Control of motoneuron function and muscle tone during REM sleep, REM sleep behavior disorder and cataplexy/narcolepsy.
REM sleep triggers a potent suppression of postural muscle tone - i.e., REM atonia. However, motor control during REM sleep is paradoxical because overall brain activity is maximal, but motor output is minimal. The skeletal motor system remains quiescent during REM sleep because somatic motoneurons are powerfully inactivated. Determining the mechanisms triggering loss of motoneuron function during REM sleep is important because breakdown in REM sleep motor control underlies sleep disorders such as REM sleep behavior disorder (RBD) and cataplexy/narcolepsy. For example, RBD is characterized by dramatic REM motor activation resulting in dream enactment and subsequent patient injury. In contrast, cataplexy a pathognomonic symptom of narcolepsy - is caused by the involuntary onset of REM-like atonia during wakefulness. This review highlights recent work from my laboratory that examines how motoneuron function is lost during normal REM sleep and it also identifies potential biochemical mechanisms underlying abnormal motor control in both RBD and cataplexy. First, I show that both GABAB and GABAA/glycine mediated inhibition of motoneurons is required for generating REM atonia. Next, I show that impaired GABA and glycine neurotransmission triggers the cardinal features of RBD in a transgenic mouse model. Last, I show that loss of an excitatory noradrenergic drive onto motoneurons is, at least in part, responsible for the loss of postural muscle tone during cataplexy in narcoleptic mice. Together, this research indicates that multiple transmitters systems are responsible for regulating postural muscle tone during REM sleep, RBD and cataplexy.
Department of Cell and Systems Biology and Physiology, University of Toronto, Toronto, Ontario, Canada. john.peever@utoronto.ca
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D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000818:Animals; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000502:physiology*; D009129:Muscle Tonus / Q000502:physiology*; D009290:Narcolepsy / Q000235:genetics / Q000473:pathology*; D020187:REM Sleep Behavior Disorder / Q000235:genetics / Q000473:pathology*; D018079:Receptors, GABA / Q000172:deficiency; D018009:Receptors, Glycine / Q000172:deficiency; D012895:Sleep, REM / Q000502:physiology*; D014276:Trigeminal Nerve / Q000166:cytology; D014278:Trigeminal Nuclei / Q000166:cytology*
D018079:Receptors, GABA; D018009:Receptors, Glycine