturing, formation flying of satellites, and basic science. Coherent laser ranging systems using dual-frequency combs provide an unprecedented combination of long range, high precision, and fast update rate. We report dual-comb distance measurement using chip-based soliton microcombs. A single pump laser was used to generate dual-frequency combs within a single microresonator as counterpropagating solitons. We demonstrated time-of-flight measurement with 200-nanometer precision at an averaging time of 500 milliseconds within a range ambiguity of 16 millimeters. Measurements at distances up to 25 meters with much lower precision were also performed. Our chip-based source is an important step toward miniature dual-comb laser ranging systems that are suitable for photonic integration.

  9. 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.

  10. Computing with Spiking Neuron Networks

    NARCIS (Netherlands)

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

    2012-01-01

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

  11. 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

  12. Optimal compensation for neuron loss

    Science.gov (United States)

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

    2016-01-01

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

  13. Hypothalamic neurones governing glucose homeostasis.

    Science.gov (United States)

    Coppari, R

    2015-06-01

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

  14. Functionalized anatomical models for EM-neuron Interaction modeling

    Science.gov (United States)

    Neufeld, Esra; Cassará, Antonino Mario; Montanaro, Hazael; Kuster, Niels; Kainz, Wolfgang

    2016-06-01

    The understanding of interactions between electromagnetic (EM) fields and nerves are crucial in contexts ranging from therapeutic neurostimulation to low frequency EM exposure safety. To properly consider the impact of in vivo induced field inhomogeneity on non-linear neuronal dynamics, coupled EM-neuronal dynamics modeling is required. For that purpose, novel functionalized computable human phantoms have been developed. Their implementation and the systematic verification of the integrated anisotropic quasi-static EM solver and neuronal dynamics modeling functionality, based on the method of manufactured solutions and numerical reference data, is described. Electric and magnetic stimulation of the ulnar and sciatic nerve were modeled to help understanding a range of controversial issues related to the magnitude and optimal determination of strength-duration (SD) time constants. The results indicate the importance of considering the stimulation-specific inhomogeneous field distributions (especially at tissue interfaces), realistic models of non-linear neuronal dynamics, very short pulses, and suitable SD extrapolation models. These results and the functionalized computable phantom will influence and support the development of safe and effective neuroprosthetic devices and novel electroceuticals. Furthermore they will assist the evaluation of existing low frequency exposure standards for the entire population under all exposure conditions.

  15. 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.

  16. Oscillating from Neurosecretion to Multitasking Dopamine Neurons

    Directory of Open Access Journals (Sweden)

    David R. Grattan

    2016-04-01

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

  17. Prediction ranges. Annual review

    Energy Technology Data Exchange (ETDEWEB)

    Parker, J.C.; Tharp, W.H.; Spiro, P.S.; Keng, K.; Angastiniotis, M.; Hachey, L.T.

    1988-01-01

    Prediction ranges equip the planner with one more tool for improved assessment of the outcome of a course of action. One of their major uses is in financial evaluations, where corporate policy requires the performance of uncertainty analysis for large projects. This report gives an overview of the uses of prediction ranges, with examples; and risks and uncertainties in growth, inflation, and interest and exchange rates. Prediction ranges and standard deviations of 80% and 50% probability are given for various economic indicators in Ontario, Canada, and the USA, as well as for foreign exchange rates and Ontario Hydro interest rates. An explanatory note on probability is also included. 23 tabs.

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

    Science.gov (United States)

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

    2017-11-07

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

  19. High-Throughput Mapping of Single-Neuron Projections by Sequencing of Barcoded RNA.

    Science.gov (United States)

    Kebschull, Justus M; Garcia da Silva, Pedro; Reid, Ashlan P; Peikon, Ian D; Albeanu, Dinu F; Zador, Anthony M

    2016-09-07

    Neurons transmit information to distant brain regions via long-range axonal projections. In the mouse, area-to-area connections have only been systematically mapped using bulk labeling techniques, which obscure the diverse projections of intermingled single neurons. Here we describe MAPseq (Multiplexed Analysis of Projections by Sequencing), a technique that can map the projections of thousands or even millions of single neurons by labeling large sets of neurons with random RNA sequences ("barcodes"). Axons are filled with barcode mRNA, each putative projection area is dissected, and the barcode mRNA is extracted and sequenced. Applying MAPseq to the locus coeruleus (LC), we find that individual LC neurons have preferred cortical targets. By recasting neuroanatomy, which is traditionally viewed as a problem of microscopy, as a problem of sequencing, MAPseq harnesses advances in sequencing technology to permit high-throughput interrogation of brain circuits. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. The pairwise phase consistency in cortical network and its relationship with neuronal activation

    Directory of Open Access Journals (Sweden)

    Wang Daming

    2017-01-01

    Full Text Available Gamma-band neuronal oscillation and synchronization with the range of 30-90 Hz are ubiquitous phenomenon across numerous brain areas and various species, and correlated with plenty of cognitive functions. The phase of the oscillation, as one aspect of CTC (Communication through Coherence hypothesis, underlies various functions for feature coding, memory processing and behaviour performing. The PPC (Pairwise Phase Consistency, an improved coherence measure, statistically quantifies the strength of phase synchronization. In order to evaluate the PPC and its relationships with input stimulus, neuronal activation and firing rate, a simplified spiking neuronal network is constructed to simulate orientation columns in primary visual cortex. If the input orientation stimulus is preferred for a certain orientation column, neurons within this corresponding column will obtain higher firing rate and stronger neuronal activation, which consequently engender higher PPC values, with higher PPC corresponding to higher firing rate. In addition, we investigate the PPC in time resolved analysis with a sliding window.

  1. Antenna Pattern Range (APR)

    Data.gov (United States)

    Federal Laboratory Consortium — TheAntenna Pattern Range (APR)features a non-metallic arch with a trolley to move the transmit antenna from the horizon to zenith. At the center of the ground plane,...

  2. Atlantic Test Range (ATR)

    Data.gov (United States)

    Federal Laboratory Consortium — ATR controls fully-instrumented and integrated test ranges that provide full-service support for cradle-to-grave testing. Airspace and surface target areas are used...

  3. EV range sensitivity analysis

    Energy Technology Data Exchange (ETDEWEB)

    Ostafew, C. [Azure Dynamics Corp., Toronto, ON (Canada)

    2010-07-01

    This presentation included a sensitivity analysis of electric vehicle components on overall efficiency. The presentation provided an overview of drive cycles and discussed the major contributors to range in terms of rolling resistance; aerodynamic drag; motor efficiency; and vehicle mass. Drive cycles that were presented included: New York City Cycle (NYCC); urban dynamometer drive cycle; and US06. A summary of the findings were presented for each of the major contributors. Rolling resistance was found to have a balanced effect on each drive cycle and proportional to range. In terms of aerodynamic drive, there was a large effect on US06 range. A large effect was also found on NYCC range in terms of motor efficiency and vehicle mass. figs.

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

    Czech Academy of Sciences Publication Activity Database

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

    2013-01-01

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

  5. Disrupting neuronal transmission: Mechanism of DBS?

    Directory of Open Access Journals (Sweden)

    Satomi eChiken

    2014-03-01

    Full Text Available Applying high-frequency stimulation to deep brain rain structure, known as deep brain stimulation (DBS, has now been recognized an effective therapeutic option for a wide range of neurological and psychiatric disorders. DBS targeting the basal ganglia thalamo-cortical loop, especially the internal segment of the globus pallidus, subthalamic nucleus and thalamus, has been widely employed as a successful surgical therapy for movement disorders, such as Parkinson’s disease, dystonia and tremor. However, the neurophysiological mechanism underling the action of DBS remains unclear and is still under debate: does DBS inhibit or excite local neuronal elements? In this review, we will examine this question and propose the alternative interpretation: DBS dissociates inputs and outputs, resulting in disruption of abnormal signal transmission.

  6. Inhibiting cholesterol degradation induces neuronal sclerosis and epileptic activity in mouse hippocampus

    Science.gov (United States)

    Chali, Farah; Djelti, Fathia; Eugene, Emmanuel; Valderrama, Mario; Marquer, Catherine; Aubourg, Patrick; Duykaerts, Charles; Miles, Richard; Cartier, Nathalie; Navarro, Vincent

    2015-01-01

    Elevations in neuronal cholesterol have been associated with several degenerative diseases. An enhanced excitability and synchronous firing in surviving neurons are among the sequels of neuronal death in these diseases and also in some epileptic syndromes. Here, we attempted to increase neuronal cholesterol levels, using a short hairpin RNA (shRNA) to suppress expression of the enzyme CYP46A1. This protein hydroxylates cholesterol and so facilitates trans-membrane extrusion. A sh-RNA CYP46A1construction coupled to an adeno-associated virus (AAV5) was injected focally and unilaterally into mouse hippocampus. It was selectively expressed first in neurons of the CA3a region. Cytoplasmic and membrane cholesterol increased, neuronal soma volume increased and then decreased before pyramidal cells died. As CA3a pyramidal cells died, inter-ictal EEG events occurred during exploration and non-REM sleep. With time, neuronal death spread to involve pyramidal cells and interneurons of the CA1 region. CA1 neuronal death was correlated with a delayed local expression of phosphorylated tau. Astrocytes were activated throughout the hippocampus and microglial activation was specific to regions of neuronal death. CA1 neuronal death was correlated with distinct aberrant EEG activity. During exploratory behaviour and rapid eye movement sleep, EEG oscillations at 7-10 Hz (theta) could accelerate to 14-21 Hz (beta) waves. They were accompanied by low amplitude, high-frequency oscillations of peak power at ~300Hz and a range of 250-350 Hz. While episodes of EEG acceleration were not correlated with changes in exploratory behaviour, they were followed in some animals by structured seizure-like discharges. These data strengthen links between increased cholesterol, neuronal sclerosis and epileptic behavior PMID:25847620

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

    Directory of Open Access Journals (Sweden)

    Meaghan C Creed

    2014-01-01

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

  8. Detection of 5-hydroxytryptamine (5-HT) in vitro using a hippocampal neuronal network-based biosensor with extracellular potential analysis of neurons.

    Science.gov (United States)

    Hu, Liang; Wang, Qin; Qin, Zhen; Su, Kaiqi; Huang, Liquan; Hu, Ning; Wang, Ping

    2015-04-15

    5-hydroxytryptamine (5-HT) is an important neurotransmitter in regulating emotions and related behaviors in mammals. To detect and monitor the 5-HT, effective and convenient methods are demanded in investigation of neuronal network. In this study, hippocampal neuronal networks (HNNs) endogenously expressing 5-HT receptors were employed as sensing elements to build an in vitro neuronal network-based biosensor. The electrophysiological characteristics were analyzed in both neuron and network levels. The firing rates and amplitudes were derived from signal to determine the biosensor response characteristics. The experimental results demonstrate a dose-dependent inhibitory effect of 5-HT on hippocampal neuron activities, indicating the effectiveness of this hybrid biosensor in detecting 5-HT with a response range from 0.01μmol/L to 10μmol/L. In addition, the cross-correlation analysis of HNNs activities suggests 5-HT could weaken HNN connectivity reversibly, providing more specificity of this biosensor in detecting 5-HT. Moreover, 5-HT induced spatiotemporal firing pattern alterations could be monitored in neuron and network levels simultaneously by this hybrid biosensor in a convenient and direct way. With those merits, this neuronal network-based biosensor will be promising to be a valuable and utility platform for the study of neurotransmitter in vitro. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Respiratory signaling of locus coeruleus neurons during hypercapnic acidosis in the bullfrog, Lithobates catesbeianus.

    Science.gov (United States)

    Santin, J M; Hartzler, L K

    2013-02-01

    The locus coeruleus (LC) in the brainstem senses alterations in CO(2)/pH and influences ventilatory adjustments that restore blood gas values to starting levels in bullfrogs (Lithobates catesbeianus). We hypothesized that neurons of the bullfrog LC are sensitive to changes in CO(2)/pH and that chemosensitive responses are intrinsic to individual neurons. In addition, we hypothesized putative respiratory control neurons of the bullfrog LC would be stimulated by hypercapnic acidosis within physiological ranges of P(CO(2))/pH. 84% of LC neurons depolarized and increased firing rates during exposure to hypercapnic acidosis (HA). A pH dose response curve shows LC neurons from bullfrogs increase firing rates during physiologically relevant CO(2)/pH changes. With chemical synapses blocked, half of chemosensitive neurons lost sensitivity to HA; however, gap junction blockade did not alter chemosensitive responses. Intrinsically chemosensitive neurons increased input resistance during HA. These data demonstrate that majority of neurons within the bullfrog LC elicit robust firing responses during physiological ΔCO(2)/pH, likely enabling adjustment of acid-base balance through breathing. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Transition Dynamics of a Dentate Gyrus-CA3 Neuronal Network during Temporal Lobe Epilepsy

    Directory of Open Access Journals (Sweden)

    Liyuan Zhang

    2017-07-01

    Full Text Available In temporal lobe epilepsy (TLE, the variation of chemical receptor expression underlies the basis of neural network activity shifts, resulting in neuronal hyperexcitability and epileptiform discharges. However, dynamical mechanisms involved in the transitions of TLE are not fully understood, because of the neuronal diversity and the indeterminacy of network connection. Hence, based on Hodgkin–Huxley (HH type neurons and Pinsky–Rinzel (PR type neurons coupling with glutamatergic and GABAergic synaptic connections respectively, we propose a computational framework which contains dentate gyrus (DG region and CA3 region. By regulating the concentration range of N-methyl-D-aspartate-type glutamate receptor (NMDAR, we demonstrate the pyramidal neuron can generate transitions from interictal to seizure discharges. This suggests that enhanced endogenous activity of NMDAR contributes to excitability in pyramidal neuron. Moreover, we conclude that excitatory discharges in CA3 region vary considerably on account of the excitatory currents produced by the excitatory pyramidal neuron. Interestingly, by changing the backprojection connection, we find that glutamatergic type backprojection can promote the dominant frequency of firings and further motivate excitatory counterpropagation from CA3 region to DG region. However, GABAergic type backprojection can reduce firing rate and block morbid counterpropagation, which may be factored into the terminations of TLE. In addition, neuronal diversity dominated network shows weak correlation with different backprojections. Our modeling and simulation studies provide new insights into the mechanisms of seizures generation and connectionism in local hippocampus, along with the synaptic mechanisms of this disease.

  11. Neuronal Entropy-Rate Feature of Entopeduncular Nucleus in Rat Model of Parkinson's Disease.

    Science.gov (United States)

    Darbin, Olivier; Jin, Xingxing; Von Wrangel, Christof; Schwabe, Kerstin; Nambu, Atsushi; Naritoku, Dean K; Krauss, Joachim K; Alam, Mesbah

    2016-03-01

    The function of the nigro-striatal pathway on neuronal entropy in the basal ganglia (BG) output nucleus, i.e. the entopeduncular nucleus (EPN) was investigated in the unilaterally 6-hyroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (PD). In both control subjects and subjects with 6-OHDA lesion of dopamine (DA) the nigro-striatal pathway, a histological hallmark for parkinsonism, neuronal entropy in EPN was maximal in neurons with firing rates ranging between 15 and 25 Hz. In 6-OHDA lesioned rats, neuronal entropy in the EPN was specifically higher in neurons with firing rates above 25 Hz. Our data establishes that the nigro-striatal pathway controls neuronal entropy in motor circuitry and that the parkinsonian condition is associated with abnormal relationship between firing rate and neuronal entropy in BG output nuclei. The neuronal firing rates and entropy relationship provide putative relevant electrophysiological information to investigate the sensory-motor processing in normal condition and conditions such as movement disorders.

  12. The Itch-Producing Agents Histamine and Cowhage Activate Separate Populations of Primate Spinothalamic Tract Neurons

    Science.gov (United States)

    Davidson, Steve; Zhang, Xijing; Yoon, Chul H.; Khasabov, Sergey G.; Simone, Donald A.; Giesler, Glenn J.

    2010-01-01

    Itch is an everyday sensation, but when associated with disease or infection it can be chronic and debilitating. Several forms of itch can be blocked using antihistamines, but others cannot and these constitute an important clinical problem. Little information is available on the mechanisms underlying itch that is produced by nonhistaminergic mechanisms. We examined the responses of spinothalamic tract neurons to histaminergic and, for the first time, nonhistaminergic forms of itch stimuli. Fifty-seven primate spinothalamic tract (STT) neurons were identified using antidromic activation techniques and examined for their responses to histamine and cowhage, the nonhistaminergic itch-producing spicules covering the pod of the legume Mucuna pruriens. Each examined neuron had a receptive field on the hairy skin of the hindlimb and responded to noxious mechanical stimulation. STT neurons were tested with both pruritogens applied in a random order and we found 12 that responded to histamine and seven to cowhage. Each pruritogen-responsive STT neuron was activated by the chemical algogen capsaicin and two-thirds responded to noxious heat stimuli, demonstrating that these neurons convey chemical, thermal, and mechanical nociceptive information as well. Histamine or cowhage responsive STT neurons were found in both the marginal zone and the deep dorsal horn and were classified as high threshold and wide dynamic range. Unexpectedly, histamine and cowhage never activated the same cell. Our results demonstrate that the spinothalamic tract contains mutually exclusive populations of neurons responsive to histamine or the nonhistaminergic itch-producing agent cowhage. PMID:17855615

  13. Neurons for hunger and thirst transmit a negative-valence teaching signal

    Science.gov (United States)

    Gong, Rong; Magnus, Christopher J.; Yu, Yang; Sternson, Scott M.

    2015-01-01

    Homeostasis is a biological principle for regulation of essential physiological parameters within a set range. Behavioural responses due to deviation from homeostasis are critical for survival, but motivational processes engaged by physiological need states are incompletely understood. We examined motivational characteristics and dynamics of two separate neuron populations that regulate energy and fluid homeostasis by using cell type-specific activity manipulations in mice. We found that starvation-sensitive AGRP neurons exhibit properties consistent with a negative-valence teaching signal. Mice avoided activation of AGRP neurons, indicating that AGRP neuron activity has negative valence. AGRP neuron inhibition conditioned preference for flavours and places. Correspondingly, deep-brain calcium imaging revealed that AGRP neuron activity rapidly reduced in response to food-related cues. Complementary experiments activating thirst-promoting neurons also conditioned avoidance. Therefore, these need-sensing neurons condition preference for environmental cues associated with nutrient or water ingestion, which is learned through reduction of negative-valence signals during restoration of homeostasis. PMID:25915020

  14. Transition Dynamics of a Dentate Gyrus-CA3 Neuronal Network during Temporal Lobe Epilepsy.

    Science.gov (United States)

    Zhang, Liyuan; Fan, Denggui; Wang, Qingyun

    2017-01-01

    In temporal lobe epilepsy (TLE), the variation of chemical receptor expression underlies the basis of neural network activity shifts, resulting in neuronal hyperexcitability and epileptiform discharges. However, dynamical mechanisms involved in the transitions of TLE are not fully understood, because of the neuronal diversity and the indeterminacy of network connection. Hence, based on Hodgkin-Huxley (HH) type neurons and Pinsky-Rinzel (PR) type neurons coupling with glutamatergic and GABAergic synaptic connections respectively, we propose a computational framework which contains dentate gyrus (DG) region and CA3 region. By regulating the concentration range of N-methyl-D-aspartate-type glutamate receptor (NMDAR), we demonstrate the pyramidal neuron can generate transitions from interictal to seizure discharges. This suggests that enhanced endogenous activity of NMDAR contributes to excitability in pyramidal neuron. Moreover, we conclude that excitatory discharges in CA3 region vary considerably on account of the excitatory currents produced by the excitatory pyramidal neuron. Interestingly, by changing the backprojection connection, we find that glutamatergic type backprojection can promote the dominant frequency of firings and further motivate excitatory counterpropagation from CA3 region to DG region. However, GABAergic type backprojection can reduce firing rate and block morbid counterpropagation, which may be factored into the terminations of TLE. In addition, neuronal diversity dominated network shows weak correlation with different backprojections. Our modeling and simulation studies provide new insights into the mechanisms of seizures generation and connectionism in local hippocampus, along with the synaptic mechanisms of this disease.

  15. Spiking sychronization regulated by noise in three types of Hodgkin—Huxley neuronal networks

    International Nuclear Information System (INIS)

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

    2012-01-01

    In this paper, we study spiking synchronization in three different types of Hodgkin—Huxley neuronal networks, which are the small-world, regular, and random neuronal networks. All the neurons are subjected to subthreshold stimulus and external noise. It is found that in each of all the neuronal networks there is an optimal strength of noise to induce the maximal spiking synchronization. We further demonstrate that in each of the neuronal networks there is a range of synaptic conductance to induce the effect that an optimal strength of noise maximizes the spiking synchronization. Only when the magnitude of the synaptic conductance is moderate, will the effect be considerable. However, if the synaptic conductance is small or large, the effect vanishes. As the connections between neurons increase, the synaptic conductance to maximize the effect decreases. Therefore, we show quantitatively that the noise-induced maximal synchronization in the Hodgkin—Huxley neuronal network is a general effect, regardless of the specific type of neuronal network

  16. Range Selection and Median

    DEFF Research Database (Denmark)

    Jørgensen, Allan Grønlund; Larsen, Kasper Green

    2011-01-01

    and several natural special cases thereof. The rst special case is known as range median, which arises when k is xed to b(j 􀀀 i + 1)=2c. The second case, denoted prex selection, arises when i is xed to 0. Finally, we also consider the bounded rank prex selection problem and the xed rank range......Range selection is the problem of preprocessing an input array A of n unique integers, such that given a query (i; j; k), one can report the k'th smallest integer in the subarray A[i];A[i+1]; : : : ;A[j]. In this paper we consider static data structures in the word-RAM for range selection...... selection problem. In the former, data structures must support prex selection queries under the assumption that k for some value n given at construction time, while in the latter, data structures must support range selection queries where k is xed beforehand for all queries. We prove cell probe lower bounds...

  17. How to make spinal motor neurons.

    Science.gov (United States)

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

    2014-02-01

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

  18. Firing dynamics of an autaptic neuron

    International Nuclear Information System (INIS)

    Wang Heng-Tong; Chen Yong

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-04-07

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

  20. Mirror neurons and motor intentionality.

    Science.gov (United States)

    Rizzolatti, Giacomo; Sinigaglia, Corrado

    2007-01-01

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

  1. Dynamic SERS nanosensor for neurotransmitter sensing near neurons.

    Science.gov (United States)

    Lussier, Félix; Brulé, Thibault; Bourque, Marie-Josée; Ducrot, Charles; Trudeau, Louis-Éric; Masson, Jean-François

    2017-12-04

    Current electrophysiology and electrochemistry techniques have provided unprecedented understanding of neuronal activity. However, these techniques are suited to a small, albeit important, panel of neurotransmitters such as glutamate, GABA and dopamine, and these constitute only a subset of the broader range of neurotransmitters involved in brain chemistry. Surface-enhanced Raman scattering (SERS) provides a unique opportunity to detect a broader range of neurotransmitters in close proximity to neurons. Dynamic SERS (D-SERS) nanosensors based on patch-clamp-like nanopipettes decorated with gold nanoraspberries can be located accurately under a microscope using techniques analogous to those used in current electrophysiology or electrochemistry experiments. In this manuscript, we demonstrate that D-SERS can measure in a single experiment ATP, glutamate (glu), acetylcholine (ACh), GABA and dopamine (DA), among other neurotransmitters, with the potential for detecting a greater number of neurotransmitters. The SERS spectra of these neurotransmitters were identified with a barcoding data processing method and time series of the neurotransmitter levels were constructed. The D-SERS nanosensor was then located near cultured mouse dopaminergic neurons. The detection of neurotransmitters was performed in response to a series of K + depolarisations, and allowed the detection of elevated levels of both ATP and dopamine. Control experiments were also performed near glial cells, showing only very low basal detection neurotransmitter events. This paper demonstrates the potential of D-SERS to detect neurotransmitter secretion events near living neurons, but also constitutes a strong proof-of-concept for the broad application of SERS to the detection of secretion events by neurons or other cell types in order to study normal or pathological cell functions.

  2. Unbalanced neuronal circuits in addiction.

    Science.gov (United States)

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

    2013-08-01

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

  3. Neurochemical phenotypes of cardiorespiratory neurons.

    Science.gov (United States)

    Pilowsky, Paul M

    2008-12-10

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

  4. Mirror Neurons from Associative Learning

    OpenAIRE

    Catmur, Caroline; Press, Clare; Heyes, Cecilia

    2016-01-01

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

  5. Trafficking of neuronal calcium channels

    Czech Academy of Sciences Publication Activity Database

    Weiss, Norbert; Zamponi, G. W.

    2017-01-01

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

  6. 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.

  7. Elasticity maps of living neurons measured by combined fluorescence and atomic force microscopy.

    Science.gov (United States)

    Spedden, Elise; White, James D; Naumova, Elena N; Kaplan, David L; Staii, Cristian

    2012-09-05

    Detailed knowledge of mechanical parameters such as cell elasticity, stiffness of the growth substrate, or traction stresses generated during axonal extensions is essential for understanding the mechanisms that control neuronal growth. Here, we combine atomic force microscopy-based force spectroscopy with fluorescence microscopy to produce systematic, high-resolution elasticity maps for three different types of live neuronal cells: cortical (embryonic rat), embryonic chick dorsal root ganglion, and P-19 (mouse embryonic carcinoma stem cells) neurons. We measure how the stiffness of neurons changes both during neurite outgrowth and upon disruption of microtubules of the cell. We find reversible local stiffening of the cell during growth, and show that the increase in local elastic modulus is primarily due to the formation of microtubules. We also report that cortical and P-19 neurons have similar elasticity maps, with elastic moduli in the range 0.1-2 kPa, with typical average values of 0.4 kPa (P-19) and 0.2 kPa (cortical). In contrast, dorsal root ganglion neurons are stiffer than P-19 and cortical cells, yielding elastic moduli in the range 0.1-8 kPa, with typical average values of 0.9 kPa. Finally, we report no measurable influence of substrate protein coating on cell body elasticity for the three types of neurons. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  8. Dynamics of intrinsic electrophysiological properties in spinal cord neurones

    DEFF Research Database (Denmark)

    Russo, R E; Hounsgaard, J

    1999-01-01

    The spinal cord is engaged in a wide variety of functions including generation of motor acts, coding of sensory information and autonomic control. The intrinsic electrophysiological properties of spinal neurones represent a fundamental building block of the spinal circuits executing these tasks. ....... Specialised, cell specific electrophysiological phenotypes gradually differentiate during development and are continuously adjusted in the adult animal by metabotropic synaptic interactions and activity-dependent plasticity to meet a broad range of functional demands....

  9. Simulating large-scale spiking neuronal networks with NEST

    OpenAIRE

    Schücker, Jannis; Eppler, Jochen Martin

    2014-01-01

    The Neural Simulation Tool NEST [1, www.nest-simulator.org] is the simulator for spiking neural networkmodels of the HBP that focuses on the dynamics, size and structure of neural systems rather than on theexact morphology of individual neurons. Its simulation kernel is written in C++ and it runs on computinghardware ranging from simple laptops to clusters and supercomputers with thousands of processor cores.The development of NEST is coordinated by the NEST Initiative [www.nest-initiative.or...

