Motor Learning & Neural Plasticity in Vestibular System

描述(由申请人提供)前庭-眼反射(VOR)在头部运动时稳定凝视，从而稳定中心凹图像。疾病或发育变化导致的VOR缺陷可能严重损害视力。VOR的神经适应是克服这些缺陷的关键。在过去的几十年里，对VOR及其适应的研究一直集中在脑干和小脑通路的贡献上。然而，大脑皮层在VOR中的作用在很大程度上仍未被探索。最近的研究表明，前庭眼场(FEF)直接投射到脑干VOR通路，FEF亚区与眼球平稳运动相关的神经元(FEFsem)显示出与眼球运动和头部运动有关的活动，提示FEFsem在VOR中起着重要作用。拟议研究的目的是采用单单位记录和化学损伤的方法来研究FEFsem在VOR的产生和适应中的贡献。第一个目标是使用单单位记录技术来定量分析FEFsem神经元如何编码猴子的头部运动。最近，我们开发了一种范式，在VOR中诱导强大的短期和长期可塑性，以补偿平移性头部运动(TVOR)。该范式的一个新特点是，这些行为变化不是由视觉信息引导的，而是由任务的空间背景引导的，即目标是在空间中静止的还是相对于头部固定的。第二个目的是利用这一范式研究FEFsem神经元在TVOR产生中的作用。本实验将对FEFsem在与任务背景相关的信息加工以及对TVOR的自愿控制和适应方面有更好的理解。第三个目的是通过可逆地使FEFsem失活并研究其对TVOR的产生和适应的影响来评估FEFsem的功能意义。这项研究将为了解人类前庭和动眼神经生理学基础，提高前庭疾病的诊断和治疗水平提供重要的知识。

DESCRIPTION (provided by applicant) The vestibulo-ocular reflex (VOR) stabilizes gaze and hence foveal images during head movements. Deficits in the VOR resulting from disease or changes in development can severely impair vision. Neural adaptation in the VOR is essential to overcome these deficits. Over the past several decades, the investigation of the VOR and its adaptation has been focused on the contributions of brainstem and cerebellar pathways. The contributions of cerebral cortex in the VOR, however, remain largely unexplored. Recent studies have demonstrated that the frontal eye field (FEF) has direct projections to brainstem VOR pathways and neurons in the subregion of the FEF linked to smooth eye movements (FEFsem) exhibit activity related to both eye movements and head movements, suggesting an important role for the FEFsem in the VOR. The objective of the proposed research is to employ single unit recording and chemical lesion approaches to study the contributions of the FEFsem in the generation and adaptation of the VOR. The first aim is to use single unit recording techniques to quantitatively analyze how the FEFsem neurons encode head motion in monkeys. Recently, we have developed a paradigm that induces robust short-term and long-term plasticity in the VOR that compensates for translational head movements (TVOR). A novel feature of the paradigm is that these behavioral changes are not guided by visual information but by the spatial context of the task, i.e. whether the target is stationary in space or fixed relative to the head. The second aim is to take advantage of this paradigm to study the role of the FEFsem neurons in the generation of the TVOR. This experiment will provide greater understanding of the FEFsem in the information processing related to the task context and in the voluntary control and adaptation of the TVOR. The third aim is to assess the functional significance of the FEFsem by reversibly inactivating the FEFsem and studying its effect on the generation and adaptation of the TVOR. This research will provide important knowledge for understanding the fundamental vestibular and oculomotor neurophysiology and improving the diagnosis and treatment of vestibular disorders in humans.