Biology of Photosensitive Ganglion Cells

我们已经发现了一种新的哺乳动物视网膜感光细胞，一种罕见的视网膜神经节细胞（RGC）， 直接支配下丘脑的昼夜节律起搏器。这些本征光敏RGC 即使当与其他视网膜神经元突触分离时，ipRGC也对光响应。它们包含 一种新的视蛋白--黑视蛋白。他们表现出较低的灵敏度和更缓慢的动力学比杆 和圆锥体。它们对外界光线的强烈反应会对周围的光线进行编码。除了他们的关键作用， 昼夜节律同步，这些细胞形成一个专门的视网膜输出通道，信号集成视网膜 辐射并驱动各种“非成像”视觉反射如瞳孔光反射， 生理学上的季节性适应，夜间褪黑激素释放的光抑制，以及睡眠的调节， 警觉性和活动性。 我们建议第一次直接调查ipRGC是否像视杆细胞和视锥细胞一样表现出光明和黑暗 适应，根据当前或最近的曝光调整其灵敏度。这种适应性极大 扩展了视杆细胞和视锥细胞的动态范围，使它们共同涵盖了 生理光照水平。在一些“非图像形成”的视觉反应中，适应显得很弱或不存在。 虽然这可能表明ipRGC缺乏适应性，但一些行为证据和我们的初步研究表明， 电生理学数据表明ipRGC在某些条件下确实适应。适应的特点 这些细胞是推进我们对昼夜光感受和其他非生物学现象的理解的关键一步。 成像光学系统。 我们将在操纵先前的光暴露后进行ipRGC对光的响应的细胞内记录。我们 将评估任何适应的幅度、时间进程和光谱依赖性。我们还将确定 这些是否发生在光感受器本身，改变光转导级联的增益，或 它们是否需要与其他视网膜细胞相互作用。这些研究还将确定ipRGC是否 敏感性受昼夜节律控制。这些发现将促进我们对功能性 哺乳动物视网膜中一种新的感光系统的组织，在昼夜节律中具有明确的作用 定时和其他与环境照明和太阳周期相关的稳态功能。

We have identified a novel photoreceptor of the mammalian retina, a rare retinal ganglion cell (RGC) that directly innervates the circadian pacemaker of the hypothalamus. These intrinsically photosensitive RGCs (ipRGCs) respond to light even when synaptically isolated from other retinal neurons. They contain the novel opsin photopigment melanopsin. They exhibit lower sensitivity and more sluggish kinetics than rods and cones. Their remarkably tonic light responses encode ambient light levels. Besides their key role in circadian synchronization, these cells form a specialized retinal output channel that signals integrated retinal irradiance and drives a variety of 'non-image-forming' visual reflexes such as the pupillary light reflex, seasonal adaptations in physiology, photic inhibition of nocturnal melatonin release, and modulation of sleep, alertness and activity. We propose the first direct investigation of whether ipRGCs, like rods and cones, exhibit light and dark adaptation, adjusting their sensitivity according to current or recent light exposure. Such adaptation greatly extends the dynamic range of rods and cones so that together they encompass the full spectrum of physiological light levels. Adaptation appears weak or absent in some 'non-image-forming' visual responses. While this might suggest a lack of adaptation in ipRGCs, some behavioral evidence and our preliminary electrophysiological data suggest that ipRGCs do adapt under some conditions. Characterizing adaptation in these cells is a critical step in advancing our understanding of circadian photoreception and other non- image-forming photic systems. We will make intracellular recordings of ipRGC responses to light after manipulating prior light exposure. We will assess the magnitude, time course and spectral dependency of any adaptation. We will also determine whether these occur within the photoreceptor itself, altering the gain of the phototransduction cascade, or whether they require interactions with other retinal cells. The studies will also determine whether ipRGCs sensitivity is under circadian control. The findings will advance our understanding of the functional organization of a novel photosensory system in the mammalian retina with well-defined roles in circadian timing and other homeostatic functions related to ambient illumination and the solar cycle.