Biology of Photosensitive Ganglion Cells

光敏神经节细胞的生物学

• 批准号: 7021536
• 负责人: David M. Berson
• 金额: $ 28.85万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7021536
• 关键词: bioperiodicity; cell cell interaction; cell population study; central neural pathway /tract; circadian rhythms; dark adaptation; electrophysiology; laboratory rat; light adaptations; photostimulus; retinal ganglion; suprachiasmatic nucleus; visual photosensitivity; visual phototransduction; visual pigments

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：我们已经确定了一种新型的哺乳动物视网膜的光感受器，这是一种罕见的视网膜神经节细胞（RGC），它直接支配了下丘脑的昼夜小动物。这些本质上具有光敏的RGC（IPRGC）即使从其他视网膜神经元中分离出突触时也会响应光。它们包含新型的Opsin Phopogment Melanopsin。与棒和锥相比，它们表现出较低的灵敏度和更慢的动力学。他们非常强调的光响应编码环境光水平。除了它们在昼夜节同步中的关键作用外，这些细胞还形成了一个专门的视网膜输出渠道，该通道信号集成了视网膜辐照度，并驱动了各种“非图像形成”的视觉反射，例如瞳孔光反射，生理学中的季节性适应，生理抑制，对夜间情蛋白释放的光学抑制作用，并释放了睡眠和调制的，以及调节的活动，活动，活动和活动。我们提出了首次直接研究IPRGC（例如杆和锥体）是否表现出光和深色适应性，并根据当前或最近的光线暴露调整其灵敏度。这种适应大大扩展了杆和锥体的动态范围，因此它们涵盖了整个生理光水平。在某些“非图像形成”的视觉反应中，适应似乎很弱或不存在。尽管这可能表明IPRGC缺乏适应性，但一些行为证据和我们的初步电生理数据表明IPRGC确实在某些条件下进行了适应。表征这些细胞中的适应性是促进我们对昼夜节律光感受和其他非图像形成的光学系统的了解的关键步骤。在操纵先前的光线暴露后，我们将对IPRGC对光的反应进行细胞内记录。我们将评估任何适应的幅度，时间过程和光谱依赖性。我们还将确定它们是否发生在感光器本身中，改变光转导级联的增益，或者它们是否需要与其他视网膜细胞相互作用。研究还将确定IPRGC敏感性是否受到昼夜节律的控制。这些发现将提高我们对哺乳动物视网膜中新型光感系统功能组织的理解，该系统在昼夜节律时机和其他与环境照明和太阳周期有关的稳态功能中有明确的角色。