Project 1: Sato

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PROJECT 1 – PROJECT SUMMARY Impairment in social behaviors is a core symptom in autism spectrum disorder (ASD), yet the underlying mechanisms of this dysfunction are not known. The current project aims to provide a mechanistic link between a highly penetrant, syndromic ASD risk gene, MEF2C, and the development of social deficits. Our preliminary data show that the reduction of Mef2c in inhibitory interneurons, rather than excitatory neurons, is critical for establishing social deficits. We will extend these preliminary data to test the hypothesis that a specific subtype of interneuron (parvalbumin-positive interneurons or PV-INs) is a critical circuit component that links Mef2c to neurotypical social behavior. In Aim 1, we will employ in vivo calcium imaging to monitor changes in the activity of PV-INs and other major neuron classes in the prefrontal cortex to better understand altered circuit activity patterns that link to social deficits in Mef2c mutant mice. In Aim 2, we will determine altered gene expression patterns in PV-INs and other types of neurons in Mef2c mutant mice, including a novel approach to tag neurons that were active during social interaction. Together, our study will clarify how excitatory and inhibitory circuits for social information processing are affected in an ASD mouse model. The project will benefit from the CNDD cores for behavioral assays, in vivo imaging, bioinformatics approaches, and advanced biostatistical consulting. The career development and mentorship will help the PI obtain future NIH R01 funding to facilitate the transition to an established investigator in the field of neurodevelopment and its disorders.