Neuronal ensembles sufficient for recovery sleep and the sedative actions of α2 adrenergic agonists
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Do sedatives engage natural sleep pathways? It is usually assumed that anesthetic-induced sedation and loss of righting reflex (LORR) arise by influencing the same circuitry to lesser or greater extents. For the α2 adrenergic receptor agonist dexmedetomidine, we found that sedation and LORR were in fact distinct states, requiring different brain areas: the preoptic hypothalamic area and locus coeruleus (LC), respectively. Selective knockdown of α2A adrenergic receptors from the LC abolished dexmedetomidine-induced LORR, but not sedation. Instead, we found that dexmedetomidine-induced sedation resembled the deep recovery sleep that follows sleep deprivation. We used TetTag pharmacogenetics in mice to functionally mark neurons activated in the preoptic hypothalamus during dexmedetomidine-induced sedation or recovery sleep. The neuronal ensembles could then be selectively reactivated. In both cases, non-rapid eye movement sleep, with the accompanying drop in body temperature, was recapitulated. Thus, α2 adrenergic receptor-induced sedation and recovery sleep share hypothalamic circuitry sufficient for producing these behavioral states.
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More sleep-promoting neurons are recruited by anesthetics in the lateral and medial preoptic hypothalamus than in the VLPO.
“Anesthetics are able to recruit more sleep-promoting neurons in the lateral and medial preoptic hypothalmus than in the VLPO itself [103].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [103]
General anesthetics coopt warm-sensing and sleep-active preoptic neurons to produce hypnosis and central body cooling.
“Recent work suggests that general anesthetics coopt such “dual purpose” warm-sensing and sleep-active subsets of neurons both to elicit hypnosis and to drive central cooling of body temperature, which occurs during anesthetics states [99, 103, 110].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [103]
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- Authors
- Zhang, Z., Ferretti, V., Güntan, İ., Moro, A., Steinberg, E. A., Ye, Z., Zecharia, A. Y., Yu, X., Vyssotski, A. L., Brickley, S. G., Yustos, R., Pillidge, Z. E., Harding, E. C., Wisden, W., & Franks, N. P.
- Affiliations
- Imperial College London (GB)
- University of Zurich (CH)
- Corresponding author
- Wisden, William
- Franks, Nicholas P
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2015-02-23
- Volume
- 18
- Issue
- 4
- Pages
- 553-561
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC4836567
- OpenAlex
- W2143449404
- Cited by
- 275
- References
- 53
- Citations by year
- 2026: 31 · 2025: 33 · 2024: 22 · 2023: 27 · 2022: 16 · 2021: 31 · 2020: 21 · 2019: 30 · 2018: 26 · 2017: 15 · 2016: 16 · 2015: 7
- FWCI
- 12.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- VU Research Portal (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Wellcome Trust (WT094211)
- Biotechnology and Biological Sciences Research Council (G021691, BB/K018159/1, 1100129, BB/F017324/1)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Keywords
- neuronal ensembles, recovery sleep, dexmedetomidine, alpha-2 adrenergic agonists, preoptic hypothalamus, sedation, loss of righting reflex, locus coeruleus, sleep deprivation, NREM sleep, body temperature
- MeSH terms
- Animals, Electroencephalography, Hypnotics and Sedatives, Hypothalamus, Hypothermia, Locus Coeruleus, Male, Mice, Inbred C57BL, Mice, Transgenic, Pharmacogenetics, Sleep, Dexmedetomidine, Mice, Deep Sedation, Adrenergic alpha-2 Receptor Agonists
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