Designer receptor manipulations reveal a role of the locus coeruleus noradrenergic system in isoflurane general anesthesia
Open accessAbstract
Significance: Thousands of people each day receive general anesthesia. Recovery from the anesthetic state is a passive process that can be variable and unpredictable. Identifying neural systems involved in recovery of consciousness after general anesthesia is fundamental to optimizing anesthetic safety and our knowledge of anesthetic action. We examined how norepinephrine from the nucleus locus coeruleus (LC) affects general anesthesia, and found that blocking the action of norepinephrine, particularly in the CNS, delayed recovery from general anesthesia. Using genetic tools to selectively activate only LC neurons, we found that LC activation was sufficient to alter EEG measurements of anesthetic depth and accelerate recovery of consciousness. Our data show that LC activity can alter the anesthetic state, and that noradrenergic medications may affect clinical responses to anesthetic agents.
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Causal reactivation of some wake-promoting neurons during emergence has been explored with electrical, optogenetic, and chemogenetic methods in rodents and suggested in humans.
“the causal reactivation of some wake-promoting neurons during emergence from the anesthetic state has been explored using approaches such as electrical stimulation, optogenetics, and chemogenetics [115–118] in rodents and suggested in humans [119].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [116]
Exogenous locus coeruleus activation primes emergence from isoflurane anesthesia but cannot antagonize continuous isoflurane anesthesia.
“Exogenously activating the locus coeruleus primes the brain for emergence from isoflurane anesthesia, without being able to antagonize a continuous isoflurane anesthetic [116].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [116]
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- Authors
- Vazey, E. M., & Aston-Jones, G.
- Affiliations
- Scripps Research Institute (US)
- Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425
- ORCID
- Vazey, Elena M.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-02-19
- Volume
- 111
- Issue
- 10
- Pages
- 3859-3864
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3956184
- OpenAlex
- W2149050501
- Cited by
- 279
- References
- 41
- Citations by year
- 2026: 11 · 2025: 29 · 2024: 24 · 2023: 17 · 2022: 24 · 2021: 23 · 2020: 31 · 2019: 26 · 2018: 33 · 2017: 19 · 2016: 16 · 2015: 17 · 2014: 7 · 2013: 1
- FWCI
- 26.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Funders
- Parkinson's Disease Foundation
- University of South Carolina
- National Institutes of Health (1c06rr015455-01a1)
- National Institute of Mental Health (R01MH092868)
- National Cancer Institute
- National Institute of Neurological Disorders and Stroke (NS064882-01)
- National Center for Research Resources (C06 RR-015455)
- Topics
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Keywords
- locus coeruleus, norepinephrine, isoflurane, general anesthesia, emergence from anesthesia, burst suppression, cortical arousal, designer receptors, viral gene delivery, adrenergic antagonists, anesthesia duration, anesthesia induction
- MeSH terms
- Red Fluorescent Protein, Anesthesia Recovery Period, Anesthesia, General, Animals, Clozapine, Electroencephalography, Isoflurane, Locomotion, Locus Coeruleus, Luminescent Proteins, Norepinephrine, Rats, Long-Evans, Rats, Adrenergic Neurons
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