Department of Neuroscience, Brown University, Box G-LN, Providence, RI, USA.
Eur J Neurosci. 2012 Feb;35(4):507-18. doi: 10.1111/j.1460-9568.2011.07975.x. Epub 2012 Feb 5.
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.
一类新型的光感受器，即内在光敏视网膜神经节细胞(ipRGCs)，表达光色素黑视蛋白，并对光产生非成像反应，如昼夜节律的光适应、瞳孔对光反射和抑制松果体夜间褪黑素的产生。由于这些细胞的一个子类——M1 型 ipRGCs——的树突与多巴胺能无长突细胞释放的多巴胺形成假定的突触接触，因此它们是多巴胺调节的主要靶点，多巴胺是一种参与视网膜昼夜节律和光适应的神经调质。在完整大鼠视网膜的 ipRGC 膜片钳记录中，多巴胺减弱了黑视蛋白基光电流。我们通过在分离的 ipRGCs 中复制这种作用证实了这是多巴胺对 ipRGCs 的直接作用，这些分离的 ipRGCs 不受其他视网膜神经元的影响。在这些记录中，D1 家族多巴胺受体激动剂 SKF38393 减弱了光电流，引起适度的去极化，并降低了 ipRGCs 的输入电阻。D2 家族激动剂 quinpirole 对光电流没有影响。单细胞逆转录聚合酶链反应显示，大多数测试的 ipRGCs 表达 drd1a，即编码 D1a 多巴胺受体的基因。这一发现得到了在表达黑视蛋白的神经节细胞中免疫组织化学定位 D1a 受体蛋白的支持。最后，腺苷酸环化酶激活剂 forskolin 与磷酸二酯酶抑制剂 IBMX（异丁基甲基黄嘌呤）联合应用，模拟了 SKF38393 对 ipRGC 光电流、膜电位和输入电阻的影响，这与 D1 受体信号通路一致。这些数据表明，多巴胺通过 D1 家族受体作用，改变了 ipRGCs 的反应，从而改变了非成像视觉。