  10. Online Sorted Range Reporting

    DEFF Research Database (Denmark)

    Brodal, Gerth Stølting; Fagerberg, Rolf; Greve, Mark

    2009-01-01

    is motivated by (and is a generalization of) a problem with applications in search engines: On a tree where leaves have associated rank values, report the highest ranked leaves in a given subtree. Finally, the problem studied generalizes the classic range minimum query (RMQ) problem on arrays....

  11. Substring Range Reporting

    DEFF Research Database (Denmark)

    Bille, Philip; Gørtz, Inge Li

    2014-01-01

    We revisit various string indexing problems with range reporting features, namely, position-restricted substring searching, indexing substrings with gaps, and indexing substrings with intervals. We obtain the following main results. We give efficient reductions for each of the above problems...

  12. Substring Range Reporting

    DEFF Research Database (Denmark)

    Bille, Philip; Gørtz, Inge Li

    2011-01-01

    We revisit various string indexing problems with range reporting features, namely, position-restricted substring searching, indexing substrings with gaps, and indexing substrings with intervals. We obtain the following main results. – We give efficient reductions for each of the above problems...

  13. Range-clustering queries

    NARCIS (Netherlands)

    Abrahamsen, M.; de Berg, M.T.; Buchin, K.A.; Mehr, M.; Mehrabi, A.D.

    2017-01-01

    In a geometric k -clustering problem the goal is to partition a set of points in R d into k subsets such that a certain cost function of the clustering is minimized. We present data structures for orthogonal range-clustering queries on a point set S : given a query box Q and an integer k>2 , compute

  14. The Effects of IGF-1 on Trk Expressing DRG Neurons with HIV-gp120- Induced Neurotoxicity.

    Science.gov (United States)

    Li, Hao; Liu, Zhen; Chi, Heng; Bi, Yanwen; Song, Lijun; Liu, Huaxiang

    2016-01-01

    HIV envelope glycoprotein gp120 is the main protein that causes HIVassociated sensory neuropathy. However, the underlying mechanisms of gp120-induced neurotoxicity are still unclear. There are lack effective treatments for relieving HIV-related neuropathic symptoms caused by gp120-induced neurotoxicity. In the present study, tyrosine kinase receptor (Trk)A, TrkB, and TrkC expression in primary cultured dorsal root ganglion (DRG) neurons with gp120-induced neurotoxicity was investigated. The effects of IGF-1 on distinct Trk-positive DRG neurons with gp120-induced neurotoxicity were also determined. The results showed that gp120 not only dose-dependently induced DRG neuronal apoptosis and inhibited neuronal survival and neurite outgrowth, but also decreased distinct Trk expression levels. IGF-1 rescued DRG neurons from apoptosis and improved neuronal survival of gp120 neurotoxic DRG neurons in vitro. IGF-1 also improved TrkA and TrkB, but not TrkC, expression in gp120 neurotoxic conditions. The effects of IGF-1 could be blocked by preincubation with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. These results suggested that gp120 may have a wide range of neurotoxicity on different subpopulations of DRG neurons, while IGF-1 might only relieve some subpopulations of DRG neurons with gp120-induced neurotoxicity. These data provide novel information of mechanisms of gp120 neurotoxicity on primary sensory neurons and the potential therapeutic effects of IGF-1 on gp120-induced neurotoxicity.

  15. Optimal Detection of a Localized Perturbation in Random Networks of Integrate-and-Fire Neurons

    Science.gov (United States)

    Bernardi, Davide; Lindner, Benjamin

    2017-06-01

    Experimental and theoretical studies suggest that cortical networks are chaotic and coding relies on averages over large populations. However, there is evidence that rats can respond to the short stimulation of a single cortical cell, a theoretically unexplained fact. We study effects of single-cell stimulation on a large recurrent network of integrate-and-fire neurons and propose a simple way to detect the perturbation. Detection rates obtained from simulations and analytical estimates are similar to experimental response rates if the readout is slightly biased towards specific neurons. Near-optimal detection is attained for a broad range of intermediate values of the mean coupling between neurons.

  16. 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.

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

    Science.gov (United States)

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

    2014-05-01

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

  18. 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

  19. Order-based representation in random networks of cortical neurons.

    Directory of Open Access Journals (Sweden)

    Goded Shahaf

    2008-11-01

    Full Text Available The wide range of time scales involved in neural excitability and synaptic transmission might lead to ongoing change in the temporal structure of responses to recurring stimulus presentations on a trial-to-trial basis. This is probably the most severe biophysical constraint on putative time-based primitives of stimulus representation in neuronal networks. Here we show that in spontaneously developing large-scale random networks of cortical neurons in vitro the order in which neurons are recruited following each stimulus is a naturally emerging representation primitive that is invariant to significant temporal changes in spike times. With a relatively small number of randomly sampled neurons, the information about stimulus position is fully retrievable from the recruitment order. The effective connectivity that makes order-based representation invariant to time warping is characterized by the existence of stations through which activity is required to pass in order to propagate further into the network. This study uncovers a simple invariant in a noisy biological network in vitro; its applicability under in vivo constraints remains to be seen.

  20. Time-warp invariant pattern detection with bursting neurons

    International Nuclear Information System (INIS)

    Gollisch, Tim

    2008-01-01

    Sound patterns are defined by the temporal relations of their constituents, individual acoustic cues. Auditory systems need to extract these temporal relations to detect or classify sounds. In various cases, ranging from human speech to communication signals of grasshoppers, this pattern detection has been found to display invariance to temporal stretching or compression of the sound signal ('linear time-warp invariance'). In this work, a four-neuron network model is introduced, designed to solve such a detection task for the example of grasshopper courtship songs. As an essential ingredient, the network contains neurons with intrinsic bursting dynamics, which allow them to encode durations between acoustic events in short, rapid sequences of spikes. As shown by analytical calculations and computer simulations, these neuronal dynamics result in a powerful mechanism for temporal integration. Finally, the network reads out the encoded temporal information by detecting equal activity of two such bursting neurons. This leads to the recognition of rhythmic patterns independent of temporal stretching or compression

  1. Estimating the biophysical properties of neurons with intracellular calcium dynamics.

    Science.gov (United States)

    Ye, Jingxin; Rozdeba, Paul J; Morone, Uriel I; Daou, Arij; Abarbanel, Henry D I

    2014-06-01

    We investigate the dynamics of a conductance-based neuron model coupled to a model of intracellular calcium uptake and release by the endoplasmic reticulum. The intracellular calcium dynamics occur on a time scale that is orders of magnitude slower than voltage spiking behavior. Coupling these mechanisms sets the stage for the appearance of chaotic dynamics, which we observe within certain ranges of model parameter values. We then explore the question of whether one can, using observed voltage data alone, estimate the states and parameters of the voltage plus calcium (V+Ca) dynamics model. We find the answer is negative. Indeed, we show that voltage plus another observed quantity must be known to allow the estimation to be accurate. We show that observing both the voltage time course V(t) and the intracellular Ca time course will permit accurate estimation, and from the estimated model state, accurate prediction after observations are completed. This sets the stage for how one will be able to use a more detailed model of V+Ca dynamics in neuron activity in the analysis of experimental data on individual neurons as well as functional networks in which the nodes (neurons) have these biophysical properties.

  2. Modeling the diffusion magnetic resonance imaging signal inside neurons

    International Nuclear Information System (INIS)

    Nguyen, D V; Li, J R; Grebenkov, D S; Le Bihan, D

    2014-01-01

    The Bloch-Torrey partial differential equation (PDE) describes the complex transverse water proton magnetization due to diffusion-encoding magnetic field gradient pulses. The integral of the solution of this PDE yields the diffusion magnetic resonance imaging (dMRI) signal. In a complex medium such as cerebral tissue, it is difficult to explicitly link the dMRI signal to biological parameters such as the cellular geometry or the cellular volume fraction. Studying the dMRI signal arising from a single neuron can provide insight into how the geometrical structure of neurons influences the measured signal. We formulate the Bloch-Torrey PDE inside a single neuron, under no water exchange condition with the extracellular space, and show how to reduce the 3D simulation in the full neuron to a 3D simulation around the soma and 1D simulations in the neurites. We show that this latter approach is computationally much faster than full 3D simulation and still gives accurate results over a wide range of diffusion times

  3. Multiplicative multifractal modeling and discrimination of human neuronal activity

    International Nuclear Information System (INIS)

    Zheng Yi; Gao Jianbo; Sanchez, Justin C.; Principe, Jose C.; Okun, Michael S.

    2005-01-01

    Understanding neuronal firing patterns is one of the most important problems in theoretical neuroscience. It is also very important for clinical neurosurgery. In this Letter, we introduce a computational procedure to examine whether neuronal firing recordings could be characterized by cascade multiplicative multifractals. By analyzing raw recording data as well as generated spike train data from 3 patients collected in two brain areas, the globus pallidus externa (GPe) and the globus pallidus interna (GPi), we show that the neural firings are consistent with a multifractal process over certain time scale range (t 1 ,t 2 ), where t 1 is argued to be not smaller than the mean inter-spike-interval of neuronal firings, while t 2 may be related to the time that neuronal signals propagate in the major neural branching structures pertinent to GPi and GPe. The generalized dimension spectrum D q effectively differentiates the two brain areas, both intra- and inter-patients. For distinguishing between GPe and GPi, it is further shown that the cascade model is more effective than the methods recently examined by Schiff et al. as well as the Fano factor analysis. Therefore, the methodology may be useful in developing computer aided tools to help clinicians perform precision neurosurgery in the operating room

  4. Self-Organized Criticality in a Simple Neuron Model Based on Scale-Free Networks

    International Nuclear Information System (INIS)

    Lin Min; Wang Gang; Chen Tianlun

    2006-01-01

    A simple model for a set of interacting idealized neurons in scale-free networks is introduced. The basic elements of the model are endowed with the main features of a neuron function. We find that our model displays power-law behavior of avalanche sizes and generates long-range temporal correlation. More importantly, we find different dynamical behavior for nodes with different connectivity in the scale-free networks.

  5. The Age of Enlightenment: Evolving Opportunities in Brain Research Through Optical Manipulation of Neuronal Activity

    OpenAIRE

    Jerome, Jason; Heck, Detlef H.

    2011-01-01

    Optical manipulation of neuronal activity has rapidly developed into the most powerful and widely used approach to study mechanisms related to neuronal connectivity over a range of scales. Since the early use of single site uncaging to map network connectivity, rapid technological development of light modulation techniques has added important new options, such as fast scanning photostimulation, massively parallel control of light stimuli, holographic uncaging, and two-photon stimulation techn...

  6. Unsupervised learning in neural networks with short range synapses

    Science.gov (United States)

    Brunnet, L. G.; Agnes, E. J.; Mizusaki, B. E. P.; Erichsen, R., Jr.

    2013-01-01

    Different areas of the brain are involved in specific aspects of the information being processed both in learning and in memory formation. For example, the hippocampus is important in the consolidation of information from short-term memory to long-term memory, while emotional memory seems to be dealt by the amygdala. On the microscopic scale the underlying structures in these areas differ in the kind of neurons involved, in their connectivity, or in their clustering degree but, at this level, learning and memory are attributed to neuronal synapses mediated by longterm potentiation and long-term depression. In this work we explore the properties of a short range synaptic connection network, a nearest neighbor lattice composed mostly by excitatory neurons and a fraction of inhibitory ones. The mechanism of synaptic modification responsible for the emergence of memory is Spike-Timing-Dependent Plasticity (STDP), a Hebbian-like rule, where potentiation/depression is acquired when causal/non-causal spikes happen in a synapse involving two neurons. The system is intended to store and recognize memories associated to spatial external inputs presented as simple geometrical forms. The synaptic modifications are continuously applied to excitatory connections, including a homeostasis rule and STDP. In this work we explore the different scenarios under which a network with short range connections can accomplish the task of storing and recognizing simple connected patterns.

  7. Neuronal Differentiation Modulated by Polymeric Membrane Properties.

    Science.gov (United States)

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

    2017-01-01

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

  8. Synaptic Circuit Organization of Motor Corticothalamic Neurons

    Science.gov (United States)

    Yamawaki, Naoki

    2015-01-01

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

  9. Extended Range Intercept Technology

    Science.gov (United States)

    1991-09-01

    1988). Desert bighorn ewes with lambs show a stronger response than do groups of only rams, only ewes, or mixed groups of adults (Miller and Smith...1985). While all startle events may affect desert bighorns, those occurring during the lambing period (February-April) would represent the highest...35807 U.S. Army Pueblo Depot Activity SDSTE-PU-EE Pueblo, CO 81001-5000 U.S. Army White Sands Missile Range STEWS -EL-N White Sands, NM 88002-5076

  10. ORANGE: RANGE OF BENEFITS

    OpenAIRE

    Parle Milind; Chaturvedi Dev

    2012-01-01

    No wonder that oranges are one of the most popular fruits in the world. Orange (citrus sinensis) is well known for its nutritional and medicinal properties throughout the world. From times immemorial, whole Orange plant including ripe and unripe fruits, juice, orange peels, leaves and flowers are used as a traditional medicine. Citrus sinensis belongs to the family Rutaceae. The fruit is a fleshy, indehiscent, berry that ranges widely in size from 4 cm to 12 cm. The major medicinal proper...

  11. Range Flight Safety Requirements

    Science.gov (United States)

    Loftin, Charles E.; Hudson, Sandra M.

    2018-01-01

    The purpose of this NASA Technical Standard is to provide the technical requirements for the NPR 8715.5, Range Flight Safety Program, in regards to protection of the public, the NASA workforce, and property as it pertains to risk analysis, Flight Safety Systems (FSS), and range flight operations. This standard is approved for use by NASA Headquarters and NASA Centers, including Component Facilities and Technical and Service Support Centers, and may be cited in contract, program, and other Agency documents as a technical requirement. This standard may also apply to the Jet Propulsion Laboratory or to other contractors, grant recipients, or parties to agreements to the extent specified or referenced in their contracts, grants, or agreements, when these organizations conduct or participate in missions that involve range flight operations as defined by NPR 8715.5.1.2.2 In this standard, all mandatory actions (i.e., requirements) are denoted by statements containing the term “shall.”1.3 TailoringTailoring of this standard for application to a specific program or project shall be formally documented as part of program or project requirements and approved by the responsible Technical Authority in accordance with NPR 8715.3, NASA General Safety Program Requirements.

  12. Coding of information about tactile stimuli by neurones of the cuneate nucleus.

    Science.gov (United States)

    Douglas, P R; Ferrington, D G; Rowe, M

    1978-12-01

    1. The responses of cuneate neurones to controlled tactile stimulation of the foot pads were examined in unanaesthetized, decerebrate cats. The neurones were divided into three functional classes; one sensitive to steady tactile stimuli, and two dynamically sensitive classes which could be readily differentiated by their responsiveness to cutaneous vibration. Each class appeared to receive an exclusive input from only one of the three known groups of tactile receptors associated with the foot pads, namely the Pacinian corpuscles, the Merkel endings and the intradermal, encapsulated endings known as Krause or Meissner corpuscles. 2. Cuneate neurones responsive to steady indentation of the skin displayed approximately linear or sigmoidal stimulus-response relations over indentation ranges up to approximately 1.5--2 mm. Response variability at a fixed stimulus intensity was relatively low and showed little systematic change over the full range of the stimulus-response curves. 3. One class of dynamically sensitive cuneate neurones responded to cutaneous vibration over a range of approximately 5-80 Hz with maximal responsiveness around 30 Hz. The other class, the Pacinian neurones, responded over a range of approximately 80- greater than 600 Hz with maximal responsiveness at 200-400 Hz. The thresholds and combined band width of vibratory sensitivity of these populations were comparable with known subjective thresholds and range of cutaneous vibratory sensibility. 4. Responses of cuneate neurones were phase-locked to the vibratory stimulus suggesting that information about vibration frequency could be coded by the patterns of impulse activity. Quantitative measures indicated that maximal phase-locking occurred in responses to vibration frequencies of 10-50 Hz with a progressive decline at higher frequencies. Above 400 Hz, impulse activity occurred almost randomly throughout the vibratory stimulus cycle and therefore carried little further signal of vibratory frequency

  13. Channel noise effects on first spike latency of a stochastic Hodgkin-Huxley neuron

    Science.gov (United States)

    Maisel, Brenton; Lindenberg, Katja

    2017-02-01

    While it is widely accepted that information is encoded in neurons via action potentials or spikes, it is far less understood what specific features of spiking contain encoded information. Experimental evidence has suggested that the timing of the first spike may be an energy-efficient coding mechanism that contains more neural information than subsequent spikes. Therefore, the biophysical features of neurons that underlie response latency are of considerable interest. Here we examine the effects of channel noise on the first spike latency of a Hodgkin-Huxley neuron receiving random input from many other neurons. Because the principal feature of a Hodgkin-Huxley neuron is the stochastic opening and closing of channels, the fluctuations in the number of open channels lead to fluctuations in the membrane voltage and modify the timing of the first spike. Our results show that when a neuron has a larger number of channels, (i) the occurrence of the first spike is delayed and (ii) the variation in the first spike timing is greater. We also show that the mean, median, and interquartile range of first spike latency can be accurately predicted from a simple linear regression by knowing only the number of channels in the neuron and the rate at which presynaptic neurons fire, but the standard deviation (i.e., neuronal jitter) cannot be predicted using only this information. We then compare our results to another commonly used stochastic Hodgkin-Huxley model and show that the more commonly used model overstates the first spike latency but can predict the standard deviation of first spike latencies accurately. We end by suggesting a more suitable definition for the neuronal jitter based upon our simulations and comparison of the two models.

  14. How structure determines correlations in neuronal networks.

    Directory of Open Access Journals (Sweden)

    Volker Pernice

    2011-05-01

    Full Text Available Networks are becoming a ubiquitous metaphor for the understanding of complex biological systems, spanning the range between molecular signalling pathways, neural networks in the brain, and interacting species in a food web. In many models, we face an intricate interplay between the topology of the network and the dynamics of the system, which is generally very hard to disentangle. A dynamical feature that has been subject of intense research in various fields are correlations between the noisy activity of nodes in a network. We consider a class of systems, where discrete signals are sent along the links of the network. Such systems are of particular relevance in neuroscience, because they provide models for networks of neurons that use action potentials for communication. We study correlations in dynamic networks with arbitrary topology, assuming linear pulse coupling. With our novel approach, we are able to understand in detail how specific structural motifs affect pairwise correlations. Based on a power series decomposition of the covariance matrix, we describe the conditions under which very indirect interactions will have a pronounced effect on correlations and population dynamics. In random networks, we find that indirect interactions may lead to a broad distribution of activation levels with low average but highly variable correlations. This phenomenon is even more pronounced in networks with distance dependent connectivity. In contrast, networks with highly connected hubs or patchy connections often exhibit strong average correlations. Our results are particularly relevant in view of new experimental techniques that enable the parallel recording of spiking activity from a large number of neurons, an appropriate interpretation of which is hampered by the currently limited understanding of structure-dynamics relations in complex networks.

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

    Directory of Open Access Journals (Sweden)

    Kummer Wolfgang

    2006-07-01

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

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

    Science.gov (United States)

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

    2015-08-01

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

  17. Mini Review: Biomaterials for Enhancing Neuronal Repair

    Science.gov (United States)

    Cangellaris, Olivia V.; Gillette, Martha U.

    2018-04-01

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

  18. Npas4: Linking Neuronal Activity to Memory.

    Science.gov (United States)

    Sun, Xiaochen; Lin, Yingxi

    2016-04-01

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

  19. Dogs Have the Most Neurons, Though Not the Largest Brain: Trade-Off between Body Mass and Number of Neurons in the Cerebral Cortex of Large Carnivoran Species

    Directory of Open Access Journals (Sweden)

    Débora Jardim-Messeder

    2017-12-01

    Full Text Available Carnivorans are a diverse group of mammals that includes carnivorous, omnivorous and herbivorous, domesticated and wild species, with a large range of brain sizes. Carnivory is one of several factors expected to be cognitively demanding for carnivorans due to a requirement to outsmart larger prey. On the other hand, large carnivoran species have high hunting costs and unreliable feeding patterns, which, given the high metabolic cost of brain neurons, might put them at risk of metabolic constraints regarding how many brain neurons they can afford, especially in the cerebral cortex. For a given cortical size, do carnivoran species have more cortical neurons than the herbivorous species they prey upon? We find they do not; carnivorans (cat, mongoose, dog, hyena, lion share with non-primates, including artiodactyls (the typical prey of large carnivorans, roughly the same relationship between cortical mass and number of neurons, which suggests that carnivorans are subject to the same evolutionary scaling rules as other non-primate clades. However, there are a few important exceptions. Carnivorans stand out in that the usual relationship between larger body, larger cortical mass and larger number of cortical neurons only applies to small and medium-sized species, and not beyond dogs: we find that the golden retriever dog has more cortical neurons than the striped hyena, African lion and even brown bear, even though the latter species have up to three times larger cortices than dogs. Remarkably, the brown bear cerebral cortex, the largest examined, only has as many neurons as the ten times smaller cat cerebral cortex, although it does have the expected ten times as many non-neuronal cells in the cerebral cortex compared to the cat. We also find that raccoons have dog-like numbers of neurons in their cat-sized brain, which makes them comparable to primates in neuronal density. Comparison of domestic and wild species suggests that the neuronal

  20. Long-range antigravity

    Energy Technology Data Exchange (ETDEWEB)

    Macrae, K.I.; Riegert, R.J. (Maryland Univ., College Park (USA). Center for Theoretical Physics)

    1984-10-01

    We consider a theory in which fermionic matter interacts via long-range scalar, vector and tensor fields. In order not to be in conflict with experiment, the scalar and vector couplings for a given fermion must be equal, as is natural in a dimensionally reduced model. Assuming that the Sun is not approximately neutral with respect to these new scalar-vector charges, and if the couplings saturate the experimental bounds, then their strength can be comparable to that of gravity. Scalar-vector fields of this strength can compensate for a solar quadrupole moment contribution to Mercury's anomalous perihelion precession.

  1. Long-range antigravity

    International Nuclear Information System (INIS)

    Macrae, K.I.; Riegert, R.J.

    1984-01-01

    We consider a theory in which fermionic matter interacts via long-range scalar, vector and tensor fields. In order not to be in conflict with experiment, the scalar and vector couplings for a given fermion must be equal, as is natural in a dimensionally reduced model. Assuming that the Sun is not approximately neutral with respect to these new scalar-vector charges, and if the couplings saturate the experimental bounds, then their strength can be comparable to that of gravity. Scalar-vector fields of this strength can compensate for a solar quadrupole moment contribution to Mercury's anomalous perihelion precession. (orig.)

  2. Neuronal Networks on Nanocellulose Scaffolds.

    Science.gov (United States)

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

    2015-11-01

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

  3. C. elegans model of neuronal aging

    OpenAIRE

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

    2011-01-01

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

  4. Spike timing precision of neuronal circuits.

    Science.gov (United States)

    Kilinc, Deniz; Demir, Alper

    2018-04-17

    Spike timing is believed to be a key factor in sensory information encoding and computations performed by the neurons and neuronal circuits. However, the considerable noise and variability, arising from the inherently stochastic mechanisms that exist in the neurons and the synapses, degrade spike timing precision. Computational modeling can help decipher the mechanisms utilized by the neuronal circuits in order to regulate timing precision. In this paper, we utilize semi-analytical techniques, which were adapted from previously developed methods for electronic circuits, for the stochastic characterization of neuronal circuits. These techniques, which are orders of magnitude faster than traditional Monte Carlo type simulations, can be used to directly compute the spike timing jitter variance, power spectral densities, correlation functions, and other stochastic characterizations of neuronal circuit operation. We consider three distinct neuronal circuit motifs: Feedback inhibition, synaptic integration, and synaptic coupling. First, we show that both the spike timing precision and the energy efficiency of a spiking neuron are improved with feedback inhibition. We unveil the underlying mechanism through which this is achieved. Then, we demonstrate that a neuron can improve on the timing precision of its synaptic inputs, coming from multiple sources, via synaptic integration: The phase of the output spikes of the integrator neuron has the same variance as that of the sample average of the phases of its inputs. Finally, we reveal that weak synaptic coupling among neurons, in a fully connected network, enables them to behave like a single neuron with a larger membrane area, resulting in an improvement in the timing precision through cooperation.

  5. Do enteric neurons make hypocretin? ☆

    OpenAIRE

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

    2007-01-01

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

  6. High-Degree Neurons Feed Cortical Computations.

    Directory of Open Access Journals (Sweden)

    Nicholas M Timme

    2016-05-01

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

  7. Design of memristive interface between electronic neurons

    Science.gov (United States)

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

    2018-05-01

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

  8. Mirror neurons: From origin to function

    OpenAIRE

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

    2014-01-01

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

  9. Geometrical Determinants of Neuronal Actin Waves

    OpenAIRE

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

    2017-01-01

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

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

    OpenAIRE

    Rau, Andrew R.; Hentges, Shane T.

    2017-01-01

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

  11. Range Process Simulation Tool

    Science.gov (United States)

    Phillips, Dave; Haas, William; Barth, Tim; Benjamin, Perakath; Graul, Michael; Bagatourova, Olga

    2005-01-01

    Range Process Simulation Tool (RPST) is a computer program that assists managers in rapidly predicting and quantitatively assessing the operational effects of proposed technological additions to, and/or upgrades of, complex facilities and engineering systems such as the Eastern Test Range. Originally designed for application to space transportation systems, RPST is also suitable for assessing effects of proposed changes in industrial facilities and large organizations. RPST follows a model-based approach that includes finite-capacity schedule analysis and discrete-event process simulation. A component-based, scalable, open architecture makes RPST easily and rapidly tailorable for diverse applications. Specific RPST functions include: (1) definition of analysis objectives and performance metrics; (2) selection of process templates from a processtemplate library; (3) configuration of process models for detailed simulation and schedule analysis; (4) design of operations- analysis experiments; (5) schedule and simulation-based process analysis; and (6) optimization of performance by use of genetic algorithms and simulated annealing. The main benefits afforded by RPST are provision of information that can be used to reduce costs of operation and maintenance, and the capability for affordable, accurate, and reliable prediction and exploration of the consequences of many alternative proposed decisions.

