Reward circuitry underpinnings for social buffering of stress

Social buffering, the phenomenon by which the presence of others can reduce the consequences of stressful experiences, has been observed in both humans and rodents, yet the precise mechanism by which social interactions can offset the negative impact of stress remains unknown. Here, utilizing a new behavioral paradigm, we demonstrate that brief social interaction with a familiar, unstressed individual after acute restraint, is sufficient to ameliorate the stress-induced deficits in reward seeking in both male and female mice. Previous studies indicate that within the ventral tegmental area (VTA), not only dopamine but also GABA neural activity has been implicated in the stress-induced reductions in reward seeking. Therefore, we aimed to investigate whether social buffering alleviates stress-induced blunting of reward seeking by modulating specific VTA neuronal populations. Using fiber photometry recordings, we observed increased activity of VTA GABA neurons during restraint stress as well as distinct calcium dynamics during social interaction and cued-reward task. Furthermore, we show that brief optogenetic inhibition of these neurons after restraint mimics the effects of social interaction on stress-induced deficits in reward anticipation, suggesting an important role of VTA GABA neurons in mediating the effects of social buffering. Together, our data suggests that social communication of affective state engages GABA neurons within the VTA to counteract negative effects of stress, providing new avenues to develop targeted therapeutic interventions for stress-related disorders.