Cortical Representations of Conspecific Sex Shape Social Behavior

A central question related to virtually all social decisions is how animals integrate sex-specific cues from conspecifics. Using microendoscopic calcium imaging in mice, we find that sex information is represented in the dorsal medial prefrontal cortex (dmPFC) across excitatory and inhibitory neurons. These cells form a distributed code that differentiates the sex of conspecifics and is strengthened with social experience. While males and females both represent sex in the dmPFC, male mice show stronger encoding of female cues, and the relative strength of these sex representations predicts sex preference behavior. Using activity-dependent optogenetic manipulations of natively active ensembles, we further show that these specific representations modulate preference behavior toward males and females. Together, these results define a functional role for native representations of sex in shaping social behavior and reveal a neural mechanism underlying male-versus female-directed sociality.