Cellular Analysis of the Vestibulo-Ocular Reflex

前庭眼反射的细胞分析

• 批准号: 7123832
• 负责人: SASCHA DU LAC
• 金额: $ 40.91万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7123832
• 关键词: NMDA receptors; action potentials; calcium channel; calcium channel blockers; electrostimulus; eye movements; glutamate receptor; head movements; interneurons; laboratory mouse; neural information processing; neural plasticity; neural transmission; neuroanatomy; neuropharmacology; nystagmus; synapses; vestibular nuclei; vestibuloocular reflex

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 intrinsic membrane properties of neurons in the medial vestibular nucleus (MVN) contribute to signaling and plasticity in the VOR. The central hypothesis is that the adaptive capabilities of the VOR are mediated, in part, by changes in the intrinsic firing properties of MVN neurons. The proposed research will use a brainstem slice preparation to examine the intrinsic firing properties and ionic currents of cerebellar target neurons, which mediate cerebellar influences on signaling and plasticity in the VOR. The influence of neuronal activity on plasticity of intrinsic firing properties will be compared in cerebellar target neurons and other identified MVN neurons. The contributions of plasticity in intrinsic firing properties to VOR plasticity will be examined by assessing intrinsic firing mechanisms of MVN neurons recorded from slices obtained at different stages of adaptive gain changes in the VOR. 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 oculomotor disorders that cause nystagmus.

描述（由申请人提供）：本研究的长期目标是了解介导前庭眼反射（VOR）正常表现和适应性可塑性的细胞和分子机制。VOR通过产生精确补偿头部运动的眼球运动来防止自我运动期间的视力模糊。可塑性的神经元机制使VOR能够准确地面对发育、创伤和疾病。虽然已经确定了特定类别的神经元对信号转换和可塑性的作用，但对细胞机制如何促进VOR的日常表现和适应能力知之甚少。这项拟议研究的目的是阐明前庭内侧核（MVN）神经元的内在膜特性如何有助于VOR的信号传导和可塑性。中心的假设是，VOR的自适应能力是介导的，在一定程度上，由MVN神经元的内在放电特性的变化。拟议的研究将使用脑干切片制备来检查小脑靶神经元的内在放电特性和离子电流，这些神经元介导小脑对VOR中的信号传导和可塑性的影响。神经元活动对内在放电特性可塑性的影响将在小脑靶神经元和其他已鉴定的MVN神经元中进行比较。在VOR可塑性的内在放电特性的可塑性的贡献将通过评估内在放电机制的MVN神经元记录在VOR的自适应增益变化的不同阶段获得的切片检查。这些研究将为前庭眼反射可塑性的分子机制的靶向研究以及引起眼球震颤的眼科疾病的药物治疗提供基础。