Genetic and neuronal regulation of sleep by neuropeptide VF
Sleep is an essential and phylogenetically conserved behavioral state, but it remains unclear to what extent genes identified in invertebrates also regulate vertebrate sleep. RFamide-related neuropeptides have been shown to promote invertebrate sleep, and here we report that the vertebrate hypothalamic RFamide neuropeptide VF (NPVF) regulates sleep in the zebrafish, a diurnal vertebrate. We found that NPVF signaling and npvf-expressing neurons are both necessary and sufficient to promote sleep, that mature peptides derived from the NPVF preproprotein promote sleep in a synergistic manner, and that stimulation of npvf-expressing neurons induces neuronal activity levels consistent with normal sleep. These results identify NPVF signaling and npvf-expressing neurons as a novel vertebrate sleep-promoting system and suggest that RFamide neuropeptides participate in an ancient and central aspect of sleep control.
Additional Information© 2017 Lee et al. This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited. Received: February 3, 2017; Accepted: November 3, 2017; Accepted Manuscript published: November 6, 2017 (version 1). We thank members of the Prober Lab, Paul Sternberg, Elly Chow, Ravi Nath and Han Wang for discussions, and Jason Rihel, Seth Blackshaw and Chanpreet Singh for manuscript comments, as well as Daisy Chilin, Tasha Cammidge, and Hannah Hurley for technical assistance. This work was supported by grants from the NIH (DAL: K99NS097683, F32NS084769; GO: F32NS082010; SEF: MH107238; DAP: NS070911, NS101158, NS095824 and NS101665); the Moore Foundation (SEF); and the Mallinckrodt (DAP), Rita Allen (DAP) and Brain and Behavior Research Foundations (DAP, DAL). We declare no competing interests . The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Ethics: Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All experiments were performed using standard protocols (Westerfield, 1993) in accordance with the California Institute of Technology and University of Southern California Institutional Animal Care and Use Committee guidelines.
Published - elife-25727-v2.pdf
Supplemental Material - elife-25727-supp-v1.zip