The neuronal network responsible for paradoxical sleep and its dysfunctions causing narcolepsy and rapid eye movement (REM) behavior disorder

Sleep Med Rev. 2011 Jun;15(3):153-63. doi: 10.1016/j.smrv.2010.08.002. Epub 2010 Nov 5.

Abstract

Rapid eye movement (REM) 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 sub-population 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 pre-motoneurons 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 phasic glutamatergic excitatory pathway from the central amygdala to the SLD PS-on neurons activated during emotion would induce such activation. In normal conditions, the glutamate excitation 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amygdala / physiopathology
  • Animals
  • Brain / physiopathology*
  • Brain Mapping
  • Cataplexy / physiopathology
  • Emotions / physiology
  • Glutamine / physiology
  • Glycine / physiology
  • Humans
  • Hypothalamus / physiopathology
  • Medulla Oblongata / physiopathology
  • Motor Neurons / physiology
  • Muscle Tonus / physiology
  • Narcolepsy / physiopathology*
  • Nerve Net / physiopathology*
  • Neurodegenerative Diseases / physiopathology
  • Neurons / physiology
  • Parkinson Disease / physiopathology
  • Pedunculopontine Tegmental Nucleus / physiopathology
  • Pons / physiopathology
  • REM Sleep Behavior Disorder / physiopathology*
  • Sleep, REM / physiology*
  • Wakefulness / physiology
  • gamma-Aminobutyric Acid / physiology

Substances

  • Glutamine
  • gamma-Aminobutyric Acid
  • Glycine