Cellular Analysis of the Vestibulo-Occular Reflex

前庭眼反射的细胞分析

基本信息

批准号：
8822456
负责人：
SASCHA DU LAC
金额：
$ 35.72万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8822456
关键词：
Ataxia Axon Blurred vision Brain Stem Brain region Calibration Cell Nucleus Cells Cerebellar Diseases Cerebellar Nuclei Cerebellum Dendrites Development Disease Dyes Electric Stimulation Ensure Exhibits Eye Movements Foundations Goals Green Fluorescent Proteins Head Head Movements Health Image Inferior Injection of therapeutic agent Investigation Label Learning Mediating Membrane Methods Modeling Molecular Motion Movement Mus Neurodegenerative Disorders Neurons Ocular Motility Disorders Oculomotor nucleus Olives - dietary Pathologic Nystagmus Pattern Performance Pharmacological Treatment Pharmacology Physiological Preparation Presynaptic Terminals Purkinje Cells Reflex action Research Reticular Formation Retina Role Route Signal Transduction Slice Specificity Spinal Cord Staging Synapses Synaptic Transmission Synaptic plasticity Techniques Testing Therapeutic Transgenic Mice Trauma Vestibular Nerve Vestibular nucleus structure base cell type design insight motor control nerve supply neural circuit novel oculomotor optogenetics postsynaptic presynaptic prevent research study signal processing tau Proteins transmission process vestibulo-ocular reflex visual image movement

项目摘要

DESCRIPTION (provided by applicant): The long-range goal of this research is to understand the cellular and molecular mechanisms that mediate the normal performance and adaptive plasticity of the vestibulo-ocular reflex (VOR). The VOR prevents blurred vision during self-motion by producing eye movements that precisely compensate for motion of the head. Neuronal mechanisms of plasticity enable the VOR to perform accurately 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 VOR. The objective of the proposed research is to elucidate how cerebellar activity influences signalling and plasticity in distinct classes of vestibular nucleus neurons. The central hypothesis is that central vestibular and cerebellar synapses onto vestibular nucleus neurons exhibit activity-dependent plasticity. The proposed research will use a brainstem slice preparation to examine the short and long term synaptic dynamics onto cerebellar target neurons, which mediate cerebellar influences on signaling and plasticity in the VOR. Distinct classes of cerebellar target neurons will be identified by their axonal projections and patterns of cerebellar synaptic cell terminals. The influence of vestibular nerve, commissural, and cerebellar synaptic activity will be examined in cerebellar target neurons and in other identified vestibular nucleus neurons. These studies will provide foundations for targeted investigations of the molecular mechanisms that underlie vestibulo-ocular reflex plasticity as well as for pharmacological treatments of cerebellar disorders and of oculomotor disorders that cause nystagmus.

描述（由申请人提供）：这项研究的远距离目标是了解介导前庭形式反射（VOR）正常性能和适应性可塑性的细胞和分子机制。通过产生精确补偿头部运动的眼睛运动，VOR可防止自我运动过程中的视力模糊。可塑性的神经元机制使VOR在发育，创伤和疾病时能够准确地性能。尽管已经确定了特定类别的神经元在信号转化和可塑性方面的作用，但几乎没有理解细胞机制如何促进VOR的日常性能和适应性能力。拟议的研究的目的是阐明小脑活性如何影响不同类别的前庭核神经元中的信号传导和可塑性。中心假设是中央前庭和小脑突触到前庭核神经元上表现出活性依赖性可塑性。拟议的研究将使用脑干切片制剂来检查小脑靶神经元的短期和长期突触动力学，从而介导小脑对VOR信号和可塑性的影响。小脑靶神经元的不同类别将通过小脑突触细胞末端的轴突投射和模式来识别。前庭神经，连合和小脑突触活动的影响将在小脑靶神经元和其他已鉴定的前庭核神经元中进行检查。这些研究将为靶向研究的基础研究，这些研究是基于前庭 - 眼反射可塑性以及小脑疾病和引起眼球震颤的眼球疾病的药理治疗的分子机制的基础。