Title: Longitudinal evaluation of striatal dysfunctions in autism spectrum disorders

Abstract

The autism spectrum disorder (ASD) is a non-lethal neurodevelopmental disorder. The adult ASD patients carry a substantial comorbidity burden leading to a “premature aging” and a reduced life expectancy. Our main question was whether this “premature aging” is a mere consequence of initial neurodevelopmental deficits or due to a cumulative pathological process. We used ex vivo electrophysiology, optogenetics, chemogenetics, behavioural assessment and neuroanatomy to characterize the dysfunctions at different ages. We focused on identifying the onset of striatal dysfunctions in mouse models of ASD. We observed a worsening in motor dysfunctions in aged ASD animals. In addition, our preliminary data showed premature morphological alterations of striatal neurons inadult ASD. In addition, our results suggest that striatal interneurons could also be dysfunctional. These results open up a new field of investigation to better understand lifelong consequences of ASD in adults.