Summary
During sleep, ensemble activity patterns encoding recent experiences are reactivated in the hippocampus and cortex. This reactivation is coordinated by hippocampal sharp-wave ripples (SWRs) and is believed to support the early stages of memory consolidation. However, only a minority of sleep SWRs are associated with memory reactivation in the hippocampus and its downstream areas. Whether that subset of SWRs have specific physiological characteristics and directly contribute to memory performance is not known. We identified a specific subset of large SWRs linked to memory reactivation in both the hippocampus and prefrontal cortex (PFC) of mice, and found that their occurrence selectively increased during sleep following new learning. Closed-loop optogenetic SWR boosting during sleep was sufficient to enhance ensemble memory reactivation in hippocampus and PFC. This manipulation also improved subsequent memory retrieval and hippocampal-PFC coordination during waking, causally linking both phenomena to SWR-associated ensemble reactivation during sleep.