Cellular Analysis of the Vestibulo-Occular Reflex

前庭眼反射的细胞分析

• 批准号: 9360620
• 负责人: SASCHA DU LAC
• 金额: $ 40.89万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9360620
• 关键词: Acceleration; Anatomy; Ataxia; Behavioral; Biological; Blurred vision; Brain Stem; Calibration; Cell Nucleus; Cells; Cerebellar Diseases; Cerebellum; Clinical; Closure by clamp; Collection; Data; Development; Disease; Dyes; Electrophysiology (science); Exhibits; Eye; Eye Movements; Feedback; Foundations; Functional disorder; Generic Drugs; Goals; Image; Immunohistochemistry; Inferior; Investigation; Label; Laboratories; Lateral; Lobe; Medial; Mediating; Membrane Potentials; Modeling; Molecular; Motion; Movement Disorders; Mus; Neurodegenerative Disorders; Neurons; Ocular Motility Disorders; Olives - dietary; Opsin; Optic tract structure; Output; Pathologic Nystagmus; Pathway interactions; Pattern; Performance; Pharmacological Treatment; Phase; Physiological; Population; Positioning Attribute; Postsynaptic Membrane; Preparation; Purkinje Cells; Reflex action; Reporter; Research; Retina; Role; Signal Transduction; Slice; Stimulus; Synapses; Synaptic Transmission; Testing; Therapeutic; Training; Trauma; Vestibular nucleus structure; Viral; Visual; Visual Motion; Visual Pathways; cell type; experience; experimental study; gaze; improved; medial vestibular nucleus; nerve supply; nucleus reticularis; oculomotor; optogenetics; photoactivation; postsynaptic; prevent; tool; vestibulo-ocular reflex; visual image movement; visual motor; visual stimulus

Project Summary The long-range goal of this research is to understand the cellular and molecular mechanisms that mediate the normal performance and adaptive plasticity of smooth eye movements. The optokinetic reflex (OKR) prevents blurred vision during self-motion by producing smooth eye movements that compensate for full field image motion. Neuronal mechanisms of plasticity enable the OKR to adapt in the face of development, trauma, and disease. Although the roles of particular classes of neurons to signal transformations and plasticity have been identified, little is understood about how cellular mechanisms contribute to the day-to-day performance and adaptive capabilities of the OKR and other smooth eye movements. The objective of the proposed research is to elucidate how cerebellar activity influences signaling and plasticity in distinct classes of brainstem neurons responsible for smooth eye movements. The central hypothesis is that cerebellar and visual pathway synapses onto vestibular nucleus and nucleus prepositus hypoglossi neurons are differentially responsible for rapid initiation vs maintained components of smooth eye movements. The proposed research will examine the influence of cerebellar activity on eye movements evoked by moving visual stimuli. Cellular and synaptic physiological experiments in brainstem slice preparations will examine the short and long term dynamics of cerebellar and visual synapses onto cerebellar recipient neurons, which mediate cerebellar influences on signaling and plasticity on smooth eye movements. Distinct classes of cerebellar target neurons will be identified by their axonal projections and patterns of cerebellar synaptic cell terminals. The influence of visual pathway and cerebellar synaptic activity will be examined in cerebellar target neurons in the vestibular and prepositus nuclei. These studies will provide foundations for targeted investigations of the molecular mechanisms that mediate smooth eye movements as well as for pharmacological treatments of cerebellar disorders and of oculomotor disorders that cause nystagmus.

项目摘要 这项研究的长期目标是了解细胞和分子 调节平滑眼正常表现和适应性可塑性的机制 动作视动反射（OKR）通过以下方式防止自我运动期间的视力模糊： 产生补偿全场图像运动的平滑眼睛运动。神经元 可塑性机制使OKR能够适应发展，创伤， 和疾病虽然特定种类的神经元在信号传递中的作用 虽然已经确定了细胞的转化和可塑性，但人们对细胞是如何形成的却知之甚少。 机制有助于日常的性能和适应能力的 OKR和其他平滑的眼球运动。拟议研究的目的是 阐明小脑活动如何影响不同类别的信号传导和可塑性， 负责平稳眼球运动的脑干神经元。核心假设是 小脑和视觉通路与前庭神经核和 舌下前置肌神经元对快速启动和 保持平稳的眼球运动。这项研究将审查 小脑活动对运动视觉刺激诱发的眼球运动的影响。 脑干切片制备中的细胞和突触生理学实验将 检查小脑和视觉突触的短期和长期动力学， 小脑受体神经元，介导小脑对信号传导的影响， 平滑眼球运动的可塑性。小脑靶神经元的不同类别将是 通过它们的轴突投射和小脑突触细胞末端的模式来识别。 视觉通路和小脑突触活动的影响将在 前庭核和前置核中的小脑靶神经元。这些研究将 为有针对性地研究分子机制提供了基础， 介导平稳的眼球运动以及用于小脑的药物治疗 引起眼球震颤的眼部疾病。