  12. Performance limitations of relay neurons.

    Directory of Open Access Journals (Sweden)

    Rahul Agarwal

    Full Text Available Relay cells are prevalent throughout sensory systems and receive two types of inputs: driving and modulating. The driving input contains receptive field properties that must be transmitted while the modulating input alters the specifics of transmission. For example, the visual thalamus contains relay neurons that receive driving inputs from the retina that encode a visual image, and modulating inputs from reticular activating system and layer 6 of visual cortex that control what aspects of the image will be relayed back to visual cortex for perception. What gets relayed depends on several factors such as attentional demands and a subject's goals. In this paper, we analyze a biophysical based model of a relay cell and use systems theoretic tools to construct analytic bounds on how well the cell transmits a driving input as a function of the neuron's electrophysiological properties, the modulating input, and the driving signal parameters. We assume that the modulating input belongs to a class of sinusoidal signals and that the driving input is an irregular train of pulses with inter-pulse intervals obeying an exponential distribution. Our analysis applies to any [Formula: see text] order model as long as the neuron does not spike without a driving input pulse and exhibits a refractory period. Our bounds on relay reliability contain performance obtained through simulation of a second and third order model, and suggest, for instance, that if the frequency of the modulating input increases or the DC offset decreases, then relay increases. Our analysis also shows, for the first time, how the biophysical properties of the neuron (e.g. ion channel dynamics define the oscillatory patterns needed in the modulating input for appropriately timed relay of sensory information. In our discussion, we describe how our bounds predict experimentally observed neural activity in the basal ganglia in (i health, (ii in Parkinson's disease (PD, and (iii in PD during

  13. Neurosemantics, neurons and system theory.

    Science.gov (United States)

    Breidbach, Olaf

    2007-08-01

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

  14. Neuronal involvement in cisplatin neuropathy

    DEFF Research Database (Denmark)

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2016-03-16

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

  16. Mechanisms of Neuronal Apoptosis In Vivo

    National Research Council Canada - National Science Library

    Martin, Lee J

    2004-01-01

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

  17. 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.

  18. Neurochemistry of olivocochlear neurons in the hamster.

    Science.gov (United States)

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

    2009-04-01

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

  19. Mirror neurons and language in schizophrenia

    OpenAIRE

    Bendová, Marie

    2016-01-01

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

  20. Beyond Critical Exponents in Neuronal Avalanches

    Science.gov (United States)

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

    2011-03-01

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

  1. 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

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

    Science.gov (United States)

    Turlejski, Kris; Djavadian, Ruzanna

    2002-01-01

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

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

    International Nuclear Information System (INIS)

    Morel, G.; Pelletier, G.

    1986-01-01

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

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

    OpenAIRE

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

    2015-01-01

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

  5. 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...

  6. Calculation of projected ranges

    International Nuclear Information System (INIS)

    Biersack, J.P.

    1980-09-01

    The concept of multiple scattering is reconsidered for obtaining the directional spreading of ion motion as a function of energy loss. From this the mean projection of each pathlength element of the ion trajectory is derived which - upon summation or integration - leads to the desired mean projected range. In special cases, the calculation can be carried out analytically, otherwise a simple general algorithm is derived which is suitable even for the smallest programmable calculators. Necessary input for the present treatment consists only of generally accessable stopping power and straggling formulas. The procedure does not rely on scattering cross sections, e.g. power potential or f(t 1 sup(/) 2 ) approximations. The present approach lends itself easily to include electronic straggling or to treat composed target materials, or even to account for the so-called time integral. (orig.)

  7. A model explaining synchronization of neuron bioelectric frequency under weak alternating low frequency magnetic field

    International Nuclear Information System (INIS)

    Moral, A. del; Azanza, María J.

    2015-01-01

    A biomagnetic-electrical model is presented that explains rather well the experimentally observed synchronization of the bioelectric potential firing rate (“frequency”), f, of single unit neurons of Helix aspersa mollusc under the application of extremely low frequency (ELF) weak alternating (AC) magnetic fields (MF). The proposed model incorporates to our widely experimentally tested model of superdiamagnetism (SD) and Ca 2+ Coulomb explosion (CE) from lipid (LP) bilayer membrane (SD–CE model), the electrical quadrupolar long range interaction between the bilayer LP membranes of synchronized neuron pairs, not considered before. The quadrupolar interaction is capable of explaining well the observed synchronization. Actual extension of our SD–CE-model shows that the neuron firing frequency field, B, dependence becomes not modified, but the bioelectric frequency is decreased and its spontaneous temperature, T, dependence is modified. A comparison of the model with synchronization experimental results of pair of neurons under weak (B 0 ≅0.2–15 mT) AC-MF of frequency f M =50 Hz is reported. From the deduced size of synchronized LP clusters under B, is suggested the formation of small neuron networks via the membrane lipid correlation. - Highlights: • Neuron pair synchronization under low frequency alternating (AC) magnetic field (MF). • Superdiamagnetism and Ca 2+ Coulomb explosion for AC MF effect in synchronized frequency. • Membrane lipid electrical quadrupolar pair interaction as synchronization mechamism. • Good agreement of model with electrophysiological experiments on mollusc Helix neurons

  8. The Role of Rab Proteins in Neuronal Cells and in the Trafficking of Neurotrophin Receptors

    Directory of Open Access Journals (Sweden)

    Cecilia Bucci

    2014-10-01

    Full Text Available Neurotrophins are a family of proteins that are important for neuronal development, neuronal survival and neuronal functions. Neurotrophins exert their role by binding to their receptors, the Trk family of receptor tyrosine kinases (TrkA, TrkB, and TrkC and p75NTR, a member of the tumor necrosis factor (TNF receptor superfamily. Binding of neurotrophins to receptors triggers a complex series of signal transduction events, which are able to induce neuronal differentiation but are also responsible for neuronal maintenance and neuronal functions. Rab proteins are small GTPases localized to the cytosolic surface of specific intracellular compartments and are involved in controlling vesicular transport. Rab proteins, acting as master regulators of the membrane trafficking network, play a central role in both trafficking and signaling pathways of neurotrophin receptors. Axonal transport represents the Achilles' heel of neurons, due to the long-range distance that molecules, organelles and, in particular, neurotrophin-receptor complexes have to cover. Indeed, alterations of axonal transport and, specifically, of axonal trafficking of neurotrophin receptors are responsible for several human neurodegenerative diseases, such as Huntington’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis and some forms of Charcot-Marie-Tooth disease. In this review, we will discuss the link between Rab proteins and neurotrophin receptor trafficking and their influence on downstream signaling pathways.

  9. The Role of Rab Proteins in Neuronal Cells and in the Trafficking of Neurotrophin Receptors

    Science.gov (United States)

    Bucci, Cecilia; Alifano, Pietro; Cogli, Laura

    2014-01-01

    Neurotrophins are a family of proteins that are important for neuronal development, neuronal survival and neuronal functions. Neurotrophins exert their role by binding to their receptors, the Trk family of receptor tyrosine kinases (TrkA, TrkB, and TrkC) and p75NTR, a member of the tumor necrosis factor (TNF) receptor superfamily. Binding of neurotrophins to receptors triggers a complex series of signal transduction events, which are able to induce neuronal differentiation but are also responsible for neuronal maintenance and neuronal functions. Rab proteins are small GTPases localized to the cytosolic surface of specific intracellular compartments and are involved in controlling vesicular transport. Rab proteins, acting as master regulators of the membrane trafficking network, play a central role in both trafficking and signaling pathways of neurotrophin receptors. Axonal transport represents the Achilles' heel of neurons, due to the long-range distance that molecules, organelles and, in particular, neurotrophin-receptor complexes have to cover. Indeed, alterations of axonal transport and, specifically, of axonal trafficking of neurotrophin receptors are responsible for several human neurodegenerative diseases, such as Huntington’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis and some forms of Charcot-Marie-Tooth disease. In this review, we will discuss the link between Rab proteins and neurotrophin receptor trafficking and their influence on downstream signaling pathways. PMID:25295627

  10. A model explaining synchronization of neuron bioelectric frequency under weak alternating low frequency magnetic field

    Energy Technology Data Exchange (ETDEWEB)

    Moral, A. del, E-mail: delmoral@unizar.es [Laboratorio de Magnetismo, Departamento de Física de Materia Condensada and Instituto de Ciencia de Materiales, Universidad de Zaragoza and Consejo Superior de Investigaciones Científicas, 50009 Zaragoza (Spain); Laboratorio de Magnetobiología, Departamento de Anatomía e Histología, Facultad de Medicina, Universidad de Zaragoza, 50009 Zaragoza (Spain); Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, 28223 Madrid (Spain); Azanza, María J., E-mail: mjazanza@unizar.es [Laboratorio de Magnetobiología, Departamento de Anatomía e Histología, Facultad de Medicina, Universidad de Zaragoza, 50009 Zaragoza (Spain); Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, 28223 Madrid (Spain)

    2015-03-01

    A biomagnetic-electrical model is presented that explains rather well the experimentally observed synchronization of the bioelectric potential firing rate (“frequency”), f, of single unit neurons of Helix aspersa mollusc under the application of extremely low frequency (ELF) weak alternating (AC) magnetic fields (MF). The proposed model incorporates to our widely experimentally tested model of superdiamagnetism (SD) and Ca{sup 2+} Coulomb explosion (CE) from lipid (LP) bilayer membrane (SD–CE model), the electrical quadrupolar long range interaction between the bilayer LP membranes of synchronized neuron pairs, not considered before. The quadrupolar interaction is capable of explaining well the observed synchronization. Actual extension of our SD–CE-model shows that the neuron firing frequency field, B, dependence becomes not modified, but the bioelectric frequency is decreased and its spontaneous temperature, T, dependence is modified. A comparison of the model with synchronization experimental results of pair of neurons under weak (B{sub 0}≅0.2–15 mT) AC-MF of frequency f{sub M}=50 Hz is reported. From the deduced size of synchronized LP clusters under B, is suggested the formation of small neuron networks via the membrane lipid correlation. - Highlights: • Neuron pair synchronization under low frequency alternating (AC) magnetic field (MF). • Superdiamagnetism and Ca{sup 2+} Coulomb explosion for AC MF effect in synchronized frequency. • Membrane lipid electrical quadrupolar pair interaction as synchronization mechamism. • Good agreement of model with electrophysiological experiments on mollusc Helix neurons.

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

    Science.gov (United States)

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

    2015-07-01

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

  12. Locus ceruleus neurons in people with autism contain no histochemically-detectable mercury.

    Science.gov (United States)

    Pamphlett, Roger; Kum Jew, Stephen

    2016-02-01

    Exposure to environmental mercury has been proposed to play a part in autism. Mercury is selectively taken up by the human locus ceruleus, a region of the brain that has been implicated in autism. We therefore looked for the presence of mercury in the locus ceruleus of people who had autism, using the histochemical technique of autometallography which can detect nanogram amounts of mercury in tissues. In addition, we sought evidence of damage to locus ceruleus neurons in autism by immunostaining for hyperphosphorylated tau. No mercury was found in any neurons of the locus ceruleus of 6 individuals with autism (5 male, 1 female, age range 16-48 years). Mercury was present in locus ceruleus neurons in 7 of 11 (64%) age-matched control individuals who did not have autism, which is significantly more than in individuals with autism. No increase in numbers of locus ceruleus neurons containing hyperphosphorylated tau was detected in people with autism. In conclusion, most people with autism have not been exposed early in life to quantities of mercury large enough to be found later in adult locus ceruleus neurons. Human locus ceruleus neurons are sensitive indicators of mercury exposure, and mercury appears to remain in these neurons indefinitely, so these findings do not support the hypothesis that mercury neurotoxicity plays a role in autism.

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

    Science.gov (United States)

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

    2013-04-10

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

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

    Science.gov (United States)

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

    2015-12-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  16. Stages of neuronal network formation

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  17. [Infantile autism and mirror neurons].

    Science.gov (United States)

    Cornelio-Nieto, J O

    2009-02-27

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

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  19. A feasibility study of multi-site,intracellular recordings from mammalian neurons by extracellular gold mushroom-shaped microelectrodes.

    Science.gov (United States)

    Ojovan, Silviya M; Rabieh, Noha; Shmoel, Nava; Erez, Hadas; Maydan, Eilon; Cohen, Ariel; Spira, Micha E

    2015-09-14

    The development of multi-electrode array platforms for large scale recording of neurons is at the forefront of neuro-engineering research efforts. Recently we demonstrated, at the proof-of-concept level, a breakthrough neuron-microelectrode interface in which cultured Aplysia neurons tightly engulf gold mushroom-shaped microelectrodes (gMμEs). While maintaining their extracellular position, the gMμEs record synaptic- and action-potentials with characteristic features of intracellular recordings. Here we examined the feasibility of using gMμEs for intracellular recordings from mammalian neurons. To that end we experimentally examined the innate size limits of cultured rat hippocampal neurons to engulf gMμEs and measured the width of the "extracellular" cleft formed between the neurons and the gold surface. Using the experimental results we next analyzed the expected range of gMμEs-neuron electrical coupling coefficients. We estimated that sufficient electrical coupling levels to record attenuated synaptic- and action-potentials can be reached using the gMμE-neuron configuration. The definition of the engulfment limits of the gMμEs caps diameter at ≤2-2.5 μm and the estimated electrical coupling coefficients from the simulations pave the way for rational development and application of the gMμE based concept for in-cell recordings from mammalian neurons.

  20. Interactive Exploration for Continuously Expanding Neuron Databases.

    Science.gov (United States)

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

    2017-02-15

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

  1. Neuron Morphology Influences Axon Initial Segment Plasticity.

    Science.gov (United States)

    Gulledge, Allan T; Bravo, Jaime J

    2016-01-01

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

  2. Transcranial Alternating Current Stimulation Attenuates Neuronal Adaptation.

    Science.gov (United States)

    Kar, Kohitij; Duijnhouwer, Jacob; Krekelberg, Bart

    2017-03-01

    We previously showed that brief application of 2 mA (peak-to-peak) transcranial currents alternating at 10 Hz significantly reduces motion adaptation in humans. This is but one of many behavioral studies showing that weak currents applied to the scalp modulate neural processing. Transcranial stimulation has been shown to improve perception, learning, and a range of clinical symptoms. Few studies, however, have measured the neural consequences of transcranial current stimulation. We capitalized on the strong link between motion perception and neural activity in the middle temporal (MT) area of the macaque monkey to study the neural mechanisms that underlie the behavioral consequences of transcranial alternating current stimulation. First, we observed that 2 mA currents generated substantial intracranial fields, which were much stronger in the stimulated hemisphere (0.12 V/m) than on the opposite side of the brain (0.03 V/m). Second, we found that brief application of transcranial alternating current stimulation at 10 Hz reduced spike-frequency adaptation of MT neurons and led to a broadband increase in the power spectrum of local field potentials. Together, these findings provide a direct demonstration that weak electric fields applied to the scalp significantly affect neural processing in the primate brain and that this includes a hitherto unknown mechanism that attenuates sensory adaptation. SIGNIFICANCE STATEMENT Transcranial stimulation has been claimed to improve perception, learning, and a range of clinical symptoms. Little is known, however, how transcranial current stimulation generates such effects, and the search for better stimulation protocols proceeds largely by trial and error. We investigated, for the first time, the neural consequences of stimulation in the monkey brain. We found that even brief application of alternating current stimulation reduced the effects of adaptation on single-neuron firing rates and local field potentials; this mechanistic

  3. Translocation and neurotoxicity of CdTe quantum dots in RMEs motor neurons in nematode Caenorhabditis elegans

    International Nuclear Information System (INIS)

    Zhao, Yunli; Wang, Xiong; Wu, Qiuli; Li, Yiping; Wang, Dayong

    2015-01-01

    Graphical abstract: - Highlights: • We investigated in vivo neurotoxicity of CdTe QDs on RMEs motor neurons in C. elegans. • CdTe QDs in the range of μg/L caused neurotoxicity on RMEs motor neurons. • Bioavailability of CdTe QDs may be the primary inducer for CdTe QDs neurotoxicity. • Both oxidative stress and cell identity regulate the CdTe QDs neurotoxicity. • CdTe QDs were translocated and deposited into RMEs motor neurons. - Abstract: We employed Caenorhabditis elegans assay system to investigate in vivo neurotoxicity of CdTe quantum dots (QDs) on RMEs motor neurons, which are involved in controlling foraging behavior, and the underlying mechanism of such neurotoxicity. After prolonged exposure to 0.1–1 μg/L of CdTe QDs, abnormal foraging behavior and deficits in development of RMEs motor neurons were observed. The observed neurotoxicity from CdTe QDs on RMEs motor neurons might be not due to released Cd 2+ . Overexpression of genes encoding Mn-SODs or unc-30 gene controlling cell identity of RMEs neurons prevented neurotoxic effects of CdTe QDs on RMEs motor neurons, suggesting the crucial roles of oxidative stress and cell identity in regulating CdTe QDs neurotoxicity. In nematodes, CdTe QDs could be translocated through intestinal barrier and be deposited in RMEs motor neurons. In contrast, CdTe@ZnS QDs could not be translocated into RMEs motor neurons and therefore, could only moderately accumulated in intestinal cells, suggesting that ZnS coating might reduce neurotoxicity of CdTe QDs on RMEs motor neurons. Therefore, the combinational effects of oxidative stress, cell identity, and bioavailability may contribute greatly to the mechanism of CdTe QDs neurotoxicity on RMEs motor neurons. Our results provide insights into understanding the potential risks of CdTe QDs on the development and function of nervous systems in animals

  4. Translocation and neurotoxicity of CdTe quantum dots in RMEs motor neurons in nematode Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Yunli; Wang, Xiong; Wu, Qiuli; Li, Yiping; Wang, Dayong, E-mail: dayongw@seu.edu.cn

    2015-02-11

    Graphical abstract: - Highlights: • We investigated in vivo neurotoxicity of CdTe QDs on RMEs motor neurons in C. elegans. • CdTe QDs in the range of μg/L caused neurotoxicity on RMEs motor neurons. • Bioavailability of CdTe QDs may be the primary inducer for CdTe QDs neurotoxicity. • Both oxidative stress and cell identity regulate the CdTe QDs neurotoxicity. • CdTe QDs were translocated and deposited into RMEs motor neurons. - Abstract: We employed Caenorhabditis elegans assay system to investigate in vivo neurotoxicity of CdTe quantum dots (QDs) on RMEs motor neurons, which are involved in controlling foraging behavior, and the underlying mechanism of such neurotoxicity. After prolonged exposure to 0.1–1 μg/L of CdTe QDs, abnormal foraging behavior and deficits in development of RMEs motor neurons were observed. The observed neurotoxicity from CdTe QDs on RMEs motor neurons might be not due to released Cd{sup 2+}. Overexpression of genes encoding Mn-SODs or unc-30 gene controlling cell identity of RMEs neurons prevented neurotoxic effects of CdTe QDs on RMEs motor neurons, suggesting the crucial roles of oxidative stress and cell identity in regulating CdTe QDs neurotoxicity. In nematodes, CdTe QDs could be translocated through intestinal barrier and be deposited in RMEs motor neurons. In contrast, CdTe@ZnS QDs could not be translocated into RMEs motor neurons and therefore, could only moderately accumulated in intestinal cells, suggesting that ZnS coating might reduce neurotoxicity of CdTe QDs on RMEs motor neurons. Therefore, the combinational effects of oxidative stress, cell identity, and bioavailability may contribute greatly to the mechanism of CdTe QDs neurotoxicity on RMEs motor neurons. Our results provide insights into understanding the potential risks of CdTe QDs on the development and function of nervous systems in animals.

  5. Response characteristics of vibration-sensitive neurons in the midbrain of the grassfrog, Rana temporaria

    DEFF Research Database (Denmark)

    Christensen-Dalsgaard, J; Jørgensen, M B

    1989-01-01

    European grassfrogs (Rana temporaria) were stimulated with pulsed sinusoidal, vertical vibrations (10-300 Hz) and the responses of 46 single midbrain neurons were recorded in awake, immobilized animals. Most units (40) had simple V-shaped excitatory vibrational tuning curves. The distribution of ...... stimuli probably play a role in communication and detection of predators and the vibration-sensitive midbrain neurons may be involved in the central processing of such behaviorally significant stimuli.......European grassfrogs (Rana temporaria) were stimulated with pulsed sinusoidal, vertical vibrations (10-300 Hz) and the responses of 46 single midbrain neurons were recorded in awake, immobilized animals. Most units (40) had simple V-shaped excitatory vibrational tuning curves. The distribution...... of best frequencies (BF's) was bimodal with peaks at 10 and 100 Hz and the thresholds ranged from 0.02 to 1.28 cm/s2 at the BF. Twenty-three neurons showed phasic-tonic and 11 neurons phasic responses. The dynamic range of seismic intensity for most neurons was 20-30 dB. In contrast to the sharp phase...

  6. Neurient: An Algorithm for Automatic Tracing of Confluent Neuronal Images to Determine Alignment

    Science.gov (United States)

    Mitchel, J.A.; Martin, I.S.

    2013-01-01

    A goal of neural tissue engineering is the development and evaluation of materials that guide neuronal growth and alignment. However, the methods available to quantitatively evaluate the response of neurons to guidance materials are limited and/or expensive, and may require manual tracing to be performed by the researcher. We have developed an open source, automated Matlab-based algorithm, building on previously published methods, to trace and quantify alignment of fluorescent images of neurons in culture. The algorithm is divided into three phases, including computation of a lookup table which contains directional information for each image, location of a set of seed points which may lie along neurite centerlines, and tracing neurites starting with each seed point and indexing into the lookup table. This method was used to obtain quantitative alignment data for complex images of densely cultured neurons. Complete automation of tracing allows for unsupervised processing of large numbers of images. Following image processing with our algorithm, available metrics to quantify neurite alignment include angular histograms, percent of neurite segments in a given direction, and mean neurite angle. The alignment information obtained from traced images can be used to compare the response of neurons to a range of conditions. This tracing algorithm is freely available to the scientific community under the name Neurient, and its implementation in Matlab allows a wide range of researchers to use a standardized, open source method to quantitatively evaluate the alignment of dense neuronal cultures. PMID:23384629

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

    Science.gov (United States)

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

    2015-12-01

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

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

    OpenAIRE

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

    2008-01-01

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

  9. Long-term optical stimulation of channelrhodopsin-expressing neurons to study network plasticity

    Science.gov (United States)

    Lignani, Gabriele; Ferrea, Enrico; Difato, Francesco; Amarù, Jessica; Ferroni, Eleonora; Lugarà, Eleonora; Espinoza, Stefano; Gainetdinov, Raul R.; Baldelli, Pietro; Benfenati, Fabio

    2013-01-01

    Neuronal plasticity produces changes in excitability, synaptic transmission, and network architecture in response to external stimuli. Network adaptation to environmental conditions takes place in time scales ranging from few seconds to days, and modulates the entire network dynamics. To study the network response to defined long-term experimental protocols, we setup a system that combines optical and electrophysiological tools embedded in a cell incubator. Primary hippocampal neurons transduced with lentiviruses expressing channelrhodopsin-2/H134R were subjected to various photostimulation protocols in a time window in the order of days. To monitor the effects of light-induced gating of network activity, stimulated transduced neurons were simultaneously recorded using multi-electrode arrays (MEAs). The developed experimental model allows discerning short-term, long-lasting, and adaptive plasticity responses of the same neuronal network to distinct stimulation frequencies applied over different temporal windows. PMID:23970852

  10. Long-term optical stimulation of channelrhodopsin-expressing neurons to study network plasticity.

    Science.gov (United States)

    Lignani, Gabriele; Ferrea, Enrico; Difato, Francesco; Amarù, Jessica; Ferroni, Eleonora; Lugarà, Eleonora; Espinoza, Stefano; Gainetdinov, Raul R; Baldelli, Pietro; Benfenati, Fabio

    2013-01-01

    Neuronal plasticity produces changes in excitability, synaptic transmission, and network architecture in response to external stimuli. Network adaptation to environmental conditions takes place in time scales ranging from few seconds to days, and modulates the entire network dynamics. To study the network response to defined long-term experimental protocols, we setup a system that combines optical and electrophysiological tools embedded in a cell incubator. Primary hippocampal neurons transduced with lentiviruses expressing channelrhodopsin-2/H134R were subjected to various photostimulation protocols in a time window in the order of days. To monitor the effects of light-induced gating of network activity, stimulated transduced neurons were simultaneously recorded using multi-electrode arrays (MEAs). The developed experimental model allows discerning short-term, long-lasting, and adaptive plasticity responses of the same neuronal network to distinct stimulation frequencies applied over different temporal windows.

  11. A neuronal model of a global workspace in effortful cognitive tasks.

    Science.gov (United States)

    Dehaene, S; Kerszberg, M; Changeux, J P

    1998-11-24

    A minimal hypothesis is proposed concerning the brain processes underlying effortful tasks. It distinguishes two main computational spaces: a unique global workspace composed of distributed and heavily interconnected neurons with long-range axons, and a set of specialized and modular perceptual, motor, memory, evaluative, and attentional processors. Workspace neurons are mobilized in effortful tasks for which the specialized processors do not suffice. They selectively mobilize or suppress, through descending connections, the contribution of specific processor neurons. In the course of task performance, workspace neurons become spontaneously coactivated, forming discrete though variable spatio-temporal patterns subject to modulation by vigilance signals and to selection by reward signals. A computer simulation of the Stroop task shows workspace activation to increase during acquisition of a novel task, effortful execution, and after errors. We outline predictions for spatio-temporal activation patterns during brain imaging, particularly about the contribution of dorsolateral prefrontal cortex and anterior cingulate to the workspace.

  12. Spiral Waves and Multiple Spatial Coherence Resonances Induced by Colored Noise in Neuronal Network

    International Nuclear Information System (INIS)

    Tang Zhao; Li Yuye; Xi Lei; Jia Bing; Gu Huaguang

    2012-01-01

    Gaussian colored noise induced spatial patterns and spatial coherence resonances in a square lattice neuronal network composed of Morris-Lecar neurons are studied. Each neuron is at resting state near a saddle-node bifurcation on invariant circle, coupled to its nearest neighbors by electronic coupling. Spiral waves with different structures and disordered spatial structures can be alternately induced within a large range of noise intensity. By calculating spatial structure function and signal-to-noise ratio (SNR), it is found that SNR values are higher when the spiral structures are simple and are lower when the spatial patterns are complex or disordered, respectively. SNR manifest multiple local maximal peaks, indicating that the colored noise can induce multiple spatial coherence resonances. The maximal SNR values decrease as the correlation time of the noise increases. These results not only provide an example of multiple resonances, but also show that Gaussian colored noise play constructive roles in neuronal network. (general)

  13. Convergent input from brainstem coincidence detectors onto delay-sensitive neurons in the inferior colliculus.

    Science.gov (United States)

    McAlpine, D; Jiang, D; Shackleton, T M; Palmer, A R

    1998-08-01

    Responses of low-frequency neurons in the inferior colliculus (IC) of anesthetized guinea pigs were studied with binaural beats to assess their mean best interaural phase (BP) to a range of stimulating frequencies. Phase plots (stimulating frequency vs BP) were produced, from which measures of characteristic delay (CD) and characteristic phase (CP) for each neuron were obtained. The CD provides an estimate of the difference in travel time from each ear to coincidence-detector neurons in the brainstem. The CP indicates the mechanism underpinning the coincidence detector responses. A linear phase plot indicates a single, constant delay between the coincidence-detector inputs from the two ears. In more than half (54 of 90) of the neurons, the phase plot was not linear. We hypothesized that neurons with nonlinear phase plots received convergent input from brainstem coincidence detectors with different CDs. Presentation of a second tone with a fixed, unfavorable delay suppressed the response of one input, linearizing the phase plot and revealing other inputs to be relatively simple coincidence detectors. For some neurons with highly complex phase plots, the suppressor tone altered BP values, but did not resolve the nature of the inputs. For neurons with linear phase plots, the suppressor tone either completely abolished their responses or reduced their discharge rate with no change in BP. By selectively suppressing inputs with a second tone, we are able to reveal the nature of underlying binaural inputs to IC neurons, confirming the hypothesis that the complex phase plots of many IC neurons are a result of convergence from simple brainstem coincidence detectors.

