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Emergence and Homeostasis of Functional Maps in Hippocampal NeuronsRathour, Rahul Kumar January 2014 (has links) (PDF)
Systematic investigations through several experimental techniques have revealed that hippocampal pyramidal neurons express voltage gated ion channels (VGICs) with well-defined gradients along their dendritic arbor. These actively maintained gradients in various dendritic VGICs effectuate several stereotypic, topographically continuous functional gradients along the topograph of the dendritic arbor, and have been referred to as intraneuronal functional maps. The prime goal of my thesis was to understand the emergence and homeostasis of the several coexistent functional maps that express within hippocampal pyramidal neurons.
In the first part of the thesis, we focus only on spatial interactions between ion channels and analyzed the role of such interactions in the emergence of functional maps. We developed a generalized quantitative framework, the influence field, to analyze the extent of influence of a spatially localized VGIC cluster. Employing this framework, we showed that a localized VGIC cluster could have spatially widespread influence, and was heavily reliant on the specific physiological property and background conductances. Using the influence field model, we reconstructed functional gradients from VGIC conductance gradients, and demonstrated that the cumulative contribution of VGIC conductances in adjacent compartments plays a critical role in determining physiological properties at a given location. These results suggested that spatial interactions among spatially segregated VGIC clusters are necessary for the emergence of the functional maps.
In the second part of the thesis, we assessed the specific roles of only kinetic interactions between ion channels in determining physiological properties by employing a single-compartmental model. In doing this, we analyzed the roles of interactions among several VGICs in regulating intrinsic response dynamics. Using global sensitivity analysis, we showed that functionally similar models could be achieved even when underlying parameters displayed tremendous variability and exhibited weak pair-wise correlations. These results suggested that that response homeostasis could be achieved through several non-unique channel combinations, as an emergent consequence of kinetic interactions among these channel conductances.
In the final part of the thesis, we analyzed the combined impact of both spatial and kinetic interactions among ion channel conductances on the emergence and homeostasis of functional maps in a neuronal model endowed with extensive dendritic arborization. To do this, we performed global sensitivity analysis on morphologically realistic conductance-based models of hippocampal pyramidal neurons that coexpressed six functional maps. We found topographically continuous functional maps to emerge from disparate model parameters with weak pair-wise correlations between parameters. These results implied that individual channel properties need not be set at constant values in achieving overall homeostasis of several coexistent functional maps. We suggest collective channelostasis, where several channels regulate their properties and expression profiles in an uncorrelated manner, as an alternative for accomplishing functional map homeostasis. Finally, we developed a methodology to assess the contribution of individual channel conductances to the various functional measurements employing virtual knockout simulations. We found that the deletion of individual channels resulted in variable, measurement-and location-specific impacts across the model population.
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Multi-Phase Modeling Of Microporosity And Microstructures During Solidification Of Aluminum AlloysKaragadde, Shyamprasad 04 1900 (has links) (PDF)
Manufacturing of light-weight materials is associated with several types of casting defects during solidification. Porosity defects are common, especially in aluminum and its alloys, which initiate crack propagation and thereby cause drastic deterioration in the mechanical properties. These defects, classified as micro and macro defects (based on their sizes), are mainly governed by release of hydrogen into the liquid at the solid-liquid interface, which triggers the nucleation and growth of hydrogen bubbles in the melt. Subsequently, these bubbles interact with solidifying interfaces such as dendritic arms and eutectic fronts, leading to the formation of pores. Macroscopic defects in the form of voids are created due to solidification shrinkage.
The primary focus of the present work is to develop phenomenological models for the evolution of microporosity and microstructures during solidification. The issues outlined above typically occur in multi-phase environments comprising of solid, liquid and gaseous phases, and over a range of length and time scales. Any phenomenological prediction would, therefore, require a multi-phase-scale approach. Principles of volume averaging are applied to equations of conservation to obtain single-field formulations. These are then solved with appropriate interface tracking techniques such as Enthalpy, Level-set, Volume-of-fluid and Immersed-boundary methods. The framework is built up on a standard pressure based incompressible fluid flow solver (SIMPLER algorithm) and coupled modeling strategies are proposed to address the interfacial dynamics. A two-dimensional framework is considered with a fixed-grid Cartesian co-ordinate system. Scaling analyses are performed to bring out the relative effects of various competing parameters in order to obtain further insights into this complex phenomenon. The numerical results and scaling predictions are validated against experimental observations published in literature.
In literature, numerical predictions of microporosity mainly include criteria based models based on empirical relations and deterministic/stochastic models based on diffusion driven growth assuming spherical bubbles. The dynamic evolution of non-spherical bubble-metal interface in a three-phase system is yet to be captured. Moreover, several in-situ experiments have shown elongated bubble shapes during the engulfment phase, therefore a criterion to define the dependence on cooling rates and the resulting bubble morphology can possibly deliver further practical insights. We propose a numerical model for hydrogen bubble growth, its movement and subsequent engulfment by a solidifying front, combining the features of level-set and enthalpy methods for tracking bubble-metal and solid-liquid interfaces, respectively. The influx of hydrogen into heterogeneously nucleated bubbles results in growth of bubbles to sizes up to a few hundreds of microns. In the first part of this numerical study, a methodology based on the level-set approach is developed to simultaneously capture hydrogen bubble growth and movement in liquid aluminum. The solidification is first assumed to occur outside the micro-domain providing a specified hydrogen influx to the bubble-in-liquid system. The level-set equation is formulated in such a way as to account for simultaneous growth and movement of the bubble. The growth of a bubble with continuous and fixed hydrogen levels in the melt is studied.
The rates of growth of bubble-liquid and solidifying interfaces are compared using an order of magnitude analysis. This scaling analysis explains the thought experiment proposed in the literature, where difference in bubble shapes was attributed to the cooling rate. Moreover, it shows explicit dependence on bubble radius and cooling rate leading to a new criterion for bubble elongation proposed in this thesis. This also highlights the comparison between solidification and hydrogen diffusion time-scales which primarily govern the competitive growth behavior. The bubble-in-liquid model is coupled with microscopic enthalpy method to incorporate effects of solidification and study the interaction of solid-liquid and bubble-liquid interfaces. The phenomena of bubble engulfment and elongation are successfully captured by the proposed model. A parametric study is carried out to estimate the bubble elongation based on different initial bubble sizes and varying cooling rates encountered in typical sand, permanent mold and die casting processes.
Although simulation of microstructures has been extensively studied in the literature, very few models address the phenomena of simultaneous growth and movement of equiaxed dendrites. The presence of different flow environments and multiple dendrites are known to alter the position and shape of the dendrites. The proposed model combines the features of the following methods, namely, the Enthalpy method for modeling growth; the Immersed Boundary Method (IBM) for handling the rigid solid-liquid interfaces; and the Volume of Fluid (VOF) method for tracking the advection of the dendrite. The algorithm also performs explicit-implicit coupling between the techniques used. Validation with available literature is performed and dendrite growth in presence of rotational and buoyancy driven flow fields is studied. The expected transformation into globular microstructure in presence of stirring induced flows is successfully simulated. A simple order estimate for time required for stirring is performed which agrees with numerical predictions. In buoyancy driven environment of a settling dendrite, the arm tip speeds show expected higher velocity of the upstream tip compared to its counterpart. The model is extended to study thermal and hydrodynamic interactions between multiple dendrites with appropriate considerations for different orientations and velocities of the dendritic solid entities. The present model can be used for the prediction of grain sizes and shapes and to simulate morphological transformations due to different melt flow scenarios.
In the final part, the methodology presented for growth and engulfment of hydrogen bubbles is extended to study the phenomenon of diffusion driven bubble growth occurring in direct foaming of metals. The source of hydrogen is determined by the rate of decomposition of the blowing agent. This is accounted for by a source term in the hydrogen species conservation equation, and growth rate of hydrogen bubbles is calculated on the basis of diffusive flux at the interface. The level-set method is used for tracking the bubble-liquid interface growth, and the macroscopic enthalpy model is used for obtaining heat transfer and solid front position. The model is validated with analytical solution by comparing the front position and the solidification time. The variation of foam density with a transient hydrogen generation source is studied and qualitatively compared with results reported in literature. The modeling strategies proposed in this work are generic and therefore have potential in simulating a variety of complex multi-phase problems.
