Dissertations / Theses: 'Neuroni corticali'

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CURCIO, LIVIA. "Effetti degli amminoacidi a catena ramificata (BCAA) sull’eccitabilità di neuroni corticali in coltura primaria e confronto con il modello murino di sclerosi laterale amiotrofica, G93A." Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2010. http://hdl.handle.net/2108/1181.

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Recenti studi epidemiologici hanno accertato che, rispetto all’intera popolazione italiana, la categoria dei calciatori presenta una maggiore incidenza di casi di Sclerosi Laterale Amiotrofica (SLA). Una delle principali ipotesi relativa a questo dato è l’eccessivo utilizzo di integratori dietetici e farmaci che servono ad aumentare la performance sportiva ed a diminuire la sensazione di fatica. In particolare, è stato riscontrato che Valina, Leucina e Isoleucina (Branched Chain AminoAcids: BCAA) sono tra i supplementi maggiormente utilizzati tra gli atleti. Per studiare i possibili effetti dei BCAA sulle proprietà elettriche neuronali sono stati effettuati esperimenti elettrofisiologici sui neuroni corticali primari provenienti da topi di controllo trattati con 200 µM di BCAA, ed i risultati ottenuti sono stati confrontati con quanto osservato nei neuroni di controllo non trattati. Questi esperimenti hanno dimostrato che il trattamento induce un significativo aumento nell’eccitabilità neuronale in maniera dose e tempo–dipendente, rispetto ai neuroni di controllo non trattati. Inoltre, altri amminoacidi dotati di una catena laterale non ramificata, come per esempio l’Alanina e la Fenilalanina, non causano alcuna alterazione come quella riscontrata in seguito all’esposizione ai BCAA. Studi condotti in modalità voltage-clamp hanno inoltre dimostrato che i neuroni trattati con i BCAA possiedono correnti voltaggio-dipendenti del Sodio persistente e del Calcio maggiori di quelle dei neuroni di controllo. Ciò indica che le modifiche delle proprietà biofisiche dei potenziali d’azione sono probabilmente dovute all’aumento nella densità in membrana dei canali specifici per queste specie ioniche. La riscontrata ipereccitabilità e le alterazioni di funzionalità dei canali ionici di Sodio persistente e di Calcio indotte dai BCAA in cellule di controllo sono paragonabili a quelle riscontrate nei neuroni ottenuti da un modello murino di SLA, il topo G93A, evidenziando un’importante correlazione tra le due condizioni sperimentali. Inoltre, è stato dimostrato che la Rapamicina, farmaco in grado di bloccare il complesso mTOR, favorisce il ripristino di una frequenza di scarica confrontabile con i valori di controllo, sia in cellule trattate con i BCAA che in neuroni G93A. Ciò potrebbe indicare che il complesso mTOR è coinvolto nelle alterazioni indotte dai BCAA e nella patogenesi della SLA. La comprensione di come i BCAA influiscano sulle proprietà fisiologiche e funzionali dei neuroni corticali può permettere di stabilire un loro possibile coinvolgimento nell’eziopatogenesi della SLA contribuendo alla comprensione del probabile meccanismo d’azione interessato, al fine di individuare nuovi trattamenti terapeutici. Some epidemiological studies have recently ascertained that, Italian soccer players present a higher risk factor for Amyotrophic Lateral Sclerosis (ALS), compared to general population. One of the main hypotheses is related to the abuse of dietary supplements and drugs to enhance sporting performance and to reduce the feeling of fatigue. In particular, it has been reported that Valine, Leucine and Isoleucine (Branched-chain Amino Acids: BCAAs) are widely used among athletes. To study the possible effect of BCAAs on neuronal electrical properties, electrophysiological experiments have been performed on primary cortical neurons treated with 200 µM of BCAA and cultured from control embryos. All data have been compared to control values. The experiments have demonstrated that the treatment induces a significant increase of neuronal excitability dose- and time-dependent respect to control. Moreover, the treatment with other aminoacids, such as Alanine and Phenilalanine, doesn’t cause any alteration. Voltage clamp experiments show that, after a long exposition to BCAA, neurons present an increase of the Sodium and Calcium voltage-dependent channel densities. So, those biophysical changes could explain the increase of action potential frequencies observed after BCAA exposure. Both hyperexcitability and the higher Sodium and Calcium densities, induced by BCAA in control cells, were comparable to those obtained in the G93A neurons underlining an important correlation between two experimental conditions. Moreover, a treatment with Rapamycin, an inhibitor of the complex mTOR, was able to revert both the BCAA-induced and the G93A hyperexcitability to control values. These findings strongly indicates that in both cases, the mTOR signalling could be activated. In this way, the understanding of the effect mediated by BCAA on the functionality of primary cortical neurons and the mechanism of action will allow us to learn better the ethiopathogenesis of ALS, thus opening up new strategies for the treatment of this pathology.

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Markov, Nikola. "Exploration of the inter-areal cortico-cortical network of the macaque monkey." Phd thesis, Université Claude Bernard - Lyon I, 2010. http://tel.archives-ouvertes.fr/tel-00863803.

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The cortex can be viewed as a network of functional areas. A cortical area, composed ofneurons forming local connections, interacts with other areas via long distance connections.Each neuron receives multiple inputs and has to integrate the incoming signals. This integrativecapacity is the basis of the computational power of the brain. Our work concentrates onunderstanding the principles that govern the structure of the cortical network i.e. the allocationof neural resources as well as the anatomical segregation between processing steams. Usingretrograde tracer injections we extract two quantitative parameters: (i) the proportion ofSupragranular Labelled Neurons (SLN) identifies the feedforward (FF) or feedback (FB)operation between the source and target area; (ii) the Fraction of Labelled Neurons (FLN)identifies the magnitude of a connection pathway.We have made repeat injections in V1, V2, V4 to investigate the consistency of corticalpathways. This showed that (i) connection weights are consistent between animals; (ii) the listof areas projecting to each injection site is highly reproducible. We find that there are fixedFLN values for each pair of interconnected areas. The FLN values of all the afferent pathwaysto a given target span over a factor of 6 levels of log and although there is some overdispersiontheir variability is not larger than one single level of log meaning that there is a specificconnectivity profile for each area. Futermore the FLN follow a lognormal distribution. Inlognormals the mode is lower than the median and the mean i.e. the majority of pathways haveFLN weaker than the average FLN, meaning that strong projections are rare. If instead thedistribution of FLN was to follow a power law, then high FLN values would have been evenrarer. We found, a regularity in that the strongest input is invariably from within the injectedarea, second strongest are the inputs from areas sharing common borders with the target area.Sub-cortical inputs have a weak FLN, even when they are associated with an importantfunctional role such as the LGN → V1 pathway. We found that projection distance is inverselyrelated to the FLN value and an exponential distance rule operates that constrains short distanceprojections to high FLN and long distance projections to low FLN.We injected a total of 26 cortical areas homogenously distributed across the cortex. Thisrevealed 1232 projection pathways. Roughly 30% of pathways that we reveal have notpreviously been reported in the literature. Our ability to find new connections is due to theimproved tracing and brain segmentation techniques. We scan the whole brain at up to 80μmintervals to detect projection neurons, and this, as discussed in the text, is a major advantage toexisting studies. The weak long distance connections were shown to contract the characteristicpath-length of the graph (number of hops needed to go between any two areas).Our analysis of the graph showed that contrary to current belief the cortical inter-areal networkis dense (i.e. 58% of the connection that could exist do exist). At such a density, models basedon binary features such as small world cannot capture the specificity of the graph. Hence thecortex does not correspond small-world network, with sparse clustered graph possessingempowered by few critical projecitons that ensure short characteristic path-lengths. Furtheranalysis of pathway efficiency showed that the short distance connections of high magnitudeprovide large bandwidth for local connectivity and form a backbone of clustered functionallyrelated areas. This backbone is embedded in a sea of weak connections providing direct linksbetween cortical areas. We refer to this architecture as a tribal-network. We speculate that thesmall scale and high density that characterize the cortico-cortical network is facilitating theemergence of synchrony between cortical areas.

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Ponce, Alvarez Adrián. "Probabilistic models for studying variability in single-neuron and neuronal ensemble activity." Thesis, Aix-Marseille 2, 2010. http://www.theses.fr/2010AIX20706.

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Une des caractéristiques les plus singulières de l’activité corticale est son degré élevé de variabilité. Ma thèse dedoctorat s’est focalisée sur l’étude de (i) l’irrégularité des intervalles entre potentiels d’action (PAs)successivement émis par un neurone, et (ii) la variabilité dans l’évolution temporelle de l’activité d’un ensemblede neurones. Premièrement, j’ai étudié l’irrégularité des neurones enregistrés dans le cortex moteur de singesmacaques performant une tâche d’estimation du temps et de préparation à l’action. J’ai montré que l’irrégularitén’est pas un paramètre libre de l’activité neuronale, contrairement au taux de PAs, mais est déterminée par lescontraintes structurelles des réseaux neuronaux. Deuxièmement, j’ai utilisé le modèle de Markov caché (MMC)pour analyser l’activité d’ensembles de neurones enregistrés dans plusieurs aires corticales, sensorielles etmotrices, de singes exécutant une tâche de discrimination tactile. J’ai montré que les processus sensoriels etdécisionnels sont distribués dans plusieurs aires corticales. Les résultats suggèrent que l’action et la décision surlaquelle elle est basée sont reliées par une cascade d’évènements non stationnaires et stochastiques. Finalement,j’ai utilisé le MMC pour caractériser l’activité spontanée d’un ensemble de neurones du cortex préfrontal d’unrat. Les résultats montrèrent que l’alternance entre les états UP et DOWN est un processus stochastique etdynamique. La variabilité apparaît donc aussi bien pendant l’activité spontanée que pendant le comportementactif et semble être contrainte par des facteurs structurels qui, à leur tour, contraignent le mode d’opération desréseaux neuronaux A hallmark of cortical activity is its high degree of variability. The present work focused on (i) the variability ofintervals between spikes that single neurons emit, called spike time irregularity (STI), and (ii) the variability inthe temporal evolution of the collective neuronal activity. First, I studied the STI of macaque motor corticalneurons during time estimation and movement preparation. I found that although the firing rate of the neuronstransmitted information about these processes, the STI of a neuron is not flexible and is determined by thebalance of excitatory and inhibitory inputs. These results were obtained by means of an irregularity measure thatI compared to other existing measures. Second, I analyzed the neuronal ensemble activity of severalsomatosensory and motor cortical areas of macaques during tactile discrimination. I showed that ensembleactivity can be effectively described by the Hidden Markov Model (HMM). Both sensory and decision-makingprocesses were distributed across many areas. Moreover, I showed that decision-related changes in neuronalactivity rely on a noise-driven mechanism and that the maintenance of the decision relies on transient dynamics,subtending the conversion of a decision into an action. Third, I characterized the statistics of spontaneous UP andDOWN states in the prefrontal cortex of a rat, using the HMM. I showed that state alternation is stochastic andthe activity during UP states is dynamic. Hence, variability is prominent both during active behavior andspontaneous activity and is determined by structural factors, thus rending it inherent to cortical organization andshaping the function of neural networks

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Grehl, Stephanie. "Stimulation-specific effects of low intensity repetitive magnetic stimulation on cortical neurons and neural circuit repair in vitro (studying the impact of pulsed magnetic fields on neural tissue)." Thesis, Paris 6, 2014. http://www.theses.fr/2014PA066706/document.

