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

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。该计划的奖项提供了联合研究的机会，并利用国外独特或互补的设施、专业知识和实验条件。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 Kamerman博士合作的为期24个月的研究奖学金。该项目旨在描述脊椎动物视网膜中由视锥细胞、水平细胞和双极细胞组成的网络的功能特征。从水平细胞到视锥细胞的负反馈通路是这一网络的重要组成部分。尽管我们正在接近对视网膜处理的这一第一阶段的定量描述，但不存在与这一网络活动相关的心理物理学。幸运的是，最近出现了一种新的工具，可以从细胞水平到行为水平分析水平细胞的功能。卡默曼斯实验室最近的研究发现，连接蛋白26(Cx26)半通道是水平细胞和视锥细胞之间通讯的关键因素。Cx26在视锥细胞谷氨酸释放部位附近的水平细胞树突上形成可能的半突。阻断这些半丘取消了视锥细胞和水平细胞中所有反馈介导的反应，暗示了一种触觉反馈机制，即视锥细胞神经递质的释放取决于水平细胞的极化。为了做到这一点，他们将产生带有修饰的显性负值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半通道在水平细胞向单个视锥感光细胞反馈中的重要性。缺乏Cx26功能的斑马鱼的创造和研究将产生对这种神经网络的定量生理描述，并将提供其在人和鱼的视觉感知中作用的心理物理关联。卡默曼斯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回路方面的专家。

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.