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

eLife

Delphine Gobert¹  Yves De Koninck²  Edward S Ruthazer³  Anne Schohl⁴  Paul W Wiseman⁵  Nicholas Marsh-Armstrong⁵  Jean-François Desjardins⁶  Perry Spratt⁶  Jennifer Tsui⁶  Mari Sild⁶  Annie Castonguay⁶  Loïs S Miraucourt⁶ 

[1] Department of Biology, University of La Verne, La Verne, United States;Neuroscience Graduate Program, University of California, San Francisco, San Francisco, United States;Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States;Department of Physics, McGill University, Montreal, Canada;Institut Universitaire en santé mentale de Québec, Université Laval, Québec, Canada;Montreal Neurological Institute, McGill University, Montreal, Canada;

关键词: visual system;    chloride;    endocannabinoid;    CB1 Receptor;    NKCC1;    retina;   

DOI  :  10.7554/eLife.15932

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown