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The hypocretins: setting the arousal threshold.

J Gregor Sutcliffe1, Luis de Lecea

  • 1Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA. gregor@scripps.edu

Nature Reviews. Neuroscience
|May 4, 2002
PubMed
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Researchers discovered the hypocretin (orexin) neuropeptide system, crucial for regulating arousal, feeding, and sleep disorders like narcolepsy. This system

Area of Science:

  • Neuroscience
  • Endocrinology
  • Sleep Medicine

Background:

  • A neuropeptide system regulating arousal, feeding, and sleep was discovered in the late 1990s.
  • This system, centered in the dorsolateral hypothalamus, is known as the hypocretin (orexin) system.
  • The hypocretin system is implicated in the sleep disorder narcolepsy.

Purpose of the Study:

  • To elucidate the circuitry and functions of the hypocretin (orexin) system.
  • To understand the role of this system in regulating arousal states, feeding, and hormone secretion.
  • To explore the hypothesis that autoimmune attacks on hypocretin neurons cause narcolepsy.

Main Methods:

  • Genomic science advancements enabled rapid discovery and study.
  • Subsequent studies focused on the system's biochemical, physiological, and anatomical components.

Related Experiment Videos

  • Research investigated the neural circuits controlling the switch between waking and sleeping.

    • Main Results:

    • The hypocretin (orexin) system's role in arousal, feeding, and autonomic homeostasis was clarified.
    • Evidence suggests most human narcolepsies stem from an autoimmune attack on hypocretin-producing neurons.
    • Key components regulating the sleep-wake cycle are increasingly understood.

    Conclusions:

    • The hypocretin (orexin) system is a critical regulator of sleep-wake states and homeostasis.
    • Narcolepsy is strongly linked to the loss of hypocretin-producing neurons, likely via autoimmunity.
    • The rapid advancement in understanding this system highlights progress in genomic science.