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Rational Design of Advanced Hybrid Nanostructures for Catalysis and ElectrocatalysisBarman, Barun Kumar January 2016 (has links) (PDF)
The hybrid nanostructures exhibit excellent performances in various fields such as catalysis, sensing, and energy conversion as compared to their individual ones. The thesis deals with the new methods for the synthesis of different type of hybrids with doped/pristine carbon nanostructures in the form of graphene, multiwall carbon nanotubes (MWCNTs) as one component and metals nanostructures (Ag, Pd, Pt and Au), carbide (Fe3C), metal chalcogenides (Ni3S2 and Co9S8) and oxide (CoO) as the other components. Various synthesis techniques such as modified galvanic replacement reaction at room temperature, hydrothermal, microwave and pyrolysis have been explored for the synthesis of different hybrid nanostructures. Furthermore, various hybrid nanostructures have been explored for various catalytic activities such as oxygen reduction reaction (ORR), oxygen evolution reaction (OER) and 4-nitrophenol (4-NP) reduction. It may be noted that the ORR and OER which are undoubtedly vital for their applications in fuel cells, metal-air batteries and water oxidation reaction. Interestingly, the catalytic activities of these hybrid nanostructures are comparable or better as compared to the commercial benchmark precious catalysts.
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A Precision Medicine Approach to Understanding KIF1A Associated Neurological DisorderBoyle, Lia January 2021 (has links)
The functional compartmentalization underlying neuronal polarity makes tightly regulated intracellular transport between the cell body, axons, and dendrites essential for proper development and homeostatic maintenance. Disruptions to neuronal trafficking are a major cause of neurodegenerative disease. Pathogenic variants in the microtubule motor protein KIF1A cause KIF1A Associated Neurological Disorder (KAND), a spectrum of rare neurodegenerative conditions. KAND is clinically and genetically heterogeneous, with a broad phenotypic spectrum and over a hundred pathogenic variants identified. KAND is poorly understood at both the clinical and molecular level, and there is currently no treatment.
This work characterizes the natural history of KAND and describes a novel heuristic severity score. This severity score is then used to show how the location of pathogenic missense variants within the KIF1A motor domain correlates with disease severity, providing evidence the clinical phenotypic heterogeneity in KAND reflects and parallels the molecular phenotypes. Insights from the neuropathology of deceased KAND patients is used to focus a histopathologic assessment of the C3-Kif1aLgdg mouse model. C3-Kif1aLgdg/Lgdg mice have a cerebellar axonal torpedo phenotype, paralleling some of the pathological changes seen in the patients. Phenotypically, the C3-Kif1aLgdg mice were found to recapitulate some of the symptoms seen in patients including progressive spasticity and gait abnormalities associated with hind limb paralysis.
To model the disease at a cellular level, iPSCs were derived from affected individuals and successfully used to generate neural stem cells and neurons. These patient-derived neurons were found to have increased markers of protein aggregates, a cellular phenotype that can be used to test potential treatments. Taken together, these studies provide foundational knowledge for future therapeutic development.
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Genes Required for Wallerian Degeneration Also Govern Dendrite Degeneration: A DissertationRooney, Timothy M. 03 April 2015 (has links)
Neurons comprise the main information processing cells of the nervous system. To integrate and transmit information, neurons elaborate dendritic structures to receive input and axons to relay that information to other cells. Due to their intricate structures, dendrites and axons are susceptible to damage whether by physical means or via disease mechanisms. Studying responses to axon injury, called Wallerian degeneration, in the neuronal processes of Drosophila melanogaster has allowed the identification of genes that are required for injury responses. Screens in Drosophila have identified dsarm and highwire as two genes required for axon degeneration; when these genes are mutated axons fail to degenerate after injury, even when completely cut off from the neuronal cell body. We found that these genes are also required for dendrite degeneration after injury in vivo. Further, we reveal differences between axon and dendrite injury responses using in vivo timelapse recordings and GCaMP indicators of intracellular and mitochondrial calcium transients. These data provide insights into the neuronal responses to injury, and better define novel targets for the treatment of neurodegenerative diseases.
