Prefrontal cortex to dorsal medial striatum neural circuitry mediates social interaction

The prefrontal cortex and striatum have been implicated in social interaction while the underpinning neuronal and circuit mechanisms remain poorly understood. Here, we report that frontostriatal neurons are strongly activated when naive male C57BL/6J mice interact with a conspecific. Furthermore, cell-type-specific inhibition or activation of these neurons substantially impairs social interaction. Moreover, optogenetic inhibition of the prefrontal cortex (PFC)–dorsomedial striatum (DMS) pathway significantly disrupts social interaction. These findings reveal a key function of frontostriatal neurons in social interaction and suggest that selectively targeting the PFC–DMS circuit may help alleviate social dysfunction in related disorders.