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dc.contributor.author
Gelegen, Cigdem
dc.contributor.author
Gent, Thomas C.
dc.contributor.author
Ferretti, Valentina
dc.contributor.author
Zhang, Zhe
dc.contributor.author
Yustos, Raquel
dc.contributor.author
Lan, Fei
dc.contributor.author
Yang, Qianzi
dc.contributor.author
Overington, Dorothy W.U.
dc.contributor.author
Vyssotski, Alexei L.
dc.contributor.author
van Lith, Hein A.
dc.contributor.author
Wisden, William
dc.contributor.author
Franks, Nicholas P.
dc.date.accessioned
2019-12-05T13:31:52Z
dc.date.available
2017-06-11T11:40:11Z
dc.date.available
2017-10-26T16:36:18Z
dc.date.available
2019-12-05T13:31:52Z
dc.date.issued
2014-07
dc.identifier.issn
0953-816X
dc.identifier.issn
1460-9568
dc.identifier.other
10.1111/ejn.12570
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/87548
dc.identifier.doi
10.3929/ethz-b-000087548
dc.description.abstract
How external stimuli prevent the onset of sleep has been little studied. This is usually considered to be a non‐specific type of phenomenon. However, the hypnotic drug dexmedetomidine, an agonist at α2 adrenergic receptors, has unusual properties that make it useful for investigating this question. Dexmedetomidine is considered to produce an ‘arousable’ sleep‐like state, so that patients or animals given dexmedetomidine become alert following modest stimulation. We hypothesized that it might be more difficult to make mice unconscious with dexmedetomidine if there was a sufficient external stimulus. Employing a motorized rotating cylinder, which provided a continuous and controlled arousal stimulus, we quantitatively measured the ability of such a stimulus to prevent dexmedetomidine loss of righting reflex in two inbred strains of mice (C57BL/6 and 129X1). We found that whereas the C57BL/6 strain required a strong stimulus to prevent dexmedetomidine‐induced hypnosis, the 129X1 strain stayed awake even with minimal stimuli. Remarkably, this could be calibrated as a simple threshold trait, i.e. a binary ‘yes–no’ response, which after crossing the two mouse strains behaved as a dominant‐like trait. We carried out a genome‐wide linkage analysis on the F2 progeny to determine if the ability of a stimulus to prevent dexmedetomidine hypnosis could be mapped to one or more chromosomal regions. We identified a locus on chromosome 4 with an associated Logarithm of Odds score exceeding the pre‐established threshold level. These results show that complex traits, such as the ability of a stimulus to reverse drug‐induced hypnosis, may have precise genetic determinants.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Wiley-Blackwell
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/3.0/
dc.subject
Alpha2a adrenergic receptor
en_US
dc.subject
Sedation
en_US
dc.subject
Sleep
en_US
dc.subject
Wakefulness
en_US
dc.title
Staying awake – a genetic region that hinders α2 adrenergic receptor agonist‐induced sleep
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 3.0 Unported
dc.date.published
2014-03-27
ethz.journal.title
European Journal of Neuroscience
ethz.journal.volume
40
en_US
ethz.journal.issue
1
en_US
ethz.journal.abbreviated
Eur. j. neurosci.
ethz.pages.start
2311
en_US
ethz.pages.end
2319
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.nebis
000510475
ethz.publication.place
Oxford
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02140 - Dep. Inf.technologie und Elektrotechnik / Dep. of Inform.Technol. Electrical Eng.::02533 - Institut für Neuroinformatik / Institute of Neuroinformatics::03774 - Hahnloser, Richard H.R. / Hahnloser, Richard H.R.
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02140 - Dep. Inf.technologie und Elektrotechnik / Dep. of Inform.Technol. Electrical Eng.::02533 - Institut für Neuroinformatik / Institute of Neuroinformatics::03774 - Hahnloser, Richard H.R. / Hahnloser, Richard H.R.
ethz.date.deposited
2017-06-11T11:40:14Z
ethz.source
ECIT
ethz.identifier.importid
imp59365228b8b0339972
ethz.ecitpid
pub:137767
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-17T10:59:39Z
ethz.rosetta.lastUpdated
2019-12-05T13:32:05Z
ethz.rosetta.versionExported
true
ethz.COinS
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