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Les champs électromagnétiques sont couramment utilisés pour stimuler de manière non-invasive le cerveau humain soit à des fins thérapeutiques ou dans un contexte de recherche. Les effets de la stimulation magnétique varient en fonction de la fréquence et de l'intensité du champ magnétique. Les mécanismes mis en jeu restent inconnus, d'autant plus lors de stimulations à faible intensité. Dans cette thèse, nous avons évalué les effets de stimulations magnétiques répétées à différentes fréquences appliqués à faible intensité (10-13 mT ; Low Intensity Repetitive Magnetic Stimulation : LI-rMS) in vitro, sur des cultures corticales primaires et sur des modèles de réparation neuronale. De plus, nous décrivons une méthodologie pour la construction d'un dispositif instrumental fait sur mesure pour stimuler des cultures cellulaires.Les résultats montrent des effets dépendant de la fréquence sur la libération du calcium des stocks intracellulaires, sur la mort cellulaire, sur la croissance des neurites, sur la réparation neuronale, sur l'activation des neurones et sur l'expression de gènes impliqués. En conclusion, nous avons montré pour la première fois un nouveau mécanisme d'activation cellulaire par les champs magnétiques à faible intensité. Cette activation se fait en l'absence d'induction de potentiels d'action. Les résultats soulignent l'importance biologique de la LI-rMS par elle-même mais aussi en association avec les effets de la rTMS à haute intensité. Une meilleure compréhension des effets fondamentaux de la LI-rMS sur les tissus biologiques est nécessaire afin de mettre au point des applications thérapeutiques efficaces pour le traitement des conditions neurologiques Electromagnetic fields are widely used to non-invasively stimulate the human brain in clinical treatment and research. This thesis investigates the effects of different low intensity (mT) repetitive magnetic stimulation (LI-rMS) parameters on single neurons and neural networks and describes key aspects of custom tailored LI-rMS delivery in vitro. Our results show stimulation specific effects of LI-rMS on cell survival, neuronal morphology, neural circuit repair and gene expression. We show novel mechanisms underlying cellular responses to stimulation below neuronal firing threshold, extending our understanding of the fundamental effects of LI-rMS on biological tissue which is essential to better tailor therapeutic applications

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BACIGALUPPI, SUSANNA. "Ruolo e potenziale delle cellule progenitrici endoteliali nel vasospamo cerebrale." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2011. http://hdl.handle.net/10281/27113.

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Title: Role and potential of endothelial progenitor cells in cerebral vasospasm Abstract: Background and aim: Despite many treatment approaches, cerebral vasospasm and delayed ischemic neuronal damage (DIND) still represent a serious threat to patients with subarachnoid haemorrhage (SAH). Endothelial progenitor cells (EPC) have been involved as prognostic indicators in several vascular diseases and mesenchymal stem cells already have shown some benefits in ischemic injury. Aim of this study was to investigate the therapeutic potential of endothelial progenitor cells (EPC) and mesenchymal stem cells (MSC) in attenuating or preventing vasospasm and DIND in patients with SAH. Methods: Given the emergent role of DIND as a result of multifactorial hypoperfusion stress in the outcome of SAH patients, the efficacy of EPC and MSC in reducing neuronal damage has been evaluated in an in vitro model of ischemia, namely the oxygen glucose deprivation (OGD), on primary rat cortical neuronal cultures. Further, we tested in a clinical observational study SAH patients with and without vasospasm for different recruitment patterns of circulating EPC. To this purpose arterial blood samples were collected at various timepoints from admission to discharge of the patients. On these samples real-time quantitative PCR (RT-qPCR) was performed to detect gene expression relative to EPCs, since cytofluorimetric analysis appeared not sensitive enough to detect this rare cell population. Results: Though present results need further confirmation, in vitro it was observed that both MSC and EPC treatment through conditioned medium or co-culture in transwell- although with some differences - mediate a survival advantage for OGD stressed neurons. Furthermore stem cell mediated treatment showed efficacy even when applied 24 hours after OGD stress induction. RT-qPCR results from a small sample of SAH patients might indicate an early mobilization of EPC related gene expression in subjects that do not develop vasospasm with a peak around day 4, whereas the expression of these genes remain invariably low in patients that develop vasospasm as in controls not affected by SAH. Conclusions: MSCs and EPCs seem to have an important potential role in preventing DIND in vitro as well as EPC recruitment might associate with lack of vasospasm in SAH patients. Further studies are needed to confirm these results and to prove a causal relationship between EPCs and vasospasm protection.

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Verzeaux, Laurie. "Etude de l'interaction du TIMP-1 avec ses récepteurs." Thesis, Reims, 2015. http://www.theses.fr/2015REIMS040/document.

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Le TIMP-1, inhibiteur naturel des métalloprotéinases matricielles, exerce des effets pléïotropes indépendants de l'inhibition des MMPs et participe au développement de certains cancers et maladies neurodégénératives. Ces effets cytokiniques du TIMP-1 impliquent sa liaison à des récepteurs membranaires dont certains sont caractérisés, la glycoprotéine CD63/intégrine beta 1 et le complexe pro MMP-9/CD44. Cependant les acides aminés ou les domaines du TIMP-1 se liant à ces récepteurs ne sont pas identifiés. Les travaux réalisés au cours de cette thèse mettent en évidence un nouveau récepteur du TIMP-1, la protéine LRP-1. Dans les neurones corticaux murins, le TIMP-1 se fixe aux domaines DII et DIV de LRP-1, est endocyté et induit une réduction de la taille des neurites ainsi qu'une augmentation du volume des cônes de croissance. Afin de caractériser cette interaction, nous avons utilisé une approche originale de modélisation moléculaire associant les analyses de modes normaux et la dynamique moléculaire. Ces analyses in silico ont permis d'identifier un mouvement de pince entre les domaines N et C-terminaux du TIMP-1. Nous avons muté trois résidus (F12, K47 et W105) localisés dans une région essentielle d'un point vue énergétique à l'exécution de ce mouvement. Ces trois mutants n'ont pas d'effet sur la longueur du réseau neuritique et ne sont pas endocytés par LRP-1. En revanche, ils interagissent avec les 2 autres récepteurs (CD63 et proMMP-9) et reproduisent les effets du TIMP-1 sauvage. De plus, nous avons identifié une séquence de 6 acides aminés localisée dans le domaine extracellulaire I de CD63 et essentielle à la liaison avec le TIMP-1. L'ensemble de ces travaux a permis l'identification de régions impliquées dans l'interaction du TIMP-1 avec ses différents récepteurs et pourrait permettre le développement de nouveaux outils pharmacologiques ciblant les activités cytokiniques du TIMP-1 TIMP-1, a natural inhibitor of matrix metalloproteinases, exerts pleiotropic effects independent of MMP inhibition and thus participates to the development of some cancers and neurodegenerative disorders. These cytokine-like activities require TIMP-1 binding to membrane receptors. Up to date two receptors, CD63/integrin beta 1 and proMMP-9/CD44, have been characterized. Nevertheless, TIMP-1 residues or regions binding these receptors remain unknown. In this work, we have identified the protein LRP-1 as a new receptor for TIMP 1. In mouse cortical neurons, TIMP-1 preferentially binds DII and DIV domains of LRP-1, is internalized via a LRP-1-dependent endocytosis, reduces neurite length and increases growth cone volume. To go deeper into TIMP-1/LRP-1 interaction, we used an original molecular modeling approach which combined normal mode analysis and molecular dynamic. These in silico studies allow us to point out a clamp movement between the N- and C-terminal domains of TIMP-1. Three residues localized in a region that seems essential for the movement have been mutated (F12, K47 and W105) and single mutants have been produced. These mutants do not reduce neurite outgrowth and are not internalized by LRP-1. In contrast, they interact with the two others receptors proMMP-9 and CD63 and induce associated biological effects. Furthermore, we have identified a sequence of six residues localized in the CD63 extracellular domain I and essential for TIMP 1 binding. The set of our data highlighted new regions of TIMP-1 interacting with its receptors and could lead to design novel therapeutic agents targeting the TIMP-1 cytokine like activities

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Dobbins, Allan C. (Allan Charles). "Difference models of visual cortical neurons." Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=39539.

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Difference operations are ubiquitous in the visual cortex. The central hypothesis in this thesis is that a nonlinear difference model can account for the functional properties of three different classes of visual cortical neurons. Abstractly each of the different neurons can be understood in terms of the same difference model although the computations they perform can be entirely different. Endstopped neurons respond to short or highly curved oriented patterns. Their behaviour results from the difference in activation of their classical receptive field and inhibitory endzones. Two models of endstopped neurons are evaluated mathematically and by computer simulation. It is concluded that a model with displaced complex cell-like endzones is both more computationally robust and more consistent with the physiological evidence. Other visual cortical neurons have inhibitory zones which are displaced normally rather than tangentially with respect to the neuron's receptive field orientation. These sidestopped cells are selective for narrow patterns. In other visual cortical neurons the side inhibition is derived from a different eye than the classical receptive field. Because of the geometry of projection these are referred to as binocular Near and Far cells. A difference model of sidestopped and Near and Far neurons is developed which captures their principal features. Neurons in visual cortical area MT of primates have been shown to exhibit a velocity-specific antagonism between the receptive field and a surrounding region. It is argued that center-surround antagonism is an attempt to resolve competing constraints. Signal reliability increases with spatial averaging, but the variation of the flow field invariably increases with area. A unifying perspective is that difference models provide a means of estimating the range over which a visual quantity is constant or linear. Varieties of these models exist with a more refined property--selectivity for sign of contour curvature or, under certain circumstances, the sign of convexity of the surface generating a binocular disparity or motion field.

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Qin, Yan. "Studies of Zinc Transport and Its Contribution to Zinc Homeostasis in Cultured Cortical Neurons." View abstract, 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:3339515.

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Lackmy, Alexandra. "Stimulation magnétique transcrânienne et inhibition intra-corticale : variabilité liée au recrutement des motoneurones spinaux et des neurones corticaux." Paris 6, 2010. http://www.theses.fr/2010PA066060.

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L’activation "transynaptique" des neurones pyramidaux du cortex moteur primaire par stimulation magnétique transcrânienne (TMS) induit des volées corticospinales (CSP) transmises aux motoneurones spinaux. Leur activation entraîne une contraction traduite par un potentiel (PEM) dans l’activité électromyographique du muscle cible. L’amplitude du PEM en mV sert à évaluer l’état d’excitabilité des neurones de la voie CSP. Si une TMS conditionnante précède de 2 à 5 ms une TMS test, le PEM évoqué par le double choc de TMS est plus petit que le PEM induit par la TMS test seule. Cette inhibition, la SICI, vient de l’activation d’interneurones inhibiteurs qui modifient la réponse des neurones pyramidaux à la TMS test. La variabilité des résultats remet en cause la fiabilité de cette méthode. Plusieurs paramètres ont été testés, mais jamais les propriétés des neurones corticaux et spinaux n’ont été suspectées. L’objectif du projet doctoral était de vérifier si les propriétés de ces neurones influencent l’évaluation de la SICI chez l’Homme. Le PEM test a été exprimé en % de la réponse motrice maximale (Mmax), plutôt qu’en mV, pour évaluer la fraction de MNs recrutés par la TMS test. Des unités motrices isolées ont été testées pour explorer les réponses des neurones corticaux à la TMS. Les résultats ont révélé que i) la sommation des volées CSP au niveau des MNs n’est pas linéaire ce qui influence l’évaluation de la SICI, ii) l’intégration des entrées synaptiques inhibitrices au niveau des réseaux corticaux afférents aux cellules pyramidales n’est pas linéaire. Ce travail a permis de proposer une nouvelle méthode d’évaluation des mécanismes corticaux révélés avec la TMS.

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Zhou, Yi-Xiong. "Responses to envelope patterns in visual cortical neurons." Thesis, McGill University, 1993. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=41806.

