Memories are replayed during non-REM sleep, but it has remained unclear how replays of recent and older experiences remain separated to avoid interference or ‘catastrophic forgetting’. Reporting in Nature, Chang, Tang and colleagues show that non-REM sleep in mice is characterized by approximately 1-min-long cycles of pupil diameter fluctuations. In mice that had performed a learning task, the authors found that memory replay of newly learned information was more likely to occur during sharp-wave ripples (SWRs) in the ‘small-pupil substate’, whereas reactivation of a previously obtained memory was more likely to occur during SWRs in the ‘large-pupil substate’. Disrupting SWRs specifically during small-pupil substates using closed-loop optogenetics impaired the consolidation of newly learned information without affecting recall of older memories, whereas disrupting SWRs during large-pupil substates did not affect the consolidation of new memories. The two substates also differed in terms of the strength of inputs to, and local feedback in, CA1 (where replay occurs). These intriguing findings point to a potential solution for catastrophic forgetting and add to the evidence that non-REM sleep is not a uniform state.

Original reference: Nature https://doi.org/10.1038/s41586-024-08340-w (2025)