title: A sleep/wake circuit controls isoflurane sensitivity in Drosophila.
abstract: 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.
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kottler
authors.forename: Hong
authors.initials: H
authors.lastname: Bao
authors.forename: Oressia
authors.initials: O
authors.lastname: Zalucki
authors.forename: Wendy
authors.initials: W
authors.lastname: Imlach
authors.forename: Michael
authors.initials: M
authors.lastname: Troup
authors.forename: Bart
authors.initials: B
authors.lastname: van Alphen
authors.forename: Angelique
authors.initials: A
authors.lastname: Paulk
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.forename: Bruno
authors.initials: B
authors.lastname: van Swinderen
mesh_terms: D000758:Anesthesia; D000818:Animals; D002211:Capsaicin; D004298:Dopamine / Q000235:genetics / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000502:physiology*; D004351:Drug Resistance / Q000235:genetics / Q000502:physiology; D005260:Female; D007530:Isoflurane / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects; D059906:Neuroimaging; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D050827:Syntaxin 1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; C557617:GAL4 protein, Drosophila; D050827:Syntaxin 1; D014157:Transcription Factors; D007530:Isoflurane; D002211:Capsaicin; D004298:Dopamine