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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：
10534734
负责人：
DAVID R WILLIAMS
金额：
$ 55.48万
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/10534734
关键词：
Acceleration Anatomy Brain Calcium Calcium Signaling Cells Classification Code Color Color Visions Complement Complex Cone Dedications 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 Optical Instrument 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 new technology 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.

经过几个世纪的研究和研究，已经确定了微小中心凹视觉的重要性。观察其通过受伤或疾病造成的破坏的破坏性后果。尽管有证据表明表明中央凹含有20多种神经节细胞的全部组成，这些神经节细胞在外周视网膜，我们对这些中心凹细胞的生理学知之甚少。我们在理解上的这种差距是从这种精致和复杂的地形中获取电生理记录的挑战的结果结构。这些挑战已经被我们实验室开发的一种方法克服了，这种方法允许视网膜中央凹神经节细胞荧光反应的同时钙成像对视觉刺激的反应。因为这项技术允许从单个细胞进行记录，而不会对活体造成损害眼睛，我们可以研究相同的细胞几个月甚至几年，提供机会来表征每个电池的性能比任何现有方法都更彻底。从第一次在提交提案后，我们在钙指示剂的表达方面取得了重大改进， GCamMP6在神经节细胞中的表达程度增加到更大的偏心率，荧光从每个细胞发出信号，并随着时间的推移减少神经节细胞的损失。此外，我们还设计了一种带有两个独立的自适应光学系统的新型检眼镜，其中一个专门用于高分辨率刺激另一台专门用于高分辨率神经节细胞记录。我们还开发了一种广泛的一组视觉刺激，用来表征每个细胞在空间、时间和颜色上的反应。这块电池将包括白噪声激励，能够识别单锥输入到中心凹神经节细胞的感受野。为了帮助细胞分类，这些生理观察将被辅以体外和体内神经节细胞树突状乔木的组织学形态分析。有了这些改进，我们将对生理学和解剖学进行全面的调查调节灵长类中心凹视觉的中心凹神经节细胞类别。