Biophysical mechanisms of photon detection

描述(申请人提供)：杆状介导性视觉检测少数光子的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被转换和处理的预见性问题。这些问题导致了我们对杆状视觉的生物物理基础的一系列突破，更广泛地说，是对神经处理的保真度的理解。锥体视觉的行为表现同样令人印象深刻，但它与生物物理机制的关系还不是很清楚。这种理解上的差距限制了行为结果在多大程度上制约视锥细胞介导信号的视网膜处理。这项工作的主要目标是阐明视杆细胞和视锥细胞感光细胞及其相关视网膜回路的生物物理机制是如何增强和限制视觉保真度的。我们将集中在三组问题上：(1)如何控制视紫红质的活性寿命以产生低试用期变异性的单光子响应？(2)什么噪声源限制了弱光下视网膜输出的保真度？(3)视锥感光细胞响应中的噪声来源是什么，它对视网膜输出保真度的影响是什么？我们将通过对小鼠和灵长类动物视网膜反应的电生理记录以及小鼠视网膜的遗传操作来回答这些问题。类似的问题出现在许多其他神经回路中；因此，所提出的工作将提高我们对神经功能的一般理解。 与公共健康相关：杆状光感受器探测单个光子的能力帮助使杆状光转导成为生物系统中许多G蛋白级联的最好理解。它也有直接的医疗益处，因为我们现在了解了这种机制，并有可能治疗几种形式的静止性夜盲。我们对视杆信号的视网膜读数以及视锥信号的产生和处理知之甚少。这里描述的工作的长期目标是帮助填补我们知识中的这一空白。正如我们过去所做的那样，我们将使用在这项工作中取得的技术和概念上的进展来测试转基因模型的视觉缺陷。

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.