A novel class of photoreceptors, the intrinsically photosensitive retinal ganglion cells (ipRGCs), express the photopigment melanopsin and drive non-image-forming responses to light such as circadian photoentrainment, the pupillary light reflex and suppression of nocturnal melatonin production in the pineal. Because dendrites from one subclass of these cells - the M1-type ipRGCs - make presumptive synaptic contacts at sites of dopamine release from dopaminergic amacrine cells, they are prime targets for modulation by dopamine, a neuromodulator implicated in retinal circadian rhythms and light adaptation. In patch-clamp recordings from ipRGCs in intact rat retinas, dopamine attenuated the melanopsin-based photocurrent. We confirmed that this was the result of direct action on ipRGCs by replicating the effect in dissociated ipRGCs that were isolated from influences of other retinal neurons. In these recordings, the D1-family dopamine receptor agonist SKF38393 attenuated the photocurrent, caused a modest depolarization, and reduced the input resistance of ipRGCs. The D2-family agonist quinpirole had no effect on the photocurrent. Single-cell reverse-transcriptase polymerase chain reaction revealed that the majority of ipRGCs tested expressed drd1a, the gene coding for the D1a dopamine receptor. This finding was supported by immunohistochemical localization of D1a receptor protein in melanopsin-expressing ganglion cells. Finally, the adenylate cyclase activator forskolin, applied in combination with the phosphodiesterase inhibitor IBMX (isobutylmethylxanthine), mimicked the effects of SKF38393 on the ipRGC photocurrent, membrane potential and input resistance, consistent with a D1-receptor signaling pathway. These data suggest that dopamine, acting via D1-family receptors, alters the responses of ipRGCs and thus of non-image-forming vision.
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机译：一类新型的光感受器，即内在光敏的视网膜神经节细胞（ipRGC），表达光色素黑素并驱动对光的非成像反应，例如昼夜节律性光夹带，瞳孔光反射以及抑制松果体夜间褪黑素的产生。由于这些细胞的一个亚类-M1型ipRGCs-的树突状细胞在多巴胺能的无长突细胞释放的多巴胺的位点进行推测的突触接触，因此它们是多巴胺（涉及视网膜昼夜节律和光适应性的神经调节剂）调节的主要靶点。在完整大鼠视网膜中ipRGC的膜片钳记录中，多巴胺减弱了基于黑素的光电流。我们证实这是对ipRGCs直接作用的结果，方法是复制与其他视网膜神经元的影响分离的解离ipRGCs的作用。在这些唱片中，D1族多巴胺受体激动剂SKF38393减弱了光电流，引起了适度的去极化，并降低了ipRGC的输入电阻。 D 2族激动剂喹吡罗对光电流没有影响。单细胞逆转录酶聚合酶链反应显示，测试的大多数ipRGCs表达drd1a，即编码D1a多巴胺受体的基因。 D1a受体蛋白在表达黑视蛋白的神经节细胞中的免疫组织化学定位支持了这一发现。最后，与磷酸二酯酶抑制剂IBMX（异丁基甲基黄嘌呤）组合使用的腺苷酸环化酶激活剂福司柯林模仿了SKF38393对ipRGC光电流，膜电位和输入电阻的影响，与D1受体信号通路一致。这些数据表明，通过D1家族受体起作用的多巴胺会改变ipRGC的反应，从而改变非成像视觉。
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