DISSECTING SOCIAL STRESS RESPONSES THROUGH A PARADIGM OF CONTEXTUAL PROCESSING

Social stress represents an intense and omnipresent stressor that can manifest as war, bullying or interpersonal violence, and that is associated with increased risk for developing anxiety and stressor-related disorders in more susceptible individuals. The environment where stress is experienced poses a great impact on the way aversive information is encoded and in fact, deficits in contextual processing are considered a contributing factor to PTSD. While protocols for social stress have been well-established, it is often studied as a separate domain from contextual processing. Here, we developed a protocol for social conditioned-place avoidance (sCPA) and we characterize its effects on behavioral, central and peripheral processes. Our results indicate that stressed mice consistently learn to avoid the defeat-associated context, exhibit increased anxiety-like behavior and develop a long-lasting and generalized memory for the aggressors. Interestingly, our analyses reveal region-specific changes in microglia density, with increased density observed in the basolateral amygdala and decreased density in the hippocampal CA1. Moreover, we observe alterations in peripheral immune markers in the aftermath of stress. Regarding indices of vulnerability, anxiety trait emerges as a potential driver for the observed behavioral variability. In fact, whereas mice stratified in high and low anxiety groups show no differences in acquiring associations between social stress and context, they, however, display a different phenotype during delayed recall, suggesting distinct behavioral adaptations between the anxiety groups. Overall, our data address diverse social stress effects on distinct behavioral and physiological domains and aim to uncover the underlying factors of stress response variability.