STUDIES OF THREE-DIMENSIONAL OCULAR KINEMATICS

描述(申请人提供)：这些研究的长期目标是了解大脑和眼外肌是如何在三维(3D)中产生眼球运动的。使用由单单位记录和电微刺激组成的综合方法，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”，该假说认为运动神经元的命令是二维的(即水平/垂直)，眼外肌滑轮负责提供与眼睛位置相关的肌肉拉动方向，从而在视觉引导的眼球运动中实施3D眼球旋转的“半角规则”。在这个应用中，我们提出了一系列系统的实验，集中在以下问题上：违反Listing定律和半角规则的眼球运动(例如，旋转前庭-眼睛反射，RVOR)如何与机械地实施半角规则的眼植物一起工作？具体地说，在RVOR和其他背离Listing定律和半角规则的情况下，依赖于眼睛位置的肌肉拉动方向是如何改变的？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个单位记录作为工具来了解这些运动中眼外肌滑车的特殊结构。具体地说，我们提出了以下目标/实验：(1)我们将使用电刺激外展神经来表征头部/身体倾斜方向(静态眼球反转)的眼外肌结构。(2)我们将使用电刺激外展神经来研究眼外肌在会聚过程中的形态。(3)我们将通过在稳态正弦和瞬时滚头旋转过程中通过电刺激外展神经来检验这样的假设，即滑轮在与眼球扭转相同的方向上的协调旋转是导致在滚转RVOR过程中偏离半角规则的原因。(4)与目标3一样，我们将通过评估平移VOR(TVOR)和偏航RVOR组合时刺激诱发的眼速对眼睛位置的依赖来研究联合旋转和平移时眼外肌滑轮的配置，这两种条件会导致不同的眼睛位置依赖。(5)最后，一旦在VOR中建立了动眼神经的组织结构，接下来我们将描述和比较上/下斜肌和上/下直肌在翻滚RVOR和联合RVOR/TVOR中作为凝视功能的神经活动。在这种情况下，眼球位置对眼球速度的依赖明显偏离半角度规则(动眼神经的默认排列)。我们期望在环状垂直运动神经元的放电率中找到这种由RVOR/TVOR驱动的扭转的相关性。这些实验的结果将极大地扩展我们目前对眼球运动过程中滑轮和眼外肌功能的理解，这些运动违反了Listing定律。与公共卫生相关的斜视，即两只眼睛的错位，是一种病因不明的疾病，由发送到眼肌和/或眼肌和眼眶组织本身的中枢神经支配问题引起。提高我们对眼球运动控制的中枢和外周方面的了解是有效临床诊断和治疗斜视患者的重要和必要的步骤。拟议实验的结果也是解决正在进行的争议的基础，并提供了对健康和疾病中的动眼功能的全面了解。

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.