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The role of insulin in retinal ganglion cell dendrite and synapse regeneration after optic nerve injury : molecular mechanisms and potential therapeutic targetsAgostinone, Jessica 12 1900 (has links)
Le glaucome, comme beaucoup d’autres maladies neurodégénératives, entraîne la mort des neurones et reste à ce jour incurable, représentant de ce fait un véritable fardeau pour la société. Il y a donc un réel besoin de développer de nouvelles stratégies thérapeutiques afin de ralentir la progression, voire de guérir les maladies neurologiques. Depuis des décennies, les chercheurs qui étudient les blessures ainsi que les maladies qui affectent le système nerveux central (SNC) ont focalisé leur attention sur la compréhension des mécanismes impliqués dans la dégénérescence axonale afin d’identifier de nouvelles cibles thérapeutiques pour la protection et la régénération des axones. Mais des données récentes indiquent que des déficits dendritiques constituent une caractéristique précoce de la neurodégénérescence, un phénomène maintenant appelé la pathologie dendritique et qui jouerait un rôle prépondérant dans la pathogénèse des maladies neurodégénératives comme le glaucome. Parce que les dendrites représentent des structures essentielles pour la communication et la fonction neuronale, il est donc crucial de protéger et de restaurer non seulement les axones mais aussi les dendrites des neurones encore vivants afin d’améliorer la condition des patients. Malgré cela, la capacité des neurones à régénérer leurs arbres dendritiques reste encore largement inconnue. L’hypothèse centrale de cette thèse propose que : 1) les neurones du SNC peuvent faire repousser leurs dendrites après une blessure axonale, et 2) l’identification des voies de signalisation impliquées pourrait offrir de nouvelles possibilités thérapeutiques permettant de ralentir, voire de prévenir la dégénérescence des neurones rétiniens lors de pathologies oculaires telles que le glaucome.
Dans la première partie de cette thèse, nous avons démontré que les neurones des mammifères sont pourvus d’une capacité à restaurer leur arbre dendritique et leurs connectivités synaptiques. Grâce à l’utilisation de souris transgénique soumis à une transsection du nerf optique (axotomie), nous avons montrés que les cellules ganglionnaires de la rétine (CGRs) subissent rapidement un rétrécissement dendritique, bien avant que les dommages axonaux ou la perte des soma ne soient visibles. Nous avons également démontré que l’administration quotidienne d’insuline, par voie topique (gouttes oculaires) ou systémique (injection intrapéritonéale) après la rétraction des dendrites mais avant la mort neuronale induit une régénération robuste des dendrites ainsi qu’une restauration des connections avec les cibles présynaptiques. De plus, cette régénération des arbres dendritiques suite au traitement d’insuline permet d’étendre la survie neuronale et de restaurer la réponse rétinienne à la lumière. Des expériences de perte de fonction ciblée via l’utilisation de petits ARN interférents ont révélé que la régénération induite par l’insuline requiert l’activité des deux complexes de la voie mTOR, mTORC1 et mTORC2. Ces derniers agissent de manière synergique, mTORC1 régulant l’apparition de nouvelles branches dendritiques pour restaurer la complexité des arbres alors que mTORC2 stimule l’élongation des dendrites.
Dans la deuxième étude présentée dans cette thèse, nous avons montré pour la première fois que morgana, une protéine chaperonne en aval de mTORC2, est exprimée par les CGRs et que son expression est sévèrement inhibée rapidement après une blessure axonale. Nous avons également démontré que morgana est nécessaire au succès de la régénération ainsi que de la neuroprotection induite par le traitement d’insuline. De plus, nous avons montré que le rétablissement de l’expression de morgana spécifiquement dans les CGRs via l’utilisation d’un vecteur viral (AAV) mène à une régénération robuste non seulement de leurs dendrites mais aussi de leurs synapses. Ainsi, nous avons identifié un nouveau rôle pour la protéine morgana dans la régulation de la morphologie des arbres dendritiques des neurones adultes chez les mammifères.
