Inhibition from the oxytocin system tunes prefrontal circuit dynamics to promote social behavior

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 social behaviors. To address this question, we developed a novel social decision-making task in which female mice chose between social and non-social options. To explore the role of a task-relevant inhibitory subpopulation in social decision-making, 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 potential mechanism by which PFC excitation-inhibition balance contributes to normal social functioning.