Foveal ganglion cell function in the living eye

活体眼睛中中心凹神经节细胞的功能

• 批准号: 10456593
• 负责人: Sara S Patterson
• 金额: $ 7.62万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-16 至 2023-06-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10456593
• 关键词: Acute; Anatomy; Area; Autopsy; Behavior; Brain; Calcium; Cell Density; Cell Polarity; Cell physiology; Cellular Morphology; Classification; Color; Cone; Conscious; Contrast Sensitivity; Development; Disease; Eye; Fluorescence; Foundations; Goals; Histology; Human; Image; Individual; Injections; Kinetics; Label; Laboratories; Light; Light Microscope; Location; Macular degeneration; Maps; Measurement; Mediating; Methods; Morphology; Mosaicism; Movement; Neurons; Optics; Output; Pathway interactions; Peripheral; Physiological; Physiology; Population; Preparation; Primates; Property; Psychophysics; Reflex action; Research; Retina; Retinal Ganglion Cells; Role; Scanning; Standardization; Stimulus; Subconscious; Surveys; Techniques; TimeLine; Tracer; Translating; Universities; Vision; Visual; Visual Acuity; Visual Perception; adaptive optics; analysis pipeline; base; blind; calcium indicator; cell type; design; experimental study; fovea centralis; ganglion cell; in vivo; insight; motion sensitivity; neuronal cell body; optogenetics; post-doctoral training; response; restoration; retinal imaging; retinal prosthesis; rhodamine dextran; sight restoration; superior colliculus Corpora quadrigemina; targeted treatment; visual information; visual stimulus

The fovea is a specialized region of the primate retina mediating color and high acuity visual perception. Foveal vision is highly susceptible to disease and is the primary target for therapies aiming to restore vision in the blind. However, our understanding of retinal ganglion cells (RGCs), the retinal output neurons that convey the retinal image to the brain, lags behind techniques to restore vision because we do not yet understand the full diversity of primate RGCs nor how they function in the fovea. Progress in these areas with conventional retinal physiology approaches has been limited by the difficulties of studying the fragile and densely packed fovea along with the challenges of reliably targeting rare RGCs in acute preparations. These obstacles can now be overcome with Functional Adaptive-optics Calcium Imaging in the Living Eye (FACILE), a powerful new technique enabling in vivo measurements of the light responses in hundreds of foveal RGCs expressing the calcium indicator GCaMP6s. This non-invasive, all-optical approach, which was developed in the laboratories of David Williams and William Merigan at the University of Rochester where my proposed postdoctoral training will occur, provides the unprecedented opportunity to record from the same foveal RGCs for months or years, allowing a more detailed characterization of the retinal output in the fovea than ever before. In Aim 1, I will determine the functional diversity of RGCs serving foveal vision by developing a stimulus battery and analysis pipeline to effectively and reliably classify the response properties of GCaMP6-expressing RGCs. In Aim Two, I will label six of the rarest RGC types with retrograde tracer injections to the superior colliculus (SC), then image their dendritic morphologies both in vivo and ex vivo. These results will create a detailed map of the topography of the foveal input to the superior colliculus, an evolutionarily ancient pathway mediating subconscious non-image-forming visual behaviors. The resulting map of rare GCaMP6-expressing RGCs will accelerate the classification in Aim 1 as many SC-projecting RGCs have never been characterized functionally and may have otherwise been lost in a region where midget RGCs make up over 90% of the retinal output. This project will produce a population-level account of foveal midget RGC function in the living eye that will guide progress in restoring visual perception. In addition, the insights gained into the diversity of foveal RGCs and the visual information they convey to the brain may ultimately enable the restoration all visual function, including the visually guided movements and reflexes mediated by rare SC-projecting RGCs.

视网膜中央凹是灵长类动物视网膜上的一个特殊区域，调节颜色和高灵敏度视觉感知。 中心凹视力对疾病高度敏感，并且是旨在恢复视力的治疗的主要目标， 盲人然而，我们对视网膜神经节细胞（RGCs）的理解，视网膜输出神经元， 视网膜图像到大脑，落后于恢复视力的技术，因为我们还不了解 灵长类RGCs的多样性以及它们在中央凹中的功能。在这些领域取得的进展 视网膜生理学方法一直受到研究脆弱和密集的困难的限制， 中心凹沿着而来的挑战是在急性制剂中可靠地靶向稀有RGC。这些障碍可以 现在可以克服功能自适应光学钙成像在活眼（FACILE），一个强大的新的 一种能够在体内测量数百个表达光敏感性的视网膜中央凹RGC中的光反应的技术。 钙指标GCaMP6s。这种非侵入性的全光学方法是在实验室里开发的， 大卫威廉姆斯和威廉Merigan在罗切斯特大学，我建议博士后培训 将发生，提供了前所未有的机会，记录从相同的中央凹RGC数月或数年， 允许比以往更详细地表征中央凹中的视网膜输出。在目标1中，我将 通过开发刺激电池和分析来确定服务于中央凹视觉的RGC的功能多样性 流水线，以有效和可靠地分类GCaMP6表达RGC的响应特性。在目标二中，我 将标记六种最罕见的RGC类型，逆行示踪剂注射到上级丘（SC），然后 在体内和离体成像其树突形态。这些结果将创建详细的地图， 中央凹输入到上级丘的地形，一个进化上古老的通路， 下意识的非图像形成视觉行为。所得到的罕见GCaMP6表达RGC的图谱将 加速目标1中的分类，因为许多SC投射的RGC从未在功能上被表征 并且可能在侏儒RGC占视网膜输出的90%以上的区域中丢失。 这个项目将产生一个人口水平的帐户中央凹侏儒RGC功能的活眼， 引导恢复视觉感知的进程。此外，对视网膜中央凹RGC多样性的认识 并且它们传达给大脑的视觉信息最终可以使所有视觉功能得以恢复， 包括由罕见的SC投射RGC介导的视觉引导的运动和反射。