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Distributed state-dependent neural ensembles across sleep stages

Mirna MerkleriD, Alba Pascual Clavel, Shuzo SakataiD

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.

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