The role of dopamine and other neuromodulators as light signals in the inner retina: a link to night blindness disorders

尽管由于使用了人造光，大多数人类活动在夜间可以像白天一样高效地进行，但夜视基础电路的正常功能是至关重要的。例如，当在夜间行驶在照明不佳的道路上时，前照灯照射的区域由视锥电路处理，该电路在视网膜中提供日光，而外围区域则由杆状驱动的夜间电路处理。夜间视力和暗光开关的损害可能会产生致命的后果。夜盲是一种症状，其特征是在黑暗中视力下降，对昏暗的光线适应缓慢。一些先天性夜盲症是由介导信号传递的光感受器钙通道突变引起的。此外，接受抗精神病药物(一组影响多巴胺系统的药物)治疗的患者会出现夜视障碍。多巴胺在视网膜中充当光信号。所有的无长突细胞都是夜视的关键神经元，将传递视觉信息的两个通道(开和关)分开。所有的细胞都受多巴胺的调节，因此是研究多巴胺在暗-光开关中作用的有趣靶点。关于多巴胺在AII细胞传导ON信号中的作用，人们已经知道很多。然而，它在非频道上的行动在很大程度上是未知的。我们认为，一些夜视障碍源于视网膜中多巴胺能系统的失衡及其对AII细胞的影响。我们将通过研究多巴胺对非通道中AII细胞及其伙伴之间钙依赖信号传递的调制作用来验证我们的假设。我们的假设将通过改变多巴胺受体功能的动物模型进一步验证。这些研究的结果将为我们提供一个宝贵的模型来理解暗光开关的生理基础以及多巴胺在夜视障碍中的作用。

Although most human activities can be performed at night as efficiently as during daytime due to the use of artificial light, normal function of the circuits underlying night vision is critical. For example, when driving at night in a poorly illuminated road where the region illuminated by the headlights is processed by the cone circuit that serves daylight in the retina whilst the peripheral areas are processed by the rod driven nighttime circuit. Impairment of night vision and of the dark-light switch can have fatal consequences. Night blindness is a symptom characterised by reduced vision in the dark and slow adaptation to dim light. Some congenital night blindness disorders are caused by mutations in the photoreceptor calcium channels which mediate signal transmission. Additionally, patients treated with neuroleptics, a group of drugs which affect the dopaminergic system, suffer night vision disorders. Dopamine acts as a light signal in the retina. AII amacrine cells are pivotal neurones for night vision segregating two channels (ON and OFF) which convey visual information. AII cells are modulated by dopamine and thus, represent interesting targets to study the role of dopamine in the dark-light switch. Much is know about the action of dopamine on transmission of ON signals channelled by AII cells. However, its action on the OFF channel is largely unknown. We believe that some night vision disorders originate by imbalance in the dopaminergic system in the retina and its effects on AII cells. We will test our hypothesis by studying the modulatory effect of dopamine on calcium dependent signal transmission between AII cells and their partners in the OFF channel. Our hypothesis will be further tested by using animal models in which dopamine receptor function is altered. The results of these studies will provide us with an invaluable model to understand the physiological basis of the dark-light switch and of the role of dopamine in night vision disorders.