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SUMMARY:Thesis defense - Théo Gauvrit
DESCRIPTION:Venue: l’ENSTBB (grosse boule bleu à l’entrée du parking étudiant)\, \nDefense in english \n\nThéo Gauvrit\nNeurocentre Magendie \nThesis supervisor: Andreas Frick \nTitle\nComputational approaches for the analysis and modeling of atypical sensory experience in autism \nAbstract\nHow does the brain encode the perception of sensory stimuli in our environment? This question\, still not fully answered\, becomes even more intriguing in the context of autism\, a neurodevelopmental condition characterized by atypical sensory experience as one of its core symptoms. These sensory alterations\, often manifesting as hyper- or hyporeactivity or variability in sensory responses\, are present in the vast majority of autistic individuals\, have a strong impact on their daily lives\, and contribute to other core symptoms of the condition. Strong neurophysiological alterations in the brain are suspected to drive these symptoms\, but limited research leaves the underlying mechanisms and potential therapeutic targets unclear. We adopted a preclinical translational approach to investigate the neurobiological underpinnings of atypical sensory experience in the tactile domain. This involved recording spontaneous and stimulus-evoked neuronal activity at the single-neuron level in the primary somatosensory cortex (S1) of anesthetized mice of the well-established Fmr1-/y mouse model of autism. This was followed by characterization of the S1 population activity with single-cell resolution in behaving animals during a perceptual decision-making task in the same mouse model. \nExamining spontaneous and stimulus-evoked neuronal activity in single neurons within the S1\, we identified significant trial-by-trial variability in the neuronal responses of Fmr1-/y mice\, a hallmark of atypical sensory processing in autistic individuals. We traced the sources of this variability to increased endogenous neuronal noise\, manifesting as random fluctuations in neuronal activity\, and to network instability\, characterized by rapid\, inconsistent\, and contrasting states. This elevated noise and instability impair the integration of sensory information in the cortex and may contribute to the sensory perception variability observed in clinical studies of autism. Furthermore\, the local (within S1) application of a BKCa channel agonist reduced local neuronal hyperexcitability and corrected many synaptic response features and their variance\, but had little effect on the trial-by-trial variability\, suggesting that this variability and hyperexcitability are less closely coupled than previously thought. \nTo evaluate the impact of these neuronal alterations on tactile detection\, we combined a translational decision-making task (back-translated from human studies) with functional imaging in S1. Our results recapitulated the multifaceted tactile alterations seen in autistic individuals\, with tactile hyposensitivity\, interindividual variability\, and unreliable behavioral responses in Fmr1-/y mice. By examining the evoked activity of pyramidal and GABAergic neurons\, we found that this altered tactile perception could be explained by weak stimulus encoding in S1\, rendering stimulus detection more vulnerable to ongoing network states and thus less reliable. By reducing local hyperexcitability in S1 using an agonist of BKCa channels\, we were able to strengthen stimulus encoding and thus improve tactile detection in Fmr1-/y mice. \nOur results emphasize the critical role of neuronal noise and variability in sensory information processing and the role of hyperexcitability and network states in shaping sensory perception. This translational approach offers mechanistic insight into the neural foundations of atypical tactile perception in autism and underscores the therapeutic potential of targeting these neural mechanisms to enhance sensory sensitivity and reliability in autistic individuals. \nKeywords: Autism\, Perception\, Tactile\, Neuronal Noise\, Cortex \nPublications\nEndogenous noise of neocortical neurons correlates with atypical sensory response variability in the Fmr1−/y mouse model of autism.\nArjun A. Bhaskaran\, Théo Gauvrit\, Yukti Vyas\, Guillaume Bonny\, Melanie Ginger\, Andreas Frick\nNature Communnications 14\, 7905 (2023). https://doi.org/10.1038/s41467-023-43777-z \nStimulus encoding shapes tactile perception and underlies alterations in autism\nbioRxiv 2024.08.08.607129; doi: https://doi.org/10.1101/2024.08.08.607129\nOurania Semelidou\, Théo Gauvrit\, Célien Vandromme\, Alexandre Cornier\, Anna Saint-Jean\, Yves Le Feuvre\, Melanie Ginger\, Andreas Frick \nJury\nRapporteur; M. Brice BATHELLIER; Directeur de Recherche; Université Paris-Cité – INSERM\nRapporteur; Mme. Elizabeth MILNE; Professeure;  University of Sheffield\nExaminateur; M. Ian DUGUID; Professeur; University of Edinburgh;\nExaminateur; Mme. Susanna PIETROPAOLO; Chargée de Recherche; Université de Bordeaux – CNRS \n
URL:https://www.bordeaux-neurocampus.fr/en/event/thesis-defense-theo-gauvrit/
CATEGORIES:Thesis
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