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Mammalian striate and circumstriate cortical neurons have long been understood as coding spatially localized retinal luminance variations, providing a basis for computing motion, stereopsis, and contours from the retinal image. However, such perceptual attributes do not always correspond to the retinal luminance variations in natural vision. Recordings from area 17 and 18 neurons revealed a specialized nonlinear processing stream that responded to stimulus attributes having no corresponding luminance variations. This nonlinear stream acts in parallel to the conventional luminance processing of single cortical neurons. The two streams were consistent in their preference for orientation and direction of motion, but distinct in processing spatial variations of the stimulus attributes. The ensemble of these neurons provides a combination of stimulus attributes with and without corresponding luminance variations.

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Lloyd, Catherine Margaret. "Aspects of cortical function in motor neurone disease." Thesis, Imperial College London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243835.

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Yang, Yanning. "Attention detection based on cortical area V2 neurons /." View abstract or full-text, 2008. http://library.ust.hk/cgi/db/thesis.pl?ECED%202008%20YANG.

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Michalikova, Martina. "Mechanisms of spikelet generation in cortical pyramidal neurons." Doctoral thesis, Humboldt-Universität zu Berlin, Lebenswissenschaftliche Fakultät, 2017. http://dx.doi.org/10.18452/17753.

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Unter Spikelets versteht man kleine Depolarisationen mit einer Spike-ähnlichen Wellenform, die man in intrazellulären Ableitungen von verschiedenen Neuronentypen messen kann. In kortikalen Pyramidenzellen wurde ausgeprägte Spikelet-Aktivität nachgewiesen, die erheblich das Membranpotential beeinflussen kann (Crochet et al., 2004; Epsztein et al., 2010; Chorev and Brecht, 2012). Nichtsdestotrotz bleibt der Ursprung von Spikelets in diesen Neuronen unbekannt. In der vorgelegten Arbeit nutzte ich theoretische Modellierung um die Mechanismen von Spikelet-Erzeugung in Pyramidenzellen zu untersuchen. Zuerst sah ich die verschiedenen Hypothesen über den Ursprung von Spikelets durch. In der Literatur entdeckte ich zwei verschiedene Typen von Spikelets. Diese Arbeit konzentriert sich auf den häufiger vorkommenden Typ von Spikelets, welcher durch relativ große Amplituden gekennzeichnet ist. Die Eigenschaften dieser Spikelets passen am besten zu einem axonal Erzeugungsmechanismus. Im zweiten Kapitel widmete ich mich der Hypothese, dass somatische Spikelets axonalen Ursprungs mit somato-dendritischen Inputs hervorgerufen werden können. Ich identifizierte Bedingungen, die es erlauben ein Aktionspotential (AP) am Initialsegment vom Axon (AIS) zu initiieren, welches sich entlang des Axons ausbreitet, aber kein AP im Soma auslöst. Schließlich simulierte ich extrazelluläre Wellenformen von APs und Spikelets und verglich sie mit experimentellen Daten (Chorev and Brecht, 2012). Dieser Vergleich zeigte auf, dass die extrazellulären Wellenformen von Spikelets, die innerhalb einer Zellen am AIS erzeugt werden, gut zu den Daten passen. Zusammenfassend unterstützen meine Ergebnisse die Hypothese, dass Spikelets in Pyramidenzellen am AIS entstehen. Dieser Mechanismus könnte ein Mittel zum Energiesparen bei der Erzeugung von Output-APs sein. Außerdem könnte dadurch die dendritische Plastizität, die auf der Rückwärtspropagierung von APs beruht, reguliert werden. Spikelets are transient spike-like depolarizations of small amplitudes that can be measured in somatic intracellular recordings of many neuron types. Pronounced spikelet activity has been demonstrated in cortical pyramidal neurons in vivo (Crochet et al., 2004; Epsztein et al., 2010; Chorev and Brecht, 2012), influencing membrane voltage dynamics including action potential initiation. Nevertheless, the origin of spikelets in these neurons remains elusive. In thi thesis, I used computational modeling to examine the mechanisms of spikelet generation in pyramidal neurons. First, I reviewed the hypotheses previously suggested to explain spikelet origin. I discovered two qualitatively different spikelet types described in the experimental literature. This thesis focuses on the more commonly reported spikelet type, characterized by relatively large amplitudes of up to 20 mV. I found that the properties of these spikelets fit best to an axonal generation mechanism. Second, I explored the hypothesis that somatic spikelets of axonal origin can be evoked with somato-dendritic inputs. I identified the conditions allowing these orthodromic inputs to trigger an action potential at the axon initial segment, which propagates along the axon to the postsynaptic targets, but fails to elicit an action potential in the soma and the dendrites. Third, I simulated extracellular waveforms of action potentials and spikelets and compared them to experimental data (Chorev and Brecht, 2012). This comparison demonstrated that the extracellular waveforms of single-cell spikelets of axonal origin are consistent with the data. Together, my results suggest that spikelets in pyramidal neurons might originate at the axon initial segment within a single cell. Such a mechanism might be a way of reducing the energetic costs associated with the generation of output action potentials. Moreover, it might allow to control the dendritic plasticity by backpropagating action potentials.

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Silva, Renato Aparecido Pimentel da. "Emprego de redes complexas no estudo das relações entre morfologia individual, topologia global e aspectos dinâmicos em neurociência." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/76/76132/tde-21082012-151906/.

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A teoria de redes complexas se consolidou nos últimos anos, graças ao seu potencial como ferramenta versátil no estudo de diversos sistemas discretos. É possível enumerar aplicações em áreas tão distintas como engenharia, sociologia, computação, linguística e biologia. Tem merecido atenção, por exemplo, o estudo da organização estrutural do cérebro, tanto em nível microscópico (em nível de neurônios) como regional (regiões corticais). Acredita-se que tal organização visa otimizar a dinâmica, favorecendo processos como sincronização e processamento paralelo. Estrutura e funcionamento, portanto, estão relacionados. Tal relação é abordada pela teoria de redes complexas nos mais diversos sistemas, sendo possivelmente seu principal objeto de estudo. Neste trabalho exploramos as relações entre aspectos estruturais de redes neuronais e corticais e a atividade nas mesmas. Especificamente, estudamos como a interconectividade entre o córtex e o tálamo pode interferir em estados de ativação do último, considerando-se o sistema tálamo-cortical do gato bem como alguns modelos para geração de rede encontrados na literatura. Também abordamos a relação entre a morfologia individual de neurônios e a conectividade em redes neuronais, e consequentemente o impacto da forma neuronal em dinâmicas atuando sobre tais redes e a eficiência das mesmas no transporte de informação. Como tal eficiência pode ter como consequência a facilitação de processos maléficos às redes, como por exemplo, ataques causados por vírus neurotrópicos, também exploramos possíveis correlações entre características individuais dos elementos que formam as redes complexas e danos causados por processos infecciosos iniciados nos mesmos. Complex network theory has been consolidated along the last years, owing to its potential as a versatile framework for the study of diverse discrete systems. It is possible to enumerate applications in fields as distinct as Engineering, Sociology, Computing, Linguistics and Biology, to name a few. For instance, the study of the structural organization of the brain at the microscopic level (neurons), as well as at regional level (cortical areas), has deserved attention. It is believed that such organization aims at optimizing the dynamics, supporting processes like synchronization and parallel processing. Structure and functioning are thus interrelated. Such relation has been addressed by complex network theory in diverse systems, possibly being its main subject. In this thesis we explore the relations between structural aspects and the activity in cortical and neuronal networks. Specifically, we study how the interconnectivity between the cortex and thalamus can interfere in activation states of the latter, taking into consideration the thalamocortical system of the cat, along with networks generated through models found in literature. We also address the relation between the individual morphology of the neurons and the connectivity in neuronal networks, and consequently the effect of the neuronal shape on dynamic processes actuating over such networks and on their efficiency on information transport. As such efficiency can consequently facilitate prejudicial processes on the networks, e.g. attacks promoted by neurotropic viruses, we also explore possible correlations between individual characteristics of the elements forming such systems and the damage caused by infectious processes started at these elements.

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PIZZI, ERIKA. "MODULATORY ROLE OF MONOMERIC AMYLOID BETA ON NEURONAL EXCITABILITY AND ITS IMPLICATIONS ON SYNAPTIC ACTIVITY OF IMMATURE CORTICAL NEURONS." Doctoral thesis, Università degli Studi di Milano, 2018. http://hdl.handle.net/2434/546416.

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So far the amyloid hypothesis has mainly driven the Alzheimer's Disease (AD) drugs development; however most of the anti Aβ-clinical trials have been suspended due to the lack of significant cognitive improvements as well as to the side effects caused in AD patients in some studies. Although the negative outcomes of β- and γ-secretases targeting therapies are reasonable explained by the significant biological functions covered by such proteases, the reason Aβ-centric therapies fail is still unclear. Thus, to design a successful therapy for AD it is therefore crucial to uncover the role of soluble endogenous Aβ in the healthy brain. Even though the amyloid peptide has been extensively studied because of its association to AD, its physiological function(s) is now being studied in much more detail. My thesis work is part of the recently emerging idea that Aβ – at low concentrations - is not just a toxic waste product of the brain but it might be a relevant element involved in the maintenance of neuronal network homeostasis. Our final goal is therefore to explore the effects of the monomeric Aβ1-42 peptide on excitable cells.

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Boulos, Sherif. "Identification and characterisation of potential neuroprotective proteins induced by erythropoietin (EPO) preconditioning of cortical neuronal cultures." University of Western Australia. School of Biomedical and Chemical Sciences, 2008. http://theses.library.uwa.edu.au/adt-WU2008.0128.

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[Truncated abstract] Clinical therapeutic agents to directly inhibit ischaemic neuronal death are presently unavailable. One approach to developing therapeutics is based upon the identification of proteins up-regulated by 'preconditioning', a natural adaptive response utilised by the neural cells to counter damaging insults, such as ischaemia. Thus, my project aimed to firstly identify proteins differentially expressed following erythropoietin (EPO) mediated neuronal preconditioning and secondly to assess whether any of these proteins possessed neuroprotective activity using in vitro ischaemia like models. To achieve the first aim, it was shown that in vitro neuronal EPO preconditioning could: (i) induce cell signal changes in neuronal cultures, (ii) protect neurons against in vitro ischaemia and (iii) induce differential protein expression. Overall, 40 differentially expressed proteins were identified in cortical neuronal cultures following EPO preconditioning. In order to investigate the neuroprotective or neurodamaging activity of proteins induced by EPO preconditioning I developed an adenoviral expression system for use in neuronal cultures. To this end, I assessed the suitability of four promoters (cytomegalovirus [CMV], rous sarcoma virus [RSV], human synapsin 1 [hSYN1], rat synapsin 1 [rSYN1]) previously used to express proteins in neuronal cultures and demonstrated the superiority of the RSV promoter for this purpose. ... Finally, in order to validate this adenoviral expression system, I over-expressed the anti-apoptotic protein Bcl-XL in neuronal cultures and subsequently confirmed its neuroprotective activity in the in vitro ischaemia and oxidative stress models used in my project. Using this adenoviral vector system and the in vitro oxidative stress model I assessed a number of proteins up-regulated by EPO preconditioning. The results of this preliminary study indicated that cyclophilin A (CyPA), peroxiredoxin 2 (PRDX2) and superoxide dismutase 1 (SOD1) over-expression were neuroprotective. It was subsequently verified that adenoviral mediated over-expression of CyPA and PRDX2, v but not SOD1 in cortical neuronal cultures could protect neurons from in vitro ischaemia. I also confirmed that CyPA mRNA increased in the rat hippocampus in response to 3 minutes of global cerebral ischaemia. Interestingly, an increase in CyPA, PRDX2 or SOD1 protein was not observed in the same experimental paradigm. To investigate CyPA's mode of action I confirmed that cultured neurons, but not astrocytes, express the CyPA receptor, CD147. It was also demonstrated that administration of exogenous CyPA protein to neuronal cultures could protect neurons against oxidative and ischaemic injury. I further demonstrated that exogenous administration of CyPA induces a rapid and transient activation of the extracellular signal-regulated kinase (ERK) 1/2 pathway in neuronal cultures. From this observation, I have proposed that the extracellular mediated neuroprotective activity of CyPA occurs via CD147 receptor signalling and activation of ERK1/2 pro-survival pathways. Based on the findings reported in this thesis, the neuroprotective activities of PRDX2 and CyPA warrant further investigation as targets for the development of new therapies to treat cerebral ischaemia.

