Cellular Analysis of the Vestibulo-Ocular Reflex

描述(申请人提供)：这项研究的长期目标是了解调节前庭-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过程中的视觉模糊。神经元的可塑性机制使VOR在面对发育、创伤和疾病时能够准确地发挥作用。虽然特定类型的神经元在信号转换和可塑性中的作用已经被识别，但关于细胞机制如何对VOR的日常表现和适应能力做出贡献的了解很少。本研究的目的是阐明前庭内侧核(MVN)神经元的固有膜特性如何影响VOR的信号传递和可塑性。中心假设是，VOR的适应能力部分是通过MVN神经元内在放电特性的变化来调节的。这项拟议的研究将使用脑干切片制备来检测小脑靶神经元的内在放电特性和离子电流，这些特性和离子电流介导小脑对VOR中的信号和可塑性的影响。在小脑靶点神经元和其他已识别的MVN神经元中，将比较神经元活动对内在放电特性可塑性的影响。通过评估在VOR适应性增益变化的不同阶段获得的脑片记录的MVN神经元的内在放电机制，将检验内在放电特性的可塑性对VOR可塑性的贡献。这些研究将为有针对性地研究前庭-眼反射可塑性的分子机制以及药物治疗引起眼球震颤的眼球运动障碍提供基础。

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.