Inhibition tunes prefrontal circuit dynamics to promote sociosexual behavior in female mice

Abstract

The prefrontal cortex (PFC) plays a central role in the selection and expression of diverse social behaviors. A balance of excitation and inhibition is necessary for normal social functioning, but it remains unclear how inhibition sculpts pyramidal activity to promote specific social behaviors. To address this question, we developed a novel decision-making task in which female mice chose between interaction with a male (sociosexual stimulus) or an appetitive non-social option (milk solution). To explore the role of a task-relevant inhibitory subpopulation, we targeted neurons in the medial PFC (mPFC) expressing oxytocin receptors (OXTR neurons). Combining optogenetic inhibition of OXTR neurons with population calcium imaging of pyramidal neural activity, we found that OXTR neurons normally promote interaction with a male compared to a non-social alternative. OXTR neurons also regulate pyramidal activity, which enables a specific ensemble to represent the male option during decision-making. Computational modeling reproduced these findings through a pyramidal competition mechanism, in which regulation by OXTR neurons allows a male-representing pyramidal ensemble to effectively compete against the remaining pyramidal population to drive male choice. These results provide a candidate mechanism by which inhibition enables mPFC pyramidal activity to select for specific social behaviors and may help explain why excitation/inhibition balance is so important for social functioning.