title: Animal models of REM dysfunctions: what they tell us about the cause of narcolepsy and RBD?
abstract: Rapid eye movement sleep behavior disorder (RBD) is a parasomnia characterized by the loss of muscle atonia during paradoxical (REM) sleep (PS). Conversely, cataplexy, one of the key symptoms of narcolepsy, is a striking sudden episode of muscle weakness triggered by emotions during wakefulness, and comparable to REM sleep atonia. The neuronal dysfunctions responsible for RBD and cataplexy are not known. In the present review, we present the most recent results on the neuronal network responsible for PS. Based on these results, we propose an updated integrated model of the mechanisms responsible for PS and explore different hypotheses explaining RBD and cataplexy. We propose that RBD is due to a specific degeneration of a subpopulation of PS-on glutamatergic neurons specifically responsible of muscle atonia, localized in the caudal pontine sublaterodorsal tegmental nucleus (SLD). Another possibility is the occurrence in RBD patients of a specific lesion of the glycinergic/GABAergic premotor-neurons localized in the medullary ventral gigantocellular reticular nucleus. Conversely, cataplexy in narcoleptics would be due to the activation during waking of the caudal PS-on SLD neurons responsible for muscle atonia. A direct or indirect pathway activated during positive emotion from the central amygdala to the SLD PS-on neurons would induce such activation. In normal conditions, the activation of SLD neurons would be blocked by the simultaneous excitation by the hypocretins of the PS-off GABAergic neurons localized in the ventrolateral periaqueductal gray and the adjacent deep mesencephalic reticular nucleus gating the activation of the PS-on SLD neurons.
authors.affiliation: UMR 5292 CNRS/U1028 INSERM, Centre de Recherche en Neurosciences de Lyon (CRNL), Team "Physiopathologie des réseaux neuronaux responsables du cycle veille-sommeil", Université Claude Bernard Lyon I, Faculté de Médecine RTH Laennec, 7 Rue Guillaume Paradin, 69372 Lyon Cedex 08, France. Email:luppi@sommeil.univ-lyon1.fr.
authors.forename: P H
authors.initials: PH
authors.lastname: Luppi
authors.affiliation: UMR 5292 CNRS/U1028 INSERM, Centre de Recherche en Neurosciences de Lyon (CRNL), Team "Physiopathologie des réseaux neuronaux responsables du cycle veille-sommeil", Université Claude Bernard Lyon I, Faculté de Médecine RTH Laennec, 7 Rue Guillaume Paradin, 69372 Lyon Cedex 08, France. Email:luppi@sommeil.univ-lyon1.fr.
authors.forename: O
authors.initials: O
authors.lastname: Clément
authors.affiliation: UMR 5292 CNRS/U1028 INSERM, Centre de Recherche en Neurosciences de Lyon (CRNL), Team "Physiopathologie des réseaux neuronaux responsables du cycle veille-sommeil", Université Claude Bernard Lyon I, Faculté de Médecine RTH Laennec, 7 Rue Guillaume Paradin, 69372 Lyon Cedex 08, France. Email:luppi@sommeil.univ-lyon1.fr.
authors.forename: E
authors.initials: E
authors.lastname: Sapin
authors.affiliation: UMR 5292 CNRS/U1028 INSERM, Centre de Recherche en Neurosciences de Lyon (CRNL), Team "Physiopathologie des réseaux neuronaux responsables du cycle veille-sommeil", Université Claude Bernard Lyon I, Faculté de Médecine RTH Laennec, 7 Rue Guillaume Paradin, 69372 Lyon Cedex 08, France. Email:luppi@sommeil.univ-lyon1.fr.
authors.forename: S V
authors.initials: SV
authors.lastname: Garcia
authors.affiliation: UMR 5292 CNRS/U1028 INSERM, Centre de Recherche en Neurosciences de Lyon (CRNL), Team "Physiopathologie des réseaux neuronaux responsables du cycle veille-sommeil", Université Claude Bernard Lyon I, Faculté de Médecine RTH Laennec, 7 Rue Guillaume Paradin, 69372 Lyon Cedex 08, France. Email:luppi@sommeil.univ-lyon1.fr.
authors.forename: C
authors.initials: C
authors.lastname: Peyron
authors.affiliation: UMR 5292 CNRS/U1028 INSERM, Centre de Recherche en Neurosciences de Lyon (CRNL), Team "Physiopathologie des réseaux neuronaux responsables du cycle veille-sommeil", Université Claude Bernard Lyon I, Faculté de Médecine RTH Laennec, 7 Rue Guillaume Paradin, 69372 Lyon Cedex 08, France. Email:luppi@sommeil.univ-lyon1.fr.
authors.forename: P
authors.initials: P
authors.lastname: Fort
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D009290:Narcolepsy / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D020187:REM Sleep Behavior Disorder / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D018377:Neurotransmitter Agents