Post-weaning parvalbumin expression in left orbitofrontal cortex shapes sociability in female mice

The adolescent social experience is essential for the maturation of the prefrontal cortex (PFC) in mammalian species. However, it is still unclear which cortical circuits mature with such experience and how it shapes adult social behaviors in a sex-specific manner. Here, we found that the post-weaning social isolation during adolescence (PWSI) caused hypersociability in female mice only and impaired both the parvalbumin (PV) expression and social sniffing-induced activity in the left orbitofrontal cortex (OFCL). Similarly, the CRISPR/Cas9-mediated knock-down of PV in the OFCL enhanced sociability and reduced the social sniffing-induced activity in female mice via decreased excitability of PV+ neurons and reduced synaptic inhibition in the OFCL. Moreover, optogenetic activation of OFCL excitatory neurons enhanced sociability in female mice. Our data demonstrate that the adolescent social experience is critical for the maturation of PV+ inhibitory circuits in the OFCL; this maturation shapes female social behavior via enhancing social representation in the OFCL.