Noradrenergic circuit control of non-REM sleep substates.
Détails
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_F481395A28B9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Noradrenergic circuit control of non-REM sleep substates.
Périodique
Current biology
ISSN
1879-0445 (Electronic)
ISSN-L
0960-9822
Statut éditorial
Publié
Date de publication
22/11/2021
Peer-reviewed
Oui
Volume
31
Numéro
22
Pages
5009-5023.e7
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
To understand what makes sleep vulnerable in disease, it is useful to look at how wake-promoting mechanisms affect healthy sleep. Wake-promoting neuronal activity is inhibited during non-rapid-eye-movement sleep (NREMS). However, sensory vigilance persists in NREMS in animals and humans, suggesting that wake promotion could remain functional. Here, we demonstrate that consolidated mouse NREMS is a brain state with recurrent fluctuations of the wake-promoting neurotransmitter noradrenaline on the ∼50-s timescale in the thalamus. These fluctuations occurred around mean noradrenaline levels greater than the ones of quiet wakefulness, while noradrenaline (NA) levels declined steeply in REMS. They coincided with a clustering of sleep spindle rhythms in the forebrain and with heart-rate variations, both of which are correlates of sensory arousability. We addressed the origins of these fluctuations by using closed-loop optogenetic locus coeruleus (LC) activation or inhibition timed to moments of low and high spindle activity during NREMS. We could suppress, lock, or entrain sleep-spindle clustering and heart-rate variations, suggesting that both fore- and hindbrain-projecting LC neurons show coordinated infraslow activity variations in natural NREMS. Noradrenergic modulation of thalamic, but not cortical, circuits was required for sleep-spindle clustering and involved NA release into primary sensory and reticular thalamic nuclei that activated both α1- and β-adrenergic receptors to cause slowly decaying membrane depolarizations. Noradrenergic signaling by LC constitutes a vigilance-promoting mechanism that renders mammalian NREMS vulnerable to disruption on the close-to-minute timescale through sustaining thalamocortical and autonomic sensory arousability. VIDEO ABSTRACT.
Mots-clé
GRAB sensors, adrenergic receptors, arousability, autonomic nervous system, dopamine-β-hydroxylase, heart rate, noradrenaline, quiet wakefulness, sleep spindles, thalamus
Pubmed
Web of science
Open Access
Oui
Financement(s)
Fonds national suisse / Projets / 310030_184759
Création de la notice
25/10/2021 9:58
Dernière modification de la notice
19/07/2023 7:17