NMDA receptors in the lateral preoptic hypothalamus are essential for sustaining NREM and REM sleep
File(s)
Author(s)
Type
Journal Article
Abstract
The lateral preoptic (LPO) hypothalamus is a center for NREM and REM sleep induction and NREM sleep homeostasis. Although LPO is needed for NREM sleep, we found that calcium signals were, surprisingly, highest in REM sleep. Furthermore, and equally surprising, NMDA26 receptors in LPO were the main drivers of excitation. Deleting the NMDA receptor GluN1 subunit from LPO abolished calcium signals in all cells and produced insomnia. Mice of both sexes had highly fragmented NREM sleep-wake patterns and could not generate conventionally classified REM sleep. The sleep phenotype produced by deleting NMDA receptors depended on where in the hypothalamus the receptors were deleted. Deleting receptors from the anterior hypothalamic area did not influence sleep-wake states. The sleep fragmentation originated from NMDA receptors on GABA neurons in LPO. Sleep fragmentation could be transiently overcome with sleeping medication (zolpidem) or sedatives (dexmedetomidine). By contrast, fragmentation persisted under high sleep
pressure produced by sleep deprivation - mice had a high propensity to sleep but woke up. By analyzing changes in delta power, sleep homeostasis (also referred to as “sleep drive”) remained intact after NMDA receptor ablation. We suggest NMDA glutamate receptor activation stabilizes firing of sleep-on neurons, and that mechanisms of sleep maintenance differ from that of the sleep drive itself.
pressure produced by sleep deprivation - mice had a high propensity to sleep but woke up. By analyzing changes in delta power, sleep homeostasis (also referred to as “sleep drive”) remained intact after NMDA receptor ablation. We suggest NMDA glutamate receptor activation stabilizes firing of sleep-on neurons, and that mechanisms of sleep maintenance differ from that of the sleep drive itself.
Date Issued
2022-06-01
Date Acceptance
2022-03-31
Citation
The Journal of Neuroscience, 2022, 42 (27), pp.5389-5409
ISSN
0270-6474
Publisher
Society for Neuroscience
Start Page
5389
End Page
5409
Journal / Book Title
The Journal of Neuroscience
Volume
42
Issue
27
Copyright Statement
© 2022 the authors
SfN exclusive license https://www.jneurosci.org/content/licenses.
SfN exclusive license https://www.jneurosci.org/content/licenses.
Sponsor
Wellcome Trust
UK DRI Ltd
Wellcome Trust
Wellcome Trust
Wellcome Trust
Commission of the European Communities
Identifier
https://www.jneurosci.org/content/42/27/5389
Grant Number
107841/Z/15/Z
DRI-CORE2020-IMP
220759/Z/20/Z
107839/Z/15/Z
107841/Z/15/Z
753548
Subjects
NMDA receptor
NREM
REM
hypothalamus
preoptic
sleep
Animals
Calcium
Electroencephalography
Female
Hypothalamus
Male
Mice
N-Methylaspartate
Receptors, N-Methyl-D-Aspartate
Sleep
Sleep Deprivation
Sleep Initiation and Maintenance Disorders
Sleep, REM
Wakefulness
Hypothalamus
Animals
Mice
Sleep Deprivation
Sleep Initiation and Maintenance Disorders
Calcium
N-Methylaspartate
Receptors, N-Methyl-D-Aspartate
Electroencephalography
Wakefulness
Sleep
Sleep, REM
Female
Male
Neurology & Neurosurgery
11 Medical and Health Sciences
17 Psychology and Cognitive Sciences
Publication Status
Published
Date Publish Online
2022-06-01