Prefrontal cortex to dorsal medial striatum neural circuitry mediates social interaction

The prefrontal cortex and striatum have been implicated in social interaction; however, 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.