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High Resolution Mapping of Foveal Ganglion Cell Receptive Fields in the Living Primate Eye

活体灵长类动物眼睛中心凹神经节细胞感受野的高分辨率绘图

基本信息

批准号：
10319191
负责人：
DAVID R WILLIAMS
金额：
$ 52.47万
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：
2021-01-01 至 2025-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10319191
关键词：
Anatomy Brain Calcium Calcium Signaling Cells Classification Code Color Color Visions Complement Complex Cone Development Disease Electrophysiology (science)Eye Floods Fluorescence Funding Grain Histologic Histology Human Image Imaging Techniques In Vitro Individual Injury Investigation Knowledge Laboratories Light Location Maps Mediating Methods Monkeys Morphology Mus Noise Ophthalmoscopes Performance Peripheral Photoreceptors Physiological Physiology Primates Property Resolution Retina Retinal Cone Retinal Ganglion Cells Scanning Signal Transduction Stimulus Structure Surveys System Techniques Time Vision Yin adaptive optics arm blind calcium indicator design flexibility fluorescence imaging fovea centralis ganglion cell improved in vivo instrument melanopsin novel novel strategies receptive field reconstruction response retinal imaging sight restoration spatial vision spatiotemporal visual stimulus

项目摘要

The importance for vision of the tiny fovea has been established by centuries of investigation as well as observations of the devastating consequences of its damage through injury or disease. Though evidence suggests that the fovea contains the full complement of the two dozen or so classes of ganglion cells found in peripheral retina, we know little about the physiology of these foveal cells. This gap in our understanding is the result of challenges in obtaining electrophysiological recordings from this delicate and topographically-complex structure. These challenges have been overcome by a method developed in our laboratory that allows simultaneous calcium imaging of the fluorescence responses of hundreds of foveal retinal ganglion cells in response to visual stimuli. Because this technique allows recording from single cells without damage in the living eye, we can study the same cells for months or even years, offering the opportunity to characterize the performance of each cell more thoroughly than has been possible with any prior method. Since the first submission of the proposal, we have made significant improvements in the expression of calcium indicator, GCamMP6s, in ganglion cells that increases the extent of expression to greater eccentricities, the fluorescence signal from each cell, as well as reducing the loss of ganglion cells over time. Moreover, we have designed a new ophthalmoscope with two independent adaptive optics systems, one dedicated to high resolution stimulus delivery and a second dedicated to high resolution ganglion cell recording. We have also developed an extensive battery of visual stimuli to characterize the responses of each cell in space, time, and color. This battery will include a white noise stimulus capable of identifying the locations and classes of single cone inputs to the receptive fields of foveal ganglion cells. To assist in cell classification, these physiological observations will be supplemented with ex vivo and in vivo histological analysis of the morphology of ganglion cell dendritic arbors. Armed with these improvements, we will undertake a comprehensive survey of both the physiology and anatomy of the foveal ganglion cell classes that mediate primate foveal vision.

几个世纪的研究和研究已经证实了微小中央凹对视力的重要性。观察其因受伤或疾病而造成的破坏性后果。虽然有证据表明中央凹包含在神经节细胞中发现的两打左右神经节细胞的完整补充。对于视网膜周边细胞，我们对这些中心凹细胞的生理学知之甚少。我们理解上的这种差距是从这个精致且地形复杂的地方获取电生理记录的挑战的结果结构。我们实验室开发的一种方法克服了这些挑战，该方法允许对数百个中心凹视网膜神经节细胞的荧光反应进行同步钙成像对视觉刺激的反应。因为这项技术可以在不损害活体细胞的情况下记录单个细胞眼睛，我们可以研究相同的细胞数月甚至数年，从而提供了表征细胞特征的机会比任何现有方法都更彻底地检测每个电池的性能。自从第一次提案提交后，我们在钙指标的表达上有了显着的改进， GCamMP6，在神经节细胞中将表达程度增加到更大的偏心率，荧光来自每个细胞的信号，以及随着时间的推移减少神经节细胞的损失。此外，我们还设计了一个新型检眼镜具有两个独立的自适应光学系统，其中一个专用于高分辨率刺激交付和第二个致力于高分辨率神经节细胞记录。我们还开发了广泛的一组视觉刺激来表征每个细胞在空间、时间和颜色方面的反应。该电池将包括白噪声刺激，能够识别单锥体输入的位置和类别中心凹神经节细胞的感受野。为了帮助细胞分类，这些生理观察将被补充神经节细胞树突乔木形态的离体和体内组织学分析。有了这些改进，我们将对生理学和解剖学进行全面的调查介导灵长类中央凹视力的中央凹神经节细胞类别。