Foveal ganglion cell function in the living eye

活体眼睛中中心凹神经节细胞的功能

基本信息

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
项目类别：
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

项目摘要

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.

中央凹是灵长类动物视网膜的一个特殊区域，负责调节颜色和高敏锐度视觉感知。中心凹视力极易患病，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（RGC）的理解，即传达信息的视网膜输出神经元将视网膜图像传输到大脑，落后于恢复视力的技术，因为我们还不了解灵长类 RGC 的全部多样性以及它们在中央凹中的功能。与传统技术相比，这些领域取得了进展视网膜生理学方法因研究脆弱和密集的视网膜的困难而受到限制中央凹以及在急性制剂中可靠地靶向稀有 RGC 的挑战。这些障碍可以现在可以通过活眼功能自适应光学钙成像 (FACILE) 来克服，这是一种强大的新功能该技术能够在体内测量数百个表达视网膜中央凹 RGC 的光反应钙指示剂GCaMP6s。这种非侵入性全光学方法是在实验室开发的罗彻斯特大学的大卫·威廉姆斯和威廉·梅里根教授，我在那里提出了博士后培训将会发生，提供前所未有的机会从同一个中心凹 RGC 进行数月或数年的记录，允许比以往更详细地描述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中央凹视觉的 RGC 的功能多样性管道有效且可靠地对表达 GCaMP6 的 RGC 的响应属性进行分类。在目标二中，我将通过向上丘 (SC) 逆行示踪剂注射来标记六种最罕见的 RGC 类型，然后对其体内和离体的树突形态进行成像。这些结果将创建详细的地图中央凹输入上丘的地形，这是一条进化上古老的介导通路潜意识的非图像形成视觉行为。所得到的罕见表达 GCaMP6 的 RGC 的图谱将加速目标 1 中的分类，因为许多 SC 投影 RGC 从未进行过功能表征否则可能会在小型 RGC 占视网膜输出 90% 以上的区域中丢失。该项目将产生活体眼睛中中心凹小型 RGC 功能的群体水平描述，指导恢复视觉感知的进展。此外，对中心凹 RGC 多样性的深入了解它们向大脑传递的视觉信息最终可能使所有视觉功能恢复，包括由罕见的 SC 投射 RGC 介导的视觉引导运动和反射。