Early life social defeat in mice reduces prefrontal innervation of downstream structures in a regionally specific manner

Physical abuse in childhood and adolescence results in long lasting effects on mental and physical health in adulthood. The prefrontal cortex of adults exposed to abuse in childhood shows both functional and structural abnormalities in comparison to healthy controls. However, the changes in prefrontal innervation of specific downstream targets as a result of early life abuse are unclear. Here we used a novel abbreviated early adolescent chronic social defeat stress paradigm (5 day eaCSDS) to assess changes to prefrontal innervation in adult male and female C57BL/6 J mice. We injected control and defeated mice with virally encoded GFP in the prelimbic region of prefrontal cortex (PL) and examined axon density in basolateral amygdala (BLA), nucleus accumbens (NAc) and ventral tegmental area (VTA). We find that both male and female mice show robust but seemingly opposing changes in social interaction after 5 day eaCSDS. We found significantly decreased PL innervation of BLA and increased fragmentation of PL axons in BLA. Males, but not females, also show increased fragmentation of PL axons in NAc. Interestingly, PL innervation of BLA significantly correlates with adult social behavior in males and females. Our findings suggest that PL innervation of downstream targets is dramatically affected by early life social defeat in both a regional and sex-specific manner. This differential change in innervation across regions and sexes may underlie the social behavioral deficits seen after early life social defeat.