Self-experience of a negative event alters responses to others in similar states through prefrontal cortex CRF mechanisms

Our own experience of emotional events influences how we approach and react to others’ emotions. Here we observe that mice exhibit divergent interindividual responses to others in stress (that is, preference or avoidance) only if they have previously experienced the same aversive event. These responses are estrus dependent in females and dominance dependent in males. Notably, silencing the expression of the corticotropin-releasing factor (CRF) within the medial prefrontal cortex (mPFC) attenuates the impact of stress self-experience on the reaction to others’ stress. In vivo microendoscopic calcium imaging revealed that mPFC CRF neurons are activated more toward others’ stress only following the same negative self-experience. Optogenetic manipulations confirmed that higher activation of mPFC CRF neurons is responsible for the switch from preference to avoidance of others in stress, but only following stress self-experience. These results provide a neurobiological substrate underlying how an individual’s emotional experience influences their approach toward others in a negative emotional state.