Prefrontal GABAergic interneurons (INs) are crucial for social behavior by maintaining excitation/inhibition balance. However, the underlying neuronal correlates and network computations are poorly understood. We identified distinct firing patterns of prefrontal parvalbumin (PV) INs and somatostatin (SST) INs upon social interaction. Moreover, social interaction closely correlated with elevated gamma rhythms particularly at low gamma band (20 to 50 Hz). Pharmacogenetic inhibition of PV INs, instead of SST INs, reduced low gamma power and impaired sociability. Optogenetic synchronization of either PV INs or SST INs at low gamma frequency improved sociability, whereas high gamma frequency or random frequency stimulation had no effect. These results reveal a functional differentiation among IN subtypes and suggest the importance of low gamma rhythms in social interaction behavior. Furthermore, our findings underscore previously unrecognized potential of SST INs as therapeutic targets for social impairments commonly observed in major neuropsychiatric disorders.

Sociability is fundamental for our daily life and is compromised in major neuropsychiatric disorders. However, the neuronal circuit mechanisms underlying prosocial behavior are still elusive. Here we identify a causal role of the basal forebrain (BF) in the control of prosocial behavior via inhibitory projections that disinhibit the midbrain ventral tegmental area (VTA) dopamine (DA) neurons. Specifically, BF somatostatin-positive (SST) inhibitory neurons were robustly activated during social interaction. Optogenetic inhibition of these neurons in BF or their axon terminals in the VTA largely abolished social preference. Electrophysiological examinations further revealed that SST neurons predominantly targeted VTA GABA neurons rather than DA neurons. Consistently, optical inhibition of SST neuron axon terminals in the VTA decreased DA release in the nucleus accumbens during social interaction, confirming a disinhibitory action. These data reveal a previously unappreciated function of the BF in prosocial behavior through a disinhibitory circuitry connected to the brain’s reward system.