Affiliated with Université Laval & CERVO Research Centre

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

TitleEndocannabinoid signaling enhances visual responses through modulation of intracellular chloride levels in retinal ganglion cells.
Publication TypeJournal Article
Year of Publication2016
AuthorsMiraucourt LS, Tsui J, Gobert D, Desjardins J-F, Schohl A, Sild M, Spratt P, Castonguay A, De Koninck Y, Marsh-Armstrong N, Wiseman PW, Ruthazer ES
JournalElife
Volume5
Date Published2016 08 08
ISSN2050-084X
KeywordsAMP-Activated Protein Kinases, Animals, Chlorides, Contrast Sensitivity, Endocannabinoids, Gene Expression Regulation, Ion Transport, Larva, Membrane Potentials, Molecular Imaging, Patch-Clamp Techniques, Receptor, Cannabinoid, CB1, Recombinant Fusion Proteins, Retinal Ganglion Cells, Signal Transduction, Solute Carrier Family 12, Member 2, Vision, Ocular, Xenopus laevis
Abstract

<p>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.</p>

DOI10.7554/eLife.15932
Alternate JournalElife
PubMed ID27501334
PubMed Central IDPMC4987138