Olfactory Tubercle mediates adaptive social behavior through distinct control of threat assessment and memory updating.

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Abstract

The ability to dynamically assess and update threat responses based on changing environmental contexts is fundamental for survival. Here, we developed a novel odor-based paradigm to investigate the neural mechanisms underlying social threat processing, where mice first encountered a non-threatening conspecific that subsequently became aggressive. This paradigm allowed us to study how mice assess the threat and update their memories when re-exposed to the aggressor in a non-threatening context. Using a combination of in vivo calcium imaging, chemogenetics, and electrophysiology, we identified the olfactory tubercle (OT) as a key region mediating 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 both the expression of avoidance behavior and subsequent memory updating. Importantly, we found that recall induced pathway-specific synaptic plasticity at the basolateral amygdala (BLA) to OT synapses. This plasticity persisted even after behavioral extinction, suggesting a neural substrate for maintaining specific social memories while allowing behavioral flexibility. Given this persistent plasticity, we finally investigated the mechanisms driving avoidance behavior during threat assessment. We found that serotonin release in the OT during recall facilitated avoidance behavior, while its blockade triggered dopamine release and promoted approach behavior, revealing a novel neuromodulatory switch controlling social behavior. Our findings reveal how the OT, through precise neuromodulatory control and synaptic plasticity, orchestrates the dynamic updating of social memories essential for adaptive behavior.

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