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

描述(申请人提供)：光线对许多非成像视觉功能(NIF)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，光通过三种光感受器类型影响这些NIF，即经典的光感受器、视杆细胞和视锥细胞，以及表达光色素黑素的固有光敏性视网膜神经节细胞(IpRGCs)。作为神经节细胞，ipRGC传递它们自身固有的光信号，也是将视杆/视锥信息传递给对这些NIF重要的脑区的唯一通道。然而，视杆细胞、视锥细胞和ipRGC相互作用的功能电路还知之甚少。新的证据表明，ipRGC比以前认识的要复杂得多，由多种形态和电生理上不同的亚型组成。这些不同的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如何相互作用来驱动非成像视觉功能(Aim I)，并研究不同的ipRGC亚型(Aim II和III)的连接性和功能。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，因为光和生物钟在时间上调节着许多影响人类睡眠、抑郁和总体健康的生理参数。 与公共健康相关：在哺乳动物中，昼夜光携带作用负责使许多生理节律与太阳日同步。在倒班工作或时差中可能会发生的常规24小时光/暗周期的中断，会导致人体内部生物钟与太阳日的不同步。这种不同步对人类健康有害，不仅会导致睡眠障碍，而且还与从抑郁症到乳腺癌等许多疾病有关。

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. PUBLIC HEALTH RELEVANCE: In mammals, circadian photoentrainment is responsible for synchronizing many physiological rhythms to the solar day. Disruption of the regular 24-hour light/dark cycle, which can occur in shift work or jet-lag, leads to de-synchronization of the body's internal circadian clock from the solar day. Such de-synchrony is detrimental to human health not only causing sleep disorders, but is has also been implicated in many diseases ranging from depression to breast cancer.