Defining the Role of Early Life Experience in mPFC Circuit Assembly

2020 Seed Grant
Laura A. DeNardo, Ph.D.
University of California, Los Angeles

The medial prefrontal cortex (mPFC) plays a critical role in complex cognitive and emotional functions including decision making, mood and social behaviors. mPFC undergoes a uniquely protracted maturation which is likely essential to produce these complex behaviors, but also opens a prolonged window during which these circuits can be perturbed. As a result, alterations in mPFC structure and function are implicated in a large number of neuropsychiatric disorders. In order to understand how early insults transform mPFC circuits to produce maladaptive behaviors in disease, we must determine how mPFC circuits wire up during critical windows of vulnerability. Here we focus on the connection between mPFC and a key target region, the nucleus accumbens (NAc). The mPFCàNAc pathway is implicated in diseases which arise early in life, including addiction, autism, anxiety and depression. We will determine how the mPFCàNAc connection forms and matures, identify the genes responsible for these developmental programs, and determine how early life stress impacts mPFC and NAc development. These studies will reveal mechanisms by which environmental insults shape circuits and aid in interpretation of human genetic data.

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