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

    Directory of Open Access Journals (Sweden)

    Thomas Nowotny

    2008-07-01

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

  15. Transfection in Primary Cultured Neuronal Cells.

    Science.gov (United States)

    Marwick, Katie F M; Hardingham, Giles E

    2017-01-01

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

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

    Science.gov (United States)

    Papanikolaou, Theodora; Ellerby, Lisa M

    2009-08-13

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

  17. Neuromodulation of vertebrate motor neuron membrane properties

    DEFF Research Database (Denmark)

    Hultborn, Hans; Kiehn, Ole

    1992-01-01

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

  18. Neuronal hyperplasia in the anal canal

    DEFF Research Database (Denmark)

    Fenger, C; Schrøder, H D

    1990-01-01

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

  19. Life and Death of a Neuron

    Science.gov (United States)

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

  20. 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…

  1. Mirror neurons: functions, mechanisms and models.

    Science.gov (United States)

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

    2013-04-12

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

  2. Chimera states in a multilayer network of coupled and uncoupled neurons

    Science.gov (United States)

    Majhi, Soumen; Perc, Matjaž; Ghosh, Dibakar

    2017-07-01

    We study the emergence of chimera states in a multilayer neuronal network, where one layer is composed of coupled and the other layer of uncoupled neurons. Through the multilayer structure, the layer with coupled neurons acts as the medium by means of which neurons in the uncoupled layer share information in spite of the absence of physical connections among them. Neurons in the coupled layer are connected with electrical synapses, while across the two layers, neurons are connected through chemical synapses. In both layers, the dynamics of each neuron is described by the Hindmarsh-Rose square wave bursting dynamics. We show that the presence of two different types of connecting synapses within and between the two layers, together with the multilayer network structure, plays a key role in the emergence of between-layer synchronous chimera states and patterns of synchronous clusters. In particular, we find that these chimera states can emerge in the coupled layer regardless of the range of electrical synapses. Even in all-to-all and nearest-neighbor coupling within the coupled layer, we observe qualitatively identical between-layer chimera states. Moreover, we show that the role of information transmission delay between the two layers must not be neglected, and we obtain precise parameter bounds at which chimera states can be observed. The expansion of the chimera region and annihilation of cluster and fully coherent states in the parameter plane for increasing values of inter-layer chemical synaptic time delay are illustrated using effective range measurements. These results are discussed in the light of neuronal evolution, where the coexistence of coherent and incoherent dynamics during the developmental stage is particularly likely.

  3. 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...

  4. Timing control by redundant inhibitory neuronal circuits

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-03-15

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

  5. Neuronal migration, apoptosis and bipolar disorder.

    Science.gov (United States)

    Uribe, Ezequiel; Wix, Richard

    2012-01-01

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

  6. Chromatin Regulation of Neuronal Maturation and Plasticity.

    Science.gov (United States)

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

    2018-05-01

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

  7. A COMPUTATIONAL MODEL OF MOTOR NEURON DEGENERATION

    Science.gov (United States)

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

    2014-01-01

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

  8. A computational model of motor neuron degeneration.

    Science.gov (United States)

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

    2014-08-20

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

  9. Interaction function of coupled bursting neurons

    International Nuclear Information System (INIS)

    Shi Xia; Zhang Jiadong

    2016-01-01

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

  10. Timing control by redundant inhibitory neuronal circuits

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  11. Reflections on mirror neurons and speech perception

    Science.gov (United States)

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

    2010-01-01

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

  12. 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.

  13. Central auditory neurons have composite receptive fields.

    Science.gov (United States)

    Kozlov, Andrei S; Gentner, Timothy Q

    2016-02-02

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

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

    Science.gov (United States)

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

    2016-12-01

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

  15. 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.

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

    International Nuclear Information System (INIS)

    Born, D.E.

    1986-01-01

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

  17. Long range trajectories

    Energy Technology Data Exchange (ETDEWEB)

    Allen, P. W.; Jessup, E. A.; White, R. E. [Air Resources Field Research Office, Las Vegas, Nevada (United States)

    1967-07-01

    A single air molecule can have a trajectory that can be described with a line, but most meteorologists use single lines to represent the trajectories of air parcels. A single line trajectory has the disadvantage that it is a categorical description of position. Like categorized forecasts it provides no qualification, and no provision for dispersion in case the parcel contains two or more molecules which may take vastly different paths. Diffusion technology has amply demonstrated that an initial aerosol cloud or volume of gas in the atmosphere not only grows larger, but sometimes divides into puffs, each having a different path or swath. Yet, the average meteorologist, faced with the problem of predicting the future motion of a cloud, usually falls back on the line trajectory approach with the explanation that he had no better tool for long range application. In his more rational moments, he may use some arbitrary device to spread his cloud with distance. One such technique has been to separate the trajectory into two or more trajectories, spaced about the endpoint of the original trajectory after a short period of travel, repeating this every so often like a chain reaction. This has the obvious disadvantage of involving a large amount of labor without much assurance of improved accuracy. Another approach is to draw a circle about the trajectory endpoint, to represent either diffusion or error. The problem then is to know what radius to give the circle and also whether to call it diffusion or error. Meteorologists at the Nevada Test Site (NTS) are asked frequently to provide advice which involves trajectory technology, such as prediction of an aerosol cloud path, reconstruction of the motion of a volume of air, indication of the dilution, and the possible trajectory prediction error over great distances. Therefore, we set out, nearly three years ago, to provide some statistical knowledge about the status of our trajectory technology. This report contains some of the

  18. MRI of neuronal migration disorders

    International Nuclear Information System (INIS)

    Engelbrecht, V.

    1996-01-01

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

  19. Neuronal responses to physiological stress

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  20. Regulation of Cortical Dynamic Range by Background Synaptic Noise and Feedforward Inhibition.

    Science.gov (United States)

    Khubieh, Ayah; Ratté, Stéphanie; Lankarany, Milad; Prescott, Steven A

    2016-08-01

    The cortex encodes a broad range of inputs. This breadth of operation requires sensitivity to weak inputs yet non-saturating responses to strong inputs. If individual pyramidal neurons were to have a narrow dynamic range, as previously claimed, then staggered all-or-none recruitment of those neurons would be necessary for the population to achieve a broad dynamic range. Contrary to this explanation, we show here through dynamic clamp experiments in vitro and computer simulations that pyramidal neurons have a broad dynamic range under the noisy conditions that exist in the intact brain due to background synaptic input. Feedforward inhibition capitalizes on those noise effects to control neuronal gain and thereby regulates the population dynamic range. Importantly, noise allows neurons to be recruited gradually and occludes the staggered recruitment previously attributed to heterogeneous excitation. Feedforward inhibition protects spike timing against the disruptive effects of noise, meaning noise can enable the gain control required for rate coding without compromising the precise spike timing required for temporal coding. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Stimulus-response functions of single avian olfactory bulb neurones.

    Science.gov (United States)

    McKeegan, Dorothy E F; Demmers, Theodorus G M; Wathes, Christopher M; Jones, R Bryan; Gentle, Michael J

    2002-10-25

    This study investigated olfactory processing in a functional context by examining the responses of single avian olfactory bulb neurones to two biologically important gases over relevant concentration ranges. Recordings of extracellular spike activity were made from 80 single units in the left olfactory bulb of 11 anaesthetised, freely breathing adult hens (Gallus domesticus). The units were spontaneously active, exhibiting widely variable firing rates (0.07-47.28 spikes/s) and variable temporal firing patterns. Single units were tested for their response to an ascending concentration series of either ammonia (2.5-100 ppm) or hydrogen sulphide (1-50 ppm), delivered directly to the olfactory epithelium. Stimulation with a calibrated gas delivery system resulted in modification of spontaneous activity causing either inhibition (47% of units) or excitation (53%) of firing. For ammonia, 20 of the 35 units tested exhibited a response, while for hydrogen sulphide, 25 of the 45 units tested were responsive. Approximate response thresholds for ammonia (median threshold 3.75 ppm (range 2.5-60 ppm, n=20)) and hydrogen sulphide (median threshold 1 ppm (range 1-10 ppm, n=25)) were determined with most units exhibiting thresholds near the lower end of these ranges. Stimulus response curves were constructed for 23 units; 16 (the most complete) were subjected to a linear regression analysis to determine whether they were best fitted by a linear, log or power function. No single function provided the best fit for all the curves (seven were linear, eight were log, one was power). These findings show that avian units respond to changes in stimulus concentration in a manner generally consistent with reported responses in mammalian olfactory bulb neurones. However, this study illustrates a level of fine-tuning to small step changes in concentration (<5 ppm) not previously demonstrated in vertebrate single olfactory bulb neurones.

  2. Responses of neurons to extreme osmomechanical stress.

    Science.gov (United States)

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

    1995-05-01

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

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

    Science.gov (United States)

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

    2016-10-01

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

  4. When long-range zero-lag synchronization is feasible in cortical networks

    Directory of Open Access Journals (Sweden)

    Atthaphon eViriyopase

    2012-07-01

    Full Text Available Many studies have reported long-range synchronization of neuronal activity between brain areas, in particular in the gamma-band with frequencies in the range of 40-80 Hz. Several studies have reported synchrony with zero phase lag, which is remarkable considering the synaptic and conduction delays inherent in the connections between distant brain areas. This result has led to many speculations about the possible functional role of zero-lag synchrony, e.g., for neuronal communication in attention, memory and feature binding. However, recent studies using recordings of single-unit activity and local field potentials report that neuronal synchronization occurs with non-zero phase lags. This raises the questions whether zero-lag synchrony can occur in the brain and, if so, under which conditions.We used analytical methods and computer simulations to investigate which connectivity between neuronal populations allows or prohibits zero-lag synchrony. We did so for a model where two oscillators interact via a relay oscillator. Analytical results and computer simulations were obtained for both type I Mirollo-Strogatz neurons and type II Hodgkin-Huxley neurons. We have investigated the dynamics of the model for various types of synaptic coupling and importantly considered the potential impact of Spike-Timing Dependent Plasticity (STDP and its learning window. We confirm previous results that zero-lag synchrony can be achieved in this configuration. This is much easier to achieve with Hodgkin-Huxley neurons, which have a biphasic phase response curve, than for type I neurons. STDP facilitates zero-lag synchrony as it adjusts the synaptic strengths such that zero-lag synchrony is feasible for a much larger range of parameters than without STDP.

  5. Differential Expression of Dopamine D5 Receptors across Neuronal Subtypes in Macaque Frontal Eye Field

    Directory of Open Access Journals (Sweden)

    Adrienne Mueller

    2018-02-01

    Full Text Available Dopamine signaling in the prefrontal cortex (PFC is important for cognitive functions, yet very little is known about the expression of the D5 class of dopamine receptors (D5Rs in this region. To address this, we co-stained for D5Rs, pyramidal neurons (neurogranin+, putative long-range projection pyramidal neurons (SMI-32+, and several classes of inhibitory interneuron (parvalbumin+, calbindin+, calretinin+, somatostatin+ within the frontal eye field (FEF: an area within the PFC involved in the control of visual spatial attention. We then quantified the co-expression of D5Rs with markers of different cell types across different layers of the FEF. We show that: (1 D5Rs are more prevalent on pyramidal neurons than on inhibitory interneurons. (2 D5Rs are disproportionately expressed on putative long-range projecting pyramidal neurons. The disproportionately high expression of D5Rs on long-range projecting pyramidals, compared to interneurons, was particularly pronounced in layers II–III. Together these results indicate that the engagement of D5R-dependent mechanisms in the FEF varies depending on cell type and cortical layer, and suggests that non-locally projecting neurons contribute disproportionately to functions involving the D5R subtype.

  6. 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).

  7. Toxic effects of lead on neuronal development and function

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  8. Stochastic multiresonance in coupled excitable FHN neurons

    Science.gov (United States)

    Li, Huiyan; Sun, Xiaojuan; Xiao, Jinghua

    2018-04-01

    In this paper, effects of noise on Watts-Strogatz small-world neuronal networks, which are stimulated by a subthreshold signal, have been investigated. With the numerical simulations, it is surprisingly found that there exist several optimal noise intensities at which the subthreshold signal can be detected efficiently. This indicates the occurrence of stochastic multiresonance in the studied neuronal networks. Moreover, it is revealed that the occurrence of stochastic multiresonance has close relationship with the period of subthreshold signal Te and the noise-induced mean period of the neuronal networks T0. In detail, we find that noise could induce the neuronal networks to generate stochastic resonance for M times if Te is not very large and falls into the interval ( M × T 0 , ( M + 1 ) × T 0 ) with M being a positive integer. In real neuronal system, subthreshold signal detection is very meaningful. Thus, the obtained results in this paper could give some important implications on detecting subthreshold signal and propagating neuronal information in neuronal systems.

  9. Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro.

    Science.gov (United States)

    Bardy, Cedric; van den Hurk, Mark; Eames, Tameji; Marchand, Cynthia; Hernandez, Ruben V; Kellogg, Mariko; Gorris, Mark; Galet, Ben; Palomares, Vanessa; Brown, Joshua; Bang, Anne G; Mertens, Jerome; Böhnke, Lena; Boyer, Leah; Simon, Suzanne; Gage, Fred H

    2015-05-19

    Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely used to culture neurons. We found that classic basal media, as well as serum, impair action potential generation and synaptic communication. To overcome this problem, we designed a new neuronal medium (BrainPhys basal + serum-free supplements) in which we adjusted the concentrations of inorganic salts, neuroactive amino acids, and energetic substrates. We then tested that this medium adequately supports neuronal activity and survival of human neurons in culture. Long-term exposure to this physiological medium also improved the proportion of neurons that were synaptically active. The medium was designed to culture human neurons but also proved adequate for rodent neurons. The improvement in BrainPhys basal medium to support neurophysiological activity is an important step toward reducing the gap between brain physiological conditions in vivo and neuronal models in vitro.

  10. Protocol for culturing low density pure rat hippocampal neurons supported by mature mixed neuron cultures.

    Science.gov (United States)

    Yang, Qian; Ke, Yini; Luo, Jianhong; Tang, Yang

    2017-02-01

    primary hippocampal neuron cultures allow for subcellular morphological dissection, easy access to drug treatment and electrophysiology analysis of individual neurons, and is therefore an ideal model for the study of neuron physiology. While neuron and glia mixed cultures are relatively easy to prepare, pure neurons are particular hard to culture at low densities which are suitable for morphology studies. This may be due to a lack of neurotrophic factors such as brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT3) and Glial cell line-derived neurotrophic factor (GDNF). In this study we used a two step protocol in which neuron-glia mixed cultures were initially prepared for maturation to support the growth of young neurons plated at very low densities. Our protocol showed that neurotrophic support resulted in physiologically functional hippocampal neurons with larger cell body, increased neurite length and decreased branching and complexity compared to cultures prepared using a conventional method. Our protocol provides a novel way to culture highly uniformed hippocampal neurons for acquiring high quality, neuron based data. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. 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.

  12. Glass promotes the differentiation of neuronal and non-neuronal cell types in the Drosophila eye

    Science.gov (United States)

    Morrison, Carolyn A.; Chen, Hao; Cook, Tiffany; Brown, Stuart

    2018-01-01

    Transcriptional regulators can specify different cell types from a pool of equivalent progenitors by activating distinct developmental programs. The Glass transcription factor is expressed in all progenitors in the developing Drosophila eye, and is maintained in both neuronal and non-neuronal cell types. Glass is required for neuronal progenitors to differentiate as photoreceptors, but its role in non-neuronal cone and pigment cells is unknown. To determine whether Glass activity is limited to neuronal lineages, we compared the effects of misexpressing it in neuroblasts of the larval brain and in epithelial cells of the wing disc. Glass activated overlapping but distinct sets of genes in these neuronal and non-neuronal contexts, including markers of photoreceptors, cone cells and pigment cells. Coexpression of other transcription factors such as Pax2, Eyes absent, Lozenge and Escargot enabled Glass to induce additional genes characteristic of the non-neuronal cell types. Cell type-specific glass mutations generated in cone or pigment cells using somatic CRISPR revealed autonomous developmental defects, and expressing Glass specifically in these cells partially rescued glass mutant phenotypes. These results indicate that Glass is a determinant of organ identity that acts in both neuronal and non-neuronal cells to promote their differentiation into functional components of the eye. PMID:29324767

  13. Parkin Mutations Reduce the Complexity of Neuronal Processes in iPSC-derived Human Neurons

    Science.gov (United States)

    Ren, Yong; Jiang, Houbo; Hu, Zhixing; Fan, Kevin; Wang, Jun; Janoschka, Stephen; Wang, Xiaomin; Ge, Shaoyu; Feng, Jian

    2015-01-01

    Parkinson’s disease (PD) is characterized by the degeneration of nigral dopaminergic (DA) neurons and non-DA neurons in many parts of the brain. Mutations of parkin, an E3 ubiquitin ligase that strongly binds to microtubules, are the most frequent cause of recessively inherited Parkinson’s disease. The lack of robust PD phenotype in parkin knockout mice suggests a unique vulnerability of human neurons to parkin mutations. Here, we show that the complexity of neuronal processes as measured by total neurite length, number of terminals, number of branch points and Sholl analysis, was greatly reduced in induced pluripotent stem cell (iPSC)-derived TH+ or TH− neurons from PD patients with parkin mutations. Consistent with these, microtubule stability was significantly decreased by parkin mutations in iPSC-derived neurons. Overexpression of parkin, but not its PD-linked mutant nor GFP, restored the complexity of neuronal processes and the stability of microtubules. Consistent with these, the microtubule-depolymerizing agent colchicine mimicked the effect of parkin mutations by decreasing neurite length and complexity in control neurons while the microtubule-stabilizing drug taxol mimicked the effect of parkin overexpression by enhancing the morphology of parkin-deficient neurons. The results suggest that parkin maintains the morphological complexity of human neurons by stabilizing microtubules. PMID:25332110

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

    Science.gov (United States)

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

    2010-08-06

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

  15. 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.

  16. Memory traces of long-range coordinated oscillations in the sleeping human brain.

    Science.gov (United States)

    Piantoni, Giovanni; Van Der Werf, Ysbrand D; Jensen, Ole; Van Someren, Eus J W

    2015-01-01

    Cognition involves coordinated activity across distributed neuronal networks. Neuronal activity during learning triggers cortical plasticity that allows for reorganization of the neuronal network and integration of new information. Animal studies have shown post-learning reactivation of learning-elicited neuronal network activity during subsequent sleep, supporting consolidation of the reorganization. However, no previous studies, to our knowledge, have demonstrated reactivation of specific learning-elicited long-range functional connectivity during sleep in humans. We here show reactivation of learning-induced long-range synchronization of magnetoencephalography power fluctuations in human sleep. Visuomotor learning elicited a specific profile of long-range cortico-cortical synchronization of slow (0.1 Hz) fluctuations in beta band (12-30 Hz) power. The parieto-occipital part of this synchronization profile reappeared in delta band (1-3.5 Hz) power fluctuations during subsequent sleep, but not during the intervening wakefulness period. Individual differences in the reactivated synchronization predicted postsleep performance improvement. The presleep resting-state synchronization profile was not reactivated during sleep. The findings demonstrate reactivation of long-range coordination of neuronal activity in humans, more specifically of reactivation of coupling of infra-slow fluctuations in oscillatory power. The spatiotemporal profile of delta power fluctuations during sleep may subserve memory consolidation by echoing coordinated activation elicited by prior learning. © 2014 Wiley Periodicals, Inc.

  17. Response of spiking neurons to correlated inputs

    International Nuclear Information System (INIS)

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

    2002-01-01

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

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

    Science.gov (United States)

    Rau, Andrew R; Hentges, Shane T

    2017-08-02

    Hypothalamic agouti-related peptide (AgRP) neurons potently stimulate food intake, whereas proopiomelanocortin (POMC) neurons inhibit feeding. Whether AgRP neurons exert their orexigenic actions, at least in part, by inhibiting anorexigenic POMC neurons remains unclear. Here, the connectivity between GABA-releasing AgRP neurons and POMC neurons was examined in brain slices from male and female mice. GABA-mediated spontaneous IPSCs (sIPSCs) in POMC neurons were unaffected by disturbing GABA release from AgRP neurons either by cell type-specific deletion of the vesicular GABA transporter or by expression of botulinum toxin in AgRP neurons to prevent vesicle-associated membrane protein 2-dependent vesicle fusion. Additionally, there was no difference in the ability of μ-opioid receptor (MOR) agonists to inhibit sIPSCs in POMC neurons when MORs were deleted from AgRP neurons, and activation of the inhibitory designer receptor hM4Di on AgRP neurons did not affect sIPSCs recorded from POMC neurons. These approaches collectively indicate that AgRP neurons do not significantly contribute to the strong spontaneous GABA input to POMC neurons. Despite these observations, optogenetic stimulation of AgRP neurons reliably produced evoked IPSCs in POMC neurons, leading to the inhibition of POMC neuron firing. Thus, AgRP neurons can potently affect POMC neuron function without contributing a significant source of spontaneous GABA input to POMC neurons. Together, these results indicate that the relevance of GABAergic inputs from AgRP to POMC neurons is state dependent and highlight the need to consider different types of transmitter release in circuit mapping and physiologic regulation. SIGNIFICANCE STATEMENT Agouti-related peptide (AgRP) neurons play an important role in driving food intake, while proopiomelanocortin (POMC) neurons inhibit feeding. Despite the importance of these two well characterized neuron types in maintaining metabolic homeostasis, communication between these

  19. Evolvable Neuronal Paths: A Novel Basis for Information and Search in the Brain

    Science.gov (United States)

    Fernando, Chrisantha; Vasas, Vera; Szathmáry, Eörs; Husbands, Phil

    2011-01-01

    We propose a previously unrecognized kind of informational entity in the brain that is capable of acting as the basis for unlimited hereditary variation in neuronal networks. This unit is a path of activity through a network of neurons, analogous to a path taken through a hidden Markov model. To prove in principle the capabilities of this new kind of informational substrate, we show how a population of paths can be used as the hereditary material for a neuronally implemented genetic algorithm, (the swiss-army knife of black-box optimization techniques) which we have proposed elsewhere could operate at somatic timescales in the brain. We compare this to the same genetic algorithm that uses a standard ‘genetic’ informational substrate, i.e. non-overlapping discrete genotypes, on a range of optimization problems. A path evolution algorithm (PEA) is defined as any algorithm that implements natural selection of paths in a network substrate. A PEA is a previously unrecognized type of natural selection that is well suited for implementation by biological neuronal networks with structural plasticity. The important similarities and differences between a standard genetic algorithm and a PEA are considered. Whilst most experiments are conducted on an abstract network model, at the conclusion of the paper a slightly more realistic neuronal implementation of a PEA is outlined based on Izhikevich spiking neurons. Finally, experimental predictions are made for the identification of such informational paths in the brain. PMID:21887266

  20. Enhanced Sensitivity to Rapid Input Fluctuations by Nonlinear Threshold Dynamics in Neocortical Pyramidal Neurons.

    Science.gov (United States)

    Mensi, Skander; Hagens, Olivier; Gerstner, Wulfram; Pozzorini, Christian

    2016-02-01

    The way in which single neurons transform input into output spike trains has fundamental consequences for network coding. Theories and modeling studies based on standard Integrate-and-Fire models implicitly assume that, in response to increasingly strong inputs, neurons modify their coding strategy by progressively reducing their selective sensitivity to rapid input fluctuations. Combining mathematical modeling with in vitro experiments, we demonstrate that, in L5 pyramidal neurons, the firing threshold dynamics adaptively adjust the effective timescale of somatic integration in order to preserve sensitivity to rapid signals over a broad range of input statistics. For that, a new Generalized Integrate-and-Fire model featuring nonlinear firing threshold dynamics and conductance-based adaptation is introduced that outperforms state-of-the-art neuron models in predicting the spiking activity of neurons responding to a variety of in vivo-like fluctuating currents. Our model allows for efficient parameter extraction and can be analytically mapped to a Generalized Linear Model in which both the input filter--describing somatic integration--and the spike-history filter--accounting for spike-frequency adaptation--dynamically adapt to the input statistics, as experimentally observed. Overall, our results provide new insights on the computational role of different biophysical processes known to underlie adaptive coding in single neurons and support previous theoretical findings indicating that the nonlinear dynamics of the firing threshold due to Na+-channel inactivation regulate the sensitivity to rapid input fluctuations.

  1. Synchronization properties of coupled chaotic neurons: The role of random shared input

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Rupesh [School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi 110067 (India); Bilal, Shakir [Department of Physics and Astrophysics, University of Delhi, Delhi 110 007 (India); Ramaswamy, Ram [School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi 110067 (India); School of Physical Sciences, Jawaharlal Nehru University, New Delhi 110067 (India)

    2016-06-15

    Spike-time correlations of neighbouring neurons depend on their intrinsic firing properties as well as on the inputs they share. Studies have shown that periodically firing neurons, when subjected to random shared input, exhibit asynchronicity. Here, we study the effect of random shared input on the synchronization of weakly coupled chaotic neurons. The cases of so-called electrical and chemical coupling are both considered, and we observe a wide range of synchronization behaviour. When subjected to identical shared random input, there is a decrease in the threshold coupling strength needed for chaotic neurons to synchronize in-phase. The system also supports lag–synchronous states, and for these, we find that shared input can cause desynchronization. We carry out a master stability function analysis for a network of such neurons and show agreement with the numerical simulations. The contrasting role of shared random input for complete and lag synchronized neurons is useful in understanding spike-time correlations observed in many areas of the brain.

  2. Synchronization properties of coupled chaotic neurons: The role of random shared input

    International Nuclear Information System (INIS)

    Kumar, Rupesh; Bilal, Shakir; Ramaswamy, Ram

    2016-01-01

    Spike-time correlations of neighbouring neurons depend on their intrinsic firing properties as well as on the inputs they share. Studies have shown that periodically firing neurons, when subjected to random shared input, exhibit asynchronicity. Here, we study the effect of random shared input on the synchronization of weakly coupled chaotic neurons. The cases of so-called electrical and chemical coupling are both considered, and we observe a wide range of synchronization behaviour. When subjected to identical shared random input, there is a decrease in the threshold coupling strength needed for chaotic neurons to synchronize in-phase. The system also supports lag–synchronous states, and for these, we find that shared input can cause desynchronization. We carry out a master stability function analysis for a network of such neurons and show agreement with the numerical simulations. The contrasting role of shared random input for complete and lag synchronized neurons is useful in understanding spike-time correlations observed in many areas of the brain.

