Ribelayga Christophe, Wang Yu, Mangel Stuart C
Department of Neurobiology, University of Alabama School of Medicine, Birmingham, 35294, USA.
J Physiol. 2002 Nov 1;544(3):801-16. doi: 10.1113/jphysiol.2002.023671.
A circadian (24-hour) clock regulates the light responses of fish cone horizontal cells, second order neurones in the retina that receive synaptic contact from cones and not from rods. Due to the action of the clock, cone horizontal cells are driven by cones in the day, but primarily driven by rods at night. We show here that dopamine, a retinal neurotransmitter, acts as a clock signal for the day by increasing cone input and decreasing rod input to cone horizontal cells. The amount of endogenous dopamine released from in vitro retinae was greater during the subjective day than the subjective night. Application of dopamine or quinpirole, a dopamine D(2)-like agonist, during the subjective night increased cone input and eliminated rod input to the cells, a state usually observed during the subjective day. In contrast, application of spiperone, a D(2)-like antagonist, or forskolin, an activator of adenylyl cyclase, during the subjective day reduced cone input and increased rod input. SCH23390, a D(1) antagonist, had no effect. Application of R(p)-cAMPS, an inhibitor of cAMP-dependent protein kinase, or octanol, an alcohol that uncouples gap junctions, during the night increased cone input and decreased rod input. Because D(2)-like receptors are on photoreceptor cells, but not horizontal cells, the results suggest that the clock-induced increase in dopamine release during the day activates D(2)-like receptors on photoreceptor cells. The resultant decrease in intracellular cyclic AMP and protein kinase A activation then mediates the increase in cone input and decrease in rod input.
昼夜节律（24小时）时钟调节鱼类视锥水平细胞的光反应，视锥水平细胞是视网膜中的二级神经元，接受来自视锥而非视杆的突触联系。由于时钟的作用，视锥水平细胞在白天由视锥驱动，但在夜间主要由视杆驱动。我们在此表明，多巴胺（一种视网膜神经递质）通过增加对视锥水平细胞的视锥输入并减少视杆输入，充当白天的时钟信号。体外视网膜释放的内源性多巴胺量在主观白天比主观夜间更多。在主观夜间应用多巴胺或喹吡罗（一种多巴胺D(2)样激动剂）可增加视锥输入并消除对这些细胞的视杆输入，这是通常在主观白天观察到的状态。相反，在主观白天应用螺哌隆（一种D(2)样拮抗剂）或福斯高林（一种腺苷酸环化酶激活剂）会减少视锥输入并增加视杆输入。D(1)拮抗剂SCH23390没有效果。在夜间应用R(p)-cAMPS（一种依赖cAMP的蛋白激酶抑制剂）或辛醇（一种使缝隙连接解偶联的醇）会增加视锥输入并减少视杆输入。由于D(2)样受体存在于光感受器细胞而非水平细胞上，结果表明白天时钟诱导的多巴胺释放增加激活了光感受器细胞上的D(2)样受体。细胞内环状AMP和蛋白激酶A激活的随之减少进而介导了视锥输入的增加和视杆输入的减少。
