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Genetic Analysis of Histamine Signaling in Larval Zebrafish Sleep

Chen, Audrey and Singh, Chanpreet and Oikonomou, Grigorios and Prober, David A. (2017) Genetic Analysis of Histamine Signaling in Larval Zebrafish Sleep. eNeuro, 4 (1). Art. No. e0286-16.2017. ISSN 2373-2822. PMCID PMC5334454. doi:10.1523/ENEURO.0286-16.2017.

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Pharmacological studies in mammals and zebrafish suggest that histamine plays an important role in promoting arousal. However, genetic studies using rodents with disrupted histamine synthesis or signaling have revealed only subtle or no sleep/wake phenotypes. Studies of histamine function in mammalian arousal are complicated by its production in cells of the immune system and its roles in humoral and cellular immunity, which can have profound effects on sleep/wake states. To avoid this potential confound, we used genetics to explore the role of histamine in regulating sleep in zebrafish, a diurnal vertebrate in which histamine production is restricted to neurons in the brain. Similar to rodent genetic studies, we found that zebrafish that lack histamine due to mutation of histidine decarboxylase (hdc) exhibit largely normal sleep/wake behaviors. Zebrafish containing predicted null mutations in several histamine receptors also lack robust sleep/wake phenotypes, although we are unable to verify that these mutants are completely nonfunctional. Consistent with some rodent studies, we found that arousal induced by overexpression of the neuropeptide hypocretin (Hcrt) or by stimulation of hcrt-expressing neurons is not blocked in hdc or hrh1 mutants. We also found that the number of hcrt-expressing or histaminergic neurons is unaffected in animals that lack histamine or Hcrt signaling, respectively. Thus, while acute pharmacological manipulation of histamine signaling has been shown to have profound effects on zebrafish and mammalian sleep, our results suggest that chronic loss of histamine signaling due to genetic mutations has only subtle effects on sleep in zebrafish, similar to rodents.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Chen, Audrey0000-0003-2139-9535
Singh, Chanpreet0000-0002-2697-3033
Oikonomou, Grigorios0000-0001-6797-7375
Prober, David A.0000-0002-7371-4675
Additional Information:Copyright © 2017 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. Received September 22, 2016; accepted February 9, 2017; First published February 15, 2017. This work was supported by National Institutes of Health Grants NS060996, NS070911, DA031367, and NS094390; the Mallinckrodt Foundation; the Rita Allen Foundation; and the Brain and Behavior Research Foundation. Author contributions: A.C., C.S., and D.A.P. designed research; A.C., C.S., and D.A.P. performed research; A.C., C.S., and G.O. analyzed data; A.C. and D.A.P. wrote the paper. The authors declare no competing financial interests.
Funding AgencyGrant Number
Edward Mallinckrodt, Jr. FoundationUNSPECIFIED
Rita Allen FoundationUNSPECIFIED
Brain and Behavior Research FoundationUNSPECIFIED
Subject Keywords:genetics; histamine; hypocretin; sleep; wake
Issue or Number:1
PubMed Central ID:PMC5334454
Record Number:CaltechAUTHORS:20170313-124518512
Persistent URL:
Official Citation:Genetic Analysis of Histamine Signaling in Larval Zebrafish Sleep Audrey Chen, Chanpreet Singh, Grigorios Oikonomou, David A. Prober eNeuro Feb 2017, 4 (1) ENEURO.0286-16.2017; DOI: 10.1523/ENEURO.0286-16.2017
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:75059
Deposited By: Tony Diaz
Deposited On:13 Mar 2017 20:27
Last Modified:29 Mar 2022 16:24

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