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.

Fovea是灵长类动物视网膜介导的颜色和高敏度视觉感知的专业区域。 动脉视力极易受到疾病的影响，是旨在恢复视力的疗法的主要目标 盲人。但是，我们对视网膜神经节细胞（RGC）的理解，即传达的视网膜输出神经元 大脑的视网膜图像，落后于恢复视力的技术，因为我们尚不了解 灵长类动物RGC的全部多样性或它们如何在中央凹中发挥作用。在这些领域的进步 视网膜生理方法受到研究脆弱且密集的困难的限制 Fovea以及可靠地针对急性制剂中稀有RGC的挑战。这些障碍可以 现在可以通过活性自适应式钙像中的功能性自适应钙成像（轻松）来克服，这是一个有力的新型 在表达数百个中央凹RGC中对光反应的体内测量的技术 钙指标GCAMP6S。这种非侵入性的全光学方法是在实验室中开发的 罗切斯特大学的戴维·威廉姆斯和威廉·梅里根的名字 将发生，提供前所未有的机会，可以从相同的Foveal RGC中记录数月或数年， 比以往任何时候都可以更详细地表征中央凹的视网膜输出。在AIM 1中，我会 通过开发刺激电池和分析来确定RGC的功能多样性 管道有效，可靠地分类了表达GCAMP6的RGC的响应特性。在目标二，我 将标记六种最稀有的RGC类型，并向上丘犬（SC）注射逆行示踪剂，然后将其标记 在体内和Ex Vivo中为它们的树突形态图像。这些结果将创建一个详细的地图 中央丘的形态学的地形，高级山脉，这是一种进化古老的途径 潜意识非图像形成的视觉行为。稀有GCAMP6表达RGC的最终地图将 加速AIM 1中的分类，因为许多SC项目的RGC从未在功能上表征 否则，在侏儒RGC占视网膜产量90％以上的地区可能会丢失。 该项目将在活眼中产生群侏儒RGC功能的人群级别的帐户 指导恢复视觉感知的进度。此外，洞察力的洞察力获得了凹入RGC的多样性 他们传达给大脑的视觉信息最终可以使所有视觉功能恢复， 包括视觉引导的运动和由罕见的SC项目介导的RGC介导的反射。