1. Neuroscience
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Endocannabinoid signaling enhances visual responses through modulation of intracellular chloride levels in retinal ganglion cells

  1. Loïs S Miraucourt
  2. Jennifer Tsui
  3. Delphine Gobert
  4. Jean-François Desjardins
  5. Anne Schohl
  6. Mari Sild
  7. Perry Spratt
  8. Annie Castonguay
  9. Yves De Koninck
  10. Nicholas Marsh-Armstrong
  11. Paul W Wiseman
  12. Edward S Ruthazer  Is a corresponding author
  1. McGill University, Canada
  2. Institut universitaire en santé mentale de Québec, Canada
  3. Johns Hopkins University School of Medicine, United States
  4. University of La Verne, United States
Research Article
  • Cited 8
  • Views 6,168
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Cite this article as: eLife 2016;5:e15932 doi: 10.7554/eLife.15932

Abstract

Type 1 cannabinoid receptors (CB1Rs) are widely expressed in the vertebrate retina but the role of endocannabinoids in vision is not fully understood. Here we identified a novel mechanism underlying a CB1R-mediated increase in retinal ganglion cell (RGC) intrinsic excitability acting through AMPK-dependent inhibition of NKCC1 activity. Clomeleon imaging and patch clamp recordings revealed that inhibition of NKCC1 downstream of CB1R activation reduces intracellular Cl- levels in RGCs, hyperpolarizing the resting membrane potential. We confirmed that such hyperpolarization enhances RGC action potential firing in response to subsequent depolarization, consistent with the increased intrinsic excitability of RGCs observed with CB1R activation. Using a dot avoidance assay in freely swimming Xenopus tadpoles we demonstrate that CB1R activation markedly improves visual contrast sensitivity under low light conditions. These results highlight a role for endocannabinoids in vision, and present a novel mechanism for cannabinoid modulation of neuronal activity through Cl- regulation.

Article and author information

Author details

  1. Loïs S Miraucourt

    Montreal Neurological Institute, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4812-6342
  2. Jennifer Tsui

    Montreal Neurological Institute, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Delphine Gobert

    Montreal Neurological Institute, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Jean-François Desjardins

    Department of Physics, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Anne Schohl

    Montreal Neurological Institute, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Mari Sild

    Montreal Neurological Institute, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Perry Spratt

    Montreal Neurological Institute, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  8. Annie Castonguay

    Institut universitaire en santé mentale de Québec, Québec, Canada
    Competing interests
    The authors declare that no competing interests exist.
  9. Yves De Koninck

    Institut universitaire en santé mentale de Québec, Québec, Canada
    Competing interests
    The authors declare that no competing interests exist.
  10. Nicholas Marsh-Armstrong

    Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Paul W Wiseman

    Department of Biology, University of La Verne, La Verne, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Edward S Ruthazer

    Montreal Neurological Institute, McGill University, Montreal, Canada
    For correspondence
    edward.ruthazer@mcgill.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0452-3151

Funding

Fonds de Recherche du Québec - Santé (research chair, postdoctoral fellowship)

  • Jennifer Tsui
  • Delphine Gobert
  • Edward S Ruthazer

Canadian Institutes of Health Research (operating grants)

  • Edward S Ruthazer

Epilepsie Canada (postdoctoral award)

  • Loïs S Miraucourt

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 Canadian Council on Animal Care. All animals were handled according to animal care committee protocols (#5071) approved by the Animal Care Committees of the Montreal Neurological Institute and McGill University.

Reviewing Editor

  1. Gary L Westbrook, Vollum Institute, United States

Publication history

  1. Received: March 10, 2016
  2. Accepted: August 4, 2016
  3. Accepted Manuscript published: August 8, 2016 (version 1)
  4. Version of Record published: August 16, 2016 (version 2)

Copyright

© 2016, Miraucourt 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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