STUDIES OF THREE-DIMENSIONAL OCULAR KINEMATICS

描述（由申请人提供）：这些研究的长期目标是了解大脑和眼外肌肉如何在三维空间（3D）中产生眼球运动。使用组合方法，包括单单元记录和电微刺激，我们提供了强有力的神经生理学证据来支持“主动滑轮假说”，该假说提出运动神经元命令是二维的（即水平/垂直），眼外肌滑轮负责提供与眼睛位置相关的肌肉牵拉方向。从而在视觉引导的眼球运动中实现3D眼球旋转的“半角规则”。在这个应用程序中，我们提出了一系列系统的猕猴实验，重点关注以下问题：违反李斯特定律和半角规则的眼球运动（例如，旋转前庭-眼反射，RVOR）如何与机械执行半角规则的眼睛植物一起工作？具体来说，在RVOR等偏离Listing’s定律和半角法则的情况下，依赖于眼睛位置的肌肉牵拉方向是如何发生改变的？我们建议使用外展神经的电微刺激和眼外运动神经元的单单位记录作为工具来了解这些运动中眼外肌滑轮的特殊结构。具体而言，我们提出以下目标/实验：(1)我们将使用外展神经的电微刺激来表征倾斜头/身体方向（静态眼反滚动）的眼外肌结构。(2)我们将利用电微刺激外展神经来研究会聚时眼外肌的形态。(3)我们将通过在稳态正弦和瞬态滚头旋转期间电刺激外展神经来验证滚轮与眼球扭转方向相同的协调旋转是滚轮RVOR中偏离半角规则的原因。(4)在目标3中，我们将通过评估在平移VOR （TVOR）和偏航RVOR组合时刺激诱发的眼速度对眼位置的依赖性来研究旋转和平移组合时眼外肌滑轮的配置，这些条件会导致不同的眼位置依赖性。(5)最后，一旦确定了VOR过程中动眼植物的组织，我们接下来将描述和比较上/下斜肌和上/下直肌在滚动RVOR和联合RVOR/TVOR过程中作为凝视函数的神经活动。在这些条件下，眼速的眼位依赖性明显偏离半角规则（动眼植物的默认安排）。我们期望找到这种RVOR/ tvor驱动的扭转在循环垂直运动神经元的放电速率的相关性。这些实验的结果将大大扩展我们目前对违反李氏定律的眼球运动中滑轮和眼外肌功能的理解。斜视，即双眼不对准，是一种病因不明的疾病，由发送到眼肌和/或眼肌和眼窝组织本身的中枢神经支配有关的问题引起。提高我们对眼动控制的中枢和外周方面的认识是有效诊断和治疗斜视患者的重要和必要的一步。提出的实验结果也是解决持续争议的基础，并提供对健康和疾病中的动眼肌功能的全面理解。

DESCRIPTION (provided by applicant): The long-term goal of these studies is to understand how the brain and the extraocular muscles generate eye movements in three-dimensions (3D). Using a combined approach, consisting of both single unit recordings and electrical microstimulation, we have provided strong neurophysiological evidence in support of the `active pulley hypothesis', which proposes that motoneuron commands are two-dimensional (i.e., horizontal/vertical) and that extraocular muscle pulleys are responsible for providing for an eye position-dependent muscle pulling direction, thus implementing the `half-angle rule' of 3D eye rotations during visually-guided eye movements. In this application, we propose a systematic series of experiments in macaques that focus on the following questions: How do eye movements that violate Listing's law and the half-angle rule (e.g., the rotational vestibulo-ocular reflex, RVOR) work with an eye plant that mechanically implements the half-angle rule? Specifically, how do the eye position-dependent muscle pulling directions become modified during the RVOR and other conditions that deviate from Listing's law and the half-angle rule? We propose to use electrical microstimulation of the abducens nerve and single unit recordings from extraocular motoneurons as tools to understand the particular configuration of the extraocular muscle pulleys during these movements. Specifically, we propose the following aims/experiments: (1) We will use electrical microstimulation of the abducens nerve to characterize extraocular muscle configuration at tilted head/body orientations (static ocular counter-rolling). (2) We will use electrical microstimulation of the abducens nerve to investigate extraocular muscle configuration during convergence. (3) We will test the hypothesis that a coordinated rotation of the pulleys in the same direction as eyeball torsion is responsible for the deviations from the half-angle rule during the roll RVOR by electrically stimulating the abducens nerve during steady-state sinusoidal and transient roll head rotations. (4) As in aim 3, we will investigate the extraocular muscle pulley configuration during combined rotations and translations by evaluating the eye position dependence of the stimulation-evoked eye velocity during combinations of translational VOR (TVOR) and yaw RVOR, conditions that result in diverse eye position dependencies. (5) Finally, once the organization of the oculomotor plant during the VOR is established, we will next characterize and compare neural activities of superior/inferior oblique and superior/inferior rectus as a function of gaze during the roll RVOR and combined RVOR/TVOR. Under these conditions, the eye position dependence of eye velocity deviates significantly from the half-angle rule (default arrangement of the oculomotor plant). We expect to find a correlate of such RVOR/TVOR-driven torsion in the firing rates of cyclovertical motoneurons. Results from these experiments will substantially expand our current understanding of pulley and extraocular muscle function during eye movements that violate Listing's law. PUBLIC HEALTH RELEVANCE Strabismus, the misalignment of the two eyes, is a disorder of unknown etiology, caused by problems related to either the central innervation sent to the eye muscles and/or the eye muscles and orbital tissues themselves. Improving our understanding of the central and peripheral aspects of eye movement control is an important and necessary step for an effective clinical diagnosis and treatment of strabismus patients. Results from the proposed experiments are also fundamental in resolving on-going controversies and providing a comprehensive understanding of oculomotor function in health and disease.