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Cheung, Suet-ting, and 張雪婷. "Effects of superoxide dismutase 1 on frontal cortical neurons." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B42924650.

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Cheung, Suet-ting. "Effects of superoxide dismutase 1 on frontal cortical neurons." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B42924650.

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Gibon, Julien. "Etude du rôle des canaux TRPC6 et de l'antidépresseur hyperforine dans l'homéostasie du zinc dans les neurones corticaux de souris." Phd thesis, Université de Grenoble, 2011. http://tel.archives-ouvertes.fr/tel-00634427.

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Les canaux TRPC6 sont des canaux cationiques non sélectifs perméables au calcium et au sodium. In vitro, ils laissent passer du manganèse, du baryum ou du fer. Ces canaux peuvent être activés par des analogues du diacylglycérol (SAG ou OAG) et par l'hyperforine (un antidépresseur d'origine végétal). Des expériences de dosages par ICP-OES, d'imagerie synchrotron et d'imagerie de fluorescence du FluoZin-3 ont montré que les cellules HEK surexprimant TRPC6 sont enrichies en zinc. Ces cellules sont plus sensibles à un stress oxydant et produisent plus d'espèces réactives de l'oxygène que les cellules HEK non transfectées. Dans les cellules HEK exprimant TRPC6, l'entrée de zinc en réponse au SAG est plus importante que celle observée dans les cellules HEK ou HEK-TRPC3. Les canaux TRPC6 sont exprimés dans les neurones corticaux. En réalisant des expériences d'imagerie de fluorescence et d'électrophysiologie, nous avons observé que l'activation de ces canaux par le SAG ou par l'hyperforine permettait l'entrée de zinc dans les neurones. La taille du pool de zinc fixé sur des protéines à groupement thiols est augmentée après un influx de zinc via TRPC6. Ceux-ci forment donc une voie d'entrée pour ce métal dans les neurones corticaux embryonnaires. Dans certains types cellulaires, les canaux TRPC6 participent à l'entrée calcique déclenchée en réponse à la déplétion du stock calcique du réticulum (canaux SOC). Cependant, dans les neurones corticaux, les voies SOC et activées par l'hyperforine possèdent des propriétés pharmacologiques distinctes suggérant que les canaux TRPC6 ne participent pas à la voie SOC. L'homéostasie des métaux dans les neurones est perturbée par l'hyperforine. Cet antidépresseur diminue la taille des pools de calcium et de zinc des mitochondries à la fois lors de traitements aigus et chroniques. Une relocalisation du zinc est observée dans les neurones traités de façon chronique à l'hyperforine ainsi qu'une augmentation de l'expression des métallothionéines à la fois in vitro et in vivo. Chez la souris, la quantité de soufre du cerveau est augmentée lors un traitement à l'hyperforine. Celle-ci serait donc un antidépresseur qui module les capacités de stockage du zinc en augmentant le nombre de groupements thiols cellulaires. L'hyperforine est présente dans les extraits de millepertuis. Ceux-ci ont diverses cibles pharmacologiques, agissant notamment sur la voie de signalisation du BDNF. Nos expériences montrent que, lors d'un traitement chronique de souris adultes, l'hyperforine augmente l'expression de TrkB et P-TrkB dans le cortex. In vitro, dans les neurones corticaux, TrkB, CREB et P-CREB sont surexprimés après un traitement de trois jours à l'hyperforine. L'inhibition de la PKA ou le blocage des canaux TRPC6 par le SKF-96365 empêche l'effet de l'hyperforine. Par ailleurs, la chélation du calcium par le BAPTA-AM supprime partiellement l'effet de l'hyperforine. Un traitement chronique avec cet extrait végétal semble agir sur une voie dépendante de la PKA et du calcium pour réguler la phosphorylation de CREB et l'expression de TrkB. Nos expériences montrent que l'effet de l'hyperforine sur les acteurs de la voie du BDNF n'est pas présent au niveau de l'hippocampe où l'expression de TrkB n'est pas affectée. De plus, ces traitements n'influencent pas la neurogenèse adulte chez la souris. L'hyperforine seule n'explique donc pas les effets complexes des extraits de millepertuis sur les activités neuronales.

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Dehghani, Nima. "Electromagnetic signature of human cortical dynamics during wakefulness and sleep : = Signature électromagnétique de la dynamique corticale pendant l'éveil et le sommeil chez l'homme." Phd thesis, Université Pierre et Marie Curie - Paris VI, 2012. http://tel.archives-ouvertes.fr/tel-00728697.

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L'analyse de la fonction cérébrale à de multiples échelles est une étape nécessaire pour comprendre ses complexités. Dans ce travail de thèse, nous avons étudié cet aspect aux niveaux microscopiques et macroscopiques en utilisant des enregistrements invasifs et non-invasifs. Nous avons utilisé une série d'outils d'analyse communicationnels et de corrélation pour étudier l'activité cérébrale pendant l'éveil et le sommeil. Dans une première étude, nous avons analyse les enregistrements simultanés d'electroencephalogramme (EEG) etmagnetoencephalogramme (MEG) dans le cerveau de sujets éveillés. Nous montrons théoriquement, que si le milieu est résistif, le comportement d'échelle en fréquence doit être le même pour les signaux EEG and MEG à basse fréquence (˂10 Hz). Afin de tester cette prédiction, nous avons analyse le spectre d'enregistrements EEG et MEG simultanés de quatre sujets humains. Le comportement d'échelle en fréquence de l'EEG montre des variations cohérentes sur la surface du cerveau, avec des exposants en général compris entre 1/ f et 1/ f 2; ces exposants tendent à être plus faibles dans les régions temporales et pariétales. Dans une région donnée, les exposants de la MEG ont une variabilité plus grande que pour l'EEG, mais les deux signaux ont systématiquement un exposant différent. Dans certains cas, les exposants sont proches, mais ces cas correspondent 'a un mauvais rapport signal/bruit pour la MEG. Plusieurs méthodes de corrections du bruit instrumental et environnemental ont été testées, et dans tous les cas, ces méthodes augmentent la différence de comportement spectral entre l'EEG et la MEG. En conclusion, il y a une différence significative de comportement d'échelle en fréquence entre EEG et MEG, ce qui peut être explique si le milieu extracellulaire (incluant d'autres couches telles que la dure-mère et le crane) est globalement non-résistif. La nature résistive ou non-résistive du milieu extracellulaire est un déterminant important pour la modélisation des potentiels extracellulaires. Au cours d'une seconde étude, nous avons analyse la dynamique spatio-temporelle de l'excitation et de l'inhibition pendant le sommeil 'a partir d'enregistrements intra-crâniens à haute densité. Ces enregistrements à haute densité permettent la séparation efficace entre cellules "regular spiking" (RS) et "fast spiking" (FS). La haute densité des électrodes permet d'obtenir des connections apparemment mono-synaptiques, et de corroborer cette séparation RS-FS avec la nature excitatrice ou inhibitrice de la connexion. Cette procédure confirme que les cellules classifiées comme FS sont toujours inhibitrices, alors que les RS sont toujours excitatrices, et donc peuvent être classifiées respectivement comme cellules pyramidales ou interneurones inhibiteurs. Finalement, nous investiguons la dynamique des corrélations au sein de chaque classe de neurone. Les corrélations entre excitateurs montrent une décroissance exponentielle avec la distance, tandis que les cellules inhibitrices restent corrélées 'a plus grande distance. L'amplitude des corrélations dépend de l'échelle temporelle du calcul de corrélation, mais pas la constante spatiale. Cette constante est compatible avec la taille typique des colonnes corticales chez l'homme. Ces résultats permettent, pour la première fois, de caractériser l'activité neuronale et l'interaction entre excitation et inhibition dans le néocortex humain. Dans une troisième étude, nous avons investigue les signatures de la dynamique complexe et l'activité auto-organisée, à partir d'enregistrements intra-crâniens chez le chat, le singe et l'homme. Nous utilisons des enregistrements à haute densité dans le cortex moteur du chat (96 électrodes), le cortex moteur et prémoteur du singe et dans le cortex temporal humain (96 électrodes) de patients épileptiques. Lors d'avalanches définies à partir d'unités (jusqu''a 160 neurones), les distributions ne se comportent pas en loi de puissance, mais tendent à être exponentielles ou intermédiaires. Nous analysons également les potentiels de champ (LFPs), et en particulier les pics négatifs (nLFPs) au sein de l'ensemble d'électrodes (de 96 a 128 sites, selon la configuration d'enregistrement). Dans ce cas, les avalanches définies à partir des nLFPs peuvent se comporter en loi d'échelle, comme observé précédemment chez le singe. Cependant, les avalanches définies à partir des pics positifs (pLFPs), qui ne sont pas directement reliées aux décharges des neurones, ont le même comportement. Une analyse plus détaillée en utilisant la représentation cumulée (CDF) ne confirme pas la présence de loi de puissance. Les mêmes résultats s'appliquent au chat, au singe et aux enregistrements humains, pendant différents états cérébraux d'éveil et de sommeil. Nous avons également testé des distributions alternatives, et des processus multi-exponentiels semblent expliquer les distributions obtenues, de fac¸on optimale pour des distributions bi-exponentielles. L'ensemble de ces résultats ne montrent pas d'évidence de loi de puissance ou d'états critiques dans le cerveau éveillé ou en sommeil de différents mammifères, du chat 'a l'homme. Finalement, dans un appendice, nous montrons des résultats préliminaires concernant les relations entre cellules excitatrices et inhibitrices, et les potentiels de champ locaux pendant le sommeil humain. Nous avons pu séparer les cellules entre "regular-spiking" (RS) et "fastspiking" (FS), ce qui a été confirmé par connections monosynaptiques (voir Peyrache et al., PNAS, 2012). Nous analysons ici la décharge spécifique des cellules RS et FS pendant différents états d'éveil et de sommeil, sélectionnés sans activité interictale. Jusqu''a 92 unités enregistrées simultanément, procurent une base solide pour la caractérisation de la dynamique de l'excitation et de l'inhibition pendant ces différents états. Pendant le sommeil lent (Stade III ou IV), domine par les ondes lentes de type delta, tous les neurones déchargent selon des états "Up" ou "Down", en relation avec les ondes lentes du LFP, comme décrit précédemment. Les cellules RS et FS sont toutes silencieuses pendant les états "Down". Pendant le sommeil REM et pendant l'éveil, les neurones déchargent de fac¸on irrégulière alors que le LFP ou l'ECoG sont désynchronisées. Dans tous les états les cellules FS déchargent plus que les cellules RS (4 ou 5 fois plus en moyenne). En conclusion, ces résultats procurent une caractérisation des différents rôles de l'excitation et de l'inhibition pendant l'éveil et le sommeil chez l'homme. En conclusion, nous avons utilisé différentes méthodes de mesure, aux échelles microscopiques (activité unitaire), mésoscopique (LFP) etmacroscopiques (ECoG, EEG,MEG), pour caractériser les états de veille et sommeil chez l'homme (ainsi que chez le chat et le singe dans une étude). Nous concluons que le cerveau suit une dynamique complexe à toutes les échelles. Il n'y a pas d'évidence de dynamique auto-organisée critique, mais l'activité du cerveau manifeste d'autres signes d'auto-organisation, comme l'activité synchrone à grande distance et des processus multi-exponentiels. Nous suggérons que ces résultats peuvent être expliques par l'interaction entre excitation et inhibition. Nous anticipons que des réseaux d'oscillateurs couples, avec interaction entre excitation et inhibition, devraient pouvoir expliquer ces résultats. Cette perspective constitue un défi pour des études futures.

