A Caltech Library Service

Neuropeptide Y Regulates Sleep by Modulating Noradrenergic Signaling

Singh, Chanpreet and Rihel, Jason and Prober, David A. (2017) Neuropeptide Y Regulates Sleep by Modulating Noradrenergic Signaling. Current Biology, 27 (24). pp. 3796-3811. ISSN 0960-9822. PMCID PMC5736401. doi:10.1016/j.cub.2017.11.018.

[img] PDF - Accepted Version
See Usage Policy.

[img] PDF (Document S1. Figures S1–S7 and Tables S1–S3) - Supplemental Material
See Usage Policy.

[img] Video (MPEG) (Movie S1. Annotation of npy Expression Domains in the Zebrafish Brain, Related to Figure 1) - Supplemental Material
See Usage Policy.

[img] Video (MPEG) (Movie S2. Hindbrain npy-Expressing Neurons Project to the LC, Related to Figure 5) - Supplemental Material
See Usage Policy.


Use this Persistent URL to link to this item:


Sleep is an essential and evolutionarily conserved behavioral state whose regulation remains poorly understood. To identify genes that regulate vertebrate sleep, we recently performed a genetic screen in zebrafish, and here we report the identification of neuropeptide Y (NPY) as both necessary for normal daytime sleep duration and sufficient to promote sleep. We show that overexpression of NPY increases sleep, whereas mutation of npy or ablation of npy-expressing neurons decreases sleep. By analyzing sleep architecture, we show that NPY regulates sleep primarily by modulating the length of wake bouts. To determine how NPY regulates sleep, we tested for interactions with several systems known to regulate sleep, and provide anatomical, molecular, genetic, and pharmacological evidence that NPY promotes sleep by inhibiting noradrenergic signaling. These data establish NPY as an important vertebrate sleep/wake regulator and link NPY signaling to an established arousal-promoting system.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Singh, Chanpreet0000-0002-2697-3033
Rihel, Jason0000-0003-4067-2066
Prober, David A.0000-0002-7371-4675
Additional Information:© 2017 Elsevier Ltd. Received 31 March 2017, Revised 11 October 2017, Accepted 6 November 2017, Available online 7 December 2017. Data and Software Availability: Custom PERL and MATLAB code used for zebrafish behavioral analysis is available upon request. We thank Daisy Chilin, Alex Mack Cruz, Axel Dominguez, and Kenna Molinder for animal husbandry assistance; Viveca Sapin and Uyen Pham for genotyping assistance; Owen Randlett, Ulrich Herget, Caroline Wee, and Marcus Ghosh for assistance with Z-Brain registration; and Grigorios Oikonomou for comments on the manuscript. This work was supported by grants from the NIH (NS070911, NS101665, NS095824, and NS101158 to D.A.P.), the Mallinckrodt, Rita Allen, and Brain and Behavior Research foundations (to D.A.P.), and a UCL Excellence Fellowship and European Research Council Starting Grant (282027 to J.R.). Author Contributions: D.A.P. and J.R. performed the genetic screen. C.S. and D.A.P. conceptualized and designed the experiments and generated reagents. C.S. performed the experiments and analyzed the data. C.S. and D.A.P. wrote the paper with assistance from J.R. D.A.P. supervised the project.
Group:Tianqiao and Chrissy Chen Institute for Neuroscience
Funding AgencyGrant Number
Mallinckrodt FoundationUNSPECIFIED
Rita Allen FoundationUNSPECIFIED
Brain and Behavior Research FoundationUNSPECIFIED
University College LondonUNSPECIFIED
European Research Council (ERC)82027
Subject Keywords:sleep; neuropeptide Y; hypothalamus; locus coeruleus; noradrenaline; locomotor activity; arousal; genetics; zebrafish
Issue or Number:24
PubMed Central ID:PMC5736401
Record Number:CaltechAUTHORS:20171208-111531827
Persistent URL:
Official Citation:Chanpreet Singh, Jason Rihel, David A. Prober, Neuropeptide Y Regulates Sleep by Modulating Noradrenergic Signaling, Current Biology, Volume 27, Issue 24, 18 December 2017, Pages 3796-3811.e5, ISSN 0960-9822, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:83754
Deposited By: Tony Diaz
Deposited On:13 Dec 2017 04:56
Last Modified:18 Mar 2022 22:28

Repository Staff Only: item control page