A sleep/wake circuit controls isoflurane sensitivity in Drosophila

Curr Biol. 2013 Apr 8;23(7):594-8. doi: 10.1016/j.cub.2013.02.021. Epub 2013 Mar 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anesthesia*
  • Animals
  • Capsaicin
  • Dopamine / genetics
  • Dopamine / metabolism
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / physiology*
  • Dose-Response Relationship, Drug
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / physiology*
  • Drug Resistance / genetics
  • Drug Resistance / physiology
  • Female
  • Isoflurane / pharmacology*
  • Locomotion / drug effects
  • Neuroimaging
  • Neuromuscular Junction / drug effects
  • Neuromuscular Junction / physiology
  • Sleep / drug effects
  • Sleep / physiology*
  • Syntaxin 1 / metabolism
  • Transcription Factors / metabolism
  • Wakefulness / drug effects
  • Wakefulness / physiology*


  • Drosophila Proteins
  • GAL4 protein, Drosophila
  • Syntaxin 1
  • Transcription Factors
  • Isoflurane
  • Capsaicin
  • Dopamine