title: Endocannabinoid signaling enhances visual responses through modulation of intracellular chloride levels in retinal ganglion cells.
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.
authors: Montreal Neurological Institute, McGill University, Montreal, Canada.
authors: Loïs S
authors: 0000-0003-4812-6342
authors: LS
authors: Miraucourt
authors: Montreal Neurological Institute, McGill University, Montreal, Canada.|Department of Biology, University of La Verne, La Verne, United States.
authors: Jennifer
authors: J
authors: Tsui
authors: Montreal Neurological Institute, McGill University, Montreal, Canada.
authors: Delphine
authors: D
authors: Gobert
authors: Department of Physics, McGill University, Montreal, Canada.
authors: Jean-François
authors: JF
authors: Desjardins
authors: Montreal Neurological Institute, McGill University, Montreal, Canada.
authors: Anne
authors: A
authors: Schohl
authors: Montreal Neurological Institute, McGill University, Montreal, Canada.
authors: Mari
authors: M
authors: Sild
authors: Montreal Neurological Institute, McGill University, Montreal, Canada.|Neuroscience Graduate Program, University of California, San Francisco, San Francisco, United States.
authors: Perry
authors: P
authors: Spratt
authors: Institut Universitaire en santé mentale de Québec, Université Laval, Québec, Canada.
authors: Annie
authors: A
authors: Castonguay
authors: Institut Universitaire en santé mentale de Québec, Université Laval, Québec, Canada.
authors: Yves
authors: Y
authors: De Koninck
authors: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States.|Kennedy Krieger Institute, Baltimore, United States.
authors: Nicholas
authors: N
authors: Marsh-Armstrong
authors: Department of Physics, McGill University, Montreal, Canada.
authors: Paul W
authors: PW
authors: Wiseman
authors: Montreal Neurological Institute, McGill University, Montreal, Canada.
authors: Edward S
authors: 0000-0003-0452-3151
authors: ES
authors: Ruthazer
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002712:Chlorides / Q000378:metabolism; D015350:Contrast Sensitivity / Q000502:physiology*; D063388:Endocannabinoids / Q000378:metabolism*; D005786:Gene Expression Regulation; D017136:Ion Transport; D007814:Larva / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D057054:Molecular Imaging; D018408:Patch-Clamp Techniques; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction; D064506:Solute Carrier Family 12, Member 2 / Q000235:genetics / Q000378:metabolism*; D014785:Vision, Ocular / Q000502:physiology; D014982:Xenopus laevis / Q000502:physiology
chemical_list: D002712:Chlorides; D063388:Endocannabinoids; D043884:Receptor, Cannabinoid, CB1; D011993:Recombinant Fusion Proteins; D064506:Solute Carrier Family 12, Member 2; C415371:clomeleon; D055372:AMP-Activated Protein Kinases
keywords: CB1 Receptor; NKCC1; chloride; endocannabinoid; neuroscience; retina; visual system; xenopus