Regional variation in cholinergic terminal activity determines the non-uniform occurrence of cortical slow waves during REM sleep in mice

Sleep consists of two basic stages: non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. NREM sleep is characterized by slow high-amplitude cortical electroencephalogram (EEG) signals, while REM sleep is characterized by desynchronized cortical rhythms. Despite this, recent electrophysiological studies have suggested the presence of slow waves (SWs) in local cortical areas during REM sleep. Electrophysiological techniques, however, have been unable to resolve the regional structure of these activities because of relatively sparse sampling. Here, we map functional gradients in cortical activity during REM sleep using mesoscale imaging in mice and show local SW patterns occurring mainly in somatomotor and auditory cortical regions with minimum presence within the default mode network. The role of the cholinergic system in local desynchronization during REM sleep is also explored by calcium imaging of cholinergic activity within the cortex and analyzing structural data. We demonstrate weaker cholinergic projections and terminal activity in regions exhibiting frequent SWs during REM sleep. [Display omitted] •There is a gradient of slow-wave activity across cortex during REM sleep•Synchronized and desynchronized states co-exist within single cortical hemisphere•Slow-wave epicenters are orthogonal to the default mode network•Slow-wave epicenters have weaker cholinergic projections and terminal activity Nazari et al. investigate the functional gradient of cortical activity during REM sleep and its relationship with the cholinergic system in the mouse brain. Their results suggest that slow waves occur in local cortical areas during REM sleep and that their spatial distribution is determined by regional variation of cholinergic activity.