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Retinal waves : theory, numerics, experiments

Abstract : Retinal waves are spontaneous bursts of activity propagating in the developing retina, playing a fundamental role in shaping the visual system and retinal circuitry. They disappear completely upon maturation. Understanding how retinal waves are initiated and propagate in the retina could enable us to design protocols to trigger such retinal waves in the adult retina, expecting to reintroduce some plasticity in the retinal tissue and the projections in the brain. In my thesis, I have focused on a specific stage of development of waves, called stage II, induced by specific cells (SACs) and mediated by the neurotransmitter acetylcholine. Immature SACs exhibit a spontaneous bursting behavior due to intrinsic cellular mechanisms, which disappears completely upon maturation. Also, immature SACs are connected by excitatory connections, leading to propagating bursts of activity. The general spirit of this thesis work, is to propose a model for retinal waves (i) sufficiently close to biophysics to explain and propose experiments and (ii) suffciently well posed mathematically to analyse its dynamics upon varying biophysical parameters. In this context, we wanted to ellucidate the mechanisms causing immature SACs to burst and how retinal waves start, propagate and stop. We proposed a mathematical model, grounded on biophysics, and through bifurcations theory we explain the possible underlying cellular mechanisms of retinal waves, highlighting the relevant biophysical parameters controlling waves propagation and disparition. On top of that, we analyzed how the evolution of cholinergic conductance due to the maturation of nicotinic receptors dramatically changes the retinal wave characteristics. Especially, there is a very narrow interval of acetylcholine conductance where retinal waves size obey a power law distribution, suggesting a specific (homeostatic) mechanism stabilizing temporarily the SACs network in this specific range. To sum up, this thesis results are mainly theoretical, but they also lead to experimental predictions directly linked to biology.
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Submitted on : Tuesday, June 19, 2018 - 11:17:06 AM
Last modification on : Friday, June 12, 2020 - 3:04:39 AM
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Theodora Karvouniari. Retinal waves : theory, numerics, experiments. Bioinformatics [q-bio.QM]. COMUE Université Côte d'Azur (2015 - 2019), 2018. English. ⟨NNT : 2018AZUR4014⟩. ⟨tel-01818522⟩



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