En conclusions, les résultats présentés dans cette thèse contribuent à une meilleure compréhension des mécanismes pathologiques impliqués dans la pathologie dendritique des CGRs et identifient des cibles prometteuses pour le développement de nouvelles stratégies thérapeutiques dans le cadre des maladies neurodégénératives telles que le glaucome. / Glaucoma, just as many other neurodegenerative diseases, triggers neuronal death and
remained incurable, hence representing a heavy burden for the society. Therefore, there is a
critical need for developing new therapeutic strategies to delay the progression of and,
ultimately, cure neurological conditions. For decades, neuroscientists studying injuries and
diseases of the CNS have largely focused on understanding the mechanisms of axon degeneration
to identify new targets for axonal protection and regeneration. But recent data indicates that
dendritic deficits represent an early feature of neurodegeneration, a phenomenon now called
dendritic pathology and playing a key role in the pathogenesis of neurodegenerative diseases
including glaucoma. Because dendrites are essential structures for neuronal communication and
function, it is therefore crucial to protect or restore connectivity as well as axons of surviving neurons
to improve patients’ condition. In spite of this, the ability of injured neurons to regenerate dendrites
remains largely ignored. The central hypothesis of the thesis is that: i) adult CNS neurons can regrow
their dendrites after axonal injury, and ii) the identification of underlying signalling pathways would
offer new therapeutic avenues to slow or prevent retinal ganglion cell death during ocular neuropathies
such as glaucoma.
In the first part of my thesis, I demonstrated that mammalian neurons are endowed with
the ability to restore their dendritic arbor and synaptic connectivity. Using adult transgenic mice
subjected to optic nerve axotomy, we have shown that retinal ganglion cells (RGCs) rapidly
undergo dendritic shrinkage before cell death or axonal damage become visible. We also
demonstrated that daily insulin, administered topically (eye drops) or systemically
(intraperitoneal) after dendritic arbour shrinkage and prior to neuronal loss results in a robust
regeneration of dendrites and successful reconnection with presynaptic targets. Moreover,
insulin-mediated restoration of dendritic arbors extended neuronal survival and rescued lighttriggered
retinal responses. Targeted loss-of-function experiments using siRNAs revealed that
insulin-dependent regeneration requires both the activity of both mTOR complexes, mTORC1
and mTORC2 which act synergistically, mTORC1 promoting new dendritic branching to restore
arbor complexity, while mTORC2 drives dendritic process elongation.
In the second study presented in my thesis, we showed for the first time that morgana, a
chaperone protein downstream of mTORC2, is expressed by RGCs and severely downregulated
soon after axonal injury. We also demonstrate that morgana is required for successful insulinmediated
regeneration of RGC dendrites and neuroprotection. Morgana specific knockdown
using siRNA designed against morgana resulted in substantial alterations of dendrite elongation,
without changes in arbor complexity. Further, we showed that AAV-mediated rescue of morgana
expression selectively in RGCs promoted striking regeneration of dendrites and synapses. Hence,
our findings identified a new role for morgana in the regulation of dendritic arbor morphology in
adult mammalian neurons
Collectively, the findings presented in this thesis contribute to a better understanding of
the pathological mechanisms underlying RGC dendritic pathology and identified promising
targets for the development of novel neuroprotective treatments for neurodegenerative
diseases such as glaucoma.
