State-dependent pontine ensemble dynamics and interactions with cortex across sleep states

Abstract

15The pontine nuclei play a crucial role in sleep-wake regulation. However, pontine ensemble 16 dynamics underlying sleep regulation remain poorly understood. By monitoring population 17 activity in multiple pontine and adjacent brainstem areas, here we show slow, state-predictive 18 pontine ensemble dynamics and state-dependent interactions between the pons and the 19 cortex in mice. On a timescale of seconds to minutes, pontine populations exhibit diverse 20 firing across vigilance states, with some of these dynamics being attributed to cell type-21 specific activity. Pontine population activity can predict pupil dilation and vigilance states: 22 pontine neurons exhibit longer predictable power compared with hippocampal neurons. On 23 a timescale of sub-seconds, pontine waves (P-waves) are observed as synchronous firing of 24 pontine neurons primarily during rapid eye movement (REM) sleep, but also during non-REM 25 (NREM) sleep. Crucially, P-waves functionally interact with cortical activity in a state-26 dependent manner: during NREM sleep, hippocampal sharp wave-ripples (SWRs) precede P-27 waves. On the other hand, P-waves during REM sleep are phase-locked with ongoing 28 hippocampal theta oscillations and are followed by burst firing in a subset of hippocampal 29 neurons. Thus, the directionality of functional interactions between the hippocampus and 30 pons changes depending on sleep states. This state-dependent global coordination between 31 pontine and cortical regions implicates distinct functional roles of sleep. 32 33 Keywords 34 brainstem, brain state, sleep, neural ensemble dynamics, neural oscillations, P/PGO waves 35