Structured and unstructured reactivations during REM sleep are modulated by novel experiences

Abstract

Mammalian sleep alternates between rapid eye movement (REM) and non-REM (NREM) phases, each with distinct patterns of neural activity. The replay of waking experience during NREM sleep is a well-established substrate for memory consolidation, but whether comparable reactivation occurs during REM sleep has remained unclear, owing to the sparse firing that characterizes this state and the lack of robust methods for detecting replay within it. Here we combined calcium imaging with electrophysiology to monitor large populations of hippocampal CA1 neurons in mice and applied complementary analytical approaches to test for neural reactivation during REM sleep. We found that structured waking activity is re-expressed during REM sleep across a range of temporal organizations, from the reactivation of co-active cell assemblies to temporally ordered sequential replay. This reactivation was selectively shaped by the behavioral context of prior experience. Novel experience enhanced sequential replay and refined assembly composition, selectively reducing the participation of weakly contributing neurons; anxiogenic experience, by contrast, increased the frequency of assembly reactivation and reinforced the recruitment of strongly contributing neurons. REM sleep thus emerges as an active stage of memory processing that reorganizes recent experience according to its behavioral significance, engaging distinct operations for novel and for emotionally salient events.