Homeostatic, circadian, and emotional regulation of sleep

J Comp Neurol. 2005 Dec 5;493(1):92-8. doi: 10.1002/cne.20770.


A good night's sleep is one of life's most satisfying experiences, while sleeplessness is stressful and causes cognitive impairment. Yet the mechanisms that regulate the ability to sleep have only recently been subjected to detailed investigation. New studies show that the control of wake and sleep emerges from the interaction of cell groups that cause arousal with other nuclei that induce sleep such as the ventrolateral preoptic nucleus (VLPO). The VLPO inhibits the ascending arousal regions and is in turn inhibited by them, thus forming a mutually inhibitory system resembling what electrical engineers call a "flip-flop switch." This switch may help produce sharp transitions between discrete behavioral states, but it is not necessarily stable. The orexin neurons in the lateral hypothalamus may help stabilize this system by exciting arousal regions during wakefulness, preventing unwanted transitions between wakefulness and sleep. The importance of this stabilizing role is apparent in narcolepsy, in which an absence of the orexin neurons causes numerous, unintended transitions in and out of sleep and allows fragments of REM sleep to intrude into wakefulness. These influences on the sleep/wake system by homeostatic and circadian drives, as well as emotional inputs, are reviewed. Understanding the pathways that underlie the regulation of sleep and wakefulness may provide important insights into how the cognitive and emotional systems interact with basic homeostatic and circadian drives for sleep.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain Stem / drug effects
  • Brain Stem / physiology
  • Circadian Rhythm / physiology*
  • Emotions / physiology*
  • Homeostasis / physiology
  • Hypothalamus / drug effects
  • Hypothalamus / physiology
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins / pharmacology
  • Narcolepsy / physiopathology
  • Neurons / physiology
  • Neuropeptides / metabolism
  • Neuropeptides / pharmacology
  • Orexins
  • Preoptic Area / drug effects
  • Preoptic Area / physiology
  • Sleep / physiology*
  • Sleep Initiation and Maintenance Disorders / physiopathology
  • Stress, Physiological / physiopathology
  • Ventral Thalamic Nuclei / physiology
  • Wakefulness / physiology


  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins