A sleep/wake circuit controls isoflurane sensitivity in Drosophila
Open accessAbstract
General anesthesia remains a mysterious phenomenon, even though a number of compelling target proteins and processes have been proposed [1]. General anesthetics such as isoflurane abolish behavioral responsiveness in all animals, and in the mammalian brain, these diverse compounds probably achieve this in part by targeting endogenous sleep mechanisms [2, 3]. However, most animals sleep [4], and they are therefore likely to have conserved sleep processes. A decade of neurogenetic studies of arousal in Drosophila melanogaster have identified a number of different neurons and brain structures that modulate sleep duration in the fly brain [5-9], but it has remained unclear until recently whether any neurons might form part of a dedicated circuit that actively controls sleep and wake states in the fly brain, as has been proposed for the mammalian brain [10]. We studied general anesthesia in Drosophila by measuring stimulus-induced locomotion under isoflurane gas exposure. Using a syntaxin1A gain-of-function construct, we found that increasing synaptic activity in different Drosophila neurons could produce hypersensitivity or resistance to isoflurane. We uncover a common pathway in the fly brain controlling both sleep duration and isoflurane sensitivity, centered on monoaminergic modulation of sleep-promoting neurons of the fan-shaped body.
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The shared circuits hypothesis between sleep and anesthesia has been replicated across invertebrates to mammals.
“This shared circuits hypothesis has been replicated across divergent species spanning invertebrates to mammals [54, 58, 82, 98, 99, 101].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [82]
A syntaxin gain-of-function mutation increasing synaptic activity in flies causes volatile anesthetic resistance when targeted to wake-promoting neurons but hypersensitivity when targeted to sleep-promoting neurons.
“the use of a syntaxin gain-of-function mutation that increases synaptic activity in flies leads to volatile anesthetic resistance when targeted to wake-promoting neurons but anesthetic hypersensitivity when targeted to sleep-promoting neurons [82].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [82]
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- Authors
- Kottler, B., Bao, H., Zalucki, O., Imlach, W., Troup, M., van Alphen, B., Paulk, A., Zhang, B., & van Swinderen, B.
- Affiliations
- The University of Queensland (AU)
- University of Oklahoma (US)
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 23
- Issue
- 7
- Pages
- 594-598
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W2089789757
- Cited by
- 63
- References
- 30
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 4 · 2018: 10 · 2017: 6 · 2016: 5 · 2015: 6 · 2014: 9 · 2013: 4
- FWCI
- 3.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- isoflurane, general anesthesia, Drosophila melanogaster, syntaxin 1A, synaptic activity, sleep-promoting neurons, fan-shaped body, locomotion, anesthetic sensitivity, sleep duration
- MeSH terms
- Anesthesia, Animals, Capsaicin, Dopamine, Dose-Response Relationship, Drug, Drosophila melanogaster, Drug Resistance, Female, Isoflurane, Locomotion, Neuromuscular Junction, Sleep, Transcription Factors, Wakefulness, Drosophila Proteins, Syntaxin 1, Dopaminergic Neurons, Neuroimaging
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