Distributed state-dependent neural ensembles across sleep stages

Abstract

Sleep architecture is organized by neural ensembles operating across multiple timescales, yet the organizing principles remain unclear. By monitoring neural populations across >40 brain regions in mice, we reveal a distributed sleep code spanning multiple temporal scales. On a slow (minutes-to-seconds) timescale, vigilance state reorganized brain-wide firing and was decodable from every region, with REM sleep emerging as a globally activated state. State transitions followed low-dimensional trajectories, with cortical and subcortical ensembles evolving in antiphase at wake-NREM boundaries but in register during transitions into REM sleep. On a fast (seconds-to-milliseconds) timescale, NREM slow/delta oscillations served as a global rhythm while hierarchically nesting spindles, sharp-wave ripples, and pontine (P) waves, whereas REM theta-P-wave coupling coordinated firing across regions. Regional sleep-related activities covaried with neuromodulatory innervation, while infraslow, history-dependent firing dynamics tracked NREM-REM cycles. Together, these findings provide a cell-resolved atlas of distributed neural population dynamics across sleep stages.