  3. Retrograde monosynaptic tracing reveals the temporal evolution of inputs onto new neurons in the adult dentate gyrus and olfactory bulb

    Science.gov (United States)

    Deshpande, Aditi; Bergami, Matteo; Ghanem, Alexander; Conzelmann, Karl-Klaus; Lepier, Alexandra; Götz, Magdalena; Berninger, Benedikt

    2013-01-01

    Identifying the connectome of adult-generated neurons is essential for understanding how the preexisting circuitry is refined by neurogenesis. Changes in the pattern of connectivity are likely to control the differentiation process of newly generated neurons and exert an important influence on their unique capacity to contribute to information processing. Using a monosynaptic rabies virus-based tracing technique, we studied the evolving presynaptic connectivity of adult-generated neurons in the dentate gyrus (DG) of the hippocampus and olfactory bulb (OB) during the first weeks of their life. In both neurogenic zones, adult-generated neurons first receive local connections from multiple types of GABAergic interneurons before long-range projections become established, such as those originating from cortical areas. Interestingly, despite fundamental similarities in the overall pattern of evolution of presynaptic connectivity, there were notable differences with regard to the development of cortical projections: although DG granule neuron input originating from the entorhinal cortex could be traced starting only from 3 to 5 wk on, newly generated neurons in the OB received input from the anterior olfactory nucleus and piriform cortex already by the second week. This early glutamatergic input onto newly generated interneurons in the OB was matched in time by the equally early innervations of DG granule neurons by glutamatergic mossy cells. The development of connectivity revealed by our study may suggest common principles for incorporating newly generated neurons into a preexisting circuit. PMID:23487772

  4. Neuronal oscillations enhance stimulus discrimination by ensuring action potential precision

    DEFF Research Database (Denmark)

    Schaefer, Andreas T; Angelo, Kamilla; Spors, Hartwig

    2006-01-01

    generated membrane potential oscillations dramatically improve action potential (AP) precision by removing the membrane potential variance associated with jitter-accumulating trains of APs. This increased AP precision occurred irrespective of cell type and--at oscillation frequencies ranging from 3 to 65 Hz......Although oscillations in membrane potential are a prominent feature of sensory, motor, and cognitive function, their precise role in signal processing remains elusive. Here we show, using a combination of in vivo, in vitro, and theoretical approaches, that both synaptically and intrinsically......, membrane potential oscillations dramatically enhance the discriminatory capabilities of individual neurons and networks of cells and provide one attractive explanation for their abundance in neurophysiological systems....

  5. Populations of striatal medium spiny neurons encode vibrotactile frequency in rats: modulation by slow wave oscillations.

    Science.gov (United States)

    Hawking, Thomas G; Gerdjikov, Todor V

    2013-01-01

    Dorsolateral striatum (DLS) is implicated in tactile perception and receives strong projections from somatosensory cortex. However, the sensory representations encoded by striatal projection neurons are not well understood. Here we characterized the contribution of DLS to the encoding of vibrotactile information in rats by assessing striatal responses to precise frequency stimuli delivered to a single vibrissa. We applied stimuli in a frequency range (45-90 Hz) that evokes discriminable percepts and carries most of the power of vibrissa vibration elicited by a range of complex fine textures. Both medium spiny neurons and evoked potentials showed tactile responses that were modulated by slow wave oscillations. Furthermore, medium spiny neuron population responses represented stimulus frequency on par with previously reported behavioral benchmarks. Our results suggest that striatum encodes frequency information of vibrotactile stimuli which is dynamically modulated by ongoing brain state.

  6. Vertical binocular disparity is encoded implicitly within a model neuronal population tuned to horizontal disparity and orientation.

    Directory of Open Access Journals (Sweden)

    Jenny C A Read

    2010-04-01

    Full Text Available Primary visual cortex is often viewed as a "cyclopean retina", performing the initial encoding of binocular disparities between left and right images. Because the eyes are set apart horizontally in the head, binocular disparities are predominantly horizontal. Yet, especially in the visual periphery, a range of non-zero vertical disparities do occur and can influence perception. It has therefore been assumed that primary visual cortex must contain neurons tuned to a range of vertical disparities. Here, I show that this is not necessarily the case. Many disparity-selective neurons are most sensitive to changes in disparity orthogonal to their preferred orientation. That is, the disparity tuning surfaces, mapping their response to different two-dimensional (2D disparities, are elongated along the cell's preferred orientation. Because of this, even if a neuron's optimal 2D disparity has zero vertical component, the neuron will still respond best to a non-zero vertical disparity when probed with a sub-optimal horizontal disparity. This property can be used to decode 2D disparity, even allowing for realistic levels of neuronal noise. Even if all V1 neurons at a particular retinotopic location are tuned to the expected vertical disparity there (for example, zero at the fovea, the brain could still decode the magnitude and sign of departures from that expected value. This provides an intriguing counter-example to the common wisdom that, in order for a neuronal population to encode a quantity, its members must be tuned to a range of values of that quantity. It demonstrates that populations of disparity-selective neurons encode much richer information than previously appreciated. It suggests a possible strategy for the brain to extract rarely-occurring stimulus values, while concentrating neuronal resources on the most commonly-occurring situations.

  7. Optogenetic stimulation of cholinergic projection neurons as an alternative for deep brain stimulation for Alzheimer's treatment

    Science.gov (United States)

    Mancuso, James; Chen, Yuanxin; Zhao, Zhen; Li, Xuping; Xue, Zhong; Wong, Stephen T. C.

    2013-03-01

    Deep brain stimulation (DBS) of the cholinergic nuclei has emerged as a powerful potential treatment for neurodegenerative disease and is currently in a clinical trial for Alzheimer's therapy. While effective in treatment for a number of conditions from depression to epilepsy, DBS remains somewhat unpredictable due to the heterogeneity of the projection neurons that are activated, including glutamatergic, GABAergic, and cholinergic neurons, leading to unacceptable side effects ranging from apathy to depression or even suicidal behavior. It would be highly advantageous to confine stimulation to specific populations of neurons, particularly in brain diseases involving complex network interactions such as Alzheimer's. Optogenetics, now firmly established as an effective approach to render genetically-defined populations of cells sensitive to light activation including mice expressing Channelrhodopsin-2 specifically in cholinergic neurons, provides just this opportunity. Here we characterize the light activation properties and cell density of cholinergic neurons in healthy mice and mouse models of Alzheimer's disease in order to evaluate the feasibility of using optogenetic modulation of cholinergic synaptic activity to slow or reverse neurodegeneration. This paper is one of the very first reports to suggest that, despite the anatomical depth of their cell bodies, cholinergic projection neurons provide a better target for systems level optogenetic modulation than cholinergic interneurons found in various brain regions including striatum and the cerebral cortex. Additionally, basal forebrain channelrhodopsin-expressing cholinergic neurons are shown to exhibit normal distribution at 60 days and normal light activation at 40 days, the latest timepoints observed. The data collected form the basis of ongoing computational modeling of light stimulation of entire populations of cholinergic neurons.

  8. Neuronal Rho GTPase Rac1 elimination confers neuroprotection in a mouse model of permanent ischemic stroke.

    Science.gov (United States)

    Karabiyik, Cansu; Fernandes, Rui; Figueiredo, Francisco Rosário; Socodato, Renato; Brakebusch, Cord; Lambertsen, Kate Lykke; Relvas, João Bettencourt; Santos, Sofia Duque

    2017-09-28

    The Rho GTPase Rac1 is a multifunctional protein involved in distinct pathways ranging from development to pathology. The aim of the present study was to unravel the contribution of neuronal Rac1 in regulating the response to brain injury induced by permanent focal cerebral ischemia (pMCAO). Our results show that pMCAO significantly increased total Rac1 levels in wild type mice, mainly through rising nuclear Rac1, while a reduction in Rac1 activation was observed. Such changes preceded cell death induced by excitotoxic stress. Pharmacological inhibition of Rac1 in primary neuronal cortical cells prevented the increase in oxidative stress induced after overactivation of glutamate receptors. However, this was not sufficient to prevent the associated neuronal cell death. In contrast, RNAi-mediated knock down of Rac1 in primary cortical neurons prevented cell death elicited by glutamate excitotoxicity and decreased the activity of NADPH oxidase. To test whether in vivo down regulation of neuronal Rac1 was neuroprotective after pMCAO, we used tamoxifen-inducible neuron-specific conditional Rac1-knockout mice. We observed a significant 50% decrease in brain infarct volume of knockout mice and a concomitant increase in HIF-1α expression compared to littermate control mice, demonstrating that ablation of Rac1 in neurons is neuroprotective. Transmission electron microscopy performed in the ischemic brain showed that lysosomes in the infarct of Rac1- knockout mice were preserved at similar levels to those of non-infarcted tissue, while littermate mice displayed a decrease in the number of lysosomes, further corroborating the notion that Rac1 ablation in neurons is neuroprotective. Our results demonstrate that Rac1 plays important roles in the ischemic pathological cascade and that modulation of its levels is of therapeutic interest. © 2017 International Society of Neuropathology.

  9. Wave-processing of long-scale information by neuronal chains.

    Directory of Open Access Journals (Sweden)

    José Antonio Villacorta-Atienza

    Full Text Available Investigation of mechanisms of information handling in neural assemblies involved in computational and cognitive tasks is a challenging problem. Synergetic cooperation of neurons in time domain, through synchronization of firing of multiple spatially distant neurons, has been widely spread as the main paradigm. Complementary, the brain may also employ information coding and processing in spatial dimension. Then, the result of computation depends also on the spatial distribution of long-scale information. The latter bi-dimensional alternative is notably less explored in the literature. Here, we propose and theoretically illustrate a concept of spatiotemporal representation and processing of long-scale information in laminar neural structures. We argue that relevant information may be hidden in self-sustained traveling waves of neuronal activity and then their nonlinear interaction yields efficient wave-processing of spatiotemporal information. Using as a testbed a chain of FitzHugh-Nagumo neurons, we show that the wave-processing can be achieved by incorporating into the single-neuron dynamics an additional voltage-gated membrane current. This local mechanism provides a chain of such neurons with new emergent network properties. In particular, nonlinear waves as a carrier of long-scale information exhibit a variety of functionally different regimes of interaction: from complete or asymmetric annihilation to transparent crossing. Thus neuronal chains can work as computational units performing different operations over spatiotemporal information. Exploiting complexity resonance these composite units can discard stimuli of too high or too low frequencies, while selectively compress those in the natural frequency range. We also show how neuronal chains can contextually interpret raw wave information. The same stimulus can be processed differently or identically according to the context set by a periodic wave train injected at the opposite end of the

  10. Activation of temperature-sensitive TRPV1-like receptors in ARC POMC neurons reduces food intake.

    Directory of Open Access Journals (Sweden)

    Jae Hoon Jeong

    2018-04-01

    Full Text Available Proopiomelanocortin (POMC neurons in the arcuate nucleus of the hypothalamus (ARC respond to numerous hormonal and neural signals, resulting in changes in food intake. Here, we demonstrate that ARC POMC neurons express capsaicin-sensitive transient receptor potential vanilloid 1 receptor (TRPV1-like receptors. To show expression of TRPV1-like receptors in ARC POMC neurons, we use single-cell reverse transcription-polymerase chain reaction (RT-PCR, immunohistochemistry, electrophysiology, TRPV1 knock-out (KO, and TRPV1-Cre knock-in mice. A small elevation of temperature in the physiological range is enough to depolarize ARC POMC neurons. This depolarization is blocked by the TRPV1 receptor antagonist and by Trpv1 gene knockdown. Capsaicin-induced activation reduces food intake that is abolished by a melanocortin receptor antagonist. To selectively stimulate TRPV1-like receptor-expressing ARC POMC neurons in the ARC, we generate an adeno-associated virus serotype 5 (AAV5 carrying a Cre-dependent channelrhodopsin-2 (ChR2-enhanced yellow fluorescent protein (eYFP expression cassette under the control of the two neuronal POMC enhancers (nPEs. Optogenetic stimulation of TRPV1-like receptor-expressing POMC neurons decreases food intake. Hypothalamic temperature is rapidly elevated and reaches to approximately 39 °C during treadmill running. This elevation is associated with a reduction in food intake. Knockdown of the Trpv1 gene exclusively in ARC POMC neurons blocks the feeding inhibition produced by increased hypothalamic temperature. Taken together, our findings identify a melanocortinergic circuit that links acute elevations in hypothalamic temperature with acute reductions in food intake.

  11. Near infrared radiation rescues mitochondrial dysfunction in cortical neurons after oxygen-glucose deprivation.

    Science.gov (United States)

    Yu, Zhanyang; Liu, Ning; Zhao, Jianhua; Li, Yadan; McCarthy, Thomas J; Tedford, Clark E; Lo, Eng H; Wang, Xiaoying

    2015-04-01

    Near infrared radiation (NIR) is known to penetrate and affect biological systems in multiple ways. Recently, a series of experimental studies suggested that low intensity NIR may protect neuronal cells against a wide range of insults that mimic diseases such as stroke, brain trauma and neurodegeneration. However, the potential molecular mechanisms of neuroprotection with NIR remain poorly defined. In this study, we tested the hypothesis that low intensity NIR may attenuate hypoxia/ischemia-induced mitochondrial dysfunction in neurons. Primary cortical mouse neuronal cultures were subjected to 4 h oxygen-glucose deprivation followed by reoxygenation for 2 h, neurons were then treated with a 2 min exposure to 810-nm NIR. Mitochondrial function markers including MTT reduction and mitochondria membrane potential were measured at 2 h after treatment. Neurotoxicity was quantified 20 h later. Our results showed that 4 h oxygen-glucose deprivation plus 20 h reoxygenation caused 33.8 ± 3.4 % of neuron death, while NIR exposure significantly reduced neuronal death to 23.6 ± 2.9 %. MTT reduction rate was reduced to 75.9 ± 2.7 % by oxygen-glucose deprivation compared to normoxic controls, but NIR exposure significantly rescued MTT reduction to 87.6 ± 4.5 %. Furthermore, after oxygen-glucose deprivation, mitochondria membrane potential was reduced to 48.9 ± 4.39 % of normoxic control, while NIR exposure significantly ameliorated this reduction to 89.6 ± 13.9 % of normoxic control. Finally, NIR significantly rescued OGD-induced ATP production decline at 20 min after NIR. These findings suggest that low intensity NIR can protect neurons against oxygen-glucose deprivation by rescuing mitochondrial function and restoring neuronal energetics.

  12. Effect of correlating adjacent neurons for identifying communications: Feasibility experiment in a cultured neuronal network

    OpenAIRE

    Yoshi Nishitani; Chie Hosokawa; Yuko Mizuno-Matsumoto; Tomomitsu Miyoshi; Shinichi Tamura

    2017-01-01

    Neuronal networks have fluctuating characteristics, unlike the stable characteristics seen in computers. The underlying mechanisms that drive reliable communication among neuronal networks and their ability to perform intelligible tasks remain unknown. Recently, in an attempt to resolve this issue, we showed that stimulated neurons communicate via spikes that propagate temporally, in the form of spike trains. We named this phenomenon “spike wave propagation”. In these previous studies, using ...

  13. 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.

  14. Fitting neuron models to spike trains

    Directory of Open Access Journals (Sweden)

    Cyrille eRossant

    2011-02-01

    Full Text Available Computational modeling is increasingly used to understand the function of neural circuitsin systems neuroscience.These studies require models of individual neurons with realisticinput-output properties.Recently, it was found that spiking models can accurately predict theprecisely timed spike trains produced by cortical neurons in response tosomatically injected currents,if properly fitted. This requires fitting techniques that are efficientand flexible enough to easily test different candidate models.We present a generic solution, based on the Brian simulator(a neural network simulator in Python, which allowsthe user to define and fit arbitrary neuron models to electrophysiological recordings.It relies on vectorization and parallel computing techniques toachieve efficiency.We demonstrate its use on neural recordings in the barrel cortex andin the auditory brainstem, and confirm that simple adaptive spiking modelscan accurately predict the response of cortical neurons. Finally, we show how a complexmulticompartmental model can be reduced to a simple effective spiking model.

  15. Toward functional classification of neuronal types.

    Science.gov (United States)

    Sharpee, Tatyana O

    2014-09-17

    How many types of neurons are there in the brain? This basic neuroscience question remains unsettled despite many decades of research. Classification schemes have been proposed based on anatomical, electrophysiological, or molecular properties. However, different schemes do not always agree with each other. This raises the question of whether one can classify neurons based on their function directly. For example, among sensory neurons, can a classification scheme be devised that is based on their role in encoding sensory stimuli? Here, theoretical arguments are outlined for how this can be achieved using information theory by looking at optimal numbers of cell types and paying attention to two key properties: correlations between inputs and noise in neural responses. This theoretical framework could help to map the hierarchical tree relating different neuronal classes within and across species. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. From quantum entanglement to mirror neuron

    International Nuclear Information System (INIS)

    Zak, Michail

    2007-01-01

    It is proposed that two fundamental phenomena: quantum entanglement in physics, and mirror neuron in biopsychology, can be described by using the same mathematical formalism, namely, the feedback from the Liouville equation to equation of motion

  17. Do enteric neurons make hypocretin? ☆

    Science.gov (United States)

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

    2008-01-01

    Hypocretins (orexins) are wake-promoting neuropeptides produced by hypothalamic neurons. These hypocretin-producing cells are lost in people with narcolepsy, possibly due to an autoimmune attack. Prior studies described hypocretin neurons in the enteric nervous system, and these cells could be an additional target of an autoimmune process. We sought to determine whether enteric hypocretin neurons are lost in narcoleptic subjects. Even though we tried several methods (including whole mounts, sectioned tissue, pre-treatment of mice with colchicine, and the use of various primary antisera), we could not identify hypocretin-producing cells in enteric nervous tissue collected from mice or normal human subjects. These results raise doubts about whether enteric neurons produce hypocretin. PMID:18191238

  18. Advances in 3D neuronal cell culture

    NARCIS (Netherlands)

    Frimat, Jean Philippe; Xie, Sijia; Bastiaens, Alex; Schurink, Bart; Wolbers, Floor; Den Toonder, Jaap; Luttge, Regina

    2015-01-01

    In this contribution, the authors present our advances in three-dimensional (3D) neuronal cell culture platform technology contributing to controlled environments for microtissue engineering and analysis of cellular physiological and pathological responses. First, a micromachined silicon sieving

  19. 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.

  20. Review Paper: Polyphenolic Antioxidants and Neuronal Regeneration

    Directory of Open Access Journals (Sweden)

    Amin Ataie

    2016-04-01

    Full Text Available Many studies indicate that oxidative stress is involved in the pathophysiology of neurodegenerative diseases. Oxidative stress can induce neuronal damages, modulate intracellular signaling and ultimately leads to neuronal death by apoptosis or necrosis. To review antioxidants preventive effects on oxidative stress and neurodegenerative diseases we accumulated data from international medical journals and academic informations' sites. According to many studies, antioxidants could reduce toxic neuronal damages and many studies confirmed the efficacy of polyphenol antioxidants in fruits and vegetables to reduce neuronal death and to diminish oxidative stress. This systematic review showed the antioxidant activities of phytochemicals which play as natural neuroprotectives with low adverse effects against some neurodegenerative diseases as Parkinson or Alzheimer diseases.

  1. AgRP neurons regulate development of dopamine neuronal plasticity and nonfood-associated behaviors

    Science.gov (United States)

    Dietrich, Marcelo O; Bober, Jeremy; Ferreira, Jozélia G; Tellez, Luis A; Mineur, Yann S; Souza, Diogo O; Gao, Xiao-Bing; Picciotto, Marina R; Araújo, Ivan; Liu, Zhong-Wu; Horvath, Tamas L

    2012-01-01

    It is not known whether behaviors unrelated to feeding are affected by hypothalamic regulators of hunger. We found that impairment of Agouti-related protein (AgRP) circuitry by either Sirt1 knockdown in AgRP-expressing neurons or early postnatal ablation of these neurons increased exploratory behavior and enhanced responses to cocaine. In AgRP circuit–impaired mice, ventral tegmental dopamine neurons exhibited enhanced spike timing–dependent long-term potentiation, altered amplitude of miniature postsynaptic currents and elevated dopamine in basal forebrain. Thus, AgRP neurons determine the set point of the reward circuitry and associated behaviors. PMID:22729177

  2. Labeling of neuronal differentiation and neuron cells with biocompatible fluorescent nanodiamonds.

    Science.gov (United States)

    Hsu, Tzu-Chia; Liu, Kuang-Kai; Chang, Huan-Cheng; Hwang, Eric; Chao, Jui-I

    2014-05-16

    Nanodiamond is a promising carbon nanomaterial developed for biomedical applications. Here, we show fluorescent nanodiamond (FND) with the biocompatible properties that can be used for the labeling and tracking of neuronal differentiation and neuron cells derived from embryonal carcinoma stem (ECS) cells. The fluorescence intensities of FNDs were increased by treatment with FNDs in both the mouse P19 and human NT2/D1 ECS cells. FNDs were taken into ECS cells; however, FNDs did not alter the cellular morphology and growth ability. Moreover, FNDs did not change the protein expression of stem cell marker SSEA-1 of ECS cells. The neuronal differentiation of ECS cells could be induced by retinoic acid (RA). Interestingly, FNDs did not affect on the morphological alteration, cytotoxicity and apoptosis during the neuronal differentiation. Besides, FNDs did not alter the cell viability and the expression of neuron-specific marker β-III-tubulin in these differentiated neuron cells. The existence of FNDs in the neuron cells can be identified by confocal microscopy and flow cytometry. Together, FND is a biocompatible and readily detectable nanomaterial for the labeling and tracking of neuronal differentiation process and neuron cells from stem cells.

  3. Neuronal growth on L- and D-cysteine self-assembled monolayers reveals neuronal chiral sensitivity.

    Science.gov (United States)

    Baranes, Koby; Moshe, Hagay; Alon, Noa; Schwartz, Shmulik; Shefi, Orit

    2014-05-21

    Studying the interaction between neuronal cells and chiral molecules is fundamental for the design of novel biomaterials and drugs. Chirality influences all biological processes that involve intermolecular interaction. One common method used to study cellular interactions with different enantiomeric targets is the use of chiral surfaces. Based on previous studies that demonstrated the importance of cysteine in the nervous system, we studied the effect of L- and D-cysteine on single neuronal growth. L-Cysteine, which normally functions as a neuromodulator or a neuroprotective antioxidant, causes damage at elevated levels, which may occur post trauma. In this study, we grew adult neurons in culture enriched with L- and D-cysteine as free compounds or as self-assembled monolayers of chiral surfaces and examined the effect on the neuronal morphology and adhesion. Notably, we have found that exposure to the L-cysteine enantiomer inhibited, and even prevented, neuronal attachment more severely than exposure to the D-cysteine enantiomer. Atop the L-cysteine surfaces, neuronal growth was reduced and degenerated. Since the cysteine molecules were attached to the surface via the thiol groups, the neuronal membrane was exposed to the molecular chiral site. Thus, our results have demonstrated high neuronal chiral sensitivity, revealing chiral surfaces as indirect regulators of neuronal cells and providing a reference for studying chiral drugs.

  4. A neuron-astrocyte transistor-like model for neuromorphic dressed neurons.

    Science.gov (United States)

    Valenza, G; Pioggia, G; Armato, A; Ferro, M; Scilingo, E P; De Rossi, D

    2011-09-01

    Experimental evidences on the role of the synaptic glia as an active partner together with the bold synapse in neuronal signaling and dynamics of neural tissue strongly suggest to investigate on a more realistic neuron-glia model for better understanding human brain processing. Among the glial cells, the astrocytes play a crucial role in the tripartite synapsis, i.e. the dressed neuron. A well-known two-way astrocyte-neuron interaction can be found in the literature, completely revising the purely supportive role for the glia. The aim of this study is to provide a computationally efficient model for neuron-glia interaction. The neuron-glia interactions were simulated by implementing the Li-Rinzel model for an astrocyte and the Izhikevich model for a neuron. Assuming the dressed neuron dynamics similar to the nonlinear input-output characteristics of a bipolar junction transistor, we derived our computationally efficient model. This model may represent the fundamental computational unit for the development of real-time artificial neuron-glia networks opening new perspectives in pattern recognition systems and in brain neurophysiology. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. NBLAST: Rapid, Sensitive Comparison of Neuronal Structure and Construction of Neuron Family Databases.

    Science.gov (United States)

    Costa, Marta; Manton, James D; Ostrovsky, Aaron D; Prohaska, Steffen; Jefferis, Gregory S X E

    2016-07-20

    Neural circuit mapping is generating datasets of tens of thousands of labeled neurons. New computational tools are needed to search and organize these data. We present NBLAST, a sensitive and rapid algorithm, for measuring pairwise neuronal similarity. NBLAST considers both position and local geometry, decomposing neurons into short segments; matched segments are scored using a probabilistic scoring matrix defined by statistics of matches and non-matches. We validated NBLAST on a published dataset of 16,129 single Drosophila neurons. NBLAST can distinguish neuronal types down to the finest level (single identified neurons) without a priori information. Cluster analysis of extensively studied neuronal classes identified new types and unreported topographical features. Fully automated clustering organized the validation dataset into 1,052 clusters, many of which map onto previously described neuronal types. NBLAST supports additional query types, including searching neurons against transgene expression patterns. Finally, we show that NBLAST is effective with data from other invertebrates and zebrafish. VIDEO ABSTRACT. Copyright © 2016 MRC Laboratory of Molecular Biology. Published by Elsevier Inc. All rights reserved.

  6. Intrinsically active and pacemaker neurons in pluripotent stem cell-derived neuronal populations.

    Science.gov (United States)

    Illes, Sebastian; Jakab, Martin; Beyer, Felix; Gelfert, Renate; Couillard-Despres, Sébastien; Schnitzler, Alfons; Ritter, Markus; Aigner, Ludwig

    2014-03-11

    Neurons generated from pluripotent stem cells (PSCs) self-organize into functional neuronal assemblies in vitro, generating synchronous network activities. Intriguingly, PSC-derived neuronal assemblies develop spontaneous activities that are independent of external stimulation, suggesting the presence of thus far undetected intrinsically active neurons (IANs). Here, by using mouse embryonic stem cells, we provide evidence for the existence of IANs in PSC-neuronal networks based on extracellular multielectrode array and intracellular patch-clamp recordings. IANs remain active after pharmacological inhibition of fast synaptic communication and possess intrinsic mechanisms required for autonomous neuronal activity. PSC-derived IANs are functionally integrated in PSC-neuronal populations, contribute to synchronous network bursting, and exhibit pacemaker properties. The intrinsic activity and pacemaker properties of the neuronal subpopulation identified herein may be particularly relevant for interventions involving transplantation of neural tissues. IANs may be a key element in the regulation of the functional activity of grafted as well as preexisting host neuronal networks.

