This project seeks to learn how certain autism-related genes may affect proteins in the brain and the function of brain circuits that underlie the behavioral disturbances observed in autism. The ubiquitin E3 ligase, Ube3a, has been implicated in autism spectrum disorder (ASD) caused by duplication in the maternal 15q 11-13 gene region (15qASD). Cells from 15qASD patients have extra copies of the UBE3A gene. The majority of children who inherit 15q11-13 duplications from their mothers develop ASD; the more copies inherited, the more severe the impairment. This project tests the hypothesis that excess Ube3a protein (created by extra copies of 15q11-13) contributes to ASD by increasing the ubiquitination and degradation of key brain proteins needed to preserve normal neuronal circuit function. Mouse models will be used to elucidate the impact of the number of copies of 15q11-13 on neural circuit function. This understanding may lead to the development of new drugs and behavioral interventions.