TY - JOUR TI - Endocannabinoid signaling enhances visual responses through modulation of intracellular chloride levels in retinal ganglion cells AU - Miraucourt, Loïs S AU - Tsui, Jennifer AU - Gobert, Delphine AU - Desjardins, Jean-François AU - Schohl, Anne AU - Sild, Mari AU - Spratt, Perry AU - Castonguay, Annie AU - De Koninck, Yves AU - Marsh-Armstrong, Nicholas AU - Wiseman, Paul W AU - Ruthazer, Edward S A2 - Westbrook, Gary L VL - 5 PY - 2016 DA - 2016/08/08 SP - e15932 C1 - eLife 2016;5:e15932 DO - 10.7554/eLife.15932 UR - https://doi.org/10.7554/eLife.15932 AB - 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. KW - visual system KW - chloride KW - endocannabinoid KW - CB1 Receptor KW - NKCC1 KW - retina JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -