Endocannabinoid signaling enhances visual responses through modulation of intracellular chloride levels in retinal ganglion cells
- McGill University, Canada
- Institut universitaire en santé mentale de Québec, Canada
- Johns Hopkins University School of Medicine, United States
- University of La Verne, United States
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.
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Author details
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.
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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Endocannabinoid signaling enhances visual responses through modulation of intracellular chloride levels in retinal ganglion cells
eLife 5:e15932.
https://doi.org/10.7554/eLife.15932
