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Effects of sleep deprivation on wake and sleep-promoting neurons: an in vitro electrophysiological approach

English title Effects of sleep deprivation on wake and sleep-promoting neurons: an in vitro electrophysiological approach
Applicant Serafin Mauro
Number 113996
Funding scheme Project funding (Div. I-III)
Research institution Dépt des Neurosciences Fondamentales Faculté de Médecine Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Neurophysiology and Brain Research
Start/End 01.10.2006 - 30.09.2011
Approved amount 296'000.00
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Keywords (6)

sleep; sleep-deprivation; wakefulness; homeostasis; hypocretin/orexin; noradrenaline

Lay Summary (English)

Lead
Lay summary
Sleep and wakefulness are thought to depend on the existence in the brain of “sleep- and wake-promoting” neuronal systems. The mechanisms by which neurons in these systems change their activity and thus contribute to sleep/wake states is a matter of crucial importance in sleep research.
In a set of recent preliminary experiments we were able to show for the first time that following a short period of sleep deprivation (SD) in young rats, it is possible to observe in vitro, in brain slices obtained immediately following the paradigm, changes that clearly reflect the homeostatic process. Indeed, following SD, hypocretin/orexin neurons, which belong to one of the wake-promoting systems, show the emergence of a noradrenergic alpha2-dependent inhibition that is absent in control condition. Such an inhibition in one of the main wake-promoting systems could contribute to the sleepiness that accompanies sleep deprivation.
These data raise multiple questions concerning the mechanisms that underlie this effect, its possible generalization to other wake-promoting systems and/or its possible generalization to other transmitters. The goal of the proposed study is to tackle these questions using an electrophysiological approach in rat brain slices. The study is subdivided in 3 different projects. The first one will be to dissect the mechanisms that underlie the up/down regulation of the alpha2 noradrenergic response following SD that was observed in the preliminary results on hypocretin/orexin neurons. The second one will be to study the regulation of noradrenergic responses on other wake-promoting systems as well as on certain thalamic and cortical neurons using a similar SD protocol. A further project will be to explore the SD modulation of other neurotransmitter responses on sleep and wake-promoting neurons.
If successful these studies could contribute to our understanding of the mechanisms that promote sleep.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Sleep-deprivation regulates α-2 adrenergic responses of rat hypocretin/orexin neurons.
Uschakov Aaron, Grivel Jeremy, Cvetkovic-Lopes Vesna, Bayer Laurence, Bernheim Laurent, Jones Barbara E, Mühlethaler Michel, Serafin Mauro (2011), Sleep-deprivation regulates α-2 adrenergic responses of rat hypocretin/orexin neurons., in PloS one, 6(2), 16672-16672.
Rat hypocretin/orexin neurons are maintained in a depolarized state by TRPC channels.
Cvetkovic-Lopes Vesna, Eggermann Emmanuel, Uschakov Aaron, Grivel Jeremy, Bayer Laurence, Jones Barbara E, Serafin Mauro, Mühlethaler Michel (2010), Rat hypocretin/orexin neurons are maintained in a depolarized state by TRPC channels., in PloS one, 5(12), 15673-15673.

Associated projects

Number Title Start Funding scheme
102060 Further studies on the monoaminergic regulation of the sleep-promoting neurones of the ventro-lateral preoptic area 01.10.2003 Project funding (Div. I-III)

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