UC Riverside

Contextual memories are initially encoded in the hippocampus and gradually undergo maturation and stabilization in the neocortex during memory consolidation. Despite extensive research, the mechanisms underlying brain reorganization between the hippocampus and neocortex remain unclear. Here, we demonstrate that the retrieval of both recent and remote contextual fear memories in mice resulted from the reactivation of engram neurons in the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and ventral hippocampus (VH). Additionally, we examined the role of the mPFC through recent to the consolidation of remote contextual memories using a novel virtual reality-based task. This approach allowed us to investigate the necessities of the mPFC in both aversive and reward contexts. Our findings reveal the inhibition of mPFC can lead to the failure of retrieval of both recent and remote contextual memories. Overall, our results identify the engram neurons involved in recent and remote contextual memories and highlight the specific involvement of the mPFC in contextual memories across both recent and remote time points.