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Published July 5, 2017 | Supplemental Material + Accepted Version
Journal Article Open

Light-Dependent Regulation of Sleep and Wake States by Prokineticin 2 in Zebrafish


Light affects sleep and wake behaviors by providing an indirect cue that entrains circadian rhythms and also by inducing a direct and rapid regulation of behavior. While circadian entrainment by light is well characterized at the molecular level, mechanisms that underlie the direct effect of light on behavior are largely unknown. In zebrafish, a diurnal vertebrate, we found that both overexpression and mutation of the neuropeptide prokineticin 2 (Prok2) affect sleep and wake behaviors in a light-dependent but circadian-independent manner. In light, Prok2 overexpression increases sleep and induces expression of galanin (galn), a hypothalamic sleep-inducing peptide. We also found that light-dependent, Prok2-induced sedation requires prokineticin receptor 2 (prokr2) and is strongly suppressed in galn mutants. These results suggest that Prok2 antagonizes the direct wake-promoting effect of light in zebrafish, in part through the induction of galn expression in the hypothalamus.

Additional Information

© 2017 Elsevier B.V. Received 25 January 2017, Revised 24 April 2017, Accepted 31 May 2017, Available online 22 June 2017. We thank Daisy Chilin, Alex Mack Cruz, and Kenna Molinder for animal husbandry, Viveca Sapin, Brett Niles, and Jae Chu for genotyping and Catherine Oikonomou and members of the Prober lab for comments on the manuscript. This work was supported by grants from the NIH (S.C.: NS077842; D.A.P.: NS070911, NS094390, and NS095824), the Mallinckrodt, Rita Allen and Brain and Behavior Research Foundations (D.A.P.), a Sir Henry Wellcome Trust Fellowship (S.R.), a UCL Excellence Fellowship (J.R.), and a European Research Council Starting Grant (J.R.: 282027).

Attached Files

Accepted Version - nihms882461.pdf

Supplemental Material - mmc1.pdf


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