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Studying Ca2+ channel function at sub-micron spatial resolution

Abstract : The physiology of ion channels is a major topic of interest in modern neuroscience since the functioning of these molecules is the biophysical ground of electrical and chemical behaviour of neurons. Ion channels are diverse membrane proteins that allow the selective passage of ions across the lipid bilayer of cells. They are involved in a variety of fundamental physiological processes from electrical signal integration, action potential generation and propagation to cell growth and even apoptosis, while their dysfunction is the cause of several diseases. Ion channels have extensively studied using electrode methods, in particular the patch-clamp technique, but these approaches are limited in studying native channels during physiological activity in situ. In particular, electrodes give limited spatial information while it is recognised that the contribution of channels in all different processes is a function not only of their discrete biophysical properties but also of their distribution across the neurons surface at the different compartments. Optical techniques, in particular those involving fluorescence imaging, can overcome intrinsic limitations of electrode techniques as they allow to record electrical and ionic signals with high spatial and temporal resolution. Finally, the ability of optical techniques combined with neuronal modelling can potentially give pivotal information significantly advancing our understanding on how neurons work.The ambitious goal of my thesis was to progress in this direction by developing novel approaches to combine cutting-edge imaging techniques with modelling to extract ion currents and channel kinetics in specific neuronal regions. The body of this work was divided in three methodological pieces, each of them described in a dedicated chapter.
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Luiza Filipis. Studying Ca2+ channel function at sub-micron spatial resolution. Neurobiology. Université Grenoble Alpes, 2019. English. ⟨NNT : 2019GREAY078⟩. ⟨tel-02936562⟩

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