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Jiexin Cao, Masaaki Ishii, Stuart C Mangel; Cannabinoid Receptors Modulate Rod-Cone Gap Junctional Coupling In The Day And Night. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):995.
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Rods and cones express both cannabinoid 1 receptors (CB1Rs) and dopamine D2 receptors (D2Rs) (Yazulla, 2008) and are connected by gap junctions. Studies of goldfish, rabbit and mouse retinas have shown that the circadian clock in the retina lowers dopamine release at night so that D2Rs are not activated, thereby increasing intracellular cAMP, which opens rod-cone gap junctions. Conversely, the clock increases dopamine release and D2R activation in the day, thereby decreasing cAMP, which closes the gap junctions (Ribelayga et al., 2008; Ribelayga, Mangel, 2010). Interestingly, although dopamine release is about 3x greater in the day than at night, the extent of rod-cone coupling is ~600x larger at night than in the day; injecting neurobiotin into a single goldfish cone results in its diffusion into 2 nearby rods in the day, but into 1,200 rods at night. We have therefore begun to study whether 1) CB1Rs modulate rod-cone coupling in the day and night and 2) an interaction between the D2Rs and CB1Rs expressed by cones increases the day/night difference in rod-cone coupling compared to the effect of D2Rs acting alone.
Intact goldfish neural retinas were studied in the dark in the day and night with and without the CB1R antagonist SR141716A. Whole cell recording was used 1) to monitor the responses of cones to dim light (scotopic) stimuli to determine whether cones are receiving rod input and 2) to inject neurobiotin tracer into single cones to determine the extent of rod-cone tracer coupling. Cut-loading was also used to assess the extent of photoreceptor coupling.
Preliminary data show that SR141716A, which blocks endogenous activation of CB1Rs, increased rod input to cones in the day (i.e., cones began to respond to very dim scotopic stimuli) but decreased rod input at night (i.e., cones ceased responding to dim stimuli). In addition, neurobiotin injections into single cones and cut-loading reveal that SR141716A increased rod-cone tracer coupling when it was applied in the day but decreased rod-cone coupling when it was applied at night.
These results suggest that endogenous activation of the CB1Rs decreases rod-cone coupling in the day but increases it at night, a finding that is consistent with the idea that CB1R activation decreases and increases intracellular cAMP in the day and night, respectively, thereby enhancing the day/night difference in rod-cone coupling.
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