1. Evolutionary Biology
  2. Neuroscience
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CNGA3 acts as a cold sensor in hypothalamic neurons

  1. Viktor V Feketa
  2. Yury A Nikolaev
  3. Dana K Merriman
  4. Sviatoslav N Bagriantsev  Is a corresponding author
  5. Elena O Gracheva  Is a corresponding author
  1. Yale University School of Medicine, United States
  2. University of Wisconsin-Oshkosh, United States
Research Article
  • Cited 4
  • Views 1,730
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Cite this article as: eLife 2020;9:e55370 doi: 10.7554/eLife.55370

Abstract

Most mammals maintain their body temperature around 37°C, whereas in hibernators it can approach 0°C without triggering a thermogenic response. The remarkable plasticity of the thermoregulatory system allowed mammals to thrive in variable environmental conditions and occupy a wide range of geographical habitats, but the molecular basis of thermoregulation remains poorly understood. Here we leverage the thermoregulatory differences between mice and hibernating thirteen-lined ground squirrels (Ictidomys tridecemlineatus) to investigate the mechanism of cold sensitivity in the preoptic area (POA) of the hypothalamus, a critical thermoregulatory region. We report that, in comparison to squirrels, mice have a larger proportion of cold-sensitive neurons in the POA. We further show that mouse cold-sensitive neurons express the cyclic nucleotide-gated ion channel CNGA3, and that mouse, but not squirrel, CNGA3 is potentiated by cold. Our data reveal CNGA3 as a hypothalamic cold sensor and a molecular marker to interrogate the neuronal circuitry underlying thermoregulation.

Data availability

The RNA sequencing data was deposited to the Gene Expression Omnibus, accession number: GSE136396. The nucleotide and protein sequences of the cloned mouse and ground squirrel CNGA3 orthologues were deposited to GenBank under the accession numbers: MN381859 (mouse Cnga3), MN381860 (ground squirrel Cnga3).

The following data sets were generated

Article and author information

Author details

  1. Viktor V Feketa

    Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4978-0581
  2. Yury A Nikolaev

    Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Dana K Merriman

    Department of Biology, University of Wisconsin-Oshkosh, Oshkosh, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Sviatoslav N Bagriantsev

    Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, United States
    For correspondence
    slav.bagriantsev@yale.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6661-3403
  5. Elena O Gracheva

    Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, United States
    For correspondence
    elena.gracheva@yale.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0846-3427

Funding

James Hudson Brown - Alexander B Coxe (Postdoctoral fellowship)

  • Viktor V Feketa

National Science Foundation (1754286)

  • Elena O Gracheva

National Institute of Neurological Disorders and Stroke (1R01NS091300-01A1)

  • Elena O Gracheva

National Science Foundation (1923127)

  • Sviatoslav N Bagriantsev

National Institute of Neurological Disorders and Stroke (1R01NS097547-01A1)

  • Sviatoslav N Bagriantsev

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal procedures were performed in compliance with the Office of Animal Research Support of Yale University (protocols 2018-11497 and 2018-11526). Thirteen-lined ground squirrels (Ictidomys tridecemlineatus), wild-type mice (Mus musculus), and frogs (Xenopus laevis) were used for this study. Wild-type C57Bl/6J mice were purchased from Jackson Laboratory (Bar Harbor, ME). All animals were housed on a 12-h light/dark cycle (lights on at 0700) under standard laboratory conditions with ad libitum access to food and water. Both male and female mice 6-16 weeks of age weighing 17-34 g and male thirteen-lined ground squirrels 6 months-3 years of age weighing approximately 150-300 g were used for experiments. All ground squirrels were in their active (non-hibernating) state verified by daily body temperature measurements and maintained on a diet of dog food (Iams) supplemented with sunflower seeds, superworms, and fresh vegetables. Frogs were housed using standard conditions.

Reviewing Editor

  1. Polina V Lishko, University of California, Berkeley, United States

Publication history

  1. Received: January 22, 2020
  2. Accepted: April 8, 2020
  3. Accepted Manuscript published: April 9, 2020 (version 1)
  4. Version of Record published: April 24, 2020 (version 2)

Copyright

© 2020, Feketa 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.

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