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Modélisation de l'intégration des entrées synaptiques excitatrices chez les cellules thalamocorticalesLajeunesse, Francis 18 April 2018 (has links)
Tableau d'honneur de la Faculté des études supérieures et postdoctorales, 2011-2012 / Les cellules thalamocorticales (TC) du noyau ventro-postéro-latéral (VPL) du thalamus relayent l'information du système somatosensoriel (synapses excitatrices lemniscales aux dendrites proximaux) à la région correspondante du cortex, mais reçoivent également en rétro-propagation des projections du cortex (synapses excitatrices corticothalamiques aux dendrites distaux). Afin d'étudier l'intégration synaptique aux différentes parties de la cellule TC, nous avons bâti un modèle multi-compartimental à partir de reconstructions tridimensionnelles de cellules du noyau VPL, ce qui consiste en une discrétisation spatiale des dendrites en une multitude de segments associés à des circuits RC interconnectés. Nous avons pu dégager quantitativement l'impact de la géométrie cellulaire (taille d'arborisation et diamètre dendritique) sur l'amplitude et sur la durée des réponses au soma. Nous avons par la suite comparé l'intégration synaptique pour différentes distributions des entrées aux dendrites proximaux et distaux et sous différentes conditions de courants intrinsèques et de potentiel membranaire. Dans tous les cas, la sommation des entrées proximales induisait une réponse indépendante de la distribution, alors que la réponse aux entrées distales saturait lorsqu'elles étaient localisées aux mêmes branches. Nos résultats ont permis d'apporter une explication physiologique au patron d'organisation synaptique chez les cellules TC. / Thalamocortical (TC) cells from the ventroposterolateral (VPL) nucleus of the thalamus relay the somatosensory inputs (excitatory lemniscal synapses at proximal dendrites) to the corresponding cortical area, but also receive feedback excitatory inputs from the cortex (corticothalamic synapses at distal dendrites). The goal of this study was to compare the synaptic integration of inputs coming to proximal vs. distal dendrites. A multicompartmental model was drawn from fully reconstructed cells of the VPL nucleus. Dendrites were spatially discretized in multiple segments associated to interconnected RC circuits. We were able to characterize the impact of neuronal size and dendritic diameter on the amplitude and on the time course of the somatic response. We also compared the synaptic integration for different distributions of proximal or distal inputs under different conditions of membrane potential and active properties. In all cases, the summation of proximal inputs was independent of their distribution, while the response induced by distal inputs saturated when those inputs were located at the same branches. The results obtained in this study suggest a physiological explanation of the synaptic pattern at TC cells.
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Influence of the dentritic morphology on electrophysiological responses of thalamocortical neuronsZomorrodi Moghaddam, Reza 18 April 2018 (has links)
Les neurones thalamiques de relai ont un rôle exclusif dans la transformation et de transfert de presque toute l'information sensorielle dans le cortex. L'intégration synaptique et la réponse électrophysiologique des neurones thalamiques de relai sont déterminées non seulement par l’état du réseau impliqué, mais ils sont également contrôlés par leurs propriétés intrinsèques tels les divers canaux ioniques voltage-dépendants ainsi que l’arborisation dendritique élaboré. Par conséquent, investiguer sur le profil complexe de morphologie dendritique et sur les propriétés dendritiques actives révèle des renseignements importants sur la fonction d'entrée-sortie de neurones thalamiques de relai. Dans cette étude, nous avons reconstruit huit neurones thalamocorticaux (TC) du noyau VPL de chat adulte. En se basant sur ces données morphologiques complètes, nous avons développé plusieurs modèles multicompartimentaux afin de trouver un rôle potentiellement important des arbres dendritiques des neurones de TC dans l'intégration synaptique et l’intégration neuronale. L'analyse des caractéristiques morphologiques des neurones TC accordent des valeurs précises à des paramètres géométriques semblables ou différents de ceux publiés antérieurement. En outre, cette analyse fait ressortir de tous nouveaux renseignements concernant le patron de connectivité entre les sections dendritiques telles que l'index de l'asymétrie et la longueur de parcours moyen (c'est-à-dire, les paramètres topologiques). Nous avons confirmé l’étendue des valeurs rapportée antérieurement pour plusieurs paramètres géométriques tels que la zone somatique (2956.24±918.89 m2), la longueur dendritique totale (168017.49±4364.64 m) et le nombre de sous-arbres (8.3±1.5) pour huit neurones TC. Cependant, contrairement aux données rapportées antérieurement, le patron de ramification dendritique (avec des cas de bifurcation 98 %) ne suit pas la règle de puissance de Rall 3/2 pour le ratio géométrique (GR), et la valeur moyenne de GR pour un signal de propagation est 2,5 fois plus grande que pour un signal rétropropagé. Nous avons également démontré une variabilité significative dans l'index de symétrie entre les sous-arbres de neurones TC, mais la longueur du parcours moyen n'a pas montré une