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。这项拟议研究的目的是阐明小脑活动如何影响不同类别前庭核神经元的信号传递和可塑性。中心假说是中央前庭和小脑与前庭核神经元的突触表现出活动依赖性的可塑性。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短期和长期突触动力学，这些突触动力学介导小脑对VOR中的信号和可塑性的影响。通过轴突投射和小脑突触细胞终末的模式，可以识别不同类别的小脑靶神经元。前庭神经、连合和小脑突触活动的影响将在小脑靶点神经元和其他已确定的前庭核神经元中进行检测。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小脑疾病和导致眼球震颤的眼球运动障碍的药物治疗提供基础。 与公众健康相关：该项目的目标是确定眼球运动表现和可塑性的细胞机制，特别关注小脑对前庭-眼睛反射的影响，这对在自我运动过程中稳定视网膜上的图像至关重要。前庭和小脑控制眼球运动的细胞学分析对于开发治疗包括共济失调和神经退行性疾病在内的小脑疾病以及包括眼球震颤和随之而来的摆动的破坏性眼球运动障碍都是至关重要的。

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. PUBLIC HEALTH RELEVANCE: The goal of this project is to identify cellular mechanisms of eye movement performance and plasticity, with a particular focus on cerebellar influence over the vestibulo-ocular reflex, which is critical for stabilizing images on the retina during self-motion. Cellular mechanistic analyses of vestibular and cerebellar control of eye movements are essential for developing therapeutic treatments both for cerebellar disorders including ataxias and neurodegenerative diseases as well as for devastating disorders of eye movements including nystagmus and consequent oscillopsia.