Philippe Mourrain leads a program focused on subcellular changes occurring during normal sleep and associated neurological pathologies (Parkinson’s and Alzheimer’s diseases and autism) using mouse and fish genetic models. Over the past years, the program has developed new approaches and whole-brain imaging tools to uncover changes and abnormalities in the fish and mouse brains. Using a custom-made two-photon microscope, they revealed for the first time in a vertebrate a role for sleep in synaptic plasticity and pruning. They then successfully developed and applied array-tomography (AT) imaging and novel synapse classification algorithms to uncover population level and subsynaptic level defects (>1 million synapses analyzed). Mourrain’s group built a light-sheet microscope to perform whole-brain whole-body imaging of zebrafish to capture cellular and subcellular sleep dynamics. This allowed them to identify slow wave sleep and REM sleep cellular dynamics in fish and uncover new molecular and cellular actors. Recently, they have revealed that abnormal synaptic excitability of the hypocretin neurons was responsible of sleep fragmentation during normal aging. Finally, the group is leveraging the conservation of genes such as Gba1 across 450 million years of vertebrate genome evolution — from human to zebrafish — to model human neurological defects in the fish using gene editing.
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