Synaptic pruning during adolescence shapes adult social behavior in both males and females.

Evolutionarily conserved, peer-directed social behaviors are essential to participate in many aspects of human society. These behaviors directly impact psychological, physiological, and behavioral maturation. Adolescence is an evolutionarily conserved period during which reward-related behaviors, including social behaviors, develop via developmental plasticity in the mesolimbic dopaminergic "reward" circuitry of the brain. The nucleus accumbens (NAc) is an intermediate reward relay center that develops during adolescence and mediates both social behaviors and dopaminergic signaling. In several developing brain regions, synaptic pruning mediated by microglia, the resident immune cells of the brain, is important for normal behavioral development. We previously demonstrated that during adolescence, in rats, microglial synaptic pruning shapes the development of NAc and social play behavior in males and females. In this report, we hypothesize that interrupting microglial pruning in NAc during adolescence will have persistent effects on male and female social behavior in adulthood. We found that inhibiting microglial pruning in the NAc during adolescence had different effects on social behavior in males and females. In males, inhibiting pruning increased familiar exploration and increased nonsocial contact. In females, inhibiting pruning did not change familiar exploration behavior but increased active social interaction. This leads us to infer that naturally occurring NAc pruning serves to reduce social behaviors toward a familiar conspecific in both males and females.