Cellular Analysis of the Vestibulo-Occular 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。这项研究的目的是阐明小脑活动如何影响不同类别的前庭核神经元的信号传导和可塑性。中心假设是，中央前庭和小脑的前庭核神经元的突触表现出活动依赖的可塑性。拟议的研究将使用脑干切片制备来检查小脑靶神经元的短期和长期突触动力学，这些神经元介导小脑对VOR中的信号传导和可塑性的影响。小脑靶神经元的不同类别将通过其轴突投射和小脑突触细胞终末的模式来识别。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经鉴定的前庭核神经元中进行检查。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导致眼球震颤的小脑疾病和眼功能障碍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 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.