Eye Movement: Physiological Organization

眼球运动：生理组织

• 批准号: 7260552
• 负责人: ROBERT G BAKER
• 金额: $ 42.25万
• 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 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7260552
• 关键词: Affect; Automobile Driving; Behavior; Behavioral; Biological Assay; Biological Neural Networks; C.I. Solvent Yellow 56; Cell Nucleus; Cells; Cerebellum; DNA; Development; Disruption; Electrophysiology (science); Enhancers; Evolution; Exhibits; Eye; Eye Movements; Fiber; Genes; Genetic; Growth; Human; Image; Immunohistochemistry; In Situ Hybridization; Individual; Inferior; Injection of therapeutic agent; Label; Larva; Link; Location; Microscopy; Morphology; Motion; Neuronal Differentiation; Neurons; Ocular Motility Disorders; Oculomotor nucleus; Oligonucleotides; Olives - dietary; Pattern; Performance; Phenotype; Physiological; Physiology; Play; Population; Positioning Attribute; Production; Property; Proteins; Purpose; RNA; Range; Reflex eye movement; Regulation; Regulator Genes; Regulatory Element; Regulatory Pathway; Reporter; Research; Research Personnel; Role; Signal Transduction; Specific qualifier value; Specimen; Structure; Subgroup; System; Testing; Time; Torsion; Tracer; Transcriptional Activation; Transgenic Organisms; Tretinoin; Up-Regulation; Visual; Work; Zebrafish; base; developmental genetics; eye velocity; hindbrain; immunocytochemistry; islet; loss of function; member; migration; oculomotor; oculomotor behavior; otoconia; paralogous gene; programs; relating to nervous system; sample fixation; transcription factor; vestibulo-ocular reflex

DESCRIPTION (provided by applicant): The purpose of this research is to study the ontogeny of oculomotor neuron physiology and behavior by exploiting the developmental genetics of zebrafish. To achieve this objective, we will investigate the physiology and genetic specification of four neuronal subtypes that contribute to the production of horizontal and torsional eye movement. The proposed research will focus on quantifiable behaviors and physiological properties of oculomotor neurons and circuits to explore the role of Hox paralog group 4 genes (hoxa4a, Hoxb4a, hoxc4a, hoxd4a) in the patterning and differentiation of three nuclei specific for horizontal eye motion that originate from hindbrain rhombomeres 7 and 8. The first nucleus, PNI, performs a neural integration to provide an eye position signal essential for horizontal fixation and vestibuloocular reflex performance. The second, VNI, encodes eye velocity and provides the major input signal to the vestibulocerebellum, and thus is instrumental in all oculomotor plasticity paradigms. A third nucleus, the inferior olive (IO), provides climbing fiber input to the cerebellum necessary for eye movement stability. In addition, the physiology and development of the tangential nucleus (TAN) will be studied. TAN is responsible for gravitoinertial compensatory eye reflexes and develops in rhombomere 5 under control of Hox paralog group 3 genes. Otolith-induced torsional eye motion will provide an assay for cross-regulatory effects between Hox4 and Hox3 genes. The first aim of the project will characterize the electrophysiology, morphology, and behavior of identified hindbrain oculomotor neurons endogenously labeled with reporter proteins driven by specific Hox gene regulatory sequences. The second aim will use targeted misexpression of each Hox4 paralog to produce changes in neuronal structure / function and eye movements (as documented in Aim 1) to test the contributions of Hox4 genes to specification of PNI, VNI, IO and TAN neurons. The third aim will use perturbation of retinoic acid-sensitive regulatory pathways to manipulate hindbrain segmentation and neuronal specification to identify additional genes required for origin, migration and function of the four oculomotor nuclei. Disruptions in the genetic regulatory cascades specifying these oculomotor subgroups will be directly linked to morphological and electrophysiological alterations in their task specific neural networks as reflected in behavioral sequelae. The overall objective of the proposed work is to analyze oculomotor neurons and behaviors that have been functionally conserved throughout vertebrate evolution to establish a basis for understanding the developmental genetic underpinnings of human oculomotor behavior and eye movement disorders.

描述（由申请人提供）：这项研究的目的是通过利用斑马鱼的发育遗传学来研究动眼神经元生理和行为的个体。为了实现这一目标，我们将研究有助于水平和扭转眼运动的四种神经元亚型的生理和遗传规范。拟议的研究将侧重于动眼神经元和电路的可量化行为和生理特性，以探索Hox Paralog 4基因（Hoxa4a，Hoxb4a，Hoxb4a，Hoxc4a，Hoxd4a，Hoxd4a）在图案中的图案和分化三核从Horigontal Eye temintion and HiNdbriant rhinsi and Hindbrian rhindbrain ryne nike and nictre nike nibol thine and Bresn nikoin rane的作用（HOXA4A，HOXB4A，HOXB4A，HOXC4A，HOXD4A）的作用。执行神经整合，为水平固定和前庭反射性能提供眼睛位置信号。第二个VNI编码眼速，并为前庭脑提供了主要的输入信号，因此在所有动眼可塑性范式中都具有重要作用。第三个核，下橄榄（IO），为眼球运动稳定性所需的小脑提供了攀爬纤维的输入。另外，将研究切向核（TAN）的生理和发育。棕褐色负责引力静脉补偿性眼反射，并在HOX旁系同源物3基因控制下在菱形5中发展。耳石诱导的扭转眼运动将为HOX4和HOX3基因之间的交叉调节作用提供一个测定。该项目的第一个目的是表征由特定HOX基因调节序列驱动的报告蛋白内源标记的鉴定后脑眼动神经元的电生理学，形态和行为。第二个目标将使用每个HOX4旁系同源物的靶向Misexpression产生神经元结构 /功能和眼动的变化（如AIM 1中所述）来测试HOX4基因对PNI，VNI，VNI，IO，IO和TAN神经元规范的贡献。第三个目标将使用视黄酸敏感的调节途径的扰动来操纵后脑分割和神经元规范，以确定四个眼球核的起源，迁移和功能所需的其他基因。指定这些动眼运动亚组的遗传调节级联反应的破坏将直接与行为后遗症所反映的任务特定神经网络中的形态和电生理改变有关。拟议工作的总体目的是分析在整个脊椎动物进化过程中在功能上保守的动眼神经元和行为，以建立理解人眼动物行为和眼睛运动障碍的发育遗传基础的基础。