Biophysical mechanisms of single photon detection

已知暗适应视觉系统检测少数光子吸收的能力 很多年了。然而，使光子探测成为可能的生物物理机制并不是 明白了。许多杆状视觉发生在很少发生光子吸收的光线水平；因此，无法 转换单个光子或通过视网膜传输产生的信号会严重损害视杆视觉。 对绝对视觉敏感度的研究使杆状光转导成为许多G- 蛋白质在生物系统中的级联，并导致了对几种固定形式的机制的理解 夜盲症。拟议工作的长期目标是使对 视杆信号的视网膜处理，以及这种处理如何失败。 光传导的研究将探索杆状光感受器产生 对每个被吸收的光子的近乎相同的反应。拟议中的实验将检验这一假设 重复性是通过一系列步骤或步骤关闭单个视紫红质分子来调节的。 过渡。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，类似的策略可能会减少 信号由其他G蛋白级联控制。 如果没有这些反应，由杆状感光器产生的信号的保真度将被浪费 通过视网膜可靠地传输。杆-杆双极突触起着特别重要的作用，因为它 是处理来自单棒的信号的最后机会。拟议的工作将决定 在视杆双极细胞的反应中存在噪声，噪声的来源以及对视觉的影响 敏感度。 单光子检测所需的放大存在将视网膜信号饱和为光的风险 水平会增加。这种饱和是由知之甚少的适应性机制起作用而防止的。 在视网膜回路中。拟议的工作将确定适应在哪里以及如何控制 Rod在低背景光水平下发出信号。这项研究将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.