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Alecu, Lucian. "Une approche neuro-dynamique de conception des processus d'auto-organisation." Phd thesis, Université Henri Poincaré - Nancy I, 2011. http://tel.archives-ouvertes.fr/tel-00606926.

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Dans ce manuscrit nous proposons une architecture neuronale d'inspiration corticale, capable de développer un traitement émergent de type auto-organisation. Afin d'implémenter cette architecture neuronale de manière distribuée, nous utilisons le modèle de champs neuronaux dynamiques, un formalisme mathématique générique conçu pour modéliser la compétition des activités neuronales au niveau cortical mésoscopique. Pour analyser en détail les propriétés dynamiques des modèles de référence de ce formalisme, nous proposons un critère formel et un instrument d'évaluation, capable d'examiner et de quantifier le comportement dynamique d'un champ neuronal quelconque dans différents contextes de stimulation. Si cet instrument nous permet de mettre en évidence les avantages pratiques de ces modèles, il nous révèle aussi l'incapacité de ces modèles à conduire l'implantation des processus d'auto-organisation (implémenté par l'architecture décrite) vers des résultats satisfaisants. Ces résultats nous amènent à proposer une alternative aux modèles classiques de champs, basée sur un mécanisme de rétro-inhibition, qui implémente un processus local de régulation neuronale. Grâce à ce mécanisme, le nouveau modèle de champ réussit à implémenter avec succès le processus d'auto-organisation décrit par l'architecture proposée d'inspiration corticale. De plus, une analyse détaillée confirme que ce formalisme garde les caractéristiques dynamiques exhibées par les modèles classiques de champs neuronaux. Ces résultats ouvrent la perspective de développement des architectures de calcul neuronal de traitement d'information pour la conception des solutions logicielles ou robotiques bio-inspirées.

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Gouder, Laura. "Etude de l'effet de mutations du gène SHANK3 dans les TSA à partir de neurones corticaux humains dérivés de cellules souches pluripotentes induites." Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCB089/document.

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Les Troubles du Spectre Autistique (TSA) affectent un individu sur 100 en France et sont caractérisés par des déficits de la communication et des interactions sociales ainsi que par la présence d’intérêts restreints et de comportements répétitifs. Le laboratoire a démontré l’implication de protéines synaptiques dans le développement des TSA et en particulier celle des protéines SHANK. Ces protéines sont des protéines d’échafaudage présentes au niveau de la densité post-synaptique (PSD) des neurones glutamatergiques et interagissant avec différents partenaires. Dans le cadre de mon projet de thèse, nous nous sommes particulièrement intéressés à la protéine SHANK3. Des mutations au sein du gène SHANK3 ont été détectées chez environ 1 à 2% des patients, selon le degré de sévérité du retard mental. Un déficit de SHANK3 altère le fonctionnement synaptique. En effet, des analyses sur modèles de souris invalidées pour le gène SHANK3 ont montré une diminution de la densité des épines dendritiques, de la taille de la densité post-synaptique et de l’expression des partenaires protéiques de SHANK3. Mon modèle principal d’analyse a consisté en la reprogrammation de fibroblastes en cellules pluripotentes induites (iPSC « induced pluripotent stem cells »). Les iPSCs ont ensuite été sélectivement dérivées en neurones corticaux. Nos études se sont focalisées sur l’analyse des conséquences fonctionnelles de mutations de novo du gène SHANK3 retrouvées chez 4 patients à l’état hétérozygote et présentes au sein de l’exon 21. Ces mutations conduisent à un codon stop prématuré. En parallèle, nous avons obtenu des cellules de 4 individus témoins ne présentant aucun trouble psychiatrique identifié. L’analyse a porté d’une part sur des aspects morphologiques et d’autre part sur des aspects fonctionnels. Nous avons étudié l’effet des mutations sur la maturation et les caractéristiques morphologiques des épines dendritiques. Nous avons établi un protocole permettant une analyse détaillée de la morphologie en 3D des épines dendritiques et suivi leur maturation. Un résultat majeur est l’observation d’une diminution de la densité des épines sur les dendrites des neurones pyramidaux issus des patients par rapport aux témoins. Comme attendu, la maturation des épines n’est pas complètement achevée mais varie peu dans son évolution d’un individu à l’autre (témoins vs. patients). Nous avons poursuivi ces études par deux approches fonctionnelles : l’imagerie calcique et des études d’électrophysiologie. Les données électrophysiologiques sont en cours d’analyse. En conclusion, nous avons pu obtenir des cultures de neurones corticaux glutamatergiques et les maintenir en culture durant 40 jours pour effectuer différentes analyses à un stade de maturation suffisant pour la mise en évidence de phénotypes morphologiques et fonctionnels. Nous avons principalement observé une diminution de des densités synaptiques et de maturation des épines dendritiques au sein des neurones issus de patients liée à des altérations d’oscillations calciques spontanées Autism Spectrum Disorders (ASD) is a neurodevelopmental disorder affecting 1% of population ; characterised by impairments in social interaction and reciprocal communication as well as repetitive and stereotyped behaviors. The work of the laboratory lead to the identification of several genes associated with ASD, among which genes of the synaptic pathway such as SHANK. The SHANK proteins are scaffolding proteins of the post-synaptic density (PSD) of glutamatergic neurons and interact with several partners. In my thesis project, we were particularly interested in SHANK3 mutations. First, Shank3 mutations represent up to 2.12% of ASD cases with moderate to high ID. A SHANK3 deficit leads to the alteration of the synaptic functioning. Indeed, studies of mice KO for SHANK3 gene showed a decrease of the dendritic spines density, of the PSD size and of the expression of SHANK3 partners. My principal model of analysis consisted in the reprogrammation of fibroblasts into induced pluripotent stem cells (iPSCs). Then, the iPSCs were selectively derived into cortical neurons. Our studies were focus on the analysis of functional consequences of SHANK3 de novo mutations found within 4 patients. These mutations are heterozygous and within the exon 21. They result in a premature stop codon. In parallel, we obtained cells from 4 healthy individuals. The work was about the morphological and functional aspects. We analysed the mutations effects on the maturation and morphological caracteristics of the dendritic spines. We finalized a protocol that enabled a detailed analysis of the spine dendritic 3D morphology and their maturation follow-up. A important result was the observation of a decrease of the spine density on pyramidal neurons dendrites from patients compared to those from controls. Moreover, spines maturation was not fully accomplished but was not much different in its evolution between individuals (controls vs patients). Then, we used two functional skills : calcium imaging and electrophysiological experiments. The electrophysiological data are in progress. To conclude, we succeeded in the obtention of glutamatergic cortical neurons and to maintain them in culture during 40 days in order to realize some analysis at a sufficient maturation stage to observe morphological and functional phenotypes. We mainly observed a decrease of the dendritic spines density and maturation for the neurons from patients, with alterations of the spontaneous calcium oscillations

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Napoli, Alessandro. "DISSOCIATED NEURONAL NETWORKS AND MICRO ELECTRODE ARRAYS FOR INVESTIGATING BRAIN FUNCTIONAL EVOLUTION AND PLASTICITY." Diss., Temple University Libraries, 2014. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/269449.

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Electrical Engineering Ph.D. For almost a century, the electrical properties of the brain and the nervous system have been investigated to gain a better understanding of their mechanisms and to find cures for pathological conditions. Despite the fact that today's advancements in surgical techniques, research, and medical imaging have improved our ability to treat brain disorders, our knowledge of the brain and its functions is still limited. Culturing dissociated cortical neurons on Micro-Electrode Array dishes is a powerful experimental tool for investigating functional and structural characteristics of in-vitro neuronal networks, such as the cellular basis of brain learning, memory and synaptic developmental plasticity. This dissertation focuses on combining MEAs with novel electrophysiology experimental paradigms and statistical data analysis to investigate the mechanisms that regulate brain development at the level of synaptic formation and growth cones. The goal is to use a mathematical approach and specifically designed experiments to investigate whether dissociated neuronal networks can dependably display long and short-term plasticity, which are thought to be the building blocks of memory formation in the brain. Quantifying the functional evolution of dissociated neuronal networks during in- vitro development, using a statistical analysis tool was the first aim of this work. The results of the False Discovery Rate analysis show an evolution in network activity with changes in both the number of statistically significant stimulus/recording pairs as well as the average length of connections and the number of connections per active node. It is therefore proposed that the FDR analysis combined with two metrics, the average connection length and the number of highly connected "supernodes" is a valuable technique for describing neuronal connectivity in MEA dishes. Furthermore, the statistical analysis indicates that cultures dissociated from the same brain tissue display trends in their temporal evolution that are more similar than those obtained with respect to different batches. The second aim of this dissertation was to investigate long and short-term plasticity responsible for memory formation in dissociated neuronal networks. In order to address this issue, a set of experiments was designed and implemented in which the MEA electrode grid was divided into four quadrants, two of which were chronically stimulated, every two days for one hour with a stimulation paradigm that varied over time. Overall network and quadrant responses were then analyzed to quantify what level of plasticity took place in the network and how this was due to the stimulation interruption. The results demonstrate that here were no spatial differences in the stimulus-evoked activity within quadrants. Furthermore, the implemented stimulation protocol induced depression effects in the neuronal networks as demonstrated by the consistently lower network activity following stimulation sessions. Finally, the analysis demonstrated that the inhibitory effects of the stimulation decreased over time, thus suggesting a habituation phenomenon. These findings are sufficient to conclude that electrical stimulation is an important tool to interact with dissociated neuronal cultures, but localized stimuli are not enough to drive spatial synaptic potentiation or depression. On the contrary, the ability to modulate synaptic temporal plasticity was a feasible task to achieve by chronic network stimulation. Temple University--Theses

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Grunwald, Lena-Marie [Verfasser], and Hans-Georg [Akademischer Betreuer] Rammensee. "iPSC-derived cortical neurons from patients with schizophrenia exhibit changes in early neuronal development / Lena-Marie Grunwald ; Betreuer: Hans-Georg Rammensee." Tübingen : Universitätsbibliothek Tübingen, 2019. http://d-nb.info/120091614X/34.

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Fisahn, Andre. "An investigation into cortical gamma frequency oscillations in vitro." Thesis, University of Oxford, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.302129.

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Pinches, Elizabeth Margery. "The contribution of population activity in motor cortex to the control of skilled hand movement in the primate." Thesis, University College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.391516.

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Dimidschstein, Jordane. "Ephrin-B1 controls the spatial distribution of cortical pyramidal neurons by restricting their tangential migration." Doctoral thesis, Universite Libre de Bruxelles, 2012. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209658.

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During development of the cerebral cortex, the various neuronal subtypes have to reach their correct final position in the post mitotic compartment where they complete their maturation and eventually establish functional networks. Precise positioning of individual neurons is acquired through tight regulation of the multiple transitions that neurons undergo on their way to the cortical plate. Neurons of the cerebral cortex are organized in layers and columns. Although several molecular mechanisms have been identified that control the final position of neurons along the radial dimension of the cortex (i.e. layer specificity), much less is known about how their final tangential, or mediolateral, distribution is controlled. However this may have a direct impact on the structural and functional organization of cortical columns, since sister neurons derived from the same progenitor display selective patterns of connectivity with each other and/or share similar functional properties. Here we studied the role of B-ephrins in the control of migration of cortical pyramidal neurons. Gain of function experiments using in utero electroporation of ephrin-B1 revealed a striking alteration of the tangential distribution of pyramidal neurons during the multipolar stage of radial migration, resulting in clustering of the pyramidal neurons in the cortical plate. Conversely, clonal analysis of migrating neurons in ephrin-B1 knockout mice showed a wider mediolateral dispersion of cortical neurons. Static and dynamic analyses of migrating neurons revealed that ephrin-B1 modulates the morphology of pyramidal neurons during their multipolar phase, thereby restricting their tangential migration at that stage. Our results demonstrate that ephrin-B1 is a specific inhibitor of non-radial migration of pyramidal neurons, thereby controlling the pattern of cortical columns. These data shed new light on this important aspect of pyramidal neuronal migration, and illustrate how alterations of patterns of migration can affect cortical column organization. Doctorat en Sciences biomédicales et pharmaceutiques info:eu-repo/semantics/nonPublished

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Fricker, M. "Bcl-2 family proteins and cell death in cortical neurons." Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.599226.

