Les fonctions locomotrices et posturales sont contrôlées par un ensemble de réseaux neuronaux qui doivent interagir afin de produire un comportement locomoteur optimal, adaptable aux contraintes internes et externes de l’organisme. Le maintien d’un équilibre dynamique au cours de la locomotion repose sur des processus internes de coordination entre les réseaux nerveux spinaux et supraspinaux qui commandent les différents segments du corps (membres, tête et tronc). C’est dans ce contexte que nous nous sommes intéressés aux interactions entre la fonction locomotrice et la fonction posturale, sur des préparations réduites de tronc cérébral-moelle épinière de rats nouveau-nés, au sein desquelles les CPGs locomoteurs spinaux et les noyaux vestibulaires sont intacts. Des approches combinées électrophysiologiques, pharmacologiques, neuroanatomique et lésionnelles nous ont permis de mettre en évidence une partie des mécanismes à l’origine du couplage entre les différents réseaux neuronaux étudiés. Dans cette étude nous avons montré que les réseaux locomoteurs lombaires contrôlent l’activité des réseaux thoraciques axiaux, de manière à produire une activation coordonnée des réseaux moteurs des membres et du tronc. Cette coordination est sous influence des entrées supraspinales. Les amines induisent une organisation temporelle spécifique de l’activité des réseaux thoraco-lombo-sacrés, et les informations en provenance des noyaux vestibulaires influencent le rythme locomoteur. Ces données apportent des éléments nouveaux concernant les processus neuronaux à l’origine de la coordination des réseaux moteurs et posturaux. / Locomotor and postural functions are controlled by a set of neural networks that must interact to produce optimal locomotor behavior, adaptable to internal and external constraints of the body. Maintaining a dynamic balance during locomotion is based on internal coordination processes between spinal and supraspinal neuronal networks controlling different parts of the body (limbs, head and trunk). In this context, we have interested in the interactions between locomotor and postural functions, in spinal and supraspinal networks. The experiments were conducted on isolated brainstem-spinal cord preparations from neonatal rats, in which the spinal locomotor CPGs and the vestibular nuclei are intact. Electrophysiological, pharmacological, and neuroanatomical approaches allowed us to highlight some of the mechanisms involved in the coupling of the different neural networks. In this study we showed that the lumbar locomotor networks control the activity of axial thoracic networks, in order to produce a coordinated activation of motors networks of limbs and trunk. This coordination is modulated by amines and information from the vestibular nuclei. These data provide new evidence for spinal mechanisms involved in the coordination of motor and postural networks.

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Le système nerveux central possède des réseaux de neurones capables de générer des commandes motrices rythmiques en l'absence d'informations sensorielles. Ces réseaux neuronaux sont communément appelés générateurs centraux de patron (CPG, central pattern generator) et sont impliqués dans plusieurs fonctions et comportements vitaux tels que la locomotion et la respiration. Dans certaines circonstances, ces réseaux neuronaux se doivent d'interagir afin de produire un comportement moteur adapté aux contraintes environnementales ainsi qu'aux exigences de l'organisme. C'est notamment le cas lors d'un effort physique où une augmentation du rythme respiratoire est rapidement observée pour subvenir aux besoins en oxygène de l'organisme. Dans ce contexte de neurosciences intégratives, mon travail doctoral a porté sur l'étude des mécanismes neurogènes responsables de l'interaction entre les CPG respiratoires du tronc cérébral et les CPG locomoteurs de la moelle épinière. Cette étude a été réalisée sur des préparations de tronc cérébral-moelle épinière isolée in vitro de rat nouveau-né (P0 à P2) au sein desquelles les centres respiratoires et locomoteurs sont conservés intacts. Par des approches électrophysiologique, pharmacologique, lésionnelle et neuroanatomique, les mécanismes de coordination entre ces sous-groupes neuronaux ont été étudiés. Dans ce contexte, un des principaux résultats de ce travail doctoral est la mise en évidence de l'existence d'une influence ascendante excitatrice issues des CPG locomoteurs spinaux sur les centres respiratoires, et plus particulièrement sur le groupe respiratoire parafacial, structure située dans le bulbe rachidien et impliquée dans la genèse de la commande respiratoire. Outre son implication dans la modulation du rythme respiratoire, cette influence ascendante module également l'activité des populations neuronales expiratoires des régions spinales thoraciques et lombaires. Ces données constituent la première mise en évidence de l'existence de neurones bi-fonctionnels au sein de la moelle-épinière chez le rat nouveau-né. / The central nervous system contains neural networks that can generate rhythmic motor drive in absence of sensory feedback. These neural networks are commonly called central pattern generators (CPG) and are involved in many vital functions and behaviors, such as locomotion or respiration. In certain circumstances, these neural networks must interact to produce motor behaviors adapted to environmental constraints and the basic needs of organism. This is the case during physical exercise when the respiratory frequency increases in order to satisfy the oxygen needs. In a context of integrative neurosciences, my doctoral work aimed at exploring the neurogenic mechanisms involved in the coordination between the medullary respiratory networks and the spinal locomotor CPG. To address this question, we used an isolated in vitro brain stem-spinal cord preparations from neonatal rats (0-2 days) in which the respiratory and the locomotor networks are kept intact. Using electrophysiological, pharmacological, lesional and neuroanatomical approaches, mechanisms involved in the coordination between locomotor and respiratory rhythms have been studied. The major finding of this doctoral work is the identification of an ascending excitatory influence from spinal locomotor CPG to the respiratory networks, acting particularly on the parafacial respiratory group, which is known to be engaged in the genesis of expiratory activity. In addition to the respiratory frequency modulation, this ascending influence also modulates the activity of spinal expiratory neurons located in lumbar and thoracic segments. These data provide the first evidence for the existence of bi-functional neurons in newborn rat spinal cord.

