International Research Fellowship Program: Functional Analysis of Electrical Feedback from Horizontal Cells to Cone Photoreceptors

国际研究奖学金计划：从水平细胞到视锥细胞的电反馈的功能分析

• 批准号: 0202703
• 负责人: Colleen Shields
• 金额: $ 12.22万
• 依托单位: Shields, Colleen
• 依托单位国家: 美国
• 项目类别: Fellowship Award
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2004-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0202703&HistoricalAwards=false
• 关键词: International; Research; Fellowship; Program; Functional

0202703ShieldsThe International Research Fellowship Program enables U.S. scientists and engineers to conduct three to twenty-four months of research abroad. The program's awards provide opportunities for joint research, and the use of unique or complementary facilities, expertise and experimental conditions abroad.This award will support a twenty-four month research fellowship by Dr. Colleen Shields to work with Dr. Maarten Kamermans at the Netherlands Ophthalmic Research Institute in Amsterdam, Netherlands.This project aims at a functional characterization of the network formed by the cones, horizontal cells, and bipolar cells in the vertebrate retina. The negative feedback pathway from horizontal cells to cones is an essential element of this network. Although we are approaching a quantitative description of this first stage of retinal processing, no psychophysical correlate for this network activity exists. Fortunately, a new tool for analysis of horizontal cell function from the cellular to the behavioral levels has recently become available. Recent studies in the Kamermans laboratory have indentified connexin 26 (Cx26) hemichannels as key actors in the communication between horizontal cells and cones. Cx26 forms putative hemichannels on horizontal cell dendrites near the glutamate release site of the cones. Blocking these hemichannels abolishes all feedback-mediated responses in cones and horizontal cells, suggesting an ephaptic feedback mechanism in which the release of neurotransmitter by the cones depends on the polarization of the horizontal cells. To do this, they will generate transgenic zebrafish with a modified dominant negative Cx26. Wild type and transgenically modified animals will be studied electrophysiologically to verify the importance of Cx26 hemichannels in the feedback from horizontal cells to individual cone photoreceptors. The creation and study of zebrafish lacking Cx26 function will yield a quantitative physiological description of this neural network and will provide a psychophysical correlate of its role in visual perception in both man and fish.The lab of Dr. Kamermans first described the role of Cx26 in horizontal cell feedback to cones. The expertise in the group encompasses electrophysiology, anatomy, psychophysics, and molecular biology. Dr. Kamermans is an expert in outer retinal circuitry.

0202703Shields国际研究奖学金计划使美国科学家和工程师能够在国外进行三到二十四个月的研究。 该项目的奖项为联合研究以及使用国外独特或互补的设施、专业知识和实验条件提供了机会。该奖项将支持 Colleen Shields 博士与荷兰阿姆斯特丹荷兰眼科研究所的 Maarten Kamermans 博士合作为期 24 个月的研究奖学金。该项目旨在对由视锥细胞、水平细胞和视锥细胞形成的网络进行功能表征。 脊椎动物视网膜中的双极细胞。 从水平细胞到视锥细胞的负反馈路径是该网络的基本要素。 尽管我们正在对视网膜处理的第一阶段进行定量描述，但这种网络活动不存在心理物理关联。 幸运的是，最近出现了一种用于分析从细胞水平到行为水平的水平细胞功能的新工具。 Kamermans 实验室最近的研究已确定连接蛋白 26 (Cx26) 半通道是水平细胞和视锥细胞之间沟通的关键角色。 Cx26 在视锥细胞谷氨酸释放位点附近的水平细胞树突上形成推定的半通道。 阻断这些半通道会消除视锥细胞和水平细胞中所有反馈介导的反应，这表明视锥细胞释放神经递质取决于水平细胞的极化的触觉反馈机制。 为此，他们将产生带有修饰的显性失活 Cx26 的转基因斑马鱼。 将对野生型和转基因动物进行电生理学研究，以验证 Cx26 半通道在从水平细胞到单个视锥光感受器的反馈中的重要性。 缺乏 Cx26 功能的斑马鱼的创造和研究将产生该神经网络的定量生理描述，并将提供其在人和鱼视觉感知中的作用的心理物理学相关性。Kamermans 博士的实验室首先描述了 Cx26 在水平细胞反馈到视锥细胞中的作用。 该小组的专业知识包括电生理学、解剖学、心理物理学和分子生物学。 卡默曼斯博士是视网膜外环路方面的专家。