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This thesis explores the function and regulation of a subset of Bcl-2 proteins, the pro-apoptotic BH3-only proteins (BOPs), in cortical neuron apoptosis. Sodium arsenite (NA) is used as a model toxin in murine cortical murine cultures. Three BOPs were upregulated, Puma, Noxa and Bim. Primary cortical neuron cultures derived from mice lacking Puma, Noxa or Bim expressions were used to demonstrate that Puma, but not Bim or Noxa, was required for execution of NA-induced apoptosis. Adenovirus-mediated expression of exogenous Puma in cortical neurons was sufficient to induce cytochrome c release form mitochondria and apoptosis in a Bax-dependent manner, implicating Puma as an important upstream activator of Bax in cortical neurons. Furthermore, Puma knockout afforded cortical neurons substantial protection against many apoptotic insults, establishing Puma as an important apoptotic mediator of a variety of disease-relevant apoptotic signalling pathways. Whilst some insults induced Puma expression and apoptosis in a p53-dependent manner, others, including NA and ER stress, were predominantly p53-independent. NA treatment resulted in an accumulation of TA-p73α and a p53-independent increase in a number of p53/p63/p73 target genes, indicating that p73 may be involved in Puma induction. Expression of the inhibitory ΔNp73α and –β isoforms largely prevented NA-mediated induction of Puma and other p53/p63/p73 target genes, as well as protecting neurons from NA-induced apoptosis. In addition, luciferase assays using Puma promoter fragments demonstrated that the promoter region encompassing the p53 response elements was required for arsenite-mediated activation of the Puma motor. Finally, a novel post-translational modification of Puma was investigated using cell lines. Puma-α is phosphorylated at several sites in cycling cells, the major site being serine 10. Initial experiments have failed to identify a functional consequence of Puma phosphorylation, although the identification if casein-kinase I as a candidate Puma kinase merits further investigation.

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Vargas-Caballero, Mariana. "NMDA receptor kinetics and synaptic integration in cortical pyramidal neurons." Thesis, University of Cambridge, 2004. https://www.repository.cam.ac.uk/handle/1810/270446.

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Understanding the synaptic function of N-methyl-D-aspartate receptors (NMDARs) and their contribution to membrane excitability requires a better comprehension of their kinetics in physiological conditions. Most previous studies of NMDAR gating have focussed on responses to jumps in agonist or blocker concentrations, or on single-channel gating at equilibrium. This thesis exposes the kinetics of NMDARs in nucleated patch and whole-cell recordings of rat cortical pyramidal neurons during nonstationary conditions of voltage and agonist concentration. It was found that the timing of voltage-dependent removal of Mg2+ block of NMDARs can determine their nonlinear contribution to excitability. At room temperature, the observed kinetics of unblock showed a very fast component (t < 1 ms), together with a slower component (t = 10-40ms). The amplitude and time constant of the slow component both increased with depolarisation, and it accounted for half of the current for steps from -70 to +40 mV. Block was effectively instantaneous for voltage steps from +40 to -70 mV, but had major slow components for steps from +40 to -40 mV, where up to 40% of current blocks with time constants between 3 and 6 ms. Additionally, the voltage-dependence of deactivation kinetics were studied in nucleated patches during fast and sustained perfusion with agonist. Currents at +40 mV had a time-constant of decay two-fold larger than those at -40 mV. The voltage dependence observed was, however, much less pronounced than suggested previously (Konnerth et al, 1990). This discrepancy may be explained by the improved space clamp conditions and calcium buffering achieved with nucleated patches as compared to whole cell recordings. Depolarisations from rest at different time intervals during the decay phase recovered a current of similar amplitude to that recorded during sustained depolarisation. The observations on block/unblock during voltage steps and voltage dependence of decay strongly suggest a Mg2+ -trapping block mechanism for the NMDAR. However, a trapping block kinetic scheme with identical rate constants for the receptor bound and unbound to Mg2+ (Sovolebsky and Yelshansky, 2000) does not predict the slow unblock and fast tail currents observed after a depolarising voltage step. Instead, the slow unblock was found to be consistent with faster closing kinetics for the channel when it is bound to Mg2+, which was termed an asymmetric trapping block (ATB) model. During nonstationary voltage conditions, the observed time-dependence of block and unblock results in a very different pattern of activation from the instantaneous I-V relation that has been assumed for the NMDAR in previous modelling studies. Voltage-clamp of nucleated patches with action potential waveforms, at both room temperature and at 33°C, during stationary NMDAR activation, showed that the rising phase of single Na+ action potentials unblocks far less NMDAR current than expected from the stationary voltage-dependence, while a large current is uncovered during the upstroke of slow Ca2+ action potentials. The repolarisation of fast Na+ action potentials uncovers an NMDAR tail current, much bigger than the predicted steady-state level of current. Thus, retarding the boosting effect of depolarisation and resisting the repolarisation, and therefore prolonging, dendritic Ca2+ spikes. The functional consequences of slow unblock were studied in a simple model of pyramidal cell excitability.

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Mikasová, Lenka. "Dynamic behavior of surface CB1R in cortical neurons in vitro." Bordeaux 2, 2008. http://www.theses.fr/2008BOR21529.

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Les récepteurs cannabinoide type 1 (CB1R) médient la plasticité synaptique rétrograde dans les synapses excitatrices et inhibitrices et participent à de multiples fonctions physiologiques. Les mouvements de surface des récepteurs présynaptiques, tels que les CB1R, restent inconnus. Nous avons analysé la mobilité latérale des CB1R natifs sur les neurones corticaux, par imagerie du suivi de quantum dot unique. Nous avons trouvé que les CB1R sont mobiles et diffusent rapidement dans les présynapses. La désensibilisation, induite par un agoniste, diminue le nombre des CB1R de surface et réduit considérablement la dynamique membranaire des CB1R restant sur la surface présynaptique. La désensibilisation éliminerait les CB1R des synapses et augmenterait le nombre des récepteurs immobiles dans le compartiment extrasynaptique. Nos résultats suggèrent que la réduction de la mobilité pourrait être un des principaux mécanismes de la désensibilisation des CB1Rs, le plus abondant récepteur couplé aux protéines G dans le cerveau Presynaptic cannabinoid type 1 receptors (CB1R) are major mediators of retrograde synaptic plasticity at both excitatory and inhibitory synapses and participate to a plethora of physiological functions. Whether presynaptic receptors, such as CB1R, display functionally relevant movements at the surface of neuronal membrane is not known. We analyzed the lateral mobility of native CB1R in cortical neurons, using single quantum dot imaging. We found that CB1R are highly mobile and rapidly diffuse in and out of presynapses. Agonist-induced desensitization reduced the number of surface CB1R and drastically decreased the membrane dynamic of the CB1R that remained at the presynaptic surface. Desensitization specifically excluded CB1R from synapses and increased the number of immobile receptors in the extrasynaptic compartment. The results suggest that decrease of mobility may be one of the core mechanisms underlying the desensitization of CB1R, the most abundant G-protein coupled receptor in the brain

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Anastasiades, Paul George. "Integration strategies of cortical neurons in the early postnatal neocortex." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/11680.

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Over the course of the first three postnatal weeks the cells of the neocortex undergo considerable maturation. My aim was to track some of the changes that occur, to create a detailed electrophysiological study of the postnatal neocortex. This would allow me to better understand the developmental journeys taken by discrete neuronal populations within the maturing network. To this end, I used glutamate uncaging and whole-cell patch-clamp electrophysiology to record from neocortical pyramidal cells and Nkx2-1 derived interneurons located in different cortical layers and regions of the cortex between postnatal days (P) 5-21. In so doing I was able to track the maturation of their intrinsic electrophysiology and synaptic connectivity. The electrophysiological properties of cortical neurons develop markedly over the course of development and there is a gradual emergence of distinct electrophysiological firing types amongst both pyramidal cells and interneurons. In terms of their synaptic inputs pyramidal neurons and interneurons possess unique methods of synaptic integration. Pyramidal neurons show a stereotyped pattern of input maturation, whereby there is a gradual emergence of the mature, canonical pattern of input. This is predicted by translaminar, NMDA receptor mediated inputs at early ages, that likely act as the substrate for the formation of mature AMPA receptor containing synapses. In contrast Nkx2-1 derived interneurons showed no shift in laminar input organization over the course of development, with prominent inputs observed from the earliest ages of the study. However, there seems to be a significant degree of heterogeneity in the organization of these inputs and I provide some insight into this variation. Taken together these findings provide a picture of the connectivity of the early network and using these data I am able to produce a final hypothesis, which shows how interneurons and pyramidal cells may interact to produce the canonical pattern of cortical connectivity.

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Honda, Kazuhiro. "Nongenomic antiapoptotic signal transduction by estrogen in cultured cortical neurons." Kyoto University, 2002. http://hdl.handle.net/2433/149665.

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Yokota, Yukako Anton Eva S. "Nap1 regulated cytoskeletal dynamics during cortical neuronal development." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2007. http://dc.lib.unc.edu/u?/etd,1272.

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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2007. Title from electronic title page (viewed Mar. 26, 2008). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Cell and Molecular Physiology, School of Medicine." Discipline: Cell and Molecular Physiology; Department/School: Medicine.

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NIGRO, MARCO. "Cortical and subcortical neuronal substrates of social behavior." Doctoral thesis, Università degli studi di Genova, 2019. http://hdl.handle.net/11567/939848.

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Social behavior is one of the most important properties of animal life and it plays a critical role in biological adaptations. However, the neural substrates of social cognitive processing are complex and largely unknown. The “social brain” network, involving a range of cortical and subcortical regions and connective pathways, varies depending on task demands. The aim of this thesis was to clarify the implication of different brain pathways and systems in different aspects of mice social behavior. The work presented in the first two chapters of the thesis was to develop and validated a new behavioral test to assess the ability to discriminate unfamiliar conspecific based on their emotional state. The results provide significant new insights on the role of the PVN-CeA oxytocin pathway and the implication of an excitatory and inhibitory imbalance in mPFC as core behavioral dysfunctions in social cognitive deficits. The last part of the thesis was focused more on the investigation of the behavioral and physiological effects produced by pharmacological treatment (oxytocin). In particular, taking advantage of the effects oxytocin produced in a mouse model of genetic liability, we investigated the physiological mechanisms of exogenous oxytocin action in the mPFC. All the results presented in this thesis indicate mixed molecular factors for the different social and brain response in mice that may be crucial in the aetiology of the social disease.

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Toups, Jonathan Vincent Tiesinga Paul. "Representation and selection of time-varying signals by single cortical neurons." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2009. http://dc.lib.unc.edu/u?/etd,2750.

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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2009. Title from electronic title page (viewed Mar. 10, 2010). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Physics and Astronomy." Discipline: Physics and Astronomy; Department/School: Physics and Astronomy.

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Woolnough, Oscar. "Cortical adaptation and frequency selectivity : from single neurons to evoked potentials." Thesis, University of Nottingham, 2017. http://eprints.nottingham.ac.uk/41169/.