Il a récemment été largement reconnu que la dynamique interne des réseaux de neurones pourraient jouer un rôle essentiel dans leur fonction. À cet régard, le "bruit synaptique" -- qui représente l'influence du réseau cortical sur les neurones individuels, et qui est une conséquence directe de la circuiterie récurrente massive du néocortex -- a récemment été identifié comme un facteur important qui affecte les propriétés intégratives des neurones. Cette activité affecte aussi l'évolution des réponses neuronales en fonction des changements d'états du cerveau, parfois en quelques secondes. Ces états d'activité générés en interne, qui résultent -- et eux-même influencent -- la plasticité des connexions synaptiques récurrentes, se combinent alors avec les entrées externes pour produire un riche répertoire de réponses aux stimuli sensoriels. Dans cette thèse, nous nous sommes concentrés sur le aspect spatial de ces dynamiques intrinsèques, en particulier la structure spatiale des oscillations corticales, à la fois dans le cas spontané et des réponses évoquées. Nous avons fait un examen approfondi de la littérature concernant la propagation d'ondes dans le thalamus et le cortex, et nous avons proposé un modèle de réseau neuronal pour examiner l'interaction entre les ondes de propagation et l'activité interne du réseau. Nous avons aussi mis en place de nouveaux outils pour la caractérisation de ce type d'activité spatio-temporelle à partir d'enregistrements multicanaux bruités. Le point culminant de ce travail est une démonstration, en utilisant les données d'imagerie par colorants voltage-sensitifs (VSD, "voltage-sensitive dye imaging") obtenues chez le singe éveillé, que la réponse de la population à un stimulus visuel se propage comme une onde sur une grande étendue du cortex visuel primaire. Ce résultat contredit une série d'études précédentes qui semblaient suggérer l'absence d'onde de propagation dans ce cas. Ensuite, nous avons commencé à étudier la structure spatio-temporelle du potentiel de champ local (``local field potential'') obtenu à partir d'enregistrements multi-électrodes chez l'homme et le singe, dans divers états cérébraux, pour répondre aux questions suscitées par l'étude initale en imagerie VSD chez le singe. En parallèle, nous avons étudié les caractéristiques de la structure de connectivité de plusieurs systèmes nerveux, en utilisant la théorie des graphes, pour identifier les aspects aléatoires ou structurés ("small-world") de cette connectivité. Le résultat principal est que, contrairement au consensus, la structure de connectivité est beaucoup plus proche d'une connectivité aléatoire. Les résultats de ces études de doctorat couvrent ainsi un grand spectre d'échelles en neurosciences, de modèles d'activité macroscopiques à des profils de connectivité microscopiques. J'espère sincèrement pouvoir exposer dans ces pages ces résultats de façon unifiée, dans le but de constituer une base pour la poursuite de ces travaux en neurosciences - une recherche de structure au sein de l'architecture interne du système nerveux central. / It has only recently been acknowledged to what large extent the internal dynamics of neural networks could play a role in their function. In this respect, synaptic "noise" -- that is, the influence of the cortical network on single neurons exerted through the massive recurrent circuity that is the hallmark of neocortex -- has recently been shown to have a profound effect on neuronal integrative properties, changing the responses of single neurons across brain states, sometimes within the matter of a few seconds. These internally generated activity states, shaped by and continually shaping the plastic synaptic recurrent connections, then combine with the external inputs to produce a rich repertoire of responses to sensory stimuli in primary cortical regions. In this thesis, we have focused on the {\it spatial} aspect of these internal dynamics, specifically the spatial structure of cortical oscillations, spontaneous and stimulus-evoked. Along the way, we have made an extensive review of the literature concerning propagating waves in thalamus and cortex, and studied network models to investigate how waves depend on network state. We have also introduced new tools for the characterization of spatiotemporal activity patterns in noisy multichannel data. The culmination of this work is a demonstration, using voltage-sensitive dye imaging data taken from the awake monkey, that the population response to a small visual stimulus propagates like a wave across a large extent of primary visual cortex during the awake state, a result contradicting a range of previous studies which seemed to suggest that propagating waves disappear in this case. Moving forward, we have begun to investigate the spatiotemporal structure of local field potential and spiking activity in multielectrode recordings taken from the human and monkey in various states of arousal, to address questions prompted by our initial voltage-sensitive dye imaging study in the monkey. In parallel, we have initiated an analysis of the extent to which neural connectivity can be characterized by the "small-world" effect, the main result of which is that neural graphs may in fact reside outside the small-world regime. The results from these PhD studies thus span the spectrum of scales in neuroscience, from macroscopic activity patterns to microscopic connectivity profiles. It is my sincere hope to expound in these pages a unified theme for these results, and a foundation for further work in neuroscience -- a search for structure within the internal architecture of the system under study.

