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Sleep Neurobiology for the Clinician
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.
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“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]
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“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]
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“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]
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Metadata
- Authors
- España, R. A., & Scammell, T. E.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Thomas E. Scammell
- 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
- 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
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