Discovering dopamine’s involvement in transition to REM sleep in mice suggests a druggable sleep disorder target

What triggers the mammalian sleep cycle’s shift between non-rapid eye movement (NREM) and rapid eye movement (REM) sleep? A new study in mice suggests increased levels of dopamine in a key region of the brain during NREM sleep play an important role in this transition. In mammals, sleep is characterized by alternating periods of NREM and REM sleeps; REM sleep – the stage in which dreams usually occur – often happens after several stages of NREM sleep, and this cycle continues until waking. However, how the brain regulates sleep and the cycle between sleep states isn’t very well understood. While pharmacological studies have indicated that dopamine (DA) can modulate REM sleep, this neurotransmitter, which is most commonly associated with pleasure and addiction, is absent in most prevailing models of REM sleep. Using fiber photometry in the brains of mice, Emi Hasegawa and colleagues observed increases in dopamine activation in the basolateral amygdala (BLA) of the brain just before the transition from NREM to REM sleep but not before the NREM-wake transition, indicating that transient DA in this brain region triggers the initiation of REM sleep. Hasegawa et al. used optogenetic manipulation in mice to excite DA fibers in the BLA during NREM sleep, which caused a transition to REM sleep. The authors also examined whether DA signaling in the BLA can trigger cataplexy, which occurs in the sleep disorder narcolepsy and manifests as a crippling pathologic intrusion of REM sleep into wakefulness that results in loss of postural motor control. They found that DA levels in the BLA increased before cataplexy attacks in narcoleptic mice but not in wild-type mice. “Hasegawa et al. provide fresh insights into the control of both REM sleep and cataplexy by DA, and their findings raise the intriguing possibility that DRD2 BLA neurons could be a selective druggable target for treating debilitating symptoms in a wide range of REM sleep disorders, including cataplexy in narcolepsy and other disorders, such as Parkinson’s disease, in which DA signaling is disrupted,” write Elda Arrigoni and Patrick Fuller in a related Perspective.