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.

Esta tese aborda o interrelacionamento entre morfologia, topologia e dinâmica de ativação em redes neuronais morfologicamente realistas, construídas com neurônios da base pública Neuromorpho. Foi desenvolvido um arcabouço computacional capaz de simular a dinâmica de ativação neuronal (através do modelo integra-e-dispara) ao longo do desenvolvimento da conexão das redes tridimensionais respectivas. Tal arcabouço permitiu investigar como aspectos da dinâmica de ativação variam ao longo das épocas de desenvolvimento das redes, incluindo antes, durante e depois da percolação. Em particular, calcularam-se correlações de Pearson entre várias medidas dinâmicas e topológicas ao longo das épocas de evolução, de forma a se quantificar de maneira objetiva os possíveis relacionamentos entre a ativação neuronal e a topologia das redes. Foram considerados três tipos de neurônios piramidais: occipitais e pré-frontais de humanos e células piramidais de macado (macaco Rhesus). Os dois primeiros tipos foram verificados (através de histogramas de médias e análise por componentes principais) possuírem características morfológicas semelhantes, enquanto o grupo de células piramidais do macaco apresentaram substancial diferenciação. Vários resultados foram obtidos respectivamente às correlações entre medidas dinâmicas e topológicas. Em particular, verificou- se que os graus médios de entrada e saída das redes estão significativamente correlacionados com as taxas médias de ativação, convergindo rapidamente após a formação do componente fraco. A correlação do grau de entrada mostrou-se mais elevada do que a obtida para o grau de saída. Além disto, a correlação entre o grau de entrada e a taxa média de disparos tendeu a diminuir ao longo das épocas finais das simulações. Verificou-se também como os perfis de evolução de várias correlações entre dinâmica e topologia implicam na diferenciação dos tipos neuronais considerados. / This thesis addresses the interrelationships between morphology, topology and activation dynamics in morphologically realistic neuronal networks, derived from the public data base Neuromorpho. A computational framework has been developed that is capable of simulating the dynamics of neuronal activation (via the integrate-and-fire dynamics) during the development of the network connection in three-dimensional spaces. This framework allowed to investigate how aspects of the activation dynamics vary over the epochs of network development, including before, during and after the critical event of percolation. In particular, we calculated Pearson correlation coefficients between various topological and dynamical measurements throughout the epochs of evolution, in order to quantify in an objective way how the relationships between neuronal activation and network topology changed along the development of the connectivity. We considered three types of neurons: occipital and prefrontal pyramidal cells of human and diverse pyramidal cells of monkey individuals (monkey Rhesus). The first two types were found (via histograms and principal component analysis) to have mostly similar morphological characteristics, while the group of pyramidal cells from apes showed substantial differentiation. Several results were obtained respectively to the correlations between measurements of dynamics and morphology along the epochs of development. In particular, it was found that the input and output average degrees of the network are significantly correlated with the average rates of activation. After a period of large variation that precedes the formation of the weakly connected component, these correlation values converge rapidly to a regime of smooth decrease which suggests saturation of the activation in the network. The correlation implied by the indegree proved to be clearly higher than that obtained for the outdegree. It was also investigated how the profiles of the various correlations along the development epochs implied in the differentiation between the neuronal types considered.

No description available.

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.