Unsilenced inhibitory cortical ensemble gates remote memory retrieval

Acquired information can be consolidated to remote memory for storage but persists in a dormant state until its retrieval. However, it remains unknown how dormant memory is reactivated. Using a combination of simultaneous two-photon calcium imaging and holographic optogenetics in the anterior cingulate cortex (ACC) in vivo, we discover a subset of GABAergic neurons that are specifically associated with dormant memory retrieval. These interneurons display persistent activity and inter-neuronal synchronization at the remote memory stage. In the absence of natural contextual cues, directly activating these interneurons reliably recalls cortical ensembles relevant to remote memory retrieval with context specificity. Conversely, targeted volumetric inactivation of these interneurons suppresses context-induced memory retrieval. Our results reveal an unexpected role of unsilenced inhibitory cortical ensembles in causally gating the retrievability of dormant remote memory.