Biophysical mechanisms of single photon detection

描述(申请人提供)：多年来，暗适应视觉系统检测少数光子吸收的能力已为人所知。然而，使光子探测成为可能的生物物理机制尚不清楚。视杆细胞的视觉大部分发生在很少发生光子吸收的光线水平；因此，不能转换单个光子或将产生的信号通过视网膜传输会严重损害视杆细胞的视觉。对绝对视觉敏感度的研究使杆状光传导成为生物系统中许多G蛋白级联的最好理解，并导致了对几种形式的静止性夜盲的机械理解。这项拟议工作的长期目标是为理解视杆细胞信号的视网膜处理以及这种处理如何失败带来类似的清晰度。 光转导的研究将探索允许杆状光感受器对每个吸收的光子产生近乎相同的反应的机制。拟议的实验将检验这样一种假设，即重复性是通过一系列步骤或转变关闭单个视紫红质分子来调节的。这与单分子关闭的传统模型有很大的不同。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，则杆状感光器产生的信号的保真度将被浪费。杆-杆双极突触起着特别重要的作用，因为它是处理单杆信号的最后机会。这项拟议的工作将确定杆状双极细胞的反应中存在多少噪声，这种噪声的来源，以及对视觉敏感度的影响。 单光子检测所需的放大存在随着光线水平的增加而饱和视网膜信号的风险。这种饱和是通过在视网膜回路中工作的鲜为人知的适应机制来防止的。这项拟议的工作将确定适应在哪里以及如何控制低背景光水平下杆状信号的增益。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.