Foxp2 genetic control of sex differences in amygdala-driven social behavior

Project Summary During adolescence the brain undergoes dramatic changes that coincide with a major transition in social- emotional behaviors and is a time of enhanced vulnerability for individuals with a host of neurodevelopmental and neurobehavioral disorders such as schizophrenia, depression, and anxiety disorders. One brain region that

is a major driver of the behavioral transition during adolescence is the amygdala. The amygdala is critical for social-emotional behavior and altered developmental trajectories and dysfunction of the amygdala are hallmark features of many neurodevelopment and neurobehavioral disorders. Here, we focus on the role played by the

transcription factor, Foxp2, in behavioral and circuit maturation of the medial subnucleus of the amygdala during adolescence in both males and females. Our focus on Foxp2 stems from our previous work and work in the field highly implicating Foxp2 gene function in social brain function and critical periods of neurodevelopment. These

findings led to our hypothesis that Foxp2 is required in a sex-specific manner for the formation of social circuitry in the medial subnucleus of the amygdala during adolescence. To study the function of Foxp2 in behavior and circuit maturation during adolescence, we will use cutting edge CRISPR-Cas gene editing approaches to delete Foxp2 gene function in male and female mice specifically

in the medial amygdala during adolescence. We will examine the consequences on social behavior and neuronal circuit function (Specific Aim 1), and using state of the art genomic profiling tools, uncover the correlate gene regulatory deficits underlying these behavioral and circuit deficits (Specific Aim 2). The overarching goal of this

project is to generate a mechanistic understanding of the genetic control of social brain formation and social behavior during adolescence. As amygdala dysfunction is a prime feature of a host of social and emotional disorders, most of which show sex biases, this work is a critical step toward understanding how brain circuit

dysfunction is linked to prevalent human disorders.