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小脑活动如何影响不同类别前庭核神经元的信号传导和可塑性。中心假设是前庭中枢和小脑突触与前庭核神经元表现出活动依赖的可塑性。本研究将利用脑干切片技术研究小脑目标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信号和可塑性的影响。不同类型的小脑目标神经元将通过它们的轴突投射和小脑突触细胞终端的模式来识别。前庭神经、联合神经和小脑突触活动的影响将在小脑目标神经元和其他已确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以及引起眼球震颤的小脑疾病和动眼肌疾病的药物治疗提供有针对性的研究基础。

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. 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.