Biophysical mechanisms of single photon detection

描述（由申请人提供）：暗适应视觉系统检测几个光子吸收的能力已经知道很多年了。然而，使光子探测成为可能的生物物理机制尚不清楚。大部分视杆视觉发生在光子反射很少发生的光水平下;因此，无法捕获单个光子或通过视网膜传输所产生的信号严重损害视杆视觉。对绝对视觉灵敏度的研究使视杆细胞光转导成为生物系统中许多G蛋白级联反应中最好的理解，并导致对几种形式的静止性夜盲症的机械理解。这项工作的长期目标是使视网膜对视杆细胞信号的处理以及这种处理如何失败的理解变得更加清晰。 光转导的研究将调查的机制，使杆光感受器产生一个几乎相同的反应，每一个吸收的光子。拟议的实验将测试这样的假设：再现性是由单个视紫红质分子通过一系列步骤或转变的关闭介导的。这是对单分子关闭的常规模型的实质性偏离。视紫红质是许多G蛋白偶联受体之一;因此类似的策略可能会降低由其他G蛋白级联反应控制的信号的可变性。 如果这些反应不能可靠地通过视网膜传输，那么由视杆细胞产生的信号的保真度将被浪费。杆对杆双极突触起着特别重要的作用，因为它是处理来自单个杆的信号的最后机会。这项工作将确定有多少噪音存在于视杆双极细胞的反应中，这种噪音的来源，以及对视觉灵敏度的影响。 单光子检测所需的放大存在随着光水平增加而使视网膜信号饱和的风险。这种饱和是由视网膜回路内的适应机制所阻止的。拟议的工作将确定在哪里以及如何适应控制杆信号在低背景光水平的增益。这项工作将把视网膜机制与视觉敏感度如何随背景光变化的经典行为测量联系起来。

DESCRIPTION (provided by applicant): The ability of the dark-adapted visual system to detect absorption of a few photons has been known for many years. However, the biophysical mechanisms that make photon detection possible are not understood. Much of rod vision occurs at light levels where photon absorptions occur rarely; thus, failure to transduce single photons or transmit the resulting signals through the retina severely impairs rod vision. Studies of absolute visual sensitivity have made rod phototransduction the best understood of the many G-protein cascades in biological systems and led to a mechanistic understanding of several forms of stationary night blindness. The long-term goal of the proposed work is to bring a similar clarity to understanding of the retinal processing of rod signals and how this processing can fail. Studies of phototransduction will investigate the mechanisms that permit rod photoreceptors to produce a near-identical response to each absorbed photon. The proposed experiments will test the hypothesis that reproducibility is mediated by the shutoff of a single rhodopsin molecule through a series of steps or transitions. This is a substantial departure from conventional models for the shutoff of single molecules. Rhodopsin is one of many G-protein-coupled receptors; thus a similar strategy may decrease variability in signals controlled by other G-protein cascades. The fidelity of signals produced by the rod photoreceptors would be wasted if these responses were not reliably transmitted across the retina. The rod-to-rod bipolar synapse plays a particularly important role as it is the last opportunity to process signals from single rods. The proposed work will determine how much noise is present in the responses of rod bipolar cells, the origins of this noise, and the impact on visual sensitivity. The amplification required for single photon detection presents a risk of saturating retinal signals as light levels increase. Such saturation is prevented by poorly understood adaptational mechanisms working within the retinal circuitry. The proposed work will determine where and how adaptation controls the gain of rod signals at low background light levels. This work will link retinal mechanisms with classic behavioral measures of how visual sensitivity changes with background light.