Olfactory tubercle mediates adaptive social behavior by controlling threat assessment and the expression of social threat memories during recall in male mice

Abstract The ability to dynamically assess and update threat responses based on changing environmental contexts is fundamental for survival. Here, we developed an odor-based paradigm where male mice encounter a restrained conspecific that subsequently becomes aggressive, allowing us to study how mice assess threats and update memories upon recall. Using calcium imaging, chemogenetics, and electrophysiology, we identified the olfactory tubercle (OT) as a key mediator of social threat assessment. While OT activity was not required during the initial aggressive encounter, it proved to be essential during recall, where its inhibition prevented the expression of avoidance behavior. Notably, recall induces persistent synaptic plasticity at basolateral amygdala (BLA)-to-OT synapses that persists after behavioral extinction. We identified a neuromodulatory switch in the OT: serotonin facilitates avoidance during recall, whereas its blockade triggers dopamine release and approach behavior. Our findings demonstrate that the OT orchestrates social threat assessment through synaptic plasticity and neuromodulatory control.