title: New aspects in the pathophysiology of rapid eye movement sleep behavior disorder: the potential role of glutamate, gamma-aminobutyric acid, and glycine.
abstract: Rapid eye movement sleep behavior disorder (RBD) is a parasomnia characterized by the occurrence of intense movements during rapid eye movement (REM) sleep, also named paradoxical sleep. The neuronal dysfunctions at the origin of the loss of atonia in RBD patients are not known. One possibility is that RBD is due to the degeneration of neurons inducing the muscle atonia of REM sleep. Therefore, in our paper we review data on the populations of neurons responsible for the atonia of REM sleep before discussing their potential role in RBD. We first review evidence that motoneurons are tonically hyperpolarized by gamma-aminobutyric acid (GABA) and glycine and phasically excited by glutamate during REM sleep. Then, we review data indicating that the atonia of REM sleep is induced by glycinergic/GABAergic REM-on premotoneurons contained within the raphe magnus and the ventral and alpha gigantocellular reticular nuclei localized in the ventral medullary reticular formation. These neurons are excited during REM sleep by a direct projection from glutamatergic REM-on neurons localized in the pontine sublaterodorsal tegmental nucleus (SLD). From these results, we discuss the possibility that RBD is due to a specific degeneration of descending REM-on glutamatergic neurons localized in the caudal SLD or that of the REM-on GABA/glycinergic premotoneurons localized in the ventral medullary reticular formation. We then propose that movements of RBD are induced by descending projections of cortical motor neurons before discussing possible modes of action of clonazepam and melatonin.
authors.affiliation: INSERM, U1028, France; CNRS, UMR5292, France. luppi@sommeil.univ-lyon1.fr
authors.forename: Pierre-Hervé
authors.initials: PH
authors.lastname: Luppi
authors.forename: Olivier
authors.initials: O
authors.lastname: Clément
authors.forename: Sara
authors.initials: S
authors.lastname: Valencia Garcia
authors.forename: Frédéric
authors.initials: F
authors.lastname: Brischoux
authors.forename: Patrice
authors.initials: P
authors.lastname: Fort
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000502:physiology*; D018698:Glutamic Acid / Q000502:physiology*; D005998:Glycine / Q000502:physiology*; D006801:Humans; D009044:Motor Cortex / Q000502:physiology*; D020187:REM Sleep Behavior Disorder / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005998:Glycine
keywords: Brainstem; GABA; Glycine; Motor cortex; Muscle twitches; Parkinson