Impact of parvalbumin interneuron inhibition during adolescence on social behaviors

Adolescence is an important period for the maturation of prefrontal circuits and the complex behaviors it regulates, including social interactions. A major component of this developmental process is the maturation of parvalbumin-expressing (PV) interneurons, which regulate excitation-inhibition balance and contribute to the refinement of cortical networks. Although PV neurons have been implicated in social behaviors, their role during adolescence in shaping social behavior development remains unclear. To address this question, we chemogenetically inhibited prefrontal PV interneurons in male and female mice during either adolescence or adulthood and assessed long-term changes in PV network characteristics and social behavior. Adolescent PV inhibition produced persistent reductions in detectable PV neurons and increased PNN labeling surrounding PV cells, as well as reduced social motivation in males following prolonged food deprivation. In contrast, adult inhibition did not alter detectable PV neurons or PNN association, but reduced cFos expression in PV-targeted cells in the prelimbic cortex in response to a social interaction and produced changes in female social interaction patterns and sex-dependent changes in anxiety-like behavior. These findings suggest that PV interneuron activity contributes to the regulation of prefrontal inhibitory circuitry and social behavior, with disruption during adolescence producing lasting changes in PV network characteristics and social motivation.