ABSTRACT Impaired social processes are a common feature in diverse psychiatric disorders such as communication disorders, autism-spectrum disorder, depression, and schizophrenia. Despite extensive studies using mouse models and human brain imaging, the mechanisms underlying deficiencies in social processes are obscure. Experiments with ArpC3 or Shank3 mice reveal that homozygous mutants from both strains are deficient in social behavior. We have developed a system where selected genes can be disrupted within a specific neural circuit and have some preliminary results that a prefrontal cortex (PFC) to basolateral amygdala (BLA) circuit can modulate social behavior. The Overall Goal of this proposal is to use this novel circuit-based gene manipulation approach to identify neural circuits in the ArpC3 and Shank3 mutant mice that may regulate social behaviors. Our Central Hypothesis is that disturbances in a PFC-BLA neural circuit produce abnormal social behaviors. In Aim #1 we will determine whether the PFC-BLA circuit is a common neural pathway controlling abnormal social behavior in ArpC3 and Shank3 mice. Aim #2 will analyze the collateral circuit projecting from the PFC to both BLA and VTA, and test the distinctive responses of recipient neurons in the BLA and VTA during social interaction. Aim #3 will focus on identifying additional neural circuits downstream of the PFC-BLA circuit that can modulate social processes.