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如何在三维（3D）中产生眼球运动。使用由单个单元记录和电微刺激组成的组合方法，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”，该假说提出运动神经元命令是二维的（即，水平/垂直），而眼外肌滑轮负责提供依赖于眼睛位置的肌肉拉动方向，从而在视觉引导的眼睛运动期间实现3D眼睛旋转的“半角规则”。在本申请中，我们提出了一系列系统的猕猴实验，重点是以下问题：眼睛运动如何违反上市定律和半角规则（例如，旋转前庭眼反射（RVOR）与机械地实现半角规则的眼装置一起工作？具体来说，在RVOR和其他偏离Listing定律和半角规则的条件下，依赖于眼睛位置的肌肉牵拉方向是如何改变的？我们建议使用电微刺激外展神经和单个单位记录从眼外运动神经元作为工具，以了解在这些运动过程中的眼外肌滑轮的特定配置。具体而言，我们提出了以下目的/实验：（1）我们将使用外展神经的电微刺激来表征倾斜头部/身体取向（静态眼球反滚动）下的眼外肌构型。(2)我们将使用电微刺激外展神经来研究在会聚过程中眼外肌的构型。(3)我们将测试的假设，即一个协调的旋转的滑轮在相同的方向，眼球扭转是负责从半角规则的偏差，在滚动RVOR通过电刺激外展神经在稳态正弦和瞬态辊头旋转。(4)如在目标3中，我们将通过评估在平移VOR（TVOR）和偏航RVOR的组合期间刺激诱发的眼速度的眼位置依赖性（导致不同眼位置依赖性的条件）来研究在组合旋转和平移期间的眼外肌滑轮配置。(5)最后，一旦VOR过程中的眼神经系统的组织建立，我们接下来将描述和比较上级/下斜肌和上级/下直肌的神经活动，作为滚动RVOR和组合RVOR/TVOR过程中凝视的函数。在这些条件下，眼睛位置的眼速依赖性明显偏离了半角规则（默认安排的oculopharyngeplant）。我们希望找到一个相关的这种RVOR/TVOR驱动的扭转的循环垂直运动神经元的放电率。这些实验的结果将大大扩展我们目前的理解滑轮和眼外肌功能的眼睛运动，违反上市的法律。斜视是一种病因不明的疾病，是由发送到眼部肌肉的中央神经支配和/或眼部肌肉和眼眶组织本身的问题引起的。提高我们对眼动控制的中心和周边方面的理解是有效的临床诊断和治疗斜视患者的重要和必要的步骤。从拟议的实验结果也是解决正在进行的争议，并提供了健康和疾病的眼科功能的全面了解的基础。

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.