Functional characteristics of rod pathways in the retina

视网膜视杆细胞通路的功能特征

• 批准号: 7454273
• 负责人: Alapakkam P Sampath
• 金额: $ 34.9万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7454273
• 关键词: Address; Arrestin; Arrestins; Behavior; Behavior Therapy; Behavioral; Brain; Cells; Characteristics; Connexins; Darkness; Eye; Gap Junctions; Goals; Kinetics; Knock-out; Light; Mammals; Mediating; Mus; Night Blindness; Pathway interactions; Perception; Phase; Photons; Photophobia; Phototransduction; Physiological; Physiology; Process; Property; Range; Recovery; Research Personnel; Retina; Retinal; Retinal Cone; Rhodopsin; Shapes; Signal Transduction; Strychnine; Testing; Transgenic Mice; Universities; Vertebrate Photoreceptors; Vision; Visual; Washington; absorption; base; design; ganglion cell; guanylate cyclase activating protein; insight; light intensity; light transmission; programs; research study; response; retinal neuron; retinal rods; rhodopsin kinase; visual process; visual processing

DESCRIPTION (provided by applicant): This proposal is aimed at understanding the properties of the rod circuitry in the mammalian retina. Our rod vision encompasses lights as dim as a single photon absorption in as many as 10,000 rod photoreceptors, up to 1000 or more photons per rod. This wide range of light sensitivity is accomplished by biophysical mechanisms that have been studied for more than a half century, but several outstanding issues of fundamental importance remain. The experiments described in this proposal are designed to address two issues: (1) Which aspects of the rod photoresponse are relevant for downstream processing?, and (2) What are the threshold and dynamic range of light intensities for each retinal pathway that relays the rod photoresponse to ganglion cells? To answer these questions we will record light-evoked responses from rod photoreceptors, bipolar cells and ganglion cells from several transgenic mouse lines lacking cone light responses (cone trasducin -/-) with: (1) knockouts in the rod phototransduction pathway that change the shape of the rod photoresponse, and (2) knockouts in the retinal circuitry that will allow the rod retinal pathways (Rod-Bipolar, Rod-Cone, and Rod-Off pathways) to be studied in isolation. The deletion of the phototransduction proteins (GCAP, Rhodopsin Kinase, Rhodopsin, and Arrestin), or the gap junction protein Connexin 36 in specific cells, will alter the transmission of light responses and allow us to infer how the properties of the photoresponse and circuitry influence rod vision. In parallel with these experiments, we will evaluate the behavioral threshold for rod vision in each mouse studied. Thus alterations in the physiology of rod signaling in the retina can be connected to a constrained and quantifiable visual behavior. Such correlations will provide insights into how the processing of the rod photoresponse influences perception, and will have consequences for understanding the mechanistic basis for deficits in rod vision (i.e. Stationary Night Blindness). Night vision in mammals is mediated by several pathways in the retina that relay information about few photon absorptions to the brain. This proposal is aimed at understanding how this remarkable sensitivity is achieved at the cellular level by establishing the properties of the rod photoreceptor response and the retinal circuitry that are important for visual processing. In order to devise therapies for conditions that influence our night vision, like Stationary Night Blindness, it is necessary to first understand the physiological mechanisms that relay information from our eyes to our brain at low light levels.

描述（由申请人提供）：本提案旨在了解哺乳动物视网膜中视杆细胞回路的特性。我们的视杆细胞视觉包含了像单个光子吸收一样暗淡的光，在多达10，000个视杆细胞中，每个视杆细胞有1000个或更多的光子。这种广泛的光敏感性是通过生物物理机制来实现的，这些机制已经研究了半个多世纪，但仍然存在一些具有根本重要性的悬而未决的问题。本提案中描述的实验旨在解决两个问题：（1）视杆光响应的哪些方面与下游处理相关？以及（2）将视杆细胞光反应传递给神经节细胞的每一条视网膜通路的光强度阈值和动态范围是多少？为了回答这些问题，我们将记录几个缺乏视锥光反应的转基因小鼠品系的视杆细胞、双极细胞和神经节细胞的光诱发反应（锥体transducin-/-），其中：（1）敲除视杆光转换途径，改变视杆光反应的形状，和（2）敲除视网膜回路，允许视杆视网膜途径（杆-双极、杆-锥和杆-离途径）单独研究。在特定细胞中，光转导蛋白（GCAP、视紫红质激酶、视紫红质和抑制蛋白）或差距连接蛋白连接蛋白36的缺失将改变光响应的传输，并使我们能够推断光响应和电路的性质如何影响视杆视觉。在这些实验的同时，我们将评估研究的每只小鼠的视杆视觉的行为阈值。因此，视网膜中视杆细胞信号生理学的改变可以与受约束且可量化的视觉行为有关。这种相关性将提供深入了解如何处理杆光反应影响知觉，并将有理解杆视觉缺陷（即静止性夜盲症）的机制基础的后果。 哺乳动物的夜视是由视网膜中的几条通路介导的，这些通路将关于少量光子反射的信息传递到大脑。这项建议的目的是了解如何实现这种显着的敏感性在细胞水平上建立的视杆细胞反应和视网膜电路，是重要的视觉处理的属性。为了设计治疗影响我们夜视的疾病，如静止性夜盲症，有必要首先了解在低光照水平下将信息从我们的眼睛传递到我们的大脑的生理机制。