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Adaptation is a reduction in a neural response to a sensory stimulus resulting from repeated presentation of the stimulus and is an important aspect of sensory neural coding. This phenomenon is sensitive to changes in parameters of the repeating stimuli and the adaptation will be greatest when the stimuli are identical and diminish with changes in stimulus parameters between repetitions. In the auditory system it has been shown the specificity of cortical adaptation relates primarily to the frequency of a stimulus, with wider frequency separations between sequentially presented stimuli resulting in a reduced level of adaptation. This frequency specific adaptation has been measured at multiple scales, in EEG recordings in humans and at the single unit level in animals but the results from each implicate different underlying neural mechanisms. This thesis attempts to elucidate some of those differences by investigating the effects of the differences in methodology between the studies, the inter-species differences in adaptation characteristics and the effects of anaesthesia on sensory neural processing. This touches upon the forward and inverse modelling problems in computational neuroscience and also the issues with relating results from EEG in awake humans with single neuron recordings in anaesthetised animals. The thesis starts by building on previous work looking at whether the frequency selectivity of adaptation can be changed by the temporal properties of the adapting stimuli. It was found that a sharpening of frequency selectivity of adaptation could be induced by using multiple repeated adapters but not with single onset, prolonged duration adapters. This repetition induced sharpening was also shown to act independently of attention despite there being an attentionally induced sharpening effect on adaptation. This EEG adaptation tuning was explained by an extension of a computational model previously proposed to explain stimulus specific adaptation and oddball responses in single neurons. The model was a two-layer network with independently adapting synapses and is able to quantitatively reproduce the observed non-monotonic adaptation and sharpening of tuning observed in our EEG responses, and the effects of repeated and prolonged adapters. To further investigate this then this study was replicated in an anaesthetised animal model with recordings directly from auditory cortex. This study showed none of the repetition induced sharpening effects and dramatically quantitatively different adaptation results compared to the human studies. To help explain these results then recordings were made in awake guinea pigs with chronically implanted intracranial EEG electrodes and invasive depth electrodes to discover whether these differences were a result of species or anaesthesia. These experiments start to explain some of the discrepancies seen before, with adaptation time constants orders of magnitude different to those in humans and differences in their innate frequency selectivity. Alongside this then the effects of anaesthesia on the results were investigated under a range of anaesthetic regimes including opiates, NMDA antagonists and GABA potentiators. It was shown that anaesthetic choice has substantial effects on sensory signalling, temporal processing and cross-modal interactions which result in multifaceted effects on the characteristics of adaptation. This thesis builds on previous work on the plasticity of frequency selectivity of adaptation in auditory cortex and helps to characterise this phenomenon and explain its mechanisms. This work also highlights the difficulties of directly relating studies and findings between humans and animal studies of the auditory system, demonstrating the magnitude of difference in temporal and frequency processing between species and also shows the substantial changes in sensory processing induced by anaesthesia and modulated by anaesthetic choice.

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Hirai, Daichi. "Shaping somatosensory responses in awake rats: cortical modulation of thalamic neurons." Kyoto University, 2018. http://hdl.handle.net/2433/232070.

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Chan, Yee-Ka Agnes. "The role of Tm5NM1/2 on early neuritogenesis." Thesis, The University of Sydney, 2009. http://hdl.handle.net/2123/5865.

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The actin cytoskeleton is important in many cellular processes such as motility, and establishing and maintaining cell morphology. Members of the tropomyosin protein family associate with the actin cytoskeleton along the major groove of actin filaments (F-actin), stabilising them and regulating actin-filament dynamics. To date over 40 non-muscle tropomyosin isoforms have been identified, which are encoded by 4 different genes (α, β, γ, δ). Individual tropomyosin isoforms define functionally distinct F-actin populations. Previous studies have shown that tropomyosins sort to distinct subcellular compartments at different stages of development in polarised cells. Neuronal growth cones are highly dynamic polarised structures, dependent on a constant reorganisation of the actin cytoskeleton. By eliminating tropomyosins in a knockout (KO) mouse model, we investigated the role of two tropomyosin isoforms, Tm5NM1 and Tm5NM2 (γTm gene products) in growth cone dynamics and neurite outgrowth. Growth cone protrusion rates were significantly increased in one day old Tm5NM1/2 KO hippocampal neurons compared to WT controls. Neuritogenesis was significantly affected by the elimination of Tm5NM1/2, with a slight decrease in neurite length and an increase in neuronal branching in neurons cultured for four days. At the molecular level, the depletion of Tm5NM1/2 had no impact on the protein levels and activity of ADF/cofilin in hippocampal neurons while in cortical neurons a subtle but significant increase in ADF/cofilin activity was observed. The subtle phenotype in the early stages of neuritogenesis observed from eliminating Tm5NM1/2 may be explained with functional compensation by other tropomyosin isoforms. Functional compensation for the loss of Tm5NM1/2 may be provided by isoforms Tm5a/5b, TmBr2 and Tm4 as they localise to the growth cones, structures where Tm5NM1/2 are normally found. These results suggest that Tm5NM1/2 may not be required for early stages of neuritogenesis but may still play a fine-tuning role for this process.

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Chan, Yee-Ka Agnes. "The role of Tm5NM1/2 on early neuritogenesis." Discipline of Paediatrics and Child Health, 2009. http://hdl.handle.net/2123/5865.

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Master of Philosophy (Medicine) The actin cytoskeleton is important in many cellular processes such as motility, and establishing and maintaining cell morphology. Members of the tropomyosin protein family associate with the actin cytoskeleton along the major groove of actin filaments (F-actin), stabilising them and regulating actin-filament dynamics. To date over 40 non-muscle tropomyosin isoforms have been identified, which are encoded by 4 different genes (α, β, γ, δ). Individual tropomyosin isoforms define functionally distinct F-actin populations. Previous studies have shown that tropomyosins sort to distinct subcellular compartments at different stages of development in polarised cells. Neuronal growth cones are highly dynamic polarised structures, dependent on a constant reorganisation of the actin cytoskeleton. By eliminating tropomyosins in a knockout (KO) mouse model, we investigated the role of two tropomyosin isoforms, Tm5NM1 and Tm5NM2 (γTm gene products) in growth cone dynamics and neurite outgrowth. Growth cone protrusion rates were significantly increased in one day old Tm5NM1/2 KO hippocampal neurons compared to WT controls. Neuritogenesis was significantly affected by the elimination of Tm5NM1/2, with a slight decrease in neurite length and an increase in neuronal branching in neurons cultured for four days. At the molecular level, the depletion of Tm5NM1/2 had no impact on the protein levels and activity of ADF/cofilin in hippocampal neurons while in cortical neurons a subtle but significant increase in ADF/cofilin activity was observed. The subtle phenotype in the early stages of neuritogenesis observed from eliminating Tm5NM1/2 may be explained with functional compensation by other tropomyosin isoforms. Functional compensation for the loss of Tm5NM1/2 may be provided by isoforms Tm5a/5b, TmBr2 and Tm4 as they localise to the growth cones, structures where Tm5NM1/2 are normally found. These results suggest that Tm5NM1/2 may not be required for early stages of neuritogenesis but may still play a fine-tuning role for this process.

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Dubreuil, Alexis. "Mémoire et connectivité corticale." Thesis, Paris 5, 2014. http://www.theses.fr/2014PA05T036/document.

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Le système nerveux central est capable de mémoriser des percepts sur de longues échelles de temps (mémoire à long terme), ainsi que de maintenir activement ces percepts en mémoire pour quelques secondes en vue d’effectuer des tâches comportementales (mémoire de travail). Ces deux phénomènes peuvent être étudiés conjointement dans le cadre de la théorie des réseaux de neurones à attracteurs. Dans ce cadre, un percept, représenté par un patron d’activité neuronale, est stocké en mémoire à long terme et peut être chargé en mémoire de travail à condition que le réseau soit capable de maintenir de manière stable et autonome ce patron d’activité. Une telle dynamique est rendue possible par la forme spécifique de la connectivité du réseau. Ici on examine des modèles de connectivité corticale à différentes échelles, dans le but d’étudier quels circuits corticaux peuvent soutenir efficacement des dynamiques de type réseau à attracteurs. Ceci est fait en montrant comment les performances de modèles théoriques, quantifiées par la capacité de stockage des réseaux (nombre de percepts qu’il est possible de stocker, puis réutiliser), dépendent des caractéristiques de la connectivité. Une première partie est dédiée à l’étude de réseaux complètement connectés où un neurone peut potentiellement être connecté à chacun des autres neurones du réseau. Cette situation modélise des colonnes corticales dont le rayon est de l’ordre de quelques centaines de microns. On s’intéresse d’abord à la capacité de stockage de réseaux où les synapses entre neurones sont décrites par des variables binaires, modifiées de manière stochastique lorsque des patrons d’activité sont imposés sur le réseau. On étend cette étude à des cas où les synapses peuvent être dans K états discrets, ce qui, par exemple, permet de modéliser le fait que les connections entre deux cellules pyramidales voisines du cortex sont connectées par l’intermédiaire de plusieurs contacts synaptiques. Dans un second temps, on étudie des réseaux modulaires où chaque module est un réseau complètement connecté et où la connectivité entre modules est diluée. On montre comment la capacité de stockage dépend de la connectivité entre modules et de l’organisation des patrons d’activité à stocker. La comparaison avec les mesures expérimentales sur la connectivité à grande échelle du cortex permet de montrer que ces connections peuvent implémenter un réseau à attracteur à l’échelle de plusieurs aires cérébrales. Enfin on étudie un réseau dont les unités sont connectées par des poids dont l’amplitude a un coût qui dépend de la distance entre unités. On utilise une approche à la Gardner pour calculer la distribution des poids qui optimise le stockage de patrons d’activité dans ce réseau. On interprète chaque unité de ce réseau comme une aire cérébrale et on compare la distribution des poids obtenue théoriquement avec des mesures expérimentales de connectivité entre aires cérébrales The central nervous system is able to memorize percepts on long time scales (long-term memory), as well as actively maintain these percepts in memory for a few seconds in order to perform behavioral tasks (working memory). These two phenomena can be studied together in the framework of the attractor neural network theory. In this framework, a percept, represented by a pattern of neural activity, is stored as a long-term memory and can be loaded in working memory if the network is able to maintain, in a stable and autonomous manner, this pattern of activity. Such a dynamics is made possible by the specific form of the connectivity of the network. Here we examine models of cortical connectivity at different scales, in order to study which cortical circuits can efficiently sustain attractor neural network dynamics. This is done by showing how the performance of theoretical models, quantified by the networks storage capacity (number of percepts it is possible to store), depends on the characteristics of the connectivity. In the first part we study fully-connected networks, where potentially each neuron connects to all the other neurons in the network. This situation models cortical columns whose radius is of the order of a few hundred microns. We first compute the storage capacity of networks whose synapses are described by binary variables that are modified in a stochastic manner when patterns of activity are imposed on the network. We generalize this study to the case in which synapses can be in K discrete states, which, for instance, allows to model the fact that two neighboring pyramidal cells in cortex touches each others at multiple contact points. In the second part, we study modular networks where each module is a fully-connected network and connections between modules are diluted. We show how the storage capacity depends on the connectivity between modules and on the organization of the patterns of activity to store. The comparison with experimental measurements of large-scale connectivity suggests that these connections can implement an attractor neural network at the scale of multiple cortical areas. Finally, we study a network in which units are connected by weights whose amplitude has a cost that depends on the distance between the units. We use a Gardner's approach to compute the distribution of weights that optimizes storage in this network. We interpret each unit of this network as a cortical area and compare the obtained theoretical weights distribution with measures of connectivity between cortical areas

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Wijekoon, Jayawan. "Mixed signal VLSI circuit implementation of the cortical microcircuit models." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/mixed-signal-vlsi-circuit-implementation-of-the-cortical-microcircuit-models(6deb2d34-5811-42ec-a4f1-e11cdb6816f1).html.

