Somatostatin interneurons in the prefrontal cortex control affective state discrimination in mice.

The prefrontal cortex (PFC) is implicated in processing of the affective state of others through non-verbal communication. This social cognitive function is thought to rely on an intact cortical neuronal excitatory and inhibitory balance. Here combining in vivo electrophysiology with a behavioral task for affective state discrimination in mice, we show a differential activation of medial PFC (mPFC) neurons during social exploration that depends on the affective state of the conspecific. Optogenetic manipulations revealed a double dissociation between the role of interneurons in social cognition. Specifically, inhibition of mPFC somatostatin (SOM), but not of parvalbumin (PV) interneurons, abolishes affective state discrimination. Accordingly, synchronized activation of mPFC SOM interneurons selectively induces social discrimination. As visualized by in vivo single-cell microendoscopic Ca imaging, an increased synchronous activity of mPFC SOM interneurons, guiding inhibition of pyramidal neurons, is associated with affective state discrimination. Our findings provide new insights into the neurobiological mechanisms of affective state discrimination.