Differential recruitment of brain circuits during fear extinction in non-stressed compared to stress resilient animals

Abstract

Abstract Dysfunctional fear responses in post-traumatic stress disorder (PTSD) may be partly explained by an inability to effectively extinguish fear responses elicited by trauma-related cues. However, only a subset of individuals exposed to traumatic stress develop PTSD. Therefore, studying fear extinction deficits in models of individual differences could help identify neural substrates that underlie vulnerability to the effects of stress. We used a rat model of social defeat in which passively coping rats exhibit vulnerability to stress and actively coping rats are stress-resilient. Adult male rats exposed to 7 days of social defeat were tested for fear extinction, retention of extinction, and persistence of retention using both shock-based contextual fear and ethologically-relevant fear tests. Passively coping rats exhibited elevated freezing in response to the previously extinguished context. Analyses of inter-region c-Fos correlations showed that actively coping rats had high correlations within hippocampal subregions, while passively coping rats had high correlations between the hippocampus and amygdala. Interestingly, although control rats and actively coping rats showed similar levels of extinction, there was little similarity between activated structures, suggesting stress resilience in response to chronic social defeat could involve an adaptive switch in brain circuits recruited to successfully extinguish fear memories.