Cellular Analysis of the Vestibulo-Ocular Reflex

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）正常功能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力模糊。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。尽管特定类型的神经元在信号转换和可塑性方面的作用已经被确定，但对于细胞机制如何影响VOR的日常表现和适应能力，人们知之甚少。本研究的目的是阐明内侧前庭核（MVN）神经元的内在膜特性如何影响VOR的信号传导和可塑性。核心假设是，VOR的适应能力部分是由MVN神经元内在放电特性的变化介导的。本研究将利用脑干切片技术研究小脑目标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信号传导和可塑性的影响。在小脑靶神经元和其他已确定的MVN神经元中，将比较神经元活动对内禀放电特性可塑性的影响。通过评估在不同阶段的自适应增益变化中获得的MVN神经元的内禀放电机制，研究内禀放电特性的可塑性对VOR可塑性的贡献。这些研究将为前庭-眼反射可塑性的分子机制的针对性研究以及引起眼球震颤的动眼病的药物治疗提供基础。

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.