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

    International Nuclear Information System (INIS)

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

    2003-01-01

    Electric fields applied to brain tissue will affect cellular properties. They will hyperpolarise the ends of cells closest to the positive part of the field, and depolarise ends closest to the negative. In the case of neurons this affects excitability. How these changes in transmembrane potential are distributed depends on the length constant of the neuron, and on its geometry; if the neuron is electrically compact, the change in transmembrane potential becomes an almost linear function of distance in the direction of the field. Neurons from the mammalian hippocampus, maintained in tissue slices in vitro, are significantly affected by fields of around 1-5 Vm -1 . (author)

  8. Statistics of Visual Responses to Image Object Stimuli from Primate AIT Neurons to DNN Neurons.

    Science.gov (United States)

    Dong, Qiulei; Wang, Hong; Hu, Zhanyi

    2018-02-01

    Under the goal-driven paradigm, Yamins et al. ( 2014 ; Yamins & DiCarlo, 2016 ) have shown that by optimizing only the final eight-way categorization performance of a four-layer hierarchical network, not only can its top output layer quantitatively predict IT neuron responses but its penultimate layer can also automatically predict V4 neuron responses. Currently, deep neural networks (DNNs) in the field of computer vision have reached image object categorization performance comparable to that of human beings on ImageNet, a data set that contains 1.3 million training images of 1000 categories. We explore whether the DNN neurons (units in DNNs) possess image object representational statistics similar to monkey IT neurons, particularly when the network becomes deeper and the number of image categories becomes larger, using VGG19, a typical and widely used deep network of 19 layers in the computer vision field. Following Lehky, Kiani, Esteky, and Tanaka ( 2011 , 2014 ), where the response statistics of 674 IT neurons to 806 image stimuli are analyzed using three measures (kurtosis, Pareto tail index, and intrinsic dimensionality), we investigate the three issues in this letter using the same three measures: (1) the similarities and differences of the neural response statistics between VGG19 and primate IT cortex, (2) the variation trends of the response statistics of VGG19 neurons at different layers from low to high, and (3) the variation trends of the response statistics of VGG19 neurons when the numbers of stimuli and neurons increase. We find that the response statistics on both single-neuron selectivity and population sparseness of VGG19 neurons are fundamentally different from those of IT neurons in most cases; by increasing the number of neurons in different layers and the number of stimuli, the response statistics of neurons at different layers from low to high do not substantially change; and the estimated intrinsic dimensionality values at the low

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

    Science.gov (United States)

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

    2018-01-01

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

  10. 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

  11. 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....

  12. Unidirectional synchronization of Hodgkin-Huxley neurons

    Energy Technology Data Exchange (ETDEWEB)

    Cornejo-Perez, Octavio [Division de Matematicas Aplicadas y Sistemas, Computacionales, IPICYT, Apdo. Postal 3-74 Tangamanga, 78231 San Luis Potosi (Mexico)]. E-mail: octavio@ipicyt.edu.mx; Femat, Ricardo [Division de Matematicas Aplicadas y Sistemas, Computacionales, IPICYT, Apdo. Postal 3-74 Tangamanga, 78231 San Luis Potosi (Mexico)]. E-mail: rfemat@ipicyt.edu.mx

    2005-07-01

    Synchronization dynamics of two noiseless Hodgkin-Huxley (HH) neurons under the action of feedback control is studied. The spiking patterns of the action potentials evoked by periodic external modulations attain synchronization states under the feedback action. Numerical simulations for the synchronization dynamics of regular-irregular desynchronized spiking sequences are displayed. The results are discussed in context of generalized synchronization. It is also shown that the HH neurons can be synchronized in face of unmeasured states.

  13. Arsenic Trioxide Modulates the Central Snail Neuron Action Potential

    Directory of Open Access Journals (Sweden)

    Guan-Ling Lu

    2009-09-01

    Conclusion: As2O3 at 10 mM elicits BoPs in central snail neurons and this effect may relate to the PLC activity of the neuron, rather than protein kinase A activity, or calcium influxes of the neuron. As2O3 at higher concentration irreversibly abolishes the spontaneous action potentials of the neuron.

  14. Super-ranging. A new ranging strategy in European badgers.

    Directory of Open Access Journals (Sweden)

    Aoibheann Gaughran

    Full Text Available We monitored the ranging of a wild European badger (Meles meles population over 7 years using GPS tracking collars. Badger range sizes varied seasonally and reached their maximum in June, July and August. We analysed the summer ranging behaviour, using 83 home range estimates from 48 individuals over 6974 collar-nights. We found that while most adult badgers (males and females remained within their own traditional social group boundaries, several male badgers (on average 22% regularly ranged beyond these traditional boundaries. These adult males frequently ranged throughout two (or more social group's traditional territories and had extremely large home ranges. We therefore refer to them as super-rangers. While ranging across traditional boundaries has been recorded over short periods of time for extraterritorial mating and foraging forays, or for pre-dispersal exploration, the animals in this study maintained their super-ranges from 2 to 36 months. This study represents the first time such long-term extra-territorial ranging has been described for European badgers. Holding a super-range may confer an advantage in access to breeding females, but could also affect local interaction networks. In Ireland & the UK, badgers act as a wildlife reservoir for bovine tuberculosis (TB. Super-ranging may facilitate the spread of disease by increasing both direct interactions between conspecifics, particularly across social groups, and indirect interactions with cattle in their shared environment. Understanding super-ranging behaviour may both improve our understanding of tuberculosis epidemiology and inform future control strategies.

  15. Ordering Dynamics in Neuron Activity Pattern Model: An Insight to Brain Functionality.

    Directory of Open Access Journals (Sweden)

    Jasleen Gundh

    Full Text Available We study the domain ordering kinetics in d = 2 ferromagnets which corresponds to populated neuron activities with both long-ranged interactions, V(r ∼ r-n and short-ranged interactions. We present the results from comprehensive Monte Carlo (MC simulations for the nonconserved Ising model with n ≥ 2, interaction range considering near and far neighbors. Our model results could represent the long-ranged neuron kinetics (n ≤ 4 in consistent with the same dynamical behaviour of short-ranged case (n ≥ 4 at far below and near criticality. We found that emergence of fast and slow kinetics of long and short ranged case could imitate the formation of connections among near and distant neurons. The calculated characteristic length scale in long-ranged interaction is found to be n independent (L(t ∼ t1/(n-2, whereas short-ranged interaction follows L(t ∼ t1/2 law and approximately preserve universality in domain kinetics. Further, we did the comparative study of phase ordering near the critical temperature which follows different behaviours of domain ordering near and far critical temperature but follows universal scaling law.

  16. Sensitivity of neurons in the middle temporal area of marmoset monkeys to random dot motion.

    Science.gov (United States)

    Chaplin, Tristan A; Allitt, Benjamin J; Hagan, Maureen A; Price, Nicholas S C; Rajan, Ramesh; Rosa, Marcello G P; Lui, Leo L

    2017-09-01

    Neurons in the middle temporal area (MT) of the primate cerebral cortex respond to moving visual stimuli. The sensitivity of MT neurons to motion signals can be characterized by using random-dot stimuli, in which the strength of the motion signal is manipulated by adding different levels of noise (elements that move in random directions). In macaques, this has allowed the calculation of "neurometric" thresholds. We characterized the responses of MT neurons in sufentanil/nitrous oxide-anesthetized marmoset monkeys, a species that has attracted considerable recent interest as an animal model for vision research. We found that MT neurons show a wide range of neurometric thresholds and that the responses of the most sensitive neurons could account for the behavioral performance of macaques and humans. We also investigated factors that contributed to the wide range of observed thresholds. The difference in firing rate between responses to motion in the preferred and null directions was the most effective predictor of neurometric threshold, whereas the direction tuning bandwidth had no correlation with the threshold. We also showed that it is possible to obtain reliable estimates of neurometric thresholds using stimuli that were not highly optimized for each neuron, as is often necessary when recording from large populations of neurons with different receptive field concurrently, as was the case in this study. These results demonstrate that marmoset MT shows an essential physiological similarity to macaque MT and suggest that its neurons are capable of representing motion signals that allow for comparable motion-in-noise judgments. NEW & NOTEWORTHY We report the activity of neurons in marmoset MT in response to random-dot motion stimuli of varying coherence. The information carried by individual MT neurons was comparable to that of the macaque, and the maximum firing rates were a strong predictor of sensitivity. Our study provides key information regarding the neural

  17. Information transmission with spiking Bayesian neurons

    International Nuclear Information System (INIS)

    Lochmann, Timm; Deneve, Sophie

    2008-01-01

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

  18. The transfer function of neuron spike.

    Science.gov (United States)

    Palmieri, Igor; Monteiro, Luiz H A; Miranda, Maria D

    2015-08-01

    The mathematical modeling of neuronal signals is a relevant problem in neuroscience. The complexity of the neuron behavior, however, makes this problem a particularly difficult task. Here, we propose a discrete-time linear time-invariant (LTI) model with a rational function in order to represent the neuronal spike detected by an electrode located in the surroundings of the nerve cell. The model is presented as a cascade association of two subsystems: one that generates an action potential from an input stimulus, and one that represents the medium between the cell and the electrode. The suggested approach employs system identification and signal processing concepts, and is dissociated from any considerations about the biophysical processes of the neuronal cell, providing a low-complexity alternative to model the neuronal spike. The model is validated by using in vivo experimental readings of intracellular and extracellular signals. A computational simulation of the model is presented in order to assess its proximity to the neuronal signal and to observe the variability of the estimated parameters. The implications of the results are discussed in the context of spike sorting. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Endocannabinoids mediate neuron-astrocyte communication.

    Science.gov (United States)

    Navarrete, Marta; Araque, Alfonso

    2008-03-27

    Cannabinoid receptors play key roles in brain function, and cannabinoid effects in brain physiology and drug-related behavior are thought to be mediated by receptors present in neurons. Neuron-astrocyte communication relies on the expression by astrocytes of neurotransmitter receptors. Yet, the expression of cannabinoid receptors by astrocytes in situ and their involvement in the neuron-astrocyte communication remain largely unknown. We show that hippocampal astrocytes express CB1 receptors that upon activation lead to phospholipase C-dependent Ca2+ mobilization from internal stores. These receptors are activated by endocannabinoids released by neurons, increasing astrocyte Ca2+ levels, which stimulate glutamate release that activates NMDA receptors in pyramidal neurons. These results demonstrate the existence of endocannabinoid-mediated neuron-astrocyte communication, revealing that astrocytes are targets of cannabinoids and might therefore participate in the physiology of cannabinoid-related addiction. They also reveal the existence of an endocannabinoid-glutamate signaling pathway where astrocytes serve as a bridge for nonsynaptic interneuronal communication.

  20. Mechanical Dissociation of Retinal Neurons with Vibration

    Science.gov (United States)

    Motomura, Tamami; Hayashida, Yuki; Murayama, Nobuki

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

  1. Divalent cations as modulators of neuronal excitability: Emphasis on copper and zinc

    Directory of Open Access Journals (Sweden)

    RICARDO DELGADO

    2006-01-01

    Full Text Available Based on indirect evidence, a role for synaptically released copper and zinc as modulators of neuronal activity has been proposed. To test this proposal directly, we studied the effect of copper, zinc, and other divalent cations on voltage-dependent currents in dissociated toad olfactory neurons and on their firing rate induced by small depolarizing currents. Divalent cations in the nanomolar range sped up the activation kinetics and increased the amplitude of the inward sodium current. In the micromolar range, they caused a dose dependent inhibition of the inward Na+ and Ca2+ currents (I Na and I Ca and reduced de amplitude of the Ca2+-dependent K+ outward current (I Ca-K. On the other hand, the firing rate of olfactory neurons increased when exposed to nanomolar concentration of divalent cations and decreased when exposed to micromolar concentrations. This biphasic effect of divalent cations on neuronal excitability may be explained by the interaction of these ions with high and low affinity sites in voltage-gated channels. Our results support the idea that these ions are normal modulators of neuronal excitability

  2. Graphene foam as a biocompatible scaffold for culturing human neurons

    Science.gov (United States)

    Mattei, Cristiana; Nasr, Babak; Hudson, Emma J.; Alshawaf, Abdullah J.; Chana, Gursharan; Everall, Ian P.; Dottori, Mirella; Skafidas, Efstratios

    2018-01-01

    In this study, we explore the use of electrically active graphene foam as a scaffold for the culture of human-derived neurons. Human embryonic stem cell (hESC)-derived cortical neurons fated as either glutamatergic or GABAergic neuronal phenotypes were cultured on graphene foam. We show that graphene foam is biocompatible for the culture of human neurons, capable of supporting cell viability and differentiation of hESC-derived cortical neurons. Based on the findings, we propose that graphene foam represents a suitable scaffold for engineering neuronal tissue and warrants further investigation as a model for understanding neuronal maturation, function and circuit formation. PMID:29657752

  3. Rock glaciers, Zailiysiky Range, Kungei Ranges, Tienshan, Kazakhstan, Version 1

    Data.gov (United States)

    National Aeronautics and Space Administration — The Zailiyskiy Alatau is the northernmost parallel latitudinal ranges of the Northern Tien Shan. The highest point of this range is the Talgar peak (4973 m a.s.l.)....

  4. Neuron matters: electric activation of neuronal tissue is dependent on the interaction between the neuron and the electric field.

    Science.gov (United States)

    Ye, Hui; Steiger, Amanda

    2015-08-12

    In laboratory research and clinical practice, externally-applied electric fields have been widely used to control neuronal activity. It is generally accepted that neuronal excitability is controlled by electric current that depolarizes or hyperpolarizes the excitable cell membrane. What determines the amount of polarization? Research on the mechanisms of electric stimulation focus on the optimal control of the field properties (frequency, amplitude, and direction of the electric currents) to improve stimulation outcomes. Emerging evidence from modeling and experimental studies support the existence of interactions between the targeted neurons and the externally-applied electric fields. With cell-field interaction, we suggest a two-way process. When a neuron is positioned inside an electric field, the electric field will induce a change in the resting membrane potential by superimposing an electrically-induced transmembrane potential (ITP). At the same time, the electric field can be perturbed and re-distributed by the cell. This cell-field interaction may play a significant role in the overall effects of stimulation. The redistributed field can cause secondary effects to neighboring cells by altering their geometrical pattern and amount of membrane polarization. Neurons excited by the externally-applied electric field can also affect neighboring cells by ephaptic interaction. Both aspects of the cell-field interaction depend on the biophysical properties of the neuronal tissue, including geometric (i.e., size, shape, orientation to the field) and electric (i.e., conductivity and dielectricity) attributes of the cells. The biophysical basis of the cell-field interaction can be explained by the electromagnetism theory. Further experimental and simulation studies on electric stimulation of neuronal tissue should consider the prospect of a cell-field interaction, and a better understanding of tissue inhomogeneity and anisotropy is needed to fully appreciate the neural

  5. Adult neuronal ceroid-lipofuscinosis.

    Science.gov (United States)

    Goebel, H H; Braak, H

    1989-01-01

    Among the different clinical forms of neuronal ceroid-lipofuscinosis (NCL), the adult type is the least frequent, most sporadic and most difficult one to diagnose. Clinical symptomatology differs from the classical childhood NCL forms in that ocular symptoms are absent while changes of behavior, dementia and seizures dominate the clinical picture. Excessive accumulation of NCL-specific lipopigments has largely been explored in the nervous system, where pigmento-architectonic investigations disclose layer-specific cortical pathology similar to but less pronounced than that of juvenile and protracted juvenile NCL. Ultrastructural analysis of lipopigments in adult NCL reveals diversity of lipopigment fine structure, but less impressive than in the childhood forms of NCL. Abnormal accretion of lipopigments outside the nervous system has rarely been demonstrated and requires ampler documentation, making in vivo diagnosis of adult NCL often difficult and sometimes equivocal. Adult NCL is now frequently considered identical to "Kufs' disease". However, in the past, the latter term has comprised a heterogeneous spectrum of lipidoses the NCL-nature of which had not been unequivocally established. Thus, one may either speak of "Kufs' syndrome" or abandon this term altogether. Although patients afflicted with adult NCL may suffer from Kufs' disease, not all who have and had Kufs disease may have or have had adult NCL. The current debate on adult NCL centers around scepticism concerning many of the earlier reports, on incorporating diagnostic studies of non-CNS organs in presumptive patients and on distinguishing adult NCL from "atypical" patients or forms of NCL, as well as other disorders marked by non-specific abnormal accumulation of lipofuscin.

  6. Neuronal Rho GTPase Rac1 elimination confers neuroprotection in a mouse model of permanent ischemic stroke

    DEFF Research Database (Denmark)

    Karabiyik, Cansu; Fernandes, Rui; Figueiredo, Francisco Rosário

    2018-01-01

    The Rho GTPase Rac1 is a multifunctional protein involved in distinct pathways ranging from development to pathology. The aim of the present study was to unravel the contribution of neuronal Rac1 in regulating the response to brain injury induced by permanent focal cerebral ischemia (pMCAO). Our ...

  7. Neuronal Rho GTPase Rac1 elimination confers neuroprotection in a mice model of permanent ischemic stroke

    DEFF Research Database (Denmark)

    Karabiyik, Cansu; Fernandes, Rui; Figueiredo, Francisci Rosário

    2017-01-01

    The Rho GTPase Rac1 is a multifunctional protein involved in distinct pathways ranging from development to pathology. The aim of the present study was to unravel the contribution of neuronal Rac1 in regulating the response to brain injury induced by permanent focal cerebral ischemia (pMCAO). Our ...

  8. Fast neuronal labeling in live tissue using a biocytin conjugated fluorescent probe

    DEFF Research Database (Denmark)

    Harsløf, Mads; Müller, Christoph Felix; Rohrberg, Julie

    2015-01-01

    of local synapses within 10min. TMR biocytin is fixable, stable during methyl salicylate clearing, and can be visualized deep in nervous tissue. COMPARISON WITH EXISTING METHODS: Retrograde labeling with TMR biocytin enables long-range neuronal visualization and concurrent calcium imaging after only a few...

  9. Knowledge Representation and Data Mining of Neuronal Morphologies Using Neuroinformatics Tools and Formal Ontologies

    Science.gov (United States)

    Polavaram, Sridevi

    2016-01-01

    Neuroscience can greatly benefit from using novel methods in computer science and informatics, which enable knowledge discovery in unexpected ways. Currently one of the biggest challenges in Neuroscience is to map the functional circuitry of the brain. The applications of this goal range from understanding structural reorganization of neurons to…

  10. Synchronization of Coupled Neurons Controlled by a Pacemaker

    International Nuclear Information System (INIS)

    Li Mei-Sheng; Zhang Hong-Hui; Zhao Yong; Shi Xia

    2011-01-01

    We investigate synchronization of Hindmarsh—Rose neurons with gap junctions under the control of a pacemaker. In a ring Hindmarsh—Rose neuronal network, the coupled neurons with the pacemaker can occur in synchronization more easily than those without the pacemaker. Furthermore, the pacemaker can induce phase synchronization or nearly-complete synchronization of nonidentical neurons. This synchronization can occur more easily when time delay is considered. Theses results can be helpful to understand the activities of the real neuronal system. (general)

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

    Science.gov (United States)

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

    2007-03-23

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

  12. Leptin signaling in GABA neurons, but not glutamate neurons, is required for reproductive function.

    Science.gov (United States)

    Zuure, Wieteke A; Roberts, Amy L; Quennell, Janette H; Anderson, Greg M

    2013-11-06

    The adipocyte-derived hormone leptin acts in the brain to modulate the central driver of fertility: the gonadotropin releasing hormone (GnRH) neuronal system. This effect is indirect, as GnRH neurons do not express leptin receptors (LEPRs). Here we test whether GABAergic or glutamatergic neurons provide the intermediate pathway between the site of leptin action and the GnRH neurons. Leptin receptors were deleted from GABA and glutamate neurons using Cre-Lox transgenics, and the downstream effects on puberty onset and reproduction were examined. Both mouse lines displayed the expected increase in body weight and region-specific loss of leptin signaling in the hypothalamus. The GABA neuron-specific LEPR knock-out females and males showed significantly delayed puberty onset. Adult fertility observations revealed that these knock-out animals have decreased fecundity. In contrast, glutamate neuron-specific LEPR knock-out mice displayed normal fertility. Assessment of the estrogenic hypothalamic-pituitary-gonadal axis regulation in females showed that leptin action on GABA neurons is not necessary for estradiol-mediated suppression of tonic luteinizing hormone secretion (an indirect measure of GnRH neuron activity) but is required for regulation of a full preovulatory-like luteinizing hormone surge. In conclusion, leptin signaling in GABAergic (but not glutamatergic neurons) plays a critical role in the timing of puberty onset and is involved in fertility regulation throughout adulthood in both sexes. These results form an important step in explaining the role of central leptin signaling in the reproductive system. Limiting the leptin-to-GnRH mediators to GABAergic cells will enable future research to focus on a few specific types of neurons.

  13. Injection of fully-defined signal mixtures: a novel high-throughput tool to study neuronal encoding and computations.

    Directory of Open Access Journals (Sweden)

    Vladimir Ilin

    Full Text Available Understanding of how neurons transform fluctuations of membrane potential, reflecting input activity, into spike responses, which communicate the ultimate results of single-neuron computation, is one of the central challenges for cellular and computational neuroscience. To study this transformation under controlled conditions, previous work has used a signal immersed in noise paradigm where neurons are injected with a current consisting of fluctuating noise that mimics on-going synaptic activity and a systematic signal whose transmission is studied. One limitation of this established paradigm is that it is designed to examine the encoding of only one signal under a specific, repeated condition. As a result, characterizing how encoding depends on neuronal properties, signal parameters, and the interaction of multiple inputs is cumbersome. Here we introduce a novel fully-defined signal mixture paradigm, which allows us to overcome these problems. In this paradigm, current for injection is synthetized as a sum of artificial postsynaptic currents (PSCs resulting from the activity of a large population of model presynaptic neurons. PSCs from any presynaptic neuron(s can be now considered as "signal", while the sum of all other inputs is considered as "noise". This allows us to study the encoding of a large number of different signals in a single experiment, thus dramatically increasing the throughput of data acquisition. Using this novel paradigm, we characterize the detection of excitatory and inhibitory PSCs from neuronal spike responses over a wide range of amplitudes and firing-rates. We show, that for moderately-sized neuronal populations the detectability of individual inputs is higher for excitatory than for inhibitory inputs during the 2-5 ms following PSC onset, but becomes comparable after 7-8 ms. This transient imbalance of sensitivity in favor of excitation may enhance propagation of balanced signals through neuronal networks. Finally, we

  14. Morphology, classification, and distribution of the projection neurons in the dorsal lateral geniculate nucleus of the rat.

    Directory of Open Access Journals (Sweden)

    Changying Ling

    Full Text Available The morphology of confirmed projection neurons in the dorsal lateral geniculate nucleus (dLGN of the rat was examined by filling these cells retrogradely with biotinylated dextran amine (BDA injected into the visual cortex. BDA-labeled projection neurons varied widely in the shape and size of their cell somas, with mean cross-sectional areas ranging from 60-340 µm(2. Labeled projection neurons supported 7-55 dendrites that spanned up to 300 µm in length and formed dendritic arbors with cross-sectional areas of up to 7.0 × 10(4 µm(2. Primary dendrites emerged from cell somas in three broad patterns. In some dLGN projection neurons, primary dendrites arise from the cell soma at two poles spaced approximately 180° apart. In other projection neurons, dendrites emerge principally from one side of the cell soma, while in a third group of projection neurons primary dendrites emerge from the entire perimeter of the cell soma. Based on these three distinct patterns in the distribution of primary dendrites from cell somas, we have grouped dLGN projection neurons into three classes: bipolar cells, basket cells and radial cells, respectively. The appendages seen on dendrites also can be grouped into three classes according to differences in their structure. Short "tufted" appendages arise mainly from the distal branches of dendrites; "spine-like" appendages, fine stalks with ovoid heads, typically are seen along the middle segments of dendrites; and "grape-like" appendages, short stalks that terminate in a cluster of ovoid bulbs, appear most often along the proximal segments of secondary dendrites of neurons with medium or large cell somas. While morphologically diverse dLGN projection neurons are intermingled uniformly throughout the nucleus, the caudal pole of the dLGN contains more small projection neurons of all classes than the rostral pole.

  15. Axonal and dendritic localization of mRNAs for glycogen-metabolizing enzymes in cultured rodent neurons.

    Science.gov (United States)

    Pfeiffer-Guglielmi, Brigitte; Dombert, Benjamin; Jablonka, Sibylle; Hausherr, Vanessa; van Thriel, Christoph; Schöbel, Nicole; Jansen, Ralf-Peter

    2014-06-04

    Localization of mRNAs encoding cytoskeletal or signaling proteins to neuronal processes is known to contribute to axon growth, synaptic differentiation and plasticity. In addition, a still increasing spectrum of mRNAs has been demonstrated to be localized under different conditions and developing stages thus reflecting a highly regulated mechanism and a role of mRNA localization in a broad range of cellular processes. Applying fluorescence in-situ-hybridization with specific riboprobes on cultured neurons and nervous tissue sections, we investigated whether the mRNAs for two metabolic enzymes, namely glycogen synthase (GS) and glycogen phosphorylase (GP), the key enzymes of glycogen metabolism, may also be targeted to neuronal processes. If it were so, this might contribute to clarify the so far enigmatic role of neuronal glycogen. We found that the mRNAs for both enzymes are localized to axonal and dendritic processes in cultured lumbar spinal motoneurons, but not in cultured trigeminal neurons. In cultured cortical neurons which do not store glycogen but nevertheless express glycogen synthase, the GS mRNA is also subject to axonal and dendritic localization. In spinal motoneurons and trigeminal neurons in situ, however, the mRNAs could only be demonstrated in the neuronal somata but not in the nerves. We could demonstrate that the mRNAs for major enzymes of neural energy metabolism can be localized to neuronal processes. The heterogeneous pattern of mRNA localization in different culture types and developmental stages stresses that mRNA localization is a versatile mechanism for the fine-tuning of cellular events. Our findings suggest that mRNA localization for enzymes of glycogen metabolism could allow adaptation to spatial and temporal energy demands in neuronal events like growth, repair and synaptic transmission.

  16. 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.

  17. Resveratrol stimulates AMP kinase activity in neurons.

    Science.gov (United States)

    Dasgupta, Biplab; Milbrandt, Jeffrey

    2007-04-24

    Resveratrol is a polyphenol produced by plants that has multiple beneficial activities similar to those associated with caloric restriction (CR), such as increased life span and delay in the onset of diseases associated with aging. CR improves neuronal health, and the global beneficial effects of CR have been postulated to be mediated by the nervous system. One key enzyme thought to be activated during CR is the AMP-activated kinase (AMPK), a sensor of cellular energy levels. AMPK is activated by increases in the cellular AMP:ATP ratio, whereupon it functions to help preserve cellular energy. In this regard, the regulation of dietary food intake by hypothalamic neurons is mediated by AMPK. The suppression of nonessential energy expenditure by activated AMPK along with the CR mimetic and neuroprotective properties of resveratrol led us to hypothesize that neuronal activation of AMPK could be an important component of resveratrol activity. Here, we show that resveratrol activated AMPK in Neuro2a cells and primary neurons in vitro as well as in the brain. Resveratrol and the AMPK-activating compound 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) promoted robust neurite outgrowth in Neuro2a cells, which was blocked by genetic and pharmacologic inhibition of AMPK. Resveratrol also stimulated mitochondrial biogenesis in an AMPK-dependent manner. Resveratrol-stimulated AMPK activity in neurons depended on LKB1 activity but did not require the NAD-dependent protein deacetylase SIRT1 during this time frame. These findings suggest that neuronal activation of AMPK by resveratrol could affect neuronal energy homeostasis and contribute to the neuroprotective effects of resveratrol.

