Molecular Mechanisms of REM Sleep
Open accessAbstract
The REM sleep is a paradoxical sleep state characterized by brain activity similar to wakefulness, rapid-eye-movement, and lack of muscle tone. REM sleep is a fundamental brain function as it is evolutionary conserved across species, including human, mouse, bird, and even reptiles. The physiological importance of REM sleep is highlighted by severe sleep disorders incurred by a failure in REM sleep regulation. Despite the intense interest in the mechanism of the REM sleep regulation, the molecular machinery is largely left to be investigated. In models of REM sleep regulation, acetylcholine has been a pivotal component. However, even newly emerged techniques such as pharmacogenetics and optogenetics, have not fully clarified the function of acetylcholine either at the cellular level or neural-circuit level. Recently, we discovered that the Gq type muscarinic acetylcholine receptor genes; Chrm1 and Chrm3, are essential for REM sleep. In this review, we attempt to develop a perspective of current knowledge on REM sleep from a molecular viewpoint. This attempt should be a starting point to clarify the molecular machinery underlying the REM sleep regulation and will provide molecular insights to explore physiological functions of REM sleep and its pathological roles in REM-sleep-related disorders such as depression, PTSD, and neurodegenerative diseases.
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REM sleep is characterized by emergence of strong theta-band EEG activity and absence of most other frequency bands.
“REM sleep is characterized by the emergence of strong theta-band EEG activity and the absence of most other frequency bands26 and is associated with processes of memory selection and storage27, which are proposed to be reflected as dreams.”
From Energy paradox in REM sleep: balancing supply and consumption in brain metabolism (2026) · cites this paper as [26]
The Introduction identifies theta oscillation as characteristic of REM sleep, and Future Perspective describes theta as dominant in the EEG during REM sleep (page numbers unavailable). Neither passage says that most other frequency bands are absent; dominance does not establish absence. (LLM, conf=0.85)
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- Authors
- Yamada, R. G., & Ueda, H. R.
- Affiliations
- RIKEN Center for Biosystems Dynamics Research (JP)
- Corresponding author
- Ueda, Hiroki R.
- Venue
- Frontiers in Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2020-01-14
- Volume
- 13
- Pages
- 1402-1402
- ISSN
- 1662-453X (ISSN-L)
- PMC
- PMC6972504
- OpenAlex
- W3000267849
- Cited by
- 49
- References
- 138
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 3 · 2023: 9 · 2022: 10 · 2021: 5 · 2020: 7 · 2019: 1
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Japan Society for the Promotion of Science (18H05270)
- 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 › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- REM sleep, REM sleep regulation, acetylcholine, muscarinic receptors, M1 muscarinic receptor, M3 muscarinic receptor, Gq signaling, sleep disorders, depression, post-traumatic stress disorder, neurodegenerative diseases
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