Hippocampus and amygdala fear memory engrams re-emerge after contextual fear reinstatement

The formation and extinction of fear memories represent two forms of learning that each engage the hippocampus and amygdala. How cell populations in these areas contribute to fear relapse, however, remains unclear. Here, we demonstrate that, in mice, cells active during fear conditioning in the dentate gyrus of hippocampus and basolateral amygdala exhibit decreased activity during extinction and are re-engaged after fear reinstatement. In vivo calcium imaging reveals that reinstatement drives population dynamics in the basolateral amygdala to revert to a network state similar to the state present during fear conditioning. Finally, we find that optogenetic inactivation of neuronal ensembles active during fear conditioning in either the hippocampus or amygdala is sufficient to disrupt fear expression after reinstatement. These results suggest that fear reinstatement triggers a partial re-emergence of the original fear memory representation, providing new insight into the neural substrates of fear relapse.