ABSTRACT Autism spectrum disorder (ASD) is a neurodevelopmental disorder classified by two major diagnostic criteria - persistent deficits in social communication and interaction, and the presence of restricted, repetitive patterns of behavior. The striatum, the main input center of the basal ganglia, has been implicated in the presentation of repetitive behaviors given its roles in action selection, motor learning and habit formation. Despite clear links between striatal functions and ASD-related behavioral alterations, the striatum, and basal ganglia in general, remain relatively underexplored in ASD research. Recent work from our lab and others has shown that striatal cell type-specific deletion of ASD risk genes in mice is sufficient to increase performance on the accelerating rotarod task, a striatum-dependent motor learning assay used as a proxy for acquired repetitive behaviors. We further showed that this enhanced motor learning is associated with increased corticostriatal excitatory connectivity. Together this work suggests that enhanced corticostriatal drive may promote the acquisition of fixed motor routines in the context of ASD-related genetic perturbations. In this proposal, I will test the hypothesis that striatal, in particular corticostriatal, connectivity and synaptic plasticity is commonly altered across mouse models of ASD that harbor mutations in a range of risk genes. In addition, I will determine how mutations in ASD-risk genes impact striatal-dependent motor and habit learning. I will focus on three mouse models of autism, with disruption in ASD-risk genes that code for a range of protein types: Cntnap2, which codes for a synaptic adhesion molecule, Pten, which codes for phosphatase that negatively regulates AKT and mTOR signaling, and Scn2a, which codes for a voltage-gated sodium channel. I will determine the potential alterations in striatum-dependent behaviors in these models by utilizing behavior assays that assess learned motor behaviors thought to be dependent on corticostriatal synaptic transmission. I will then assess the impact of these mutations on the physiological properties of spiny projection neurons (SPNs), the main output cells of the striatum, and attempt to rescue alterations in habitual motor behaviors by modifying SPN excitability. These experiments will increase our understanding of how striatal pathophysiology contributes to ASD and may identify points of convergence at the synaptic or circuit level that are shared across genetically diverse forms of ASD. Such an outcome may enable the design of therapeutics that can restore striatal function in the context of ASD.