EYE MOVEMENT--PHYSIOLOGICAL ORGANIZATION

眼球运动--生理组织

• 批准号: 6688290
• 负责人: ROBERT G BAKER
• 金额: $ 28.45万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-09-30 至 2005-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6688290
• 关键词: alternatives to animals in research; confocal scanning microscopy; developmental genetics; developmental neurobiology; electrophysiology; eye movements; gene mutation; in situ hybridization; myogenesis; neural information processing; neuroanatomy; neurogenesis; neurons; oculomotor nerve; oculomotor nuclei; rhombencephalon; sensorimotor system; single cell analysis; vestibular nerve; visual pathways; visual stimulus; voltage /patch clamp; zebrafish

DESCRIPTION (Adapted from applicant's abstract): The goal of this research project is to provide a better understanding of the anatomy and physiology of neurons responsible for oculomotor behavior by taking advantage of the unique genetic and developmental features of the zebrafish model system. The structural blueprint responsible for eye movements derives from highly conserved genetic and anatomical profiles specific to each of the 8 embryonic hindbrain compartments. A multidisciplinary approach will focus on the central processing of visual and vestibular sensory signals in three distinct brainstem nuclei, each performing a unique integrative role in oculomotor behavior and representing a separate genetic/rhombomeric (rh) origin. Two nuclei that convert head angular acceleration and other velocity-related inputs to horizontal eye velocity and eye position related signals are located in rh 7 and 8 respectively. The third nucleus, located in rh 5 orients the eyes in a manner compensatory for head tilt. Genetic and fluorescent reporters will be used to visualize these neurons allowing direct analysis of single cell morphology and physiology during the formation of each specific eye movement-related network. Since cell laser perturbations along with structural and behavioral analysis of single gene mutations will distinguish novel roles for particular neurons and genes in the assembly and function of these oculomotor networks. Aim 1 will study normal ontogeny, physiology and behavior during formation of operational neural circuits using transgenic GFP markers. Aim 2 will investigate neuronal and network dynamics in larval and juvenile stages using single cell laser photochemical uncaging/ablation and altered visual experience. Aim 3 will manipulate the expression of Hox paralog group 3 and 4 genes to alter genetic and developmental properties underlying neuronal and network specificity as well as analyze adult viable and embryonic-lethal mutations. Aim 4 will screen for the role of single genes in the development and function of dentified neurons and proto-networks. This project will utilize contemporary electrophysiological, computational and genetic approaches in conjunction with non-invasive two photon laser scanning microscopy to identify genes essential for oculomotor signal processing in vertebrates.

描述（改编自申请人的摘要）：这项研究的目的 项目是为了更好地了解 通过利用独特的神经元来负责动眼行为的神经元 斑马鱼模型系统的遗传和发育特征。这 负责眼动的结构蓝图源自高度 保守的遗传和解剖学特征对8个胚胎中的每一个 后脑室。多学科的方法将集中于中心 在三个不同的脑干中处理视觉和前庭感觉信号 细胞核，每个核在眼球行为中扮演独特的综合作用， 代表单独的遗传/菱形（RH）起源。两个核 将头角加速度和其他速度相关的输入转换为 水平眼速度和眼睛位置相关信号位于RH 7中 和8分。第三个核位于RH 5中 倾斜的方式补偿性。遗传和荧光记者将是 用于可视化这些神经元以直接分析单细胞 每只特定眼睛的形成过程中的形态和生理学 与运动有关的网络。由于细胞激光扰动以及结构 单基因突变的行为分析将区分新作用 对于这些特定神经元和基因的组装和功能 眼球网络。 AIM 1将研究正常的本体发育，生理和行为 在使用转基因GFP标记形成操作神经回路的过程中。 AIM 2将研究幼虫和少年的神经元和网络动力学 使用单细胞激光器光化学脱位/消融阶段 视觉体验。 AIM 3将操纵HOX Paralog组3的表达 和4个基因以改变神经元的遗传和发育特性 以及网络特异性以及分析成人可行和胚胎致命的 突变。 AIM 4将筛选单个基因在开发中的作用 牙齿神经元和原始网络的功能。这个项目将利用 当代电生理，计算和遗传方法 与非侵入性两个光子激光扫描显微镜的结合以识别 基因对于脊椎动物中的动眼信号处理必不可少的基因。