Reconstructing a new hippocampal engram for systems reconsolidation and remote memory updating.

Recalling systems-consolidated neocortex-dependent remote memories re-engages the hippocampus in a process called systems reconsolidation. However, underlying mechanisms, particularly for the origin of the reinstated hippocampal memory engram, remain elusive. By developing a triple-event labeling tool and employing two-photon imaging, we trace hippocampal engram ensembles from memory acquisition to systems reconsolidation and find that remote recall recruits a new engram ensemble in the hippocampus for subsequent memory retrieval. Consistently, recruiting new engrams is supported by adult hippocampal neurogenesis-mediated silencing of original engrams. This new engram ensemble receives currently experienced contextual information, incorporates new information into the remote memory, and supports remote memory updating. Such a reconstructed hippocampal memory is then integrated with the valence of remote memory via medial prefrontal cortex projection-mediated activity coordination between the hippocampus and amygdala. Thus, the reconstruction of new memory engrams underlies systems reconsolidation, which explains how remote memories are updated with new information.