  18. 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.

  19. Bax regulates neuronal Ca2+ homeostasis.

    Science.gov (United States)

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

    2015-01-28

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

  20. Estradiol Protects Proopiomelanocortin Neurons Against Insulin Resistance.

    Science.gov (United States)

    Qiu, Jian; Bosch, Martha A; Meza, Cecilia; Navarro, Uyen-Vy; Nestor, Casey C; Wagner, Edward J; Rønnekleiv, Oline K; Kelly, Martin J

    2018-02-01

    Insulin resistance is at the core of the metabolic syndrome, and men exhibit a higher incidence of metabolic syndrome than women in early adult life, but this sex advantage diminishes sharply when women reach the postmenopausal state. Because 17β-estradiol (E2) augments the excitability of the anorexigenic proopiomelanocortin (POMC) neurons, we investigated the neuroprotective effects of E2 against insulin resistance in POMC neurons from diet-induced obese (DIO) female and male mice. The efficacy of insulin to activate canonical transient receptor potential 5 (TRPC5) channels and depolarize POMC neurons was significantly reduced in DIO male mice but not in DIO female mice. However, the insulin response in POMC neurons was abrogated in ovariectomized DIO females but restored with E2 replacement. E2 increased T-type calcium channel Cav3.1 messenger RNA (mRNA) expression and whole-cell currents but downregulated stromal-interaction molecule 1 mRNA, which rendered POMC neurons more excitable and responsive to insulin-mediated TRPC5 channel activation. Moreover, E2 prevented the increase in suppressor of cytokine signaling-3 mRNA expression with DIO as seen in DIO males. As proof of principle, insulin [intracerebroventricular injection into the third ventricle (ICV)] decreased food intake and increased metabolism in female but not male guinea pigs fed a high-fat diet. The uncoupling of the insulin receptor from its downstream effector system was corroborated by the reduced expression of phosphorylated protein kinase B in the arcuate nucleus of male but not female guinea pigs following insulin. Therefore, E2 protects female POMC neurons from insulin resistance by enhancing POMC neuronal excitability and the coupling of insulin receptor to TRPC5 channel activation. Copyright © 2018 Endocrine Society.

  1. Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro

    NARCIS (Netherlands)

    Bardy, C.; Hurk, M. van den; Eames, T.; Marchand, C.; Hernandez, R.V.; Kellogg, M.; Gorris, M.A.J.; Galet, B.; Palomares, V.; Brown, J.; Bang, A.G.; Mertens, J.; Bohnke, L.; Boyer, L.; Simon, S.; Gage, F.H.

    2015-01-01

    Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely

  2. 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.

  3. Transgenic tools to characterize neuronal properties of discrete populations of zebrafish neurons.

    Science.gov (United States)

    Satou, Chie; Kimura, Yukiko; Hirata, Hiromi; Suster, Maximiliano L; Kawakami, Koichi; Higashijima, Shin-ichi

    2013-09-01

    The developing nervous system consists of a variety of cell types. Transgenic animals expressing reporter genes in specific classes of neuronal cells are powerful tools for the study of neuronal network formation. We generated a wide variety of transgenic zebrafish that expressed reporter genes in specific classes of neurons or neuronal progenitors. These include lines in which neurons of specific neurotransmitter phenotypes expressed fluorescent proteins or Gal4, and lines in which specific subsets of the dorsal progenitor domain in the spinal cord expressed fluorescent proteins. Using these, we examined domain organization in the developing dorsal spinal cord, and found that there are six progenitor domains in zebrafish, which is similar to the domain organization in mice. We also systematically characterized neurotransmitter properties of the neurons that are produced from each domain. Given that reporter gene expressions occurs in a wide area of the nervous system in the lines generated, these transgenic fish should serve as powerful tools for the investigation of not only the neurons in the dorsal spinal cord but also neuronal structures and functions in many other regions of the nervous system.

  4. CRISPR Epigenome Editing of AKAP150 in DRG Neurons Abolishes Degenerative IVD-Induced Neuronal Activation.

    Science.gov (United States)

    Stover, Joshua D; Farhang, Niloofar; Berrett, Kristofer C; Gertz, Jason; Lawrence, Brandon; Bowles, Robby D

    2017-09-06

    Back pain is a major contributor to disability and has significant socioeconomic impacts worldwide. The degenerative intervertebral disc (IVD) has been hypothesized to contribute to back pain, but a better understanding of the interactions between the degenerative IVD and nociceptive neurons innervating the disc and treatment strategies that directly target these interactions is needed to improve our understanding and treatment of back pain. We investigated degenerative IVD-induced changes to dorsal root ganglion (DRG) neuron activity and utilized CRISPR epigenome editing as a neuromodulation strategy. By exposing DRG neurons to degenerative IVD-conditioned media under both normal and pathological IVD pH levels, we demonstrate that degenerative IVDs trigger interleukin (IL)-6-induced increases in neuron activity to thermal stimuli, which is directly mediated by AKAP and enhanced by acidic pH. Utilizing this novel information on AKAP-mediated increases in nociceptive neuron activity, we developed lentiviral CRISPR epigenome editing vectors that modulate endogenous expression of AKAP150 by targeted promoter histone methylation. When delivered to DRG neurons, these epigenome-modifying vectors abolished degenerative IVD-induced DRG-elevated neuron activity while preserving non-pathologic neuron activity. This work elucidates the potential for CRISPR epigenome editing as a targeted gene-based pain neuromodulation strategy. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

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

    NARCIS (Netherlands)

    H. Peng (Hanchuan); M. Hawrylycz (Michael); J. Roskams (Jane); S. Hill (Sean); N. Spruston (Nelson); E. Meijering (Erik); G.A. Ascoli (Giorgio A.)

    2015-01-01

    textabstractUnderstanding the structure of single neurons is critical for understanding how they function within neural circuits. BigNeuron is a new community effort that combines modern bioimaging informatics, recent leaps in labeling and microscopy, and the widely recognized need for openness and

  6. Optogenetic identification of hypothalamic orexin neuron projections to paraventricular spinally projecting neurons.

    Science.gov (United States)

    Dergacheva, Olga; Yamanaka, Akihiro; Schwartz, Alan R; Polotsky, Vsevolod Y; Mendelowitz, David

    2017-04-01

    Orexin neurons, and activation of orexin receptors, are generally thought to be sympathoexcitatory; however, the functional connectivity between orexin neurons and a likely sympathetic target, the hypothalamic spinally projecting neurons (SPNs) in the paraventricular nucleus of the hypothalamus (PVN) has not been established. To test the hypothesis that orexin neurons project directly to SPNs in the PVN, channelrhodopsin-2 (ChR2) was selectively expressed in orexin neurons to enable photoactivation of ChR2-expressing fibers while examining evoked postsynaptic currents in SPNs in rat hypothalamic slices. Selective photoactivation of orexin fibers elicited short-latency postsynaptic currents in all SPNs tested ( n = 34). These light-triggered responses were heterogeneous, with a majority being excitatory glutamatergic responses (59%) and a minority of inhibitory GABAergic (35%) and mixed glutamatergic and GABAergic currents (6%). Both glutamatergic and GABAergic responses were present in the presence of tetrodotoxin and 4-aminopyridine, suggesting a monosynaptic connection between orexin neurons and SPNs. In addition to generating postsynaptic responses, photostimulation facilitated action potential firing in SPNs (current clamp configuration). Glutamatergic, but not GABAergic, postsynaptic currents were diminished by application of the orexin receptor antagonist almorexant, indicating orexin release facilitates glutamatergic neurotransmission in this pathway. This work identifies a neuronal circuit by which orexin neurons likely exert sympathoexcitatory control of cardiovascular function. NEW & NOTEWORTHY This is the first study to establish, using innovative optogenetic approaches in a transgenic rat model, that there are robust heterogeneous projections from orexin neurons to paraventricular spinally projecting neurons, including excitatory glutamatergic and inhibitory GABAergic neurotransmission. Endogenous orexin release modulates glutamatergic, but not

  7. Crosstalks between kisspeptin neurons and somatostatin neurons are not photoperiod dependent in the ewe hypothalamus.

    Science.gov (United States)

    Dufourny, Laurence; Lomet, Didier

    2017-12-01

    Seasonal reproduction is under the control of gonadal steroid feedback, itself synchronized by day-length or photoperiod. As steroid action on GnRH neurons is mostly indirect and therefore exerted through interneurons, we looked for neuroanatomical interactions between kisspeptin (KP) neurons and somatostatin (SOM) neurons, two populations targeted by sex steroids, in three diencephalic areas involved in the central control of ovulation and/or sexual behavior: the arcuate nucleus (ARC), the preoptic area (POA) and the ventrolateral part of the ventromedial hypothalamus (VMHvl). KP is the most potent secretagogue of GnRH secretion while SOM has been shown to centrally inhibit LH pulsatile release. Notably, hypothalamic contents of these two neuropeptides vary with photoperiod in specific seasonal species. Our hypothesis is that SOM inhibits KP neuron activity and therefore indirectly modulate GnRH release and that this effect may be seasonally regulated. We used sections from ovariectomized estradiol-replaced ewes killed after photoperiodic treatment mimicking breeding or anestrus season. We performed triple immunofluorescent labeling to simultaneously detect KP, SOM and synapsin, a marker for synaptic vesicles. Sections from the POA and from the mediobasal hypothalamus were examined using a confocal microscope. Randomly selected KP or SOM neurons were observed in the POA and ARC. SOM neurons were also observed in the VMHvl. In both the ARC and POA, nearly all KP neurons presented numerous SOM contacts. SOM neurons presented KP terminals more frequently in the ARC than in the POA and VMHvl. Quantitative analysis failed to demonstrate major seasonal variations of KP and SOM interactions. Our data suggest a possible inhibitory action of SOM on all KP neurons in both photoperiodic statuses. On the other hand, the physiological significance of KP modulation of SOM neuron activity and vice versa remain to be determined. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. PCB 136 Atropselectively Alters Morphometric and Functional Parameters of Neuronal Connectivity in Cultured Rat Hippocampal Neurons via Ryanodine Receptor-Dependent Mechanisms

    Science.gov (United States)

    Yang, Dongren; Kania-Korwel, Izabela; Ghogha, Atefeh; Chen, Hao; Stamou, Marianna; Bose, Diptiman D.; Pessah, Isaac N.; Lehmler, Hans-Joachim; Lein, Pamela J.

    2014-01-01

    We recently demonstrated that polychlorinated biphenyl (PCB) congeners with multiple ortho chlorine substitutions sensitize ryanodine receptors (RyRs), and this activity promotes Ca2+-dependent dendritic growth in cultured neurons. Many ortho-substituted congeners display axial chirality, and we previously reported that the chiral congener PCB 136 (2,2′,3,3′,6,6′-hexachlorobiphenyl) atropselectively sensitizes RyRs. Here, we test the hypothesis that PCB 136 atropisomers differentially alter dendritic growth and other parameters of neuronal connectivity influenced by RyR activity. (−)-PCB 136, which potently sensitizes RyRs, enhances dendritic growth in primary cultures of rat hippocampal neurons, whereas (+)-PCB 136, which lacks RyR activity, has no effect on dendritic growth. The dendrite-promoting activity of (−)-PCB 136 is observed at concentrations ranging from 0.1 to 100nM and is blocked by pharmacologic RyR antagonism. Neither atropisomer alters axonal growth or cell viability. Quantification of PCB 136 atropisomers in hippocampal cultures indicates that atropselective effects on dendritic growth are not due to differential partitioning of atropisomers into cultured cells. Imaging of hippocampal neurons loaded with Ca2+-sensitive dye demonstrates that (−)-PCB 136 but not (+)-PCB 136 increases the frequency of spontaneous Ca2+ oscillations. Similarly, (−)-PCB 136 but not (+)-PCB 136 increases the activity of hippocampal neurons plated on microelectrode arrays. These data support the hypothesis that atropselective effects on RyR activity translate into atropselective effects of PCB 136 atropisomers on neuronal connectivity, and suggest that the variable atropisomeric enrichment of chiral PCBs observed in the human population may be a significant determinant of individual susceptibility for adverse neurodevelopmental outcomes following PCB exposure. PMID:24385416

  9. Binding by asynchrony: the neuronal phase code

    Directory of Open Access Journals (Sweden)

    Zoltan Nadasdy

    2010-09-01

    Full Text Available Neurons display continuous subthreshold oscillations and discrete action potentials. When action potentials are phase-locked to the subthreshold oscillation, we hypothesize they represent two types of information: the presence/absence of a sensory feature and the phase of subthreshold oscillation. If subthreshold oscillation phases are neuron-specific, then the sources of action potentials can be recovered based on the action potential times. If the spatial information about the stimulus is converted to action potential phases, then action potentials from multiple neurons can be combined into a single axon and the spatial configuration reconstructed elsewhere. For the reconstruction to be successful, we introduce two assumptions: that a subthreshold oscillation field has a constant phase gradient and that coincidences between action potentials and intracellular subthreshold oscillations are neuron-specific as defined by the "interference principle." Under these assumptions, a phase coding model enables information transfer between structures and reproduces experimental phenomenons such as phase precession, grid cell architecture, and phase modulation of cortical spikes. This article reviews a recently proposed neuronal algorithm for information encoding and decoding from the phase of action potentials (Nadasdy 2009. The focus is given to the principles common across different systems instead of emphasizing system specific differences.

  10. Synchronous behavior of two coupled electronic neurons

    International Nuclear Information System (INIS)

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

    2000-01-01

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

  11. Bursting synchronization in clustered neuronal networks

    International Nuclear Information System (INIS)

    Yu Hai-Tao; Wang Jiang; Deng Bin; Wei Xi-Le

    2013-01-01

    Neuronal networks in the brain exhibit the modular (clustered) property, i.e., they are composed of certain subnetworks with differential internal and external connectivity. We investigate bursting synchronization in a clustered neuronal network. A transition to mutual-phase synchronization takes place on the bursting time scale of coupled neurons, while on the spiking time scale, they behave asynchronously. This synchronization transition can be induced by the variations of inter- and intracoupling strengths, as well as the probability of random links between different subnetworks. Considering that some pathological conditions are related with the synchronization of bursting neurons in the brain, we analyze the control of bursting synchronization by using a time-periodic external signal in the clustered neuronal network. Simulation results show a frequency locking tongue in the driving parameter plane, where bursting synchronization is maintained, even in the presence of external driving. Hence, effective synchronization suppression can be realized with the driving parameters outside the frequency locking region. (interdisciplinary physics and related areas of science and technology)

  12. Epigenetic Basis of Neuronal and Synaptic Plasticity.

    Science.gov (United States)

    Karpova, Nina N; Sales, Amanda J; Joca, Samia R

    2017-01-01

    Neuronal network and plasticity change as a function of experience. Altered neural connectivity leads to distinct transcriptional programs of neuronal plasticity-related genes. The environmental challenges throughout life may promote long-lasting reprogramming of gene expression and the development of brain disorders. The modifications in neuronal epigenome mediate gene-environmental interactions and are required for activity-dependent regulation of neuronal differentiation, maturation and plasticity. Here, we highlight the latest advances in understanding the role of the main players of epigenetic machinery (DNA methylation and demethylation, histone modifications, chromatin-remodeling enzymes, transposons, and non-coding RNAs) in activity-dependent and long- term neural and synaptic plasticity. The review focuses on both the transcriptional and post-transcriptional regulation of gene expression levels, including the processes of promoter activation, alternative splicing, regulation of stability of gene transcripts by natural antisense RNAs, and alternative polyadenylation. Further, we discuss the epigenetic aspects of impaired neuronal plasticity and the pathogenesis of neurodevelopmental (Rett syndrome, Fragile X Syndrome, genomic imprinting disorders, schizophrenia, and others), stressrelated (mood disorders) and neurodegenerative Alzheimer's, Parkinson's and Huntington's disorders. The review also highlights the pharmacological compounds that modulate epigenetic programming of gene expression, the potential treatment strategies of discussed brain disorders, and the questions that should be addressed during the development of effective and safe approaches for the treatment of brain disorders.

  13. Spin orbit torque based electronic neuron

    Energy Technology Data Exchange (ETDEWEB)

    Sengupta, Abhronil, E-mail: asengup@purdue.edu; Choday, Sri Harsha; Kim, Yusung; Roy, Kaushik [School of Electrical and Computer Engineering, Purdue University, West Lafayette, Indiana 47907 (United States)

    2015-04-06

    A device based on current-induced spin-orbit torque (SOT) that functions as an electronic neuron is proposed in this work. The SOT device implements an artificial neuron's thresholding (transfer) function. In the first step of a two-step switching scheme, a charge current places the magnetization of a nano-magnet along the hard-axis, i.e., an unstable point for the magnet. In the second step, the SOT device (neuron) receives a current (from the synapses) which moves the magnetization from the unstable point to one of the two stable states. The polarity of the synaptic current encodes the excitatory and inhibitory nature of the neuron input and determines the final orientation of the magnetization. A resistive crossbar array, functioning as synapses, generates a bipolar current that is a weighted sum of the inputs. The simulation of a two layer feed-forward artificial neural network based on the SOT electronic neuron shows that it consumes ∼3× lower power than a 45 nm digital CMOS implementation, while reaching ∼80% accuracy in the classification of 100 images of handwritten digits from the MNIST dataset.

  14. Spin orbit torque based electronic neuron

    International Nuclear Information System (INIS)

    Sengupta, Abhronil; Choday, Sri Harsha; Kim, Yusung; Roy, Kaushik

    2015-01-01

    A device based on current-induced spin-orbit torque (SOT) that functions as an electronic neuron is proposed in this work. The SOT device implements an artificial neuron's thresholding (transfer) function. In the first step of a two-step switching scheme, a charge current places the magnetization of a nano-magnet along the hard-axis, i.e., an unstable point for the magnet. In the second step, the SOT device (neuron) receives a current (from the synapses) which moves the magnetization from the unstable point to one of the two stable states. The polarity of the synaptic current encodes the excitatory and inhibitory nature of the neuron input and determines the final orientation of the magnetization. A resistive crossbar array, functioning as synapses, generates a bipolar current that is a weighted sum of the inputs. The simulation of a two layer feed-forward artificial neural network based on the SOT electronic neuron shows that it consumes ∼3× lower power than a 45 nm digital CMOS implementation, while reaching ∼80% accuracy in the classification of 100 images of handwritten digits from the MNIST dataset

  15. Large-scale modelling of neuronal systems

    International Nuclear Information System (INIS)

    Castellani, G.; Verondini, E.; Giampieri, E.; Bersani, F.; Remondini, D.; Milanesi, L.; Zironi, I.

    2009-01-01

    The brain is, without any doubt, the most, complex system of the human body. Its complexity is also due to the extremely high number of neurons, as well as the huge number of synapses connecting them. Each neuron is capable to perform complex tasks, like learning and memorizing a large class of patterns. The simulation of large neuronal systems is challenging for both technological and computational reasons, and can open new perspectives for the comprehension of brain functioning. A well-known and widely accepted model of bidirectional synaptic plasticity, the BCM model, is stated by a differential equation approach based on bistability and selectivity properties. We have modified the BCM model extending it from a single-neuron to a whole-network model. This new model is capable to generate interesting network topologies starting from a small number of local parameters, describing the interaction between incoming and outgoing links from each neuron. We have characterized this model in terms of complex network theory, showing how this, learning rule can be a support For network generation.

  16. Memristors Empower Spiking Neurons With Stochasticity

    KAUST Repository

    Al-Shedivat, Maruan

    2015-06-01

    Recent theoretical studies have shown that probabilistic spiking can be interpreted as learning and inference in cortical microcircuits. This interpretation creates new opportunities for building neuromorphic systems driven by probabilistic learning algorithms. However, such systems must have two crucial features: 1) the neurons should follow a specific behavioral model, and 2) stochastic spiking should be implemented efficiently for it to be scalable. This paper proposes a memristor-based stochastically spiking neuron that fulfills these requirements. First, the analytical model of the memristor is enhanced so it can capture the behavioral stochasticity consistent with experimentally observed phenomena. The switching behavior of the memristor model is demonstrated to be akin to the firing of the stochastic spike response neuron model, the primary building block for probabilistic algorithms in spiking neural networks. Furthermore, the paper proposes a neural soma circuit that utilizes the intrinsic nondeterminism of memristive switching for efficient spike generation. The simulations and analysis of the behavior of a single stochastic neuron and a winner-take-all network built of such neurons and trained on handwritten digits confirm that the circuit can be used for building probabilistic sampling and pattern adaptation machinery in spiking networks. The findings constitute an important step towards scalable and efficient probabilistic neuromorphic platforms. © 2011 IEEE.

  17. Neuronal replacement therapy: previous achievements and challenges ahead

    Science.gov (United States)

    Grade, Sofia; Götz, Magdalena

    2017-10-01

    Lifelong neurogenesis and incorporation of newborn neurons into mature neuronal circuits operates in specialized niches of the mammalian brain and serves as role model for neuronal replacement strategies. However, to which extent can the remaining brain parenchyma, which never incorporates new neurons during the adulthood, be as plastic and readily accommodate neurons in networks that suffered neuronal loss due to injury or neurological disease? Which microenvironment is permissive for neuronal replacement and synaptic integration and which cells perform best? Can lost function be restored and how adequate is the participation in the pre-existing circuitry? Could aberrant connections cause malfunction especially in networks dominated by excitatory neurons, such as the cerebral cortex? These questions show how important connectivity and circuitry aspects are for regenerative medicine, which is the focus of this review. We will discuss the impressive advances in neuronal replacement strategies and success from exogenous as well as endogenous cell sources. Both have seen key novel technologies, like the groundbreaking discovery of induced pluripotent stem cells and direct neuronal reprogramming, offering alternatives to the transplantation of fetal neurons, and both herald great expectations. For these to become reality, neuronal circuitry analysis is key now. As our understanding of neuronal circuits increases, neuronal replacement therapy should fulfill those prerequisites in network structure and function, in brain-wide input and output. Now is the time to incorporate neural circuitry research into regenerative medicine if we ever want to truly repair brain injury.

  18. Autapse-induced synchronization in a coupled neuronal network

    International Nuclear Information System (INIS)

    Ma, Jun; Song, Xinlin; Jin, Wuyin; Wang, Chuni

    2015-01-01

    Highlights: • The functional effect of autapse on neuronal activity is detected. • Autapse driving plays active role in regulating electrical activities as pacemaker. • It confirms biological experimental results for rhythm synchronization between heterogeneous cells. - Abstract: The effect of autapse on coupled neuronal network is detected. In our studies, three identical neurons are connected with ring type and autapse connected to one neuron of the network. The autapse connected to neuron can impose time-delayed feedback in close loop on the neuron thus the dynamics of membrane potentials can be changed. Firstly, the effect of autapse driving on single neuron is confirmed that negative feedback can calm down the neuronal activity while positive feedback can excite the neuronal activity. Secondly, the collective electrical behaviors of neurons are regulated by a pacemaker, which associated with the autapse forcing. By using appropriate gain and time delay in the autapse, the neurons can reach synchronization and the membrane potentials of all neurons can oscillate with the same rhythm under mutual coupling. It indicates that autapse forcing plays an important role in changing the collective electric activities of neuronal network, and appropriate electric modes can be selected due to the switch of feedback type(positive or negative) in autapse. And the autapse-induced synchronization in network is also consistent with some biological experiments about synchronization between nonidentical neurons.

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

    Science.gov (United States)

    Sabado, Virginie; Vienne, Ludovic; Nagoshi, Emi

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Virginie Sabado

    2017-10-01

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

  1. Shenfu injection attenuates neurotoxicity of bupivacaine in cultured mouse spinal cord neurons

    Institute of Scientific and Technical Information of China (English)

    XIONG Li-ze; WANG Qiang; LIU Mu-yun; PENG Ye; LI Qing-bo; LU Zhi-hong; LEI Chong

    2007-01-01

    Background Our previous in vivo study in the rat demonstrates that Shenfu injection, a clinically used extract preparation from Chinese herbs, attenuates neural and cardiac toxicity induced by intravenous infusion of bupivacaine, a local anesthetic. This study was designed to investigate whether bupivacaine could induce a toxic effect in primary cultured mouse spinal cord neuron and if so, whether the Shenfu injection had a similar neuroprotective effect in the cell model. Methods The spinal cords from 11- to 14-day-old fetal mice were minced and incubated. Cytarabine was added into the medium to inhibit the proliferation of non-neuronal cells. The immunocytochemical staining of β-tubulin was used to determine the identity of cultured cells. The cultured neurons were randomly assigned into three sets treated with various doses of bupivacaine, Shenfu and bupivacaine+Shenfu, for 48 hours respectively. Cell viability in each group was analyzed by methyl thiazoleterazolium (MTT) assay. Results The viability of the cultured neurons treated with bupivacaine at concentrations of 0.01%, 0.02%, 0.04% and 0.08% was decreased in a dose-dependent manner. Although the Shenfu injection at concentrations ranging from 1/50 to 1/12.5 (V/V) had no significant influence on the viability of cultured neurons (P<0.05 vs control), the injection significantly increased the cellular viability of cultured neurons pretreated with 0.03% bupivacaine (P<0.05). Conclusion Although Shenfu injection itself has no effect on spinal neurons, it was able to reduce the bupivacaine induced neurotoxicity in vitro.

  2. Peroxiredoxin distribution in the mouse brain with emphasis on neuronal populations affected in neurodegenerative disorders.

    Science.gov (United States)

    Goemaere, Julie; Knoops, Bernard

    2012-02-01

    Redox changes are observed in neurodegenerative diseases, ranging from increased levels of reactive oxygen/nitrogen species and disturbance of antioxidant systems, to nitro-oxidative damage. By reducing hydrogen peroxide, peroxynitrite, and organic hydroperoxides, peroxiredoxins (Prdxs) represent a major potential protective barrier against nitro-oxidative insults in the brain. While recent works have investigated the putative role of Prdxs in neurodegenerative disorders, less is known about their expression in the healthy brain. Here we used immunohistochemistry to map basal expression of Prdxs throughout C57BL/6 mouse brain. We first confirmed the neuronal localization of Prdx2-5 and the glial expression of Prdx1, Prdx4, and Prdx6. Then we performed an in-depth analysis of neuronal Prdx distribution in the brain. Our results show that Prdx2-5 are widely detected in the different neuronal populations, and especially well expressed in the olfactory bulb, in the cerebral cortex, in pons nuclei, in the red nucleus, in all cranial nerve nuclei, in the cerebellum, and in motor neurons of the spinal cord. In contrast, Prdx expression is very low in the dopaminergic neurons of substantia nigra pars compacta and in the CA1/2 pyramidal cells of hippocampus. This low basal expression may contribute to the vulnerability of these neurons to nitro-oxidative attacks occurring in Parkinson's disease and Alzheimer's disease. In addition, we found that Prdx expression levels are unevenly distributed among neurons of a determined region and that distinct regional patterns of expression are observed between isoforms, reinforcing the hypothesis of the nonredundant function of Prdxs. Copyright © 2011 Wiley-Liss, Inc.

