Guy Bouvier: Impaired cerebellar plasticity hypersensitizes the VOR in SCN2A Autism

Children diagnosed with autism spectrum disorder (ASD) commonly present with sensory hypersensitivity, or abnormally strong reactions to sensory stimuli. Such hypersensitivity can be overwhelming, causing high levels of distress that contribute markedly to the negative aspects of the disorder. Here, we identify the mechanisms that underlie hypersensitivity in a sensorimotor reflex found to be altered in humans and in mice with loss-of-function in the ASD risk-factor gene SCN2A. The vestibulo-ocular reflex (VOR), which helps maintain one’s gaze during movement, was hypersensitized due to deficits in cerebellar synaptic plasticity. Heterozygous loss of SCN2A-encoded NaV1.2 sodium channels in granule cells impaired high-frequency transmission to Purkinje cells and long-term potentiation, a form of synaptic plasticity important for modulating VOR gain. VOR plasticity could be rescued in adolescent mice via a CRISPR-activator approach that increases Scn2a expression, highlighting how evaluation of simple reflexes can be used as quantitative readout of therapeutic interventions. Guy Bouvier studied with Boris Barbour and Mariano Casado (IBENS, Paris) during his PhD to dissect synaptic plasticity rules and their impact on motor learning, using the parallel fibre-Purkinje cells synapse of the cerebellum. After earning his PhD Guy joined the laboratory of Massimo Scanziani at the University of California, San Francisco/HHMI (USA) where he worked on circuit computations in neuronal populations. At UCSF Guy explored how the vestibulo-cerebellar circuit could modulate the activity of sensory cortices, such as the primary visual cortex. Supported by the European Research Council, Guy established the SensoMotion Lab in the summer of 2023 at the Neuroscience Institute of Paris-Saclay. His lab aims to unravel how our own motion impacts sensory processing, and ultimately our internal model of the world.