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Hypocretin underlies the evolution of sleep loss in the Mexican cavefish

Jaggard, James B. and Stahl, Bethany A. and Lloyd, Evan and Prober, David A. and Duboue, Erik R. and Keene, Alex C. (2018) Hypocretin underlies the evolution of sleep loss in the Mexican cavefish. eLife, 7 . Art. No. 32637. ISSN 2050-084X. PMCID PMC5800846.

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The duration of sleep varies dramatically between species, yet little is known about the genetic basis or evolutionary factors driving this variation in behavior. The Mexican cavefish, Astyanax mexicanus, exists as surface populations that inhabit rivers, and multiple cave populations with convergent evolution on sleep loss. The number of Hypocretin/Orexin (HCRT)-positive hypothalamic neurons is increased significantly in cavefish, and HCRT is upregulated at both the transcript and protein levels. Pharmacological or genetic inhibition of HCRT signaling increases sleep in cavefish, suggesting enhanced HCRT signaling underlies the evolution of sleep loss. Ablation of the lateral line or starvation, manipulations that selectively promote sleep in cavefish, inhibit hcrt expression in cavefish while having little effect on surface fish. These findings provide the first evidence of genetic and neuronal changes that contribute to the evolution of sleep loss, and support a conserved role for HCRT in sleep regulation.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle Paper
Jaggard, James B.0000-0003-4091-9946
Stahl, Bethany A.0000-0001-9218-2996
Prober, David A.0000-0002-7371-4675
Duboue, Erik R.0000-0003-3303-5149
Keene, Alex C.0000-0001-6118-5537
Additional Information:© 2018 Copyright Jaggard et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.eLife Sciences Publications Ltd. Received: 10 October 2017. Accepted: 25 November 2017. Published: 06 February 2018. Reviewing editor: Marianne Bronner, California Institute of Technology, United States This work was funded by National Science Foundation Award IOS-125762 to ACK. The authors are grateful to Masato Yoshizawa (Hawai’i) for technical guidance and the Department of Comparative Medicine at FAU for support maintaining the fish facility. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Author contributions: James B Jaggard, Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Writing—original draft, Writing—review and editing; Bethany A Stahl, Conceptualization, Formal analysis, Investigation, Writing—original draft, Writing—review and editing; Evan Lloyd, Formal anal- ysis, Investigation, Methodology, Writing—original draft, Writing—review and editing; David A Prober, Conceptualization, Resources, Validation, Writing—original draft, Writing—review and edit- ing; Erik R Duboue, Conceptualization, Resources, Software, Formal analysis, Visualization, Method- ology, Writing—original draft, Writing—review and editing; Alex C Keene, Conceptualization, Supervision, Funding acquisition, Visualization, Writing—original draft, Project administration, Writing—review and editing The authors declare that no competing interests exist.
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PubMed Central ID:PMC5800846
Record Number:CaltechAUTHORS:20180212-084202846
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:84781
Deposited By: Ruth Sustaita
Deposited On:13 Feb 2018 18:46
Last Modified:03 Oct 2019 19:22

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