Biophysical mechanisms of single photon detection

已知暗适应视觉系统检测几个光子的吸收的能力， 多年然而，使光子探测成为可能的生物物理机制并不 明白大部分视杆细胞视觉发生在光子反射很少发生的光照水平;因此， 通过视网膜反射单个光子或传输产生的信号严重损害视杆细胞视力。 对绝对视觉敏感度的研究使视杆细胞光转导成为许多G- 蛋白质级联在生物系统中，并导致了几种形式的固定的机械理解 夜盲症拟议工作的长期目标是使人们对 视杆细胞信号的视网膜处理以及这种处理如何失败。 光转导的研究将探讨杆细胞感光器产生 对每一个被吸收的光子都有几乎相同的反应拟议中的实验将检验以下假设： 通过一系列步骤关闭单个视紫红质分子来介导再现性， 过渡。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，类似的策略可以减少细胞内的变异性。 由其他G蛋白级联控制的信号。 如果这些反应不完全，那么由视杆细胞光感受器产生的信号的保真度将被浪费。 可靠地通过视网膜传输。杆对杆双极突触起着特别重要的作用，因为它 是最后一次处理来自单个燃料棒的信号拟议的工作将决定 噪声存在于视杆双极细胞的反应中，这种噪声的来源以及对视觉的影响 灵敏度 单光子检测所需的放大存在使视网膜信号饱和为光的风险 水平提高。这种饱和是由人们知之甚少的适应机制所阻止的。 在视网膜回路中。拟议的工作将确定适应在何处以及如何控制 视杆细胞在低背景光水平下发出信号。这项工作将把视网膜机制与经典的行为学联系起来， 测量视觉敏感度如何随背景光变化。

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 mechanismsthat 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 backgroundlight.