Regulation of REM sleep by inhibitory neurons in the dorsomedial medulla

Abstract

The two major stages of mammalian sleep-rapid eye movement sleep (REMs) and non-REM sleep (NREMs)-are characterized by distinct brain rhythms ranging from millisecond to minute-long (infraslow) oscillations. The mechanisms controlling transitions between sleep stages and how they are synchronized with infraslow rhythms remain poorly understood. Using opto- and chemogenetic manipulation in mice, we show that GABAergic neurons in the dorsomedial medulla (dmM) promote the initiation and maintenance of REMs, in part through their projections to the dorsal and median raphe nuclei. Fiber photometry revealed that their activity is strongly increased during REMs and fluctuates during NREMs in close synchrony with infraslow oscillations in the sleep spindle band of the electroencephalogram. The phase of this rhythm influenced the latency and probability with which dmM activation induced REMs. Thus, dmM inhibitory neurons strongly promote REMs, and their slow activity fluctuations may coordinate the timing of REMs episodes with infraslow brain rhythms.

Keywords: REM sleep; brain state regulation; brainstem; calcium imaging; infraslow oscillations; medulla; optogenetics; sleep.