CoChat
Sign Up
Cited by 151Sleep and Wakefulness ResearchNeuroscience of respiration and sleepCircadian rhythm and melatonin

Sleep Neurobiology for the Clinician

Rodrigo A. España, Thomas E. Scammell·2004·Sleep
DOI 10.1093/sleep/27.4.811
Open this paper in CoChat — free account

Abstract

Many neurochemically distinct systems interact to regulate wakefulness and sleep. Wakefulness is promoted by brainstem and hypothalamic neurons producing acetylcholine, norepinephrine, dopamine, serotonin, histamine, and orexin/hypocretin. Each of these arousal systems is capable of increasing wakefulness, but coordinated activity in all these pathways is required for complete alertness and cortical activation. Neurons in the pons and preoptic area control rapid eye movement and non-rapid eye movement sleep. Mutual inhibition between these wake- and sleep-regulating regions likely helps generate discrete behavioral states. An up-to-date understanding of these systems should allow clinicians and researchers to better understand the effects of drugs, lesions, and neurologic disease on sleep and wakefulness.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1093/sleep/27.4.811

Cites

155 of 155 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Injury to ascending arousal pathways from the brainstem may contribute to chronic sleepiness after head trauma.

    “Injury to ascending arousal pathways from the brainstem may contribute, but recent findings suggest a key role for the neuropeptides hypocretin-1 and -2 (also known as orexin-A and -B).2,4,5”

    From Loss of hypocretin (orexin) neurons with traumatic brain injury (2009) · cites this paper as [5]

    The review’s Arousal Network section says lesions of the rostral reticular formation can disrupt wakefulness because they also damage arousal fibers. Its introductory discussion reports excessive sleepiness after injury to wake-promoting regions, but it does not establish that brainstem pathway injury contributes to chronic sleepiness specifically after head trauma. Page numbers are unavailable in our copy. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Hypocretins are made by a small cluster of neurons in the lateral hypothalamus that play an essential role in promoting wakefulness.

    “Hypocretins are made by a small cluster of neurons in the lateral hypothalamus that play an essential role in promoting wakefulness.”

    From Loss of hypocretin (orexin) neurons with traumatic brain injury (2009) · cites this paper as [5]

    The Orexin/Hypocretin section says hypocretins are produced by neurons in the lateral and posterior hypothalamus and that these neurons play an essential role in stabilizing wakefulness. It does not establish that they form a small cluster, and it names the posterior hypothalamus as well as the lateral hypothalamus. (LLM, conf=0.79)

    Experimental — accuracy not yet measured

  • Selective loss of hypocretin-producing neurons causes sleepiness and cataplexy in over 90% of patients with narcolepsy.

    “Selective loss of the hypocretin-producing neurons causes sleepiness and cataplexy in over 90% of patients with narcolepsy,5–9”

    From Loss of hypocretin (orexin) neurons with traumatic brain injury (2009) · cites this paper as [5]

    The Orexin/Hypocretin section (page unavailable) links loss of orexin neurons to difficulty maintaining wakefulness and describes cataplexy with deficient orexin signaling. But its figure is about 90% of patients with narcolepsy *and cataplexy* having undetectable cerebrospinal-fluid orexin—not over 90% of all patients with narcolepsy having selective neuronal loss that causes both symptoms. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

1 of the 156 references couldn’t be matched to a known paper.

Research works printed but not linked: 11

  1. Jones B. Reticular formation. Cytoarchitecture, transmitters and projections. The Rat Nervous System. New South Wales: Academic Press Australia, 1995: 155-171.
  2. Jones BE. Arousal systems. Front Biosci 2003; 8:s438-s451.
  3. De Sarro GB, Ascioti C, Froio F, Libri V, Nistico G. Evidence that locus coeruleus is the site where clonidine and drugs acting at alpha 1-and alpha 2-adrenoceptors affect sleep and arousal mechanisms. Br J Pharmacol 1987; 90:675-685.
  4. Berridge CW, España RA. Synergistic sedative effects of noradren- ergic alpha(1)-and beta-receptor blockade on forebrain electroen- cephalographic and behavioral indices. Neuroscience 2000; 99:495-505.
  5. Törk I. Anatomy of the serotonergic system. Ann N Y Acad Sci 1990; 600:9-34.
  6. Koella WP. Serotonin and sleep. Exp Med Surg 1969; 27:157-168.
  7. Monti JM, Jantos H. Dose-dependent effects of the 5-HT1A recep- tor agonist 8-OH-DPAT on sleep and wakefulness in the rat. J Sleep Res 1992; 1:169-175.
  8. Boutrel B, Monaca C, Hen R, Hamon M, Adrien J. Involvement of 5-HT1A receptors in homeostatic and stress-induced adaptive reg- ulations of paradoxical sleep: studies in 5-HT1A knock-out mice. J Neurosci 2002; 22:4686-4692.
  9. Bjorvatn B, Ursin R. Effects of the selective 5-HT1B agonist, CGS 12066B, on sleep/waking stages and EEG power spectrum in rats. J Sleep Res 1994; 3:97-105.
  10. Boutrel B, Franc B, Hen R, Hamon M, Adrien J. Key role of 5- HT1B receptors in the regulation of paradoxical sleep as evidenced in 5-HT1B knock-out mice. J Neurosci 1999; 19:3204-3212.
  11. Chemelli RM, Willie JT, Sinton CM et al. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 1999; 98:437-451.

Cited by

Sorted by citations

Related

Authors
España, R. A., & Scammell, T. E.
Affiliations
Beth Israel Deaconess Medical Center (US)
Corresponding author
Thomas E. Scammell
ORCID
Venue
Sleep
Publisher
Oxford University Press (OUP)
Published
2004-06-01
Volume
27
Issue
4
Pages
811-20
ISSN
  • 0161-8105 (ISSN-L)
  • 1550-9109
DOI
10.1093/sleep/27.4.811
OpenAlex
W76516690
Cited by
151
References
156
Citations by year
2025: 1 · 2024: 4 · 2023: 3 · 2022: 2 · 2021: 5 · 2020: 3 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 6 · 2014: 6 · 2013: 13 · 2012: 10
FWCI
6.73
Type
journal article
Language
en
Open access
closed
Locations
  • SLEEP (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (HL02013)
  • National Institute of Mental Health (MH 62589, R01MH062589)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Keywords
sleep regulation, wakefulness, arousal system, acetylcholine, norepinephrine, dopamine, serotonin, histamine, hypocretin/orexin, brainstem, hypothalamus, passive optical networks, preoptic area, REM sleep, NREM sleep, sleep-wake states, neurochemical systems
MeSH terms
Orexins, Acetylcholine, Brain Stem, Carrier Proteins, Dopamine, Histamine, Humans, Hypothalamus, Neurons, Neuropeptides, Norepinephrine, Serotonin, Sleep, REM, Wakefulness, Intracellular Signaling Peptides and Proteins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review