Parvalbumin-expressing neurons in the ventral medulla are active during wakefulness and promote NREM sleep.

A longstanding hypothesis contends that sleep is promoted by sleep-active inhibitory neurons that suppress arousal centers. Sleep may also be facilitated by mechanisms active during wakefulness; however, evidence for wake-active sleep-promoting neurons is scarce. Here, we use chemogenetics, fiber photometry, and circuit mapping to identify subset(s) of inhibitory neurons that promote NREM sleep. We targeted the ventrolateral retropontine (VLRP) region of the medulla because of its proximity to REM and NREM sleep centers. We found that selective activation of parvalbumin (VLRPPvalb) neurons but not somatostatin or cholecystokinin-expressing VLRP neurons resulted in NREM-like sleep. Interestingly, VLRPPvalb neurons are most active during natural wakefulness and send inhibitory projections to the parabrachial nucleus, which presumably underlies their sleep-promoting function. These results identify VLRPPvalb neurons as a potential source of wake-active inhibitory input to wake-promoting centers in the dorsolateral pons that serve to constrain arousal.