The Sublaterodorsal Tegmental Nucleus Functions to Couple Brain State and Motor Activity during REM Sleep and Wakefulness

Appropriate levels of muscle tone are needed to support waking behaviors such as sitting or standing. However, it is unclear how the brain functions to couple muscle tone with waking behaviors. Cataplexy is a unique experiment of nature in which muscle paralysis involuntarily intrudes into otherwise normal periods of wakefulness. Cataplexy therefore provides the opportunity to identify the circuit mechanisms that couple muscle tone and waking behaviors. Here, we tested the long-standing hypothesis that muscle paralysis during cataplexy is caused by recruitment of the brainstem circuit that induces muscle paralysis during REM sleep. Using behavioral, electrophysiological, and chemogenetic strategies, we found that muscle tone and arousal state can be decoupled by manipulation of the REM sleep circuit (the sublaterodorsal tegmental nucleus [SLD]). First, we show that silencing SLD neurons prevents motor suppression during REM sleep. Second, we show that activating these same neurons promotes cataplexy in narcoleptic (orexin−/−) mice, whereas silencing these neurons prevents cataplexy. Most importantly, we show that SLD neurons can decouple motor activity and arousal state in healthy mice. We show that SLD activation triggers cataplexy-like attacks in wild-type mice that are behaviorally and electrophysiologically indistinguishable from cataplexy in orexin−/− mice. We conclude that the SLD functions to engage arousal-motor synchrony during both wakefulness and REM sleep, and we propose that pathological recruitment of SLD neurons could underlie cataplexy in narcolepsy. •Muscle tone and arousal state are decoupled by manipulation of the SLD•SLD activation promotes cataplexy, whereas SLD silencing prevents cataplexy•SLD activation triggers cataplexy in wild-type mice•The SLD couples arousal state and motor activity during REM sleep and wakefulness It is unclear how the brain functions to couple muscle tone with waking behaviors. Torontali et al. find that the sublaterodorsal tegmental nucleus (SLD) functions to couple muscle tone and brain state during both wakefulness and REM sleep. The authors propose that abnormal SLD function could underlie arousal-motor desynchrony in cataplexy.