Neuronal substrates of sleep homeostasis; lessons from flies, rats and mice
Abstract
Sleep homeostasis is a fundamental property of vigilance state regulation that is highly conserved across species. Neuronal systems and circuits that underlie sleep homeostasis are not well understood. In Drosophila, a neuronal circuit involving neurons in the ellipsoid body and in the dorsal Fan-shaped body is a candidate for both tracing sleep need during waking and translating it to increased sleep drive and expression. Sleep homeostasis in rats and mice involves multiple neuromodulators acting on multiple wake- and sleep-promoting neuronal systems. A functional central homeostat emerges from A 1 receptor mediated actions of adenosine on wake-promoting neurons in the basal forebrain and hypothalamus, and A 2A adenosine receptor-mediated actions on sleep-promoting neurons in the preoptic hypothalamus and nucleus accumbens.
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Fatigue in individuals with hypothalamic syndrome could potentially be related to disordered signaling from GABAergic neurons in the suprachiasmatic, ventrolateral, and preoptic nuclei.
“Commonly reported fatigue (72, 73) could potentially be related to disordered signaling from γ-aminobutyric acid (GABA)-ergic neurons in the suprachiasmatic, ventrolateral, and preoptic nuclei (74, 75).”
From Approach to the patient with acquired hypothalamic syndrome (2026) · cites this paper as [75]
Cites
The Neurobiology of Sleep and Wakefulness
Schwartz, M. D., & Kilduff, T. S. (2015) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2015.07.002 · Cited by 207 · see citing works
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Neuronal Mechanisms for Sleep/Wake Regulation and Modulatory Drive
Eban-Rothschild, A., Appelbaum, L., & de Lecea, L. (2018) · Neuropsychopharmacology · doi:10.1038/npp.2017.294 · Cited by 282 · see citing works
Approach to the patient with acquired hypothalamic syndrome
Grishman, E. K., & McCormack, S. E. (2026) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgag197
- Authors
- Donlea, J. M., Alam, M. N., & Szymusiak, R.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Szymusiak, Ronald
- Venue
- Current Opinion in Neurobiology
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 44
- Pages
- 228-235
- ISSN
- 0959-4388 (ISSN-L)
- OpenAlex
- W2686514674
- Cited by
- 56
- References
- 1
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 8 · 2021: 11 · 2020: 6 · 2019: 8 · 2018: 8 · 2017: 1
- FWCI
- 0.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Department of Veterans Affairs (BX00155605, BX000936)
- National Institutes of Health (NS092383)
- Sleep Research Society Foundation
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- sleep homeostasis, sleep drive, sleep need, Drosophila, ellipsoid body, adenosine A1 receptor, adenosine A2A receptor, wake-promoting neurons, sleep-promoting neurons, hypothalamus, basal forebrain, preoptic hypothalamus, nucleus accumbens, neuromodulators, neural circuits
- MeSH terms
- Adenosine, Animals, Homeostasis, Neurons, Sleep, Wakefulness
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