A sleep/wake circuit controls isoflurane sensitivity in drosophila

Benjamin Kottler, Hong Bao, Oressia H. Zalucki, Wendy Imlach, Michael Troup, Bart Van Alphen, Angelique C Paulk, Bing Zhang, Bruno van Swinderen

Research output: Contribution to journalArticleResearchpeer-review

37 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)594-598
Number of pages5
JournalCurrent Biology
Volume23
Issue number7
DOIs
Publication statusPublished - 8 Apr 2013
Externally publishedYes

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