Role of mammalian retinal photoreceptors in non-image-forming visual functions

描述（由申请人提供）：光对许多非成像视觉功能（NIFs）有深远的影响，包括昼夜节律、睡眠、抑郁和瞳孔光反射。在哺乳动物中，光通过三种类型的光感受器影响这些nif，即经典光感受器、视杆细胞和视锥细胞，以及表达光色素黑视素的内在光敏视网膜神经节细胞（ipRGCs）。作为神经节细胞，ipRGCs传递自身固有的光信号，并作为唯一的通道将杆状/锥体信息信号传递到对这些NIFs重要的大脑区域。然而，视杆细胞、视锥细胞和iprgc相互作用的功能回路却知之甚少。新出现的证据表明，iprgc比以前认为的要复杂得多，由多种形态和电生理上不同的亚型组成。这些不同ipRGC亚型的功能意义尚不清楚。我们提出了实验来确定视杆细胞、视锥细胞和ipRGC如何相互作用以驱动非图像形成的视觉功能（Aim I），并研究不同ipRGC亚型（Aim II和III）的连通性和功能。这些研究将有助于更好地理解光对行为影响的回路和生理结果。这是最重要的，因为光和生物钟暂时调节许多影响睡眠、抑郁和人类整体健康的生理参数。

DESCRIPTION (provided by applicant): Light has profound influences on many non-image forming visual functions (NIFs) including circadian rhythms, sleep, depression and pupillary light reflex. In mammals, light influences these NIFs through three photoreceptor types, namely the classical photoreceptors, rods and cones, and the intrinsically photosensitive retinal ganglion cells (ipRGCs), which express the photopigment melanopsin. As ganglion cells, ipRGCs transmit their own intrinsic light signals and also serve as the sole conduit to signal rod/cone information to brain regions important for these NIFs. However, the functional circuitry by which rods, cones and ipRGCs interact is poorly understood. Emerging evidence suggests that ipRGCs are much more complex than previously appreciated, consisting of multiple morphologically and electrophysiologically distinct subtypes. The functional significance of these different ipRGC subtypes remains unknown. We propose experiments to determine how rods, cones and ipRGCs interact to drive non-image-forming visual functions (Aim I), and to investigate the connectivity and function of the distinct ipRGC subtypes (Aim II and III). These studies will allow better understanding of the circuitry and physiological outcome of light effects on behaviors. This is of prime importance because light and the circadian clock temporally regulate many physiological parameters that influence sleep, depression, and general health in humans.