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Theses

Modélisation fonctionnelle de l'activité neuronale hippocampique : Applications pharmacologiques

Abstract : The work of this thesis aims to apply modeling and simulation techniques to mechanisms underlying neuronal activity, in order to promote drug discovery for the treatment of nervous system diseases. The models are developed and integrated at different scales: 1) the so-called "elementary models" permit to simulate dynamics of receptors, ion channels and biochemical reactions in intracellular signaling pathways; 2) models at the neuronal level allow to study the electrophysiological activity of these cells; and 3) microcircuits models help to understand the emergent properties of these complex systems, while maintaining the basic mechanisms that are the targets of pharmaceutical molecules. After a bibliographic synthesis of necessary elements of neurobiology, and an outline of the implemented mathematical and computational tools, the manuscript describes the developed models, as well as their validation process, ranging from the neurotransmitter receptor to the microcircuit. Moreover, these developments have been applied to three studies aiming to understand: 1) pharmacological modulation of the long-term potentiation (LTP) of glutamatergic synapses in the hippocampus, 2) mechanisms of neuronal hyperexcitability in the mesial temporal lobe epilepsy (MTLE), based on in vitro and in vivo experimental results, and 3) cholinergic modulation of hippocampal activity, particularly the theta rhythm associated with septo-hippocampal pathway.
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https://tel.archives-ouvertes.fr/tel-01649876
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Arnaud Legendre. Modélisation fonctionnelle de l'activité neuronale hippocampique : Applications pharmacologiques. Automatique. Université de Haute Alsace - Mulhouse, 2015. Français. ⟨NNT : 2015MULH7271⟩. ⟨tel-01649876⟩

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