Format

Send to

Choose Destination
Elife. 2016 Aug 8;5. pii: e15932. doi: 10.7554/eLife.15932.

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

Author information

1
Montreal Neurological Institute, McGill University, Montreal, Canada.
2
Department of Biology, University of La Verne, La Verne, United States.
3
Department of Physics, McGill University, Montreal, Canada.
4
Neuroscience Graduate Program, University of California, San Francisco, San Francisco, United States.
5
Institut Universitaire en santé mentale de Québec, Université Laval, Québec, Canada.
6
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States.
7
Kennedy Krieger Institute, Baltimore, 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.

KEYWORDS:

CB1 Receptor; NKCC1; chloride; endocannabinoid; neuroscience; retina; visual system; xenopus

PMID:
27501334
PMCID:
PMC4987138
DOI:
10.7554/eLife.15932
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center