Hippocampal replay sequences reorganise during sleep following spatial rule reversal in mice

Abstract

Sharp-wave ripple replay is thought to support the consolidation of spatial memory, but how replay content adapts when a learned rule becomes invalid is unclear. We recorded from dorsal CA1 in mice performing a spatial alternation task before and after an unsignalled rule reversal, and tracked replay content across subsequent sleep. Replay of the now-invalid trajectory persisted through the first post-reversal sleep session, then declined sharply, while replay of the newly rewarded trajectory rose in proportion to the animal's behavioural adaptation on the following day. Critically, animals showing the largest overnight shift in replay content also showed the fastest behavioural switch, and pharmacological suppression of ripples during the second sleep session delayed the behavioural switch without impairing initial learning. Replay does not simply rehearse recent experience; it arbitrates between competing representations, and that arbitration is itself a substrate of flexible behaviour.