  3. Prostaglandin E2 facilitates neurite outgrowth in a motor neuron-like cell line, NSC-34

    Directory of Open Access Journals (Sweden)

    Hiroshi Nango

    2017-10-01

    Full Text Available Prostaglandin E2 (PGE2 exerts various biological effects by binding to E-prostanoid receptors (EP1-4. Although recent studies have shown that PGE2 induces cell differentiation in some neuronal cells such as mouse DRG neurons and sensory neuron-like ND7/23 cells, it is unclear whether PGE2 plays a role in differentiation of motor neurons. In the present study, we investigated the mechanism of PGE2-induced differentiation of motor neurons using NSC-34, a mouse motor neuron-like cell line. Exposure of undifferentiated NSC-34 cells to PGE2 and butaprost, an EP2-selective agonist, resulted in a reduction of MTT reduction activity without increase the number of propidium iodide-positive cells and in an increase in the number of neurite-bearing cells. Sulprostone, an EP1/3 agonist, also significantly lowered MTT reduction activity by 20%; however, no increase in the number of neurite-bearing cells was observed within the concentration range tested. PGE2-induced neurite outgrowth was attenuated significantly in the presence of PF-0441848, an EP2-selective antagonist. Treatment of these cells with dibutyryl-cAMP increased the number of neurite-bearing cells with no effect on cell proliferation. These results suggest that PGE2 promotes neurite outgrowth and suppresses cell proliferation by activating the EP2 subtype, and that the cAMP-signaling pathway is involved in PGE2-induced differentiation of NSC-34 cells. Keywords: Prostaglandin E2, E-prostanoid receptors, Motor neuron, Neurite outgrowth, cAMP

  4. Impacts of brain serotonin deficiency following Tph2 inactivation on development and raphe neuron serotonergic specification.

    Directory of Open Access Journals (Sweden)

    Lise Gutknecht

    Full Text Available Brain serotonin (5-HT is implicated in a wide range of functions from basic physiological mechanisms to complex behaviors, including neuropsychiatric conditions, as well as in developmental processes. Increasing evidence links 5-HT signaling alterations during development to emotional dysregulation and psychopathology in adult age. To further analyze the importance of brain 5-HT in somatic and brain development and function, and more specifically differentiation and specification of the serotonergic system itself, we generated a mouse model with brain-specific 5-HT deficiency resulting from a genetically driven constitutive inactivation of neuronal tryptophan hydroxylase-2 (Tph2. Tph2 inactivation (Tph2-/- resulted in brain 5-HT deficiency leading to growth retardation and persistent leanness, whereas a sex- and age-dependent increase in body weight was observed in Tph2+/- mice. The conserved expression pattern of the 5-HT neuron-specific markers (except Tph2 and 5-HT demonstrates that brain 5-HT synthesis is not a prerequisite for the proliferation, differentiation and survival of raphe neurons subjected to the developmental program of serotonergic specification. Furthermore, although these neurons are unable to synthesize 5-HT from the precursor tryptophan, they still display electrophysiological properties characteristic of 5-HT neurons. Moreover, 5-HT deficiency induces an up-regulation of 5-HT(1A and 5-HT(1B receptors across brain regions as well as a reduction of norepinephrine concentrations accompanied by a reduced number of noradrenergic neurons. Together, our results characterize developmental, neurochemical, neurobiological and electrophysiological consequences of brain-specific 5-HT deficiency, reveal a dual dose-dependent role of 5-HT in body weight regulation and show that differentiation of serotonergic neuron phenotype is independent from endogenous 5-HT synthesis.

  5. Comparative neuronal morphology of the cerebellar cortex in afrotherians, carnivores, cetartiodactyls, and primates

    Directory of Open Access Journals (Sweden)

    Bob eJacobs

    2014-04-01

    Full Text Available Although the basic morphological characteristics of neurons in the cerebellar cortex have been documented in several species, virtually nothing is known about the quantitative morphological characteristics of these neurons across different taxa. To that end, the present study investigated cerebellar neuronal morphology among eight different, large-brained mammalian species comprising a broad phylogenetic range: afrotherians (African elephant, Florida manatee, carnivores (Siberian tiger, clouded leopard, cetartiodactyls (humpback whale, giraffe and primates (human, common chimpanzee. Specifically, several neuron types (e.g., stellate, basket, Lugaro, Golgi, and granule neurons; N = 317 of the cerebellar cortex were stained with a modified rapid Golgi technique and quantified on a computer-assisted microscopy system. There was a 64-fold variation in brain mass across species in our sample (from clouded leopard to the elephant and a 103-fold variation in cerebellar volume. Most dendritic measures tended to increase with cerebellar volume. The cerebellar cortex in these species exhibited the trilaminate pattern common to all mammals. Morphologically, neuron types in the cerebellar cortex were generally consistent with those described in primates (Fox et al., 1967 and rodents (Palay and Chan-Palay, 1974, although there was substantial quantitative variation across species. In particular, Lugaro neurons in the elephant appeared to be disproportionately larger than those in other species. To explore potential quantitative differences in dendritic measures across species, MARSplines analyses were used to evaluate whether species could be differentiated from each other based on dendritic characteristics alone. Results of these analyses indicated that there were significant differences among all species in dendritic measures.

  6. The effect of noise correlations in populations of diversely tuned neurons.

    Science.gov (United States)

    Ecker, Alexander S; Berens, Philipp; Tolias, Andreas S; Bethge, Matthias

    2011-10-05

    The amount of information encoded by networks of neurons critically depends on the correlation structure of their activity. Neurons with similar stimulus preferences tend to have higher noise correlations than others. In homogeneous populations of neurons, this limited range correlation structure is highly detrimental to the accuracy of a population code. Therefore, reduced spike count correlations under attention, after adaptation, or after learning have been interpreted as evidence for a more efficient population code. Here, we analyze the role of limited range correlations in more realistic, heterogeneous population models. We use Fisher information and maximum-likelihood decoding to show that reduced correlations do not necessarily improve encoding accuracy. In fact, in populations with more than a few hundred neurons, increasing the level of limited range correlations can substantially improve encoding accuracy. We found that this improvement results from a decrease in noise entropy that is associated with increasing correlations if the marginal distributions are unchanged. Surprisingly, for constant noise entropy and in the limit of large populations, the encoding accuracy is independent of both structure and magnitude of noise correlations.

  7. Transgenic Mouse Lines Subdivide External Segment of the Globus Pallidus (GPe) Neurons and Reveal Distinct GPe Output Pathways

    Science.gov (United States)

    Mastro, Kevin J.; Bouchard, Rachel S.; Holt, Hiromi A. K.

    2014-01-01

    Cell-type diversity in the brain enables the assembly of complex neural circuits, whose organization and patterns of activity give rise to brain function. However, the identification of distinct neuronal populations within a given brain region is often complicated by a lack of objective criteria to distinguish one neuronal population from another. In the external segment of the globus pallidus (GPe), neuronal populations have been defined using molecular, anatomical, and electrophysiological criteria, but these classification schemes are often not generalizable across preparations and lack consistency even within the same preparation. Here, we present a novel use of existing transgenic mouse lines, Lim homeobox 6 (Lhx6)–Cre and parvalbumin (PV)–Cre, to define genetically distinct cell populations in the GPe that differ molecularly, anatomically, and electrophysiologically. Lhx6–GPe neurons, which do not express PV, are concentrated in the medial portion of the GPe. They have lower spontaneous firing rates, narrower dynamic ranges, and make stronger projections to the striatum and substantia nigra pars compacta compared with PV–GPe neurons. In contrast, PV–GPe neurons are more concentrated in the lateral portions of the GPe. They have narrower action potentials, deeper afterhyperpolarizations, and make stronger projections to the subthalamic nucleus and parafascicular nucleus of the thalamus. These electrophysiological and anatomical differences suggest that Lhx6–GPe and PV–GPe neurons participate in different circuits with the potential to contribute to different aspects of motor function and dysfunction in disease. PMID:24501350

  8. Control of bursting synchronization in networks of Hodgkin-Huxley-type neurons with chemical synapses.

    Science.gov (United States)

    Batista, C A S; Viana, R L; Ferrari, F A S; Lopes, S R; Batista, A M; Coninck, J C P

    2013-04-01

    Thermally sensitive neurons present bursting activity for certain temperature ranges, characterized by fast repetitive spiking of action potential followed by a short quiescent period. Synchronization of bursting activity is possible in networks of coupled neurons, and it is sometimes an undesirable feature. Control procedures can suppress totally or partially this collective behavior, with potential applications in deep-brain stimulation techniques. We investigate the control of bursting synchronization in small-world networks of Hodgkin-Huxley-type thermally sensitive neurons with chemical synapses through two different strategies. One is the application of an external time-periodic electrical signal and another consists of a time-delayed feedback signal. We consider the effectiveness of both strategies in terms of protocols of applications suitable to be applied by pacemakers.

  9. Role of Noise in Complex Networks of FitzHugh-Nagumo Neurons

    International Nuclear Information System (INIS)

    Fortuna, Luigi; Frasca, Mattia; La Rosa, Manuela

    2005-01-01

    This paper deals with the open question related to the role of noise in complex networks of interconnected FitzHugh-Nagumo neurons. In this paper this problem is faced with extensive simulations of different network topologies. The results show that several topologies behave in an optimal way with respect to the range of noise level leading to an improvement in the stimulus-response coherence, while other with respect to the maximum values of the performance index. The best results in terms of both the suitable noise level and high stimulus response coherence have been obtained when a diversity in neuron characteristic parameters has been introduced and the neurons have been connected in a small-world topology

  10. Astrocytes control GABAergic inhibition of neurons in the mouse barrel cortex

    Science.gov (United States)

    Benedetti, B; Matyash, V; Kettenmann, H

    2011-01-01

    Astrocytes in the barrel cortex respond with a transient Ca2+ increase to neuronal stimulation and this response is restricted to the stimulated barrel field. In the present study we suppressed the astrocyte response by dialysing these cells with the Ca2+ chelator BAPTA. Electrical stimulation triggered a depolarization in stellate or pyramidal ‘regular spiking’ neurons from cortex layer 4 and 2/3 and this response was augmented in amplitude and duration after astrocytes were dialysed with BAPTA. Combined blockade of GABAA and GABAB receptors mimicked the effect of BAPTA dialysis, while glutamate receptor blockers had no effect. Moreover, the frequency of spontaneous postsynaptic currents was increased after BAPTA dialysis. Outside the range of BAPTA dialysis astrocytes responded with a Ca2+ increase, but in contrast to control, the response was no longer restricted to one barrel field. Our findings indicate that astrocytes control neuronal inhibition in the barrel cortex. PMID:21224221

  11. Astrocytes control GABAergic inhibition of neurons in the mouse barrel cortex.

    Science.gov (United States)

    Benedetti, B; Matyash, V; Kettenmann, H

    2011-03-01

    Astrocytes in the barrel cortex respond with a transient Ca2+ increase to neuronal stimulation and this response is restricted to the stimulated barrel field. In the present study we suppressed the astrocyte response by dialysing these cells with the Ca2+ chelator BAPTA. Electrical stimulation triggered a depolarization in stellate or pyramidal ‘regular spiking' neurons from cortex layer 4 and 2/3 and this response was augmented in amplitude and duration after astrocytes were dialysed with BAPTA. Combined blockade of GABAA and GABAB receptors mimicked the effect of BAPTA dialysis, while glutamate receptor blockers had no effect. Moreover, the frequency of spontaneous postsynaptic currents was increased after BAPTA dialysis. Outside the range of BAPTA dialysis astrocytes responded with a Ca2+ increase, but in contrast to control, the response was no longer restricted to one barrel field. Our findings indicate that astrocytes control neuronal inhibition in the barrel cortex.

  12. Nanosecond laser pulse stimulation of spiral ganglion neurons and model cells.

    Science.gov (United States)

    Rettenmaier, Alexander; Lenarz, Thomas; Reuter, Günter

    2014-04-01

    Optical stimulation of the inner ear has recently attracted attention, suggesting a higher frequency resolution compared to electrical cochlear implants due to its high spatial stimulation selectivity. Although the feasibility of the effect is shown in multiple in vivo experiments, the stimulation mechanism remains open to discussion. Here we investigate in single-cell measurements the reaction of spiral ganglion neurons and model cells to irradiation with a nanosecond-pulsed laser beam over a broad wavelength range from 420 nm up to 1950 nm using the patch clamp technique. Cell reactions were wavelength- and pulse-energy-dependent but too small to elicit action potentials in the investigated spiral ganglion neurons. As the applied radiant exposure was much higher than the reported threshold for in vivo experiments in the same laser regime, we conclude that in a stimulation paradigm with nanosecond-pulses, direct neuronal stimulation is not the main cause of optical cochlea stimulation.

  13. The age of enlightenment: evolving opportunities in brain research through optical manipulation of neuronal activity

    Directory of Open Access Journals (Sweden)

    Jason eJerome

    2011-12-01

    Full Text Available Optical manipulation of neuronal activity has rapidly developed into the most powerful and widely used approach to study mechanisms related to neuronal connectivity over a range of scales. Since the early use of single site uncaging to map network connectivity, rapid technological development of light modulation techniques has added important new options, such as fast scanning photostimulation, massively parallel control of light stimuli, holographic uncaging and 2-photon stimulation techniques. Exciting new developments in optogenetics complement neurotransmitter uncaging techniques by providing cell-type specificity and in vivo usability, providing optical access to the neural substrates of behavior. Here we review the rapid evolution of methods for the optical manipulation of neuronal activity, emphasizing crucial recent developments.

  14. The age of enlightenment: evolving opportunities in brain research through optical manipulation of neuronal activity.

    Science.gov (United States)

    Jerome, Jason; Heck, Detlef H

    2011-01-01

    Optical manipulation of neuronal activity has rapidly developed into the most powerful and widely used approach to study mechanisms related to neuronal connectivity over a range of scales. Since the early use of single site uncaging to map network connectivity, rapid technological development of light modulation techniques has added important new options, such as fast scanning photostimulation, massively parallel control of light stimuli, holographic uncaging, and two-photon stimulation techniques. Exciting new developments in optogenetics complement neurotransmitter uncaging techniques by providing cell-type specificity and in vivo usability, providing optical access to the neural substrates of behavior. Here we review the rapid evolution of methods for the optical manipulation of neuronal activity, emphasizing crucial recent developments.

  15. Double sliding-window technique: a new method to calculate the neuronal response onset latency.

    Science.gov (United States)

    Berényi, Antal; Benedek, György; Nagy, Attila

    2007-10-31

    Neuronal response onset latency provides important data on the information processing within the central nervous system. In order to enhance the quality of the onset latency estimation, we have developed a 'double sliding-window' technique, which combines the advantages of mathematical methods with the reliability of standard statistical processes. This method is based on repetitive series of statistical probes between two virtual time windows. The layout of the significance curve reveals the starting points of changes in neuronal activity in the form of break-points between linear segments. A second-order difference function is applied to determine the position of maximum slope change, which corresponds to the onset of the response. In comparison with Poisson spike-train analysis, the cumulative sum technique and the method of Falzett et al., this 'double sliding-window, technique seems to be a more accurate automated procedure to calculate the response onset latency of a broad range of neuronal response characteristics.

  16. Ranging Behaviour of Commercial Free-Range Laying Hens.

    Science.gov (United States)

    Chielo, Leonard Ikenna; Pike, Tom; Cooper, Jonathan

    2016-04-26

    In this study, the range use and behaviour of laying hens in commercial free-range flocks was explored. Six flocks were each visited on four separate days and data collected from their outdoor area (divided into zones based on distance from shed and available resources). These were: apron (0-10 m from shed normally without cover or other enrichments); enriched belt (10-50 m from shed where resources such as manmade cover, saplings and dust baths were provided); and outer range (beyond 50 m from shed with no cover and mainly grass pasture). Data collection consisted of counting the number of hens in each zone and recording behaviour, feather condition and nearest neighbour distance (NND) of 20 birds per zone on each visit day. In addition, we used techniques derived from ecological surveys to establish four transects perpendicular to the shed, running through the apron, enriched belt and outer range. Number of hens in each 10 m × 10 m quadrat was recorded four times per day as was the temperature and relative humidity of the outer range. On average, 12.5% of hens were found outside. Of these, 5.4% were found in the apron; 4.3% in the enriched zone; and 2.8% were in the outer range. This pattern was supported by data from quadrats, where the density of hens sharply dropped with increasing distance from shed. Consequently, NND was greatest in the outer range, least in the apron and intermediate in the enriched belt. Hens sampled in outer range and enriched belts had better feather condition than those from the apron. Standing, ground pecking, walking and foraging were the most commonly recorded activities with standing and pecking most likely to occur in the apron, and walking and foraging more common in the outer range. Use of the outer range declined with lower temperatures and increasing relative humidity, though use of apron and enriched belt was not affected by variation in these measures. These data support previous findings that outer range areas tend to be

  17. Ranging Behaviour of Commercial Free-Range Laying Hens

    Directory of Open Access Journals (Sweden)

    Leonard Ikenna Chielo

    2016-04-01

    Full Text Available In this study, the range use and behaviour of laying hens in commercial free-range flocks was explored. Six flocks were each visited on four separate days and data collected from their outdoor area (divided into zones based on distance from shed and available resources. These were: apron (0–10 m from shed normally without cover or other enrichments; enriched belt (10–50 m from shed where resources such as manmade cover, saplings and dust baths were provided; and outer range (beyond 50 m from shed with no cover and mainly grass pasture. Data collection consisted of counting the number of hens in each zone and recording behaviour, feather condition and nearest neighbour distance (NND of 20 birds per zone on each visit day. In addition, we used techniques derived from ecological surveys to establish four transects perpendicular to the shed, running through the apron, enriched belt and outer range. Number of hens in each 10 m × 10 m quadrat was recorded four times per day as was the temperature and relative humidity of the outer range. On average, 12.5% of hens were found outside. Of these, 5.4% were found in the apron; 4.3% in the enriched zone; and 2.8% were in the outer range. This pattern was supported by data from quadrats, where the density of hens sharply dropped with increasing distance from shed. Consequently, NND was greatest in the outer range, least in the apron and intermediate in the enriched belt. Hens sampled in outer range and enriched belts had better feather condition than those from the apron. Standing, ground pecking, walking and foraging were the most commonly recorded activities with standing and pecking most likely to occur in the apron, and walking and foraging more common in the outer range. Use of the outer range declined with lower temperatures and increasing relative humidity, though use of apron and enriched belt was not affected by variation in these measures. These data support previous findings that outer range

  18. Decoding spikes in a spiking neuronal network

    Energy Technology Data Exchange (ETDEWEB)

    Feng Jianfeng [Department of Informatics, University of Sussex, Brighton BN1 9QH (United Kingdom); Ding, Mingzhou [Department of Mathematics, Florida Atlantic University, Boca Raton, FL 33431 (United States)

    2004-06-04

    We investigate how to reliably decode the input information from the output of a spiking neuronal network. A maximum likelihood estimator of the input signal, together with its Fisher information, is rigorously calculated. The advantage of the maximum likelihood estimation over the 'brute-force rate coding' estimate is clearly demonstrated. It is pointed out that the ergodic assumption in neuroscience, i.e. a temporal average is equivalent to an ensemble average, is in general not true. Averaging over an ensemble of neurons usually gives a biased estimate of the input information. A method on how to compensate for the bias is proposed. Reconstruction of dynamical input signals with a group of spiking neurons is extensively studied and our results show that less than a spike is sufficient to accurately decode dynamical inputs.

  19. Current Source Density Estimation for Single Neurons

    Directory of Open Access Journals (Sweden)

    Dorottya Cserpán

    2014-03-01

    Full Text Available Recent developments of multielectrode technology made it possible to measure the extracellular potential generated in the neural tissue with spatial precision on the order of tens of micrometers and on submillisecond time scale. Combining such measurements with imaging of single neurons within the studied tissue opens up new experimental possibilities for estimating distribution of current sources along a dendritic tree. In this work we show that if we are able to relate part of the recording of extracellular potential to a specific cell of known morphology we can estimate the spatiotemporal distribution of transmembrane currents along it. We present here an extension of the kernel CSD method (Potworowski et al., 2012 applicable in such case. We test it on several model neurons of progressively complicated morphologies from ball-and-stick to realistic, up to analysis of simulated neuron activity embedded in a substantial working network (Traub et al, 2005. We discuss the caveats and possibilities of this new approach.

  20. Runx transcription factors in neuronal development

    Directory of Open Access Journals (Sweden)

    Shiga Takashi

    2008-08-01

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

  1. GABAergic actions on cholinergic laterodorsal tegmental neurons

    DEFF Research Database (Denmark)

    Kohlmeier, K A; Kristiansen, Uffe

    2010-01-01

    Cholinergic neurons of the pontine laterodorsal tegmentum (LDT) play a critical role in regulation of behavioral state. Therefore, elucidation of mechanisms that control their activity is vital for understanding of how switching between wakefulness, sleep and anesthetic states is effectuated....... In vivo studies suggest that GABAergic mechanisms within the pons play a critical role in behavioral state switching. However, the postsynaptic, electrophysiological actions of GABA on LDT neurons, as well as the identity of GABA receptors present in the LDT mediating these actions is virtually unexplored...... neurons. Post-synaptic location of GABA(A) receptors was demonstrated by persistence of muscimol-induced inward currents in TTX and low Ca(2+) solutions. THIP, a selective GABA(A) receptor agonist with a preference for d-subunit containing GABA(A) receptors, induced inward currents, suggesting...

  2. Decoding spikes in a spiking neuronal network

    International Nuclear Information System (INIS)

    Feng Jianfeng; Ding, Mingzhou

    2004-01-01

    We investigate how to reliably decode the input information from the output of a spiking neuronal network. A maximum likelihood estimator of the input signal, together with its Fisher information, is rigorously calculated. The advantage of the maximum likelihood estimation over the 'brute-force rate coding' estimate is clearly demonstrated. It is pointed out that the ergodic assumption in neuroscience, i.e. a temporal average is equivalent to an ensemble average, is in general not true. Averaging over an ensemble of neurons usually gives a biased estimate of the input information. A method on how to compensate for the bias is proposed. Reconstruction of dynamical input signals with a group of spiking neurons is extensively studied and our results show that less than a spike is sufficient to accurately decode dynamical inputs

  3. Mechanosensor Channels in Mammalian Somatosensory Neurons

    Directory of Open Access Journals (Sweden)

    Patrick Delmas

    2007-09-01

    Full Text Available Mechanoreceptive sensory neurons innervating the skin, skeletal muscles andviscera signal both innocuous and noxious information necessary for proprioception, touchand pain. These neurons are responsible for the transduction of mechanical stimuli intoaction potentials that propagate to the central nervous system. The ability of these cells todetect mechanical stimuli impinging on them relies on the presence of mechanosensitivechannels that transduce the external mechanical forces into electrical and chemical signals.Although a great deal of information regarding the molecular and biophysical properties ofmechanosensitive channels in prokaryotes has been accumulated over the past two decades,less is known about the mechanosensitive channels necessary for proprioception and thesenses of touch and pain. This review summarizes the most pertinent data onmechanosensitive channels of mammalian somatosensory neurons, focusing on theirproperties, pharmacology and putative identity.

  4. MR imaging of neuronal migration anomaly

    International Nuclear Information System (INIS)

    Hong, Hyun Sook; Choi, Eun Wan; Kim, Dae Ho; Chung, Moo Chan; Kwon, Kuy Hyang; Kim, Ki Jung

    1991-01-01

    Abnormalities of neuronal migration are characterized by anectopic location of neurons in the cerebral cortex. This broad group of anomalies includes agyria, pachygyria, schizencephaly, unilateral megalencephaly, and gray matter heterotopia. Patients with this anomaly present clinically with a variety of symptoms which are proportional to the extent of the brain involved. These abnormalities have characterized pathologically in vivo by sonography and CT scan. MR appears to be an imaging technique of choice in evaluating these anomalies because it is capable of exceptionally good differentiation between gray and white matter, high contrast resolution, multiplanar display of the anatomy, and lack of overlying bone artifac. The purpose of this paper is to describe the MR findings of neuronal migration anomaly. The results of our study support that MR appears to be the imaging method of choice for diagnosing migration anomalies and the primary screening method for infants or children who have seisure/and delayed development

  5. Mirror Neurons and Mirror-Touch Synesthesia.

    Science.gov (United States)

    Linkovski, Omer; Katzin, Naama; Salti, Moti

    2016-05-30

    Since mirror neurons were introduced to the neuroscientific community more than 20 years ago, they have become an elegant and intuitive account for different cognitive mechanisms (e.g., empathy, goal understanding) and conditions (e.g., autism spectrum disorders). Recently, mirror neurons were suggested to be the mechanism underlying a specific type of synesthesia. Mirror-touch synesthesia is a phenomenon in which individuals experience somatosensory sensations when seeing someone else being touched. Appealing as it is, careful delineation is required when applying this mechanism. Using the mirror-touch synesthesia case, we put forward theoretical and methodological issues that should be addressed before relying on the mirror-neurons account. © The Author(s) 2016.

  6. Merkel cells and neurons keep in touch

    Science.gov (United States)

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

    2014-01-01

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

  7. Descending Command Neurons in the Brainstem that Halt Locomotion

    DEFF Research Database (Denmark)

    Bouvier, Julien; Caggiano, Vittorio; Leiras, Roberto

    2015-01-01

    identifiable brainstem populations to a potential locomotor stop signal, we used developmental genetics and considered a discrete neuronal population in the reticular formation: the V2a neurons. We find that those neurons constitute a major excitatory pathway to locomotor areas of the ventral spinal cord....... Selective activation of V2a neurons of the rostral medulla stops ongoing locomotor activity, owing to an inhibition of premotor locomotor networks in the spinal cord. Moreover, inactivation of such neurons decreases spontaneous stopping in vivo. Therefore, the V2a "stop neurons" represent a glutamatergic...

  8. Mirror neurons: Enigma of the metaphysical modular brain.

    Science.gov (United States)

    Acharya, Sourya; Shukla, Samarth

    2012-07-01

    Mirror neurons are one of the most important discoveries in the last decade of neuroscience. These are a variety of visuospatial neurons which indicate fundamentally about human social interaction. Essentially, mirror neurons respond to actions that we observe in others. The interesting part is that mirror neurons fire in the same way when we actually recreate that action ourselves. Apart from imitation, they are responsible for myriad of other sophisticated human behavior and thought processes. Defects in the mirror neuron system are being linked to disorders like autism. This review is a brief introduction to the neurons that shaped our civilization.

  9. The contribution of ketone bodies to basal and activity-dependent neuronal oxidation in vivo.

    Science.gov