Abstract
KEY POINTS: Although cone and rod photoreceptor cells in the retina have a type of cannabinoid receptor called a CB1 receptor, little is known about how cannabinoids, the active component in marijuana, affect retinal function. Studies have shown that a circadian (24-h) clock in the retina uses dopamine receptors, which are also on photoreceptors, to regulate gap junctions (a type of cell-to-cell communication) between rods and cones, so that they are functional (open) at night but closed in the day. We show that CB(1) receptors have opposite effects on rod-cone gap junctions in day and night, decreasing communication in the day when dopamine receptors are active and increasing communication when dopamine receptors are inactive. CB(1) and dopamine receptors thus work together to enhance the day/night difference in rod-cone gap junction communication. The increased rod-cone communication at night due to cannabinoid CB(1) receptors may help improve night vision. ABSTRACT: Cannabinoid CB(1) receptors and dopamine D(4) receptors in the brain form receptor complexes that interact but the physiological function of these interactions in intact tissue remains unclear. In vertebrate retina, rods and cones, which are connected by gap junctions, express both CB(1) and D(4) receptors. Because the retinal circadian clock uses cone D(4) receptors to decrease rod-cone gap junction coupling in the day and to increase it at night, we studied whether an interaction between cone CB(1) and D(4) receptors increases the day/night difference in rod-cone coupling compared to D(4) receptors acting alone. Using electrical recording and injections of Neurobiotin tracer into individual cones in intact goldfish retinas, we found that SR141716A (a CB(1) receptor antagonist) application alone in the day increased both the extent of rod-cone tracer coupling and rod input to cones, which reaches cones via open gap junctions. Conversely, SR141716A application alone at night or SR141716A application in the day following 30-min spiperone (a D(4) receptor antagonist) application decreased both rod-cone tracer coupling and rod input to cones. These results show that endogenous activation of cone CB(1) receptors decreases rod-cone coupling in the day when D(4) receptors are activated but increases it at night when D(4) receptors are not activated. Therefore, the D(4) receptor-dependent day/night switch in the effects of CB(1) receptor activation results in an enhancement of the day/night difference in rod-cone coupling. This synergistic interaction increases detection of very dim large objects at night and fine spatial details in the day.