Biophysical mechanisms of photon detection

光子探测的生物物理机制

• 批准号: 8038634
• 负责人: FREDERICK M RIEKE
• 金额: $ 22.46万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8038634
• 关键词: Arrestins; Behavior; Behavioral; Binding; Biophysical Process; Brain; Detection; Event; GTP-Binding Proteins; Generations; Goals; Human; Knowledge; Light; Measurement; Mediating; Medical; Modeling; Mus; Neurophysiology - biologic function; Night Blindness; Noise; Output; Performance; Phosphorylation; Phosphorylation Site; Photons; Phototransduction; Primates; Process; Property; Reading; Relative (related person); Reproducibility; Retina; Retinal; Retinal Cone; Retinal Ganglion Cells; Rhodopsin; Role; Series; Serine; Signal Transduction; Site; Source; Stream; Synapses; Testing; Threonine; Transgenic Model; Vertebrate Photoreceptors; Vision; Visual; Work; absorption; active control; base; biological systems; computerized data processing; ganglion cell; genetic manipulation; improved; neural circuit; operation; relating to nervous system; research study; response; retinal rods

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.

描述（由申请人提供）：视杆介导的视觉检测少数光子吸收的能力已经导致了一组关于单光子反射如何在视网膜中转导和处理的精确问题。这些问题导致了我们对视杆视觉的生物物理基础的理解的一系列突破，以及更普遍的神经处理的保真度。锥体视觉的行为表现同样令人印象深刻，但它与生物物理机制的关系却不太清楚。我们理解的这一差距限制了行为结果对视锥细胞介导的信号的视网膜处理的约束程度。这里提出的工作的广泛目标是阐明生物物理机制如何在杆和锥光感受器和相关的视网膜电路增强和限制视觉保真度。 我们将集中在三组问题：（1）如何控制视紫红质的活性寿命，以产生低试验间变异性的单光子响应？(2)什么样的噪声源限制了视网膜输出在低光水平下的保真度？(3)在视锥光感受器的反应中，噪声的来源是什么？它对视网膜输出的保真度有什么影响？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;因此，拟议的工作将提高我们对神经功能的一般理解。 公共卫生关系：视杆光感受器检测单个光子的能力有助于使视杆光转导成为生物系统中许多G蛋白级联反应中最好理解的。它也有直接的医疗效益，因为我们现在了解了几种形式的静止性夜盲症的机制和潜在的治疗方法。我们对视网膜视杆细胞信号的读出以及视锥细胞信号的产生和处理知之甚少。这里所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，我们将利用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。