Somatostatin neurons in the medial amygdala orchestrate flexible, sex-specific social behavior in male mice

Intraspecific social interactions are essential for species survival and require behavioral flexibility to adapt to changing social environments. These behaviors are orchestrated by neural circuits such as those in the medial amygdala (MeA). Within this region, somatostatin-expressing neurons (MeA ^SST+ ) have been associated with maladaptive social outcomes, particularly following early-life stress. However, whether these neurons contribute to the flexibility of adult male social behavior— modulating responses according to social context and stimulus type—remains unclear. Here, using chemogenetic approaches combined with machine learning-based behavioral tracking, we showed that activation of MeA ^SST+ neurons reduced sociability, social novelty preference, inter-male aggression, and attention toward males, while enhancing sexual motivation and dominance toward females. Inhibition increased social novelty preference and impaired stress-coping behavior without affecting other social traits. Notably, both manipulations heightened escape-like responses to inanimate stimuli, indicating increased defensive reactivity to non-social cues. These findings identify MeA ^SST+ neurons as modulators of social context-specific behavior, advancing understanding of circuit-level mechanisms supporting adaptive social responses.