Explaining general anesthesia: A two-step hypothesis linking sleep circuits and the synaptic release machinery

van Swinderen, Bruno and Kottler, Benjamin (2014) Explaining general anesthesia: A two-step hypothesis linking sleep circuits and the synaptic release machinery. BioEssays, 36 4: 372-381. doi:10.1002/bies.201300154


Author van Swinderen, Bruno
Kottler, Benjamin
Title Explaining general anesthesia: A two-step hypothesis linking sleep circuits and the synaptic release machinery
Journal name BioEssays   Check publisher's open access policy
ISSN 0265-9247
1521-1878
Publication date 2014-01-01
Year available 2014
Sub-type Article (original research)
DOI 10.1002/bies.201300154
Open Access Status DOI
Volume 36
Issue 4
Start page 372
End page 381
Total pages 10
Place of publication Chichester, West Sussex, United Kingdom
Publisher John Wiley and Sons Inc.
Language eng
Subject 1300 Biochemistry, Genetics and Molecular Biology
Abstract Several general anesthetics produce their sedative effect by activating endogenous sleep pathways. We propose that general anesthesia is a two-step process targeting sleep circuits at low doses, and synaptic release mechanisms across the entire brain at the higher doses required for surgery. Our hypothesis synthesizes data from a variety of model systems, some which require sleep (e.g. rodents and adult flies) and others that probably do not sleep (e.g. adult nematodes and cultured cell lines). Non-sleeping systems can be made insensitive (or hypersensitive) to some anesthetics by modifying a single pre-synaptic protein, syntaxin1A. This suggests that the synaptic release machinery, centered on the highly conserved SNARE complex, is an important target of general anesthetics in all animals. A careful consideration of SNARE architecture uncovers a potential mechanism for general anesthesia, which may be the primary target in animals that do not sleep, but a secondary target in animals that sleep.
Keyword Caenorhabditis elegans
Drosophila
General anesthesia
Neuroscience
Sleep
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 10 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 10 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 08 Apr 2014, 10:14:33 EST by System User on behalf of Queensland Brain Institute