Galanin neurons unite sleep homeostasis and α2-adrenergic sedation
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Supporting information
Published version
Author(s)
Type
Journal Article
Abstract
Our urge to sleep increases with time spent awake, until sleep becomes inescapable. The sleep following sleep deprivation is longer and deeper, with an increased power of delta (0.5 - 4 Hz) oscillations, a phenomenon termed sleep homeostasis [1-4]. Although widely-expressed genes regulate sleep homeostasis [1, 4-10], and the process is tracked by somnogens and phosphorylation [1, 3, 7, 11-14], at the circuit level sleep homeostasis has remained mysterious. Previously we found that sedation induced with 2 adrenergic agonists (e.g. dexmedetomidine) and sleep homeostasis both depend on the preoptic (PO) hypothalamus [15, 16]. Dexmedetomidine, increasingly used for long-term sedation in intensive care units [17], induces a NREM-like sleep but with undesirable hypothermia [18, 19]. Within the PO, various neuronal subtypes (e.g. GABA/galanin and glutamate/NOS1) induce NREM sleep [20-22] and concomitant body cooling [21, 22]. This could be because NREM sleep’s restorative effects depend on lower body temperature [23, 24]. Here, we show that mice with lesioned PO galanin neurons have reduced sleep homeostasis: in the recovery sleep following sleep deprivation, there is a diminished increase in delta power, and the mice catch up little on lost sleep. Furthermore, dexmedetomidine cannot induce high-power delta oscillations or sustained hypothermia. Some hours after dexmedetomidine administration to wild-type mice there is a rebound in delta power when they enter normal NREM sleep, reminiscent of emergence from torpor. This delta rebound is reduced in mice lacking PO galanin neurons. Thus, sleep homeostasis and dexmedetomidine-induced sedation require PO galanin neurons and likely share common mechanisms.
Date Issued
2019-10-07
Date Acceptance
2019-07-30
Citation
Current Biology, 2019, 29 (19), pp.3315-3322.e3
ISSN
1879-0445
Publisher
Elsevier (Cell Press)
Start Page
3315
End Page
3322.e3
Journal / Book Title
Current Biology
Volume
29
Issue
19
Copyright Statement
© 2019 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Sponsor
Wellcome Trust
UK DRI Ltd
Wellcome Trust
Wellcome Trust
Biotechnology and Biological Sciences Research Council (BBSRC)
Identifier
https://www.sciencedirect.com/science/article/pii/S0960982219310115?via%3Dihub
Grant Number
107841/Z/15/Z
4050641385
107839/Z/15/Z
107841/Z/15/Z
BB/L015129/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Biology
Cell Biology
Life Sciences & Biomedicine - Other Topics
VENTROLATERAL PREOPTIC NUCLEUS
GROUND-SQUIRRELS SLEEP
BODY-TEMPERATURE
DEXMEDETOMIDINE
ADENOSINE
AREA
MODULATION
ACTIVATION
MECHANISMS
AGONIST
NREM
body temperature
dexmedetomidine
galanin
preoptic hypothalamus
sedation
sleep homeostasis
torpor
Adrenergic alpha-2 Receptor Agonists
Animals
Dexmedetomidine
Female
Galanin
Homeostasis
Hypnotics and Sedatives
Male
Mice
Neurons
Sleep
Sleep Deprivation
Neurons
Animals
Mice
Sleep Deprivation
Dexmedetomidine
Galanin
Hypnotics and Sedatives
Sleep
Homeostasis
Female
Male
Adrenergic alpha-2 Receptor Agonists
Developmental Biology
06 Biological Sciences
11 Medical and Health Sciences
17 Psychology and Cognitive Sciences
Publication Status
Published
Date Publish Online
2019-09-19