grande variation à travers les ramifications dendritiques des différents neurones. Nous avons examiné la conséquence d’une distribution non-uniforme des canaux T le long de l'arbre dendritique sur la réponse électrophysiologique émergeante, soit le potentiel Ca 2+ à seuil bas (low-threshold calcium spike, LTS) des neurones TC. En appliquant l'hypothèse du «coût minimal métabolique», nous avons constaté que le neurone modélisé nécessite un nombre minimal de canaux-T pour générer un LTS, lorsque les canaux-T sont situés dans les dendrites proximales. Dans la prochaine étude, notre modèle informatique a illustré l'étendue d'une rétropropagation du potentiel d'action et de l'efficacité de la propagation vers des PPSEs générés aux branches dendritiques distales. Nous avons démontré que la propagation dendritique des signaux électriques est fortement contrôlée par les paramètres morphologiques comme illustré par les différents paliers de polarisation obtenus par un neurone à équidistance de soma pendant la propagation et la rétropropagation des signaux électriques. Nos résultats ont révélé que les propriétés géométriques (c.-à-d. diamètre, GR) ont un impact plus fort sur la propagation du signal électrique que les propriétés topologiques. Nous concluons que (1) la diversité dans les propriétés morphologiques entre les sous-arbres d'un seul neurone TC donne une capacité spécifique pour l'intégration synaptique et l’intégration neuronale des différents dendrites, (2) le paramètre géométrique d'un arbre dendritique fournissent une influence plus élevée sur le contrôle de l'efficacité synaptique et l'étendue du potentiel d'action rétropropagé que les propriétés topologiques, (3) neurones TC suivent le principe d’optimisation pour la distribution de la conductance voltage-dépendant sur les arbres dendritiques. / Thalamic relay neurons have an exclusive role in processing and transferring nearly all sensory information into the cortex. The synaptic integration and the electrophysiological response of thalamic relay neurons are determined not only by a state of the involved network, but they are also controlled by their intrinsic properties; such as diverse voltage-dependent ionic channels as well as by elaborated dendritic arborization. Therefore, investigating the complex pattern of dendritic morphology and dendritic active properties reveals important information on the input-output function of thalamic relay neurons. In this study, we reconstructed eight thalamocortical (TC) neurons from the VPL nucleus of adult cats. Based on these complete morphological data, we developed several multi-compartment models in order to find a potentially important role for dendritic trees of TC neurons in the synaptic integration and neuronal computation. The analysis of morphological features of TC neurons yield precise values of geometrical parameters either similar or different from those previously reported. In addition, this analysis extracted new information regarding the pattern of connectivity between dendritic sections such as asymmetry index and mean path length (i.e., topological parameters). We confirmed the same range of previously reported value for several geometric parameters such as the somatic area (2956.24±918.89 m2), the total dendritic length (168017.49±4364.64 m) and the number of subtrees (8.3±1.5) for eight TC neurons. However, contrary to previously reported data, the dendritic branching pattern (with 98% bifurcation cases) does not follow Rall’s 3/2 power rule for the geometrical ratio (GR), and the average GR value for a forward propagation signal was 2.5 times bigger than for a backward propagating signal. We also demonstrated a significant variability in the symmetry index between subtrees of TC neurons, but the mean path length did not show a large variation through the dendritic arborizations of different neurons. We examined the consequence of non-uniform distribution of T-channels along the dendritic tree on the prominent electrophysiological response, the low-threshold Ca2+ spike (LTS) of TC neurons. By applying the hypothesis of “minimizing metabolic cost”, we found that the modeled neuron needed a minimum number of T-channels to generate low-threshold Ca2+ spike (LTS), when T-channels were located in proximal dendrites. In the next study, our computational model illustrated the extent of an action potential back propagation and the efficacy of forward propagation of EPSPs arriving at the distal dendritic branches. We demonstrated that dendritic propagation of electrical signals is strongly controlled by morphological parameters as shown by different levels of polarization achieved by a neuron at equidistance from the soma during back and forward propagation of electrical signals. Our results revealed that geometrical properties (i.e. diameter, GR) have a stronger impact on the electrical signal propagation than topological properties. We conclude that (1) diversity in the morphological properties between subtrees of a single TC neuron lead to a specific ability for synaptic integration and neuronal computation of different dendrites, (2) geometrical parameter of a dendritic tree provide higher influence on the control of synaptic efficacy and the extent of the back propagating action potential than topological properties, (3) TC neurons follow the optimized principle for distribution of voltage-dependent conductance on dendritic trees.
