Revisiting contextual fear processes using a novel social conditioned place aversion protocol

Context processing is an essential function in the cognitive repertoire of numerous species, including humans and mice, allowing them to learn from their environment and adapt their future behavior. Impairments or alterations in contextual processing are hypothesized to be at the core etiology of psychopathologies such as post-traumatic stress disorder (PTSD). Current treatment options for anxiety- and trauma-related disorders are limited, mainly due to gaps in our knowledge regarding underlying brain circuits. These gaps are exacerbated since most conclusions from basic research were derived from fear conditioning protocols using electric shocks as unconditioned stimuli. Yet, as social stress is an omnipresent and ethologically relevant stressor for social species, protocols in animal models based on social trauma can reveal brain circuitries and neurotransmitters/-modulators that are particularly sensitive and thus, pertinent for translational interventions. Here, based on social defeat paradigms, we developed a novel social conditioned-place aversion (sCPA) protocol in adult mice. Our data revealed that whereas most mice learnt to avoid the context where they repeatedly received aggression, a small subset of animals did not show a clear avoidance. Interestingly, our analyses indicated that avoidance indices did not correlate with the amount of aggression received. Thus, it is possible that other factors, such as individual differences in anxiety-like behavior or in valence attribution to positive or negative cues, could account for this variability. Developing and validating a social trauma-based conditioning protocol will aid to study stress vulnerability aspects and allow us to dissect the brain circuit involved in contextual processing.