Local inhibitory circuits mediate cortical reactivations and memory consolidation

Highly salient events activate neurons across various brain regions. During subsequent rest or sleep, the activity patterns of these neurons often correlate with those observed during the preceding experience. Growing evidence suggests that these reactivations play a crucial role in memory consolidation, the process by which experiences are solidified in cortical networks for long-term storage. Here, we use longitudinal two-photon Ca²⁺ imaging alongside paired LFP recordings in the hippocampus and cortex, to show that targeted manipulation of PV⁺ inhibitory neurons in the lateral visual cortex after daily training selectively attenuates cue-specific reactivations and learning, with only minute effects on spontaneous activity and no apparent effect on normal function such as visual cue-elicited responses during training. In control mice, reactivations were biased toward salient cues, persisted for hours after training had ended, and the prevalence of reactivations was aligned with the learning process. Overall, our results underscore a crucial role for cortical reactivations in memory consolidation.