SLEEP-STAGE-DEPENDENT, BRAIN-WIDE NEURAL ENSEMBLES ASSOCIATED WITH PONTINE WAVES

Sleep is essential for homeostatic functions, including memory consolidation. Different sleep stages exhibit distinct neural events: non-rapid eye movement (NREM) sleep features slow/delta oscillations, spindles, and sharp wave-ripples (SWRs), while REM sleep is characterized by theta oscillations and ponto-geniculo-occipital waves (“P-waves” in rodents). While P-waves appear in both sleep stages and couple with SWRs during NREM sleep and theta oscillations during REM sleep, their roles in global brain activity and memory consolidation remain poorly understood.
Combining Neuropixels-based mapping, closed-loop optogenetics and behavioral approaches in mice, we show that P-waves are part of sleep-stage-dependent, brain-wide activity and play a role in memory consolidation.
We simultaneously recorded neuronal activity across multiple brain regions with pontine local field potentials (LFPs) throughout sleep-wake cycles. While we observed temporal coupling of NREM- and REM-specific events with P-waves, we found that P-wave-related neural dynamics across the brain vary depending on sleep stages: during NREM sleep, neuronal activity across most areas peaked before P-wave onset, while during REM sleep, peak activity often aligned with P-waves.
Since mesopontine cholinergic neurons play an essential role in P-wave generation, we performed closed-loop optogenetic modulation of cholinergic neurons to assess the role of P-waves in spatial memory consolidation. We found that memory performance is perturbed by optogenetic activation during NREM sleep and inhibition during REM sleep, suggesting sleep-stage-specific roles of P-waves in memory consolidation.
Our findings reveal brain-wide coordinated neural ensembles across sleep stages. P-waves are essential elements of such coordinated activity, and their perturbations interfere with systems memory consolidation.