Montreal Neurological Institute, McGill University, Montreal, Canada
Jennifer Tsui
Montreal Neurological Institute, McGill University, Montreal, Canada; Department of Biology, University of La Verne, La Verne, United States
Delphine Gobert
Montreal Neurological Institute, McGill University, Montreal, Canada
Jean-François Desjardins
Department of Physics, McGill University, Montreal, Canada
Anne Schohl
Montreal Neurological Institute, McGill University, Montreal, Canada
Mari Sild
Montreal Neurological Institute, McGill University, Montreal, Canada
Perry Spratt
Montreal Neurological Institute, McGill University, Montreal, Canada; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, United States
Annie Castonguay
Institut Universitaire en santé mentale de Québec, Université Laval, Québec, Canada
Yves De Koninck
Institut Universitaire en santé mentale de Québec, Université Laval, Québec, Canada
Nicholas Marsh-Armstrong
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States; Kennedy Krieger Institute, Baltimore, United States
Paul W Wiseman
Department of Physics, McGill University, Montreal, Canada
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.
