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

0202703盾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。该计划的奖励为联合研究提供了机会，并利用独特或互补的设施、专业知识和国外的实验条件。该奖项将支持Colleen Shields博士与荷兰阿姆斯特丹眼科研究所的Maarten Kamermans博士开展为期24个月的研究。本项目旨在对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进行功能表征。从水平细胞到锥体的负反馈通路是该网络的重要组成部分。虽然我们正在接近视网膜处理的第一阶段的定量描述，没有心理物理相关的网络活动存在。幸运的是，最近出现了一种新的工具，可以分析从细胞到行为水平的水平细胞功能。Kamermans实验室最近的研究已经确定了连接蛋白26 （Cx26）半通道在水平细胞和视锥细胞之间的通信中起关键作用。Cx26在锥体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。阻断这些半通道可消除视锥细胞和水平细胞中所有反馈介导的反应，提示视锥细胞释放神经递质依赖于水平细胞极化的视觉反馈机制。为了做到这一点，他们将产生具有改良显性阴性Cx26基因的转基因斑马鱼。将对野生型和转基因动物进行电生理学研究，以验证Cx26半通道在水平细胞反馈到单个视锥细胞光感受器中的重要性。对缺乏Cx26功能的斑马鱼的创造和研究将产生对该神经网络的定量生理描述，并将提供其在人类和鱼类视觉感知中的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.