FIGHT, FLIGHT, OR FLIRT: SOMATOSTATIN NEURONS IN THE MEDIAL AMYGDALA GATE FLEXIBLE SOCIAL STRATEGIES 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 flexible adult male social behavior across context remains unclear. Here, using chemogenetic manipulations and miniscope calcium imaging combined with machine learning-based behavioral tracking, we show that activation of MeA^SST+ neurons reduced male-directed sociability, social novelty preference, inter-male aggression, and attention toward males, while enhancing sexual motivation and dominance toward females. Conversely, inhibition increases social novelty preference and impaires stress-coping behavior without affecting other social traits. Notably, both manipulations heighten escape-like responses to inanimate stimuli, indicating increased defensive reactivity to non-social cues. Together, these findings identify MeA^SST+ neurons as key modulators of context-dependent social strategies, advancing understanding of circuit mechanisms supporting adaptive social behavior.
Acknowledgments: The authors thank “Servei Central d’Instrumentació Científica (SCIC)” and “Servei d’Experimentació Animal (SEA)” at Universitat Jaume I for their technical support. Authors belong to “Red Española de Investigación en Estrés (REIS)” financed by MCIN/AEI /10.13039/501100011033 and FEDER (RED2022-134191-T).
Funding: Spanish Ministry of Science, Innovation, and Universities: grant PID2023-153074OB-I00 (ECG, FOB). Spanish Ministry of Health: grant PNSD-2025I052 (ECG), Generalitat Valenciana: grant CIAICO/2023/244 (ECG), Universitat Jaume I: grant GACUJIMB/2024/30 (ECG, FOB), European Commission grant MSCA-SE101086247 (FOB, ML).