Neuropeptide VF Neurons Promote Sleep Via the Serotonergic Raphe

Overview

Journal Elife

Specialty Biology

Date 2020 Dec 18

PMID 33337320

Citations 11

Authors

Daniel A Lee

Grigorios Oikonomou

Tasha Cammidge

Andrey Andreev

Young Hong

Hannah Hurley

David A Prober

Affiliations

Soon will be listed here.

Abstract

Although several sleep-regulating neuronal populations have been identified, little is known about how they interact with each other to control sleep/wake states. We previously identified neuropeptide VF (NPVF) and the hypothalamic neurons that produce it as a sleep-promoting system (Lee et al., 2017). Here we show using zebrafish that -expressing neurons control sleep via the serotonergic raphe nuclei (RN), a hindbrain structure that is critical for sleep in both diurnal zebrafish and nocturnal mice. Using genetic labeling and calcium imaging, we show that -expressing neurons innervate and can activate serotonergic RN neurons. We also demonstrate that chemogenetic or optogenetic stimulation of expressing neurons induces sleep in a manner that requires NPVF and serotonin in the RN. Finally, we provide genetic evidence that NPVF acts upstream of serotonin in the RN to maintain normal sleep levels. These findings reveal a novel hypothalamic-hindbrain neuronal circuit for sleep/wake control.

Citing Articles

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References

Liu Q, Guan X, Martin W, McDONALD T, Clements M, Jiang Q . Identification and characterization of novel mammalian neuropeptide FF-like peptides that attenuate morphine-induced antinociception. J Biol Chem. 2001; 276(40):36961-9. DOI: 10.1074/jbc.M105308200. View

Cheng R, Krishnan S, Jesuthasan S . Activation and inhibition of tph2 serotonergic neurons operate in tandem to influence larval zebrafish preference for light over darkness. Sci Rep. 2016; 6:20788. PMC: 4751628. DOI: 10.1038/srep20788. View

Lee D, Liu J, Hong Y, Lane J, Hill A, Hou S . Evolutionarily conserved regulation of sleep by epidermal growth factor receptor signaling. Sci Adv. 2019; 5(11):eaax4249. PMC: 6853770. DOI: 10.1126/sciadv.aax4249. View

Campbell S, Tobler I . Animal sleep: a review of sleep duration across phylogeny. Neurosci Biobehav Rev. 1984; 8(3):269-300. DOI: 10.1016/0149-7634(84)90054-x. View

Lane J, Jones S, Dashti H, Wood A, Aragam K, van Hees V . Biological and clinical insights from genetics of insomnia symptoms. Nat Genet. 2019; 51(3):387-393. PMC: 6415688. DOI: 10.1038/s41588-019-0361-7. View

Urasaki A, Morvan G, Kawakami K . Functional dissection of the Tol2 transposable element identified the minimal cis-sequence and a highly repetitive sequence in the subterminal region essential for transposition. Genetics. 2006; 174(2):639-49. PMC: 1602067. DOI: 10.1534/genetics.106.060244. View

Oikonomou G, Altermatt M, Zhang R, Coughlin G, Montz C, Gradinaru V . The Serotonergic Raphe Promote Sleep in Zebrafish and Mice. Neuron. 2019; 103(4):686-701.e8. PMC: 6706304. DOI: 10.1016/j.neuron.2019.05.038. View

Shang Y, Donelson N, Vecsey C, Guo F, Rosbash M, Griffith L . Short neuropeptide F is a sleep-promoting inhibitory modulator. Neuron. 2013; 80(1):171-83. PMC: 3792499. DOI: 10.1016/j.neuron.2013.07.029. View

Bonini J, Jones K, Adham N, Forray C, Artymyshyn R, Durkin M . Identification and characterization of two G protein-coupled receptors for neuropeptide FF. J Biol Chem. 2000; 275(50):39324-31. DOI: 10.1074/jbc.M004385200. View

10.

Yelin-Bekerman L, Elbaz I, Diber A, Dahary D, Gibbs-Bar L, Alon S . Hypocretin neuron-specific transcriptome profiling identifies the sleep modulator Kcnh4a. Elife. 2015; 4:e08638. PMC: 4718730. DOI: 10.7554/eLife.08638. View

11.

Nelson M, Lee K, Churgin M, Hill A, Van Buskirk C, Fang-Yen C . FMRFamide-like FLP-13 neuropeptides promote quiescence following heat stress in Caenorhabditis elegans. Curr Biol. 2014; 24(20):2406-10. PMC: 4254296. DOI: 10.1016/j.cub.2014.08.037. View

12.

Elbaz I, Yelin-Bekerman L, Nicenboim J, Vatine G, Appelbaum L . Genetic ablation of hypocretin neurons alters behavioral state transitions in zebrafish. J Neurosci. 2012; 32(37):12961-72. PMC: 6703801. DOI: 10.1523/JNEUROSCI.1284-12.2012. View

13.

Qian Y, Cao Y, Deng B, Yang G, Li J, Xu R . Sleep homeostasis regulated by 5HT2b receptor in a small subset of neurons in the dorsal fan-shaped body of drosophila. Elife. 2017; 6. PMC: 5648528. DOI: 10.7554/eLife.26519. View

14.

Lenz O, Xiong J, Nelson M, Raizen D, Williams J . FMRFamide signaling promotes stress-induced sleep in Drosophila. Brain Behav Immun. 2015; 47:141-8. PMC: 4467992. DOI: 10.1016/j.bbi.2014.12.028. View

15.

Dashti H, Jones S, Wood A, Lane J, van Hees V, Wang H . Genome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates. Nat Commun. 2019; 10(1):1100. PMC: 6405943. DOI: 10.1038/s41467-019-08917-4. View

16.

Kim J, Lee S, Li L, Park H, Park J, Lee K . High cleavage efficiency of a 2A peptide derived from porcine teschovirus-1 in human cell lines, zebrafish and mice. PLoS One. 2011; 6(4):e18556. PMC: 3084703. DOI: 10.1371/journal.pone.0018556. View

17.

Oikonomou G, Prober D . Attacking sleep from a new angle: contributions from zebrafish. Curr Opin Neurobiol. 2017; 44:80-88. PMC: 5659277. DOI: 10.1016/j.conb.2017.03.009. View

18.

Lane J, Liang J, Vlasac I, Anderson S, Bechtold D, Bowden J . Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits. Nat Genet. 2016; 49(2):274-281. PMC: 5491693. DOI: 10.1038/ng.3749. View

19.

Prober D, Rihel J, Onah A, Sung R, Schier A . Hypocretin/orexin overexpression induces an insomnia-like phenotype in zebrafish. J Neurosci. 2006; 26(51):13400-10. PMC: 6675014. DOI: 10.1523/JNEUROSCI.4332-06.2006. View

20.

Kawashima T, Zwart M, Yang C, Mensh B, Ahrens M . The Serotonergic System Tracks the Outcomes of Actions to Mediate Short-Term Motor Learning. Cell. 2016; 167(4):933-946.e20. DOI: 10.1016/j.cell.2016.09.055. View