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Published December 18, 2017 | Accepted Version + Supplemental Material
Journal Article Open

Neuropeptide Y Regulates Sleep by Modulating Noradrenergic Signaling


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.

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.

Attached Files

Accepted Version - nihms919667.pdf

Supplemental Material - mmc1.pdf

Supplemental Material - mmc2.mp4

Supplemental Material - mmc3.mp4


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