Orexin neurons inhibit sleep to promote arousal.

Autor: De Luca R; Department of Neurology, Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA., Nardone S; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism. Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA., Grace KP; Department of Neurology, Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA.; Department of Neurological Surgery, University of California Davis School of Medicine, Davis, CA, USA., Venner A; Department of Neurology, Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA., Cristofolini M; Department of Neurology, Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA., Bandaru SS; Department of Neurology, Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA., Sohn LT; Department of Neurology, Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA., Kong D; Department of Pediatrics, Division of Endocrinology, F.M. Kirby Neurobiology Center. Children's Hospital and Harvard Medical School, Boston, MA, USA., Mochizuki T; Department of Biology, Graduate School of Science and Engineering. University of Toyama, Toyama, Japan., Viberti B; Department of Neurology, Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA., Zhu L; Department of Neurology, Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA., Zito A; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, 02114, USA.; Department of Genetics, Harvard Medical School, Boston, MA, 02114, USA., Scammell TE; Department of Neurology, Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA., Saper CB; Department of Neurology, Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA., Lowell BB; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism. Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA., Fuller PM; Department of Neurology, Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA. pmfuller@ucdavis.edu.; Department of Neurological Surgery, University of California Davis School of Medicine, Davis, CA, USA. pmfuller@ucdavis.edu., Arrigoni E; Department of Neurology, Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA. earrigon@bidmc.harvard.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Jul 18; Vol. 13 (1), pp. 4163. Date of Electronic Publication: 2022 Jul 18.
DOI: 10.1038/s41467-022-31591-y
Abstrakt: Humans and animals lacking orexin neurons exhibit daytime sleepiness, sleep attacks, and state instability. While the circuit basis by which orexin neurons contribute to consolidated wakefulness remains unclear, existing models posit that orexin neurons provide their wake-stabilizing influence by exerting excitatory tone on other brain arousal nodes. Here we show using in vivo optogenetics, in vitro optogenetic-based circuit mapping, and single-cell transcriptomics that orexin neurons also contribute to arousal maintenance through indirect inhibition of sleep-promoting neurons of the ventrolateral preoptic nucleus. Activation of this subcortical circuit rapidly drives wakefulness from sleep by differentially modulating the activity of ventrolateral preoptic neurons. We further identify and characterize a feedforward circuit through which orexin (and co-released glutamate) acts to indirectly target and inhibit sleep-promoting ventrolateral preoptic neurons to produce arousal. This revealed circuitry provides an alternate framework for understanding how orexin neurons contribute to the maintenance of consolidated wakefulness and stabilize behavioral state.
(© 2022. The Author(s).)
Databáze: MEDLINE
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