Research in human populations indicates that the number of genetic loci associated with autism exceeds 15. Of specific relevance to this proposal is the phosphatase and tensin homolog (Pten). This cancer-causing gene regulates the growth of post-mitotic neurons. The PTEN signaling pathway is emerging as one of two major pathways that regulate the susceptibility to autism spectrum disorders. Mice with a cortical Pten deletion exhibit many of the characteristics associated with autism, including macrocephaly, deficits in social interactions, impaired social learning, hyperactivity, and increased anxiety-like behavior. Many of these deficits are reversible with chronic treatment of the mTOR inhibitor, rapamycin. This project uses mice in which the Pten gene is deleted specifically from the cortex beginning some 6-8 weeks after birth. Preliminary data show a unique growth of apical dendrites of pyramidal neurons following PTEN deletion. The goal of this project is to fully characterize any changes in basic physiology and sensory information processing in these growing neurons using in vivo whole cell patch recordings and 2-photon in vivo imaging of network activity. Results from these studies may provide targets for the development of rationally based therapeutics for autism spectrum disorders.