Optogenetic and pharmacogenetic probing of rapid eye movement (REM) sleep circuitry

Degeneration of rapid eye movement sleep circuitry underlies rapid eye movement sleep behavior disorder

“…In cats and rats, physical lesions or genetically targeted inactivation of cells in the ventromedial medulla can result in apparent dream‐like enacting behaviors, which include simple jerking movements and more complex motor behaviors . However, in mice chemogenetic inactivation of GABA and glycine cells in the ventral medulla only prevents REM sleep paralysis, it does not trigger overt motor behaviors . Together these experiments indicate that cells in the ventromedial medulla are capable of generating REM sleep paralysis, and similar to the subcoeruleus nucleus, their degeneration would be expected to prevent REM sleep atonia and cause movement during REM sleep.…”

“…Genetically targeted deletion of bona fide glutamate cells in mice resulted in increased phasic muscle twitching and the prevention of normal REM sleep atonia, which enabled mice to engage in simple motor events such as walking‐like behaviors . Similar genetic approaches (termed optogenetics ) have also been used to show that switching off glutamate subcoeruleus cells during an individual REM sleep episode can prevent REM sleep atonia, whereas hyper‐activating these same cells during REM sleep strengthens REM sleep paralysis . Together, these experiments indicate that glutamate cells in the subcoeruleus nucleus are both necessary and sufficient for generating REM sleep paralysis and that their degeneration would be predicted to evoke the types of REM sleep‐specific movements that are observed in RBD.…”