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This thesis proposes a novel set of generic and compact biologically plausible VLSI (Very Large Scale Integration) neural circuits, suitable for implementing a parallel VLSI network that closely resembles the function of a small-scale neocortical network. The proposed circuits include a cortical neuron, two different long-term plastic synapses and four different short-term plastic synapses. These circuits operate in accelerated-time, where the time scale of neural responses is approximately three to four orders of magnitude faster than the biological-time scale of the neuronal activities, providing higher computational throughput in computing neural dynamics. Further, a novel biological-time cortical neuron circuit with similar dynamics as of the accelerated-time neuron is proposed to demonstrate the feasibility of migrating accelerated-time circuits into biological-time circuits. The fabricated accelerated-time VLSI neuron circuit is capable of replicating distinct firing patterns such as regular spiking, fast spiking, chattering and intrinsic bursting, by tuning two external voltages. It reproduces biologically plausible action potentials. This neuron circuit is compact and enables implementation of many neurons in a single silicon chip. The circuit consumes extremely low energy per spike (8pJ). Incorporating this neuron circuit in a neural network facilitates diverse non-linear neuron responses, which is an important aspect in neural processing. Two of the proposed long term plastic synapse circuits include spike-time dependent plasticity (STDP) synapse, and dopamine modulated STDP synapse. The short-term plastic synapses include excitatory depressing, inhibitory facilitating, inhibitory depressing, and excitatory facilitating synapses. Many neural parameters of short- and long- term synapses can be modified independently using externally controlled tuning voltages to obtain distinct synaptic properties. Having diverse synaptic dynamics in a network facilitates richer network behaviours such as learning, memory, stability and dynamic gain control, inherent in a biological neural network. To prove the concept in VLSI, different combinations of these accelerated-time neural circuits are fabricated in three integrated circuits (ICs) using a standard 0.35 µm CMOS technology. Using first two ICs, functions of cortical neuron and STDP synapses have been experimentally verified. The third IC, the Cortical Neural Layer (CNL) Chip is designed and fabricated to facilitate cortical network emulations. This IC implements neural circuits with a similar composition to the cortical layer of the neocortex. The CNL chip comprises 120 cortical neurons and 7 560 synapses. Many of these CNL chips can be combined together to form a six-layered VLSI neocortical network to validate the network dynamics and to perform neural processing of small-scale cortical networks. The proposed neuromorphic systems can be used as a simulation acceleration platform to explore the processing principles of biological brains and also move towards realising low power, real-time intelligent computing devices and control systems.

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42

Chouchane, Malek. "Reprogramming of distinct astroglial populations into specific neuronal subtypes in vitro and in vivo." Universidade Federal do Rio Grande do Norte, 2016. http://repositorio.ufrn.br/handle/123456789/21277.

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Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-08-25T20:54:16Z No. of bitstreams: 1 MalekChouchane_TESE.pdf: 3043835 bytes, checksum: b90ef34a2d4072ef5abda48d216aebb4 (MD5) Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-08-26T21:40:31Z (GMT) No. of bitstreams: 1 MalekChouchane_TESE.pdf: 3043835 bytes, checksum: b90ef34a2d4072ef5abda48d216aebb4 (MD5) Made available in DSpace on 2016-08-26T21:40:31Z (GMT). No. of bitstreams: 1 MalekChouchane_TESE.pdf: 3043835 bytes, checksum: b90ef34a2d4072ef5abda48d216aebb4 (MD5) Previous issue date: 2016-02-29 Recently, the field of cellular reprogramming has been revolutionized by works showing the potential to directly lineage-reprogram somatic cells into neurons upon overexpression of specific transcription factors. This technique offers a promising strategy to study the molecular mechanisms of neuronal specification, identify potential therapeutic targets for neurological diseases and eventually repair the central nervous system damaged by neurological conditions. Notably, studies with cortical astroglia revealed the high potential of these cells to reprogram into neurons using a single neuronal transcription factor. However, it remains unknown whether astroglia isolated from different regions of the central nervous system have the same neurogenic potential and generate induced neurons (iN) with similar phenotypes. Similarly, little is known about the fate that iNs could adopt after transplantation in the brain of host animals. In this study we compare the potential to reprogram astroglial cells isolated from the postnatal cerebral cortex and cerebellum into iNs both in vitro and in vivo using the proneural transcription factors Neurogenin-2 (Neurog2) and Achaete scute homolog-1 (Ascl1). Our results indicate cerebellar astroglia can be reprogrammed into induced neurons (iNs) with similar efficiencies to cerebral cortex astroglia. Notably however, while iNs in vitro adopt fates reminiscent of cortical or cerebellar neurons depending on the astroglial population used for reprogramming, in situ, after transplantation in the postnatal and adult mouse brain, iNs adopt fates compatible with the region of integration. Thus, our data suggest that the origin of the astroglial population used for lineage-reprogramming affects the fate of iNs in vitro, but this imprinting can be overridden by environmental cues after grafting.

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Fernandez, Alejandra. "Disrupted Mitochondrial Metabolism Alters Cortical Layer II/III Projection Neuron Differentiation." Thesis, The George Washington University, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10620943.

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Mitochondrial metabolism of reactive oxygen species (ROS) is tightly regulated during brain development. Imbalance has been correlated to neuropsychiatric disorders. Nevertheless, the contribution of ROS accumulation to aberrant cortical circuit organization and function remains unknown. Individuals with 22q11 deletion syndrome (22q11DS) are highly susceptible to psychiatric disorders; therefore, 22q11DS has been suggested as a model for studying the neurodevelopmental origins of these disorders. Six genes –Mrpl40, Tango2, Prodh, Zdhhc8, Txnrd2 and Scl25a1– located in the 22q11DS commonly deleted region encode proteins that localize to mitochondria. This project aimed to characterize the effects of altered mitochondrial function, due to diminished dosage of these genes, on cortical projection neuron development, using the LgDel mouse model of 22q11DS. I found growth deficits in LgDel neurons that are due to increased mitochondrial ROS and are Txnrd2-dependent. Antioxidant treatment, by n-acetyl cysteine (NAC), rescues neuronal morphogenesis in LgDel and Txnrd2-depleted neurons in vitro and in vivo. Electroporation of Txnrd2 restores ROS levels and normal dendritic and axonal growth. Txnrd2-dependent redox regulation underlies a key aspect of cortical circuit differentiation in a mouse model of 22q11DS. These studies define the effects of mitochondrial accumulation of ROS on neuronal integrity, and establish the role of altered pyramidal neuron differentiation in the formation of circuits in 22q11DS. These data provide novel insight into the role of redox imbalance in aberrant development of cortical circuits.

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Grant, Sarah. "Measuring cortical thickness and neuronal density in stroke patients." Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=97249.

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Ischemic stroke causes necrosis of the cortex leading to atrophy in directly affected tissue. However, little is known about what occurs to the cortex surrounding the lesion due to the indirect effects of stroke. This thesis aims to develop a method to assess cortical thickness and neuronal density in vivo in stroke patients using surface-based cortical thickness mapping from MRI and high resolution [18F]Flumazenil positron emission tomography respectively. No significant changes in cortical thickness were found in stroke patients' affected hemispheres as compared to the contralateral hemisphere and control brains. [18F]Flumazenil binding was significantly reduced in the affected hemisphere in regions surrounding the infarct compared to the contralateral hemisphere and gradually increased farther from the lesion. With our methods, cortical thickness can reliably be measured in very close proximity to lesions and changes in neuronal density can be detected in stroke affected hemispheres as compared to the contralateral hemisphere. L'accident vasculaire cérébral (AVC) ischémique cause une nécrose de la région du cortex cérébral directement affectée et mène à une atrophie du tissu touché. Cependant, les effets indirects causé par l'AVC dans la région péri-lésionnelle sont peut connus. Ce mémoire a pour objectif d'évaluer l'épaisseur corticale et la densité neuronale in vivo chez des patients ayant eu un AVC ischémique en utilisant l'analyse automatisée de l'épaisseur du cortex à partir d'imagerie par résonance magnétique ainsi que la tomographie par émission de positrons au [18F]flumazénil à haute résolution. Aucun changement significatif n'a été détecté au niveau de l'épaisseur corticale entre l'hémisphère affecté par l'AVC et l'hémisphère contra-lésionnel ou en comparaison avec des sujets contrôles. Toutefois, la fixation du [18F]flumazénil était significativement réduite dans les régions adjacentes de l'hémisphère affecté en comparaison avec l'hémisphère contra-lésionnel et augmente graduellement en s'éloignant de la lésion. Notre méthode a permis de déterminer que l'épaisseur corticale peu être mesurée dans la région péri-lésionnelle et les changements de densité neuronale peuvent être détectés dans les régions cérébrales affectées par un AVC ainsi que dans les régions contra-lésionnelles.

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Major, Guy. "The physiology, morphology and modelling of cortical pyramidal neurones." Thesis, University of Oxford, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.306063.

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Hoerder, Anna. "Mouse cortical subplate neurones : molecular markers, connectivity and development." Thesis, University of Oxford, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.442449.

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Litwin-Kumar, Ashok. "Relationship between neuronal architecture and variability in cortical circuits." Research Showcase @ CMU, 2013. http://repository.cmu.edu/dissertations/312.

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The connectivity of cortical neuronal networks is complex, exhibiting clustered network motifs and ensembles of neurons with high connection probability. However, the significance of these connectivity properties for computation and dynamics in cortex is unclear. In this thesis, I present several studies concerning the behavior of model cortical neurons receiving input from a surrounding network. I begin by studying pairs of neurons, investigating how overlapping excitatory and inhibitory inputs control the statistics of their outputs. I then study fully recurrent networks of neurons with nonuniform connection structures in the form of highly connected neuronal assemblies. These assemblies represent functionally related subsets of neurons, and I investigate their collective behavior in both spontaneously generated activity and evoked conditions. I show that the presence of assembly structure in recurrently coupled, balanced excitatory-inhibitory networks introduces slow timescales in the networks’ dynamics and relate these modeling results to the experimental literature. Next, I present results on how these assemblies form and are maintained with realistic models of synaptic plasticity. In total, these results represent a step toward understanding how connectivity can be modified by sensory experience, and how these changes in turn shape cortical dynamics.

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Le, Roux Nicolas. "Contrôle homéostatique de l'activité corticale: Etude de la balance Excitation / Inhibition des neurones pyramidaux de couche 5 du cortex visuel." Phd thesis, Université Paris Sud - Paris XI, 2007. http://tel.archives-ouvertes.fr/tel-00159415.

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La plasticité homéostatique est un processus qui consiste à réguler l'efficacité globale des entrées synaptiques (excitatrices et inhibitrices) sur un neurone afin d'empêcher des modifications trop importantes de son niveau d'activité. Afin de caractériser les mécanismes à l'origine de ce processus, la balance Excitation/Inhibition des neurones pyramidaux de couche 5 du cortex visuel a été estimée. Elle est composée de 20 % d'excitation et de 80 % d'inhibition. A l'aide de protocoles de stimulation induisant des changements à long terme de l'efficacité des entrées synaptiques, les phénomènes de potentiation homéostatique et de dépression homéostatique ont été mis en évidence. L'induction de ces phénomènes, qui requiert l'activation de récepteurs NMDA et d'un signal NO, est sous le contrôle des systèmes inhibiteurs GABAergique et glycinergique. La récurrence entre signaux excitateurs et inhibiteurs apparaît comme l'élément clé de la régulation de l'activité neuronale.

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Smith, David E. "Age-related memory decline is associated with focal loss of cortical neurons and selective degeneration of subcortical neurons /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2002. http://wwwlib.umi.com/cr/ucsd/fullcit?p3064448.

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Shi, Yichen. "Modelling Alzheimer's disease with human pluripotent stem cell-derived cerebral cortical neurons." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608130.

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Dissertations / Theses on the topic 'Neuroni corticali'

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