Biophysical mechanisms of photon detection

描述（由申请人提供）：杆状视觉检测少量光子吸收的能力导致了一系列关于单光子吸收如何在视网膜中传导和处理的精确问题。这些问题导致了我们对杆视觉的生物物理基础的理解的一系列突破，更广泛地说，神经处理的保真度。锥体视觉的行为表现同样令人印象深刻，但其与生物物理机制的关系却不太清楚。我们在理解上的差距限制了行为结果对视锥介导信号的视网膜处理的强烈约束。这里提出的工作的总体目标是阐明在杆状和锥状光感受器以及相关的视网膜回路中运作的生物物理机制如何增强和限制视觉保真度。我们将关注三组问题：(1)如何控制视紫质的活性寿命以产生低试验间可变性的单光子响应？(2)在低光照条件下，哪些噪声源限制了视网膜输出的保真度？(3)锥体光感受器响应中的噪声来源是什么？噪声对视网膜输出的保真度有何影响？我们将通过小鼠和灵长类动物视网膜反应的电生理记录和小鼠视网膜的遗传操作相结合来回答这些问题。类似的问题也出现在许多其他的神经回路中；因此，提出的工作将提高我们对神经功能的一般理解。

DESCRIPTION (provided by applicant): The ability of rod-mediated vision to detect absorption of a handful of photons has led to a set of pre-cise questions about how single photon absorptions are transduced and processed in the retina. These questions have led to a series of breakthroughs in our understanding of the biophysical basis of rod vision, and more generally of the fidelity of neural processing. The behavioral performance of cone vision is similarly impressive, but its relation to biophysical mechanisms is much less clear. This gap in our understanding limits how strongly behavioral results constrain retinal processing of cone-mediated signals. The broad goal of the work proposed here is to elucidate how biophysical mechanisms operating in the rod and cone photoreceptors and the associated retinal circuits enhance and limit visual fidelity. We will focus on three sets of questions: (1) How is rhodopsin's active lifetime controlled to generate single photon responses with low trial-to-trial variability? (2) What sources of noise limit the fidelity of the retinal outputs at low light levels? (3) What is the origin of noise in the responses of cone photoreceptors and what is its impact on the fidelity of the retinal output? We will answer these questions through a combination of electrophysiological recordings of responses in mouse and primate retina and genetic manipulations in mouse retina. Similar issues arise in many other neural circuits; thus the proposed work will improve our general understanding of neural function. PUBLIC HEALTH RELEVANCE: The ability of rod photoreceptors to detect single photons has helped make rod phototransduction the best understood of the many G-protein cascades in biological systems. It also has had direct medical benefits, as we now understand the mechanisms and have potential treatments for several forms of stationary night blindness. We know much less about the retinal readout of rod signals and the generation and processing of cone signals. The long-term aim of the work described here is to help fill this gap in our knowledge. As we have in the past, we will use the technical and conceptual progress made in this work to test transgenic models for visual deficits.