SEROTONIN MODULATION OF SOCIAL BEHAVIOR AND NEUROPLASTICITY

Social stress profoundly alters behavior, yet the neuromodulatory mechanisms underlying these changes remain poorly understood. In mice, even a single episode of social defeat induces long-lasting defensive behaviors, including avoidance, immobility, and escape. Here, we investigated the role of serotonin in the processing of acute social trauma. Using fiber photometry, we found that serotonergic neurons in the median raphe and serotonin release in the ventral hippocampus are selectively engaged during social defeat, but not during neutral social interactions. Causal manipulations combining pharmacological depletion, chemogenetic inhibition, and optogenetics revealed temporally distinct contributions of serotonin during and after defeat in shaping defensive responses. In addition, we validated a novel transgenic mouse line (SNAP-GluR1) as a reliable tool to study AMPA receptor dynamics in stress-related circuits. Together, these findings identify serotonin as a key regulator of both immediate and persistent behavioral adaptations to social stress, providing insight into mechanisms of vulnerability and resilience.