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Influence d'un champ magnétique glissant sur la solidification dirigée des alliages métalliques binaireszaidat, kader 02 November 2005 (has links) (PDF)
Dans le domaine de l'élaboration des alliages métalliques, les principaux enjeux industriels résident dans la possibilité de maîtriser la structure métallurgique ainsi que les défauts qui surviennent lors de la phase de solidification. Lors de la solidification, les mouvements hydrodynamiques dans la phase liquide ont une influence importante sur les propriétés du produit solidifié. Dans cette étude, la conception d'un nouveau dispositif BATMAF (Bridgman Apparatus with a Travelling MAgnetic Field) constitué d'un four de solidification dirigée et d'une bobine de Bitter permettant de produire un champ magnétique glissant a permis d'étudier l'influence d'une convection forcée sur la solidification dirigée des alliages métalliques binaires. Notre attention s'est plus particulièrement portée sur deux effets majeurs influencés par la présence de convection forcée ou non : la macroségrégation et la structure de grains pour un alliage d'Al-3.5%pdsNi en présence ou non de particules affinantes. La vitesse ainsi que le sens de l'écoulement forcé peuvent être contrôlés par l'application du champ magnétique glissant. Nous avons montré que dans le cas de notre alliage, la macroségrégation peut-être contrôlée et que de plus, l'espacement primaire dendritique est modifié en fonction du champ appliqué. En ce qui concerne les structures de grains, à l'aide d'un modèle analytique, nous montrons que l'extension de la couche solutale en avant du front de solidification varie en fonction du sens de l'écoulement au voisinage de la zone pâteuse. Ceci conditionne la possibilité pour les grains équiaxes de germer puis de croître et, par conséquent, l'obtention du régime équiaxe ou non. Enfin, dans le cas des alliages non affinés, dans un domaine d'intensité de brassage, un régime de grains libres allongés a pu être obtenu probablement par fragmentation. Cette étude démontre s'il en était besoin, l'importance cruciale de la maîtrise de la convection sur les macroségrégations et la structure des grains et ouvre des perspectives quant à l'utilisation du champ magnétique glissant pour leur contrôle
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Characterization Of Al-Si Alloy Engine Bores For Tribological StudiesVijayalakshmi, S R 09 1900 (has links) (PDF)
Aluminum - Silicon alloys are recognized as appropriate materials for high performance cast components used in transportation powertrain applications. A combination of excellent wear resistance, good thermal conductivity and low density make these materials good candidates for engine bore applications. It is well accepted that the tribological properties of these alloys are dictated by the presence of hard eutectic silicon particles and their distribution in the soft aluminum matrix. Three near-eutectic aluminum-silicon engine bore alloys manufactured by different processing routes such as sand casting, chill casting and spray compaction were investigated to determine the influence of solidification on evolution of microstructure of these alloys and to establish correlation of microstructure with tribological properties. The spatial distribution of the silicon particles in aluminum matrix is analyzed using various image analysis techniques and contact distribution studies. The chill cast alloy shows large columnar primary aluminum dendrites interspersed with coarse silicon particles. The sand cast and spray compacted alloys show better spatial distribution of refined silicon particles. Microstructures generated under different solidification modes are found to have varying morphologies. The crystallographic orientations of the dendritic and eutectic aluminum as well as that of the eutectic silicon were studied using electron backscatter diffraction (EBSD). The eutectic silicon nucleating in chill cast alloy is found to exhibit strong orientation relationship with the aluminum matrix. The crystallographic orientation relationship shows that the solidification modes of the eutectics in these three alloys are different, from alloy to alloy, due to their different solidification rates and due to the addition of grain refiners and modifiers.
The hardness values of the aluminum matrix and silicon particles of these alloys were found using nanoindentation and micro indentation tests. Preliminary wear studies were carried out on etched and unetched test alloys in dry reciprocating sliding. The results show that of the three test alloys, the alloy in which eutectic regions nucleate heterogeneously from the primary aluminum dendrites gives the best wear resistance and the highest hardness. The very low friction coefficient recorded for the etched alloys is accounted for by the insitu formation of a thin sheet of tribofilm on the protruding silicon particles. The physical and chemical natures of this protective film are being investigated.
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