Parallel cholinergic circuit in oculomotor nucleus to control EMs and REM sleep

The neuronal circuits regulating sleep and those controlling autonomic and somatic motor functions suggest that a primary function of sleep is to suppress motor activity. Interestingly, the muscle twitches including eye movements (EMs) that occur during rapid eye movement sleep (REMs) represent a retained form of motor activity. Here, we identify a subset of cholinergic neurons within the oculomotor nucleus (nIII ^ChAT ) whose activity progressively increases prior to REM termination. Distinct from the extraocular muscles (EOMs)-projecting nIII ^ChAT neurons, we identified a subpopulation of nIII ^ChAT neurons projecting to the vlPAG. Optogenetic activation of these vlPAG-projecting nIII ^ChAT neurons robustly suppressed REMs without affecting EMs. Conversely, selective activation of EOMs-projecting nIII ^ChAT neurons reliably induced EMs but have no effect on the sleep-wake states. Clustering analysis of endoscopic imaging data revealed that these two identified subgroups of nIII ^ChAT neurons are organized into partially overlapping but functionally distinct networks. Viral tracing and in vivo electrophysiological recordings further demonstrate that these motor and sleep-modulating functions of nIII ^ChAT neurons are coordinated by genetically distinct populations of upstream nucleus papilio (NP) neurons. Our findings revealed the microcircuitry responsible for neural mechanism of REMs exit, where motor related function of the nIII is preparing the mammal to enter the subsequent wakefulness with elevated motor capabilities.