Alternating vigilance states: new insights regarding neuronal networks and mechanisms

Eur J Neurosci. 2009 May;29(9):1741-53. doi: 10.1111/j.1460-9568.2009.06722.x. Epub 2009 Apr 28.


Since the discovery of rapid eye movement (REM) sleep (also known as paradoxical sleep; PS), it is accepted that sleep is an active process. PS is characterized by EEG rhythmic activity resembling that of waking with a disappearance of muscle tone and the occurrence of REMs, in contrast to slow-wave sleep (SWS, also known as non-REM sleep) identified by the presence of delta waves. Here, we review the most recent data on the mechanisms responsible for the genesis of SWS and PS. Based on these data, we propose an updated integrated model of the mechanisms responsible for the sleep-wake cycle. This model introduces for the first time the notion that the entrance and exit of PS are induced by different mechanisms. We hypothesize that the entrance from SWS to PS is due to the intrinsic activation of PS-active GABAergic neurons localized in the posterior hypothalamus (co-containing melanin-concentrating hormone), ventrolateral periaqueductal gray and the dorsal paragigantocellular reticular nucleus. In contrast, the exit from PS is induced by the inhibition of these neurons by a PS-gating system composed of GABAergic neurons localized in the ventrolateral periaqueductal gray and just ventral to it, and waking systems such as the pontine and medullary noradrenergic neurons and the hypothalamic hypocretin neurons. Finally, we review human neurological disorders of the network responsible for sleep and propose hypotheses on the mechanisms responsible for REM behavior disorder and narcolepsy.

Publication types

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

MeSH terms

  • Acetylcholine / metabolism
  • Animals
  • Biogenic Monoamines / metabolism
  • Brain / physiology*
  • Brain / physiopathology
  • Glutamic Acid / metabolism
  • Humans
  • Hypothalamic Hormones / metabolism
  • Melanins / metabolism
  • Models, Neurological
  • Narcolepsy / physiopathology
  • Neural Pathways / physiology
  • Neural Pathways / physiopathology
  • Neurons / physiology*
  • Pituitary Hormones / metabolism
  • REM Sleep Behavior Disorder / physiopathology
  • Sleep / physiology*
  • Wakefulness / physiology
  • gamma-Aminobutyric Acid / metabolism


  • Biogenic Monoamines
  • Hypothalamic Hormones
  • Melanins
  • Pituitary Hormones
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • melanin-concentrating hormone
  • Acetylcholine