Neural mechanisms of active gaze stabilization (AGS) in monkeys

 描述(申请人提供)：在人类和其他具有中心凹视觉系统的动物中，眼球运动对于清晰的视觉、视觉信息处理和认知是必不可少的。我们工作的首要目标是阐明眼动控制的神经机制，以便了解眼球运动障碍(例如，眼球震颤、斜视等)的病因。在神经系统疾病方面，并开发鉴别诊断和有效治疗方法。眼球运动系统有多个子系统，执行两个基本功能：移动目光以获得新的感兴趣目标，以及针对头部或目标运动稳定对目标的凝视。我们建议研究凝视稳定的神经机制，以对抗自身产生的或主动的头部运动。这项提议的目的是受到我们最近的三项发现的推动，这些发现挑战了当前的凝视控制模式。首先，我们训练猴子在保持稳定凝视的同时进行主动头部运动，发现针对主动头部运动的补偿性眼球运动不是由潜伏期~7ms的前庭感觉信号驱动的前庭-眼睛反射(VOR)介导的。相反，它是由先前未被识别的主动凝视稳定(AGS)反应介导的，该反应是由相对于主动头部旋转零潜伏期的主动头部运动指令的必然放电驱动的。我们进一步表明，VOR的适应性变化不会转移到AGS，这表明AGS不仅独立于VOR，而且在主动头部旋转过程中取代了VOR。作为一种新的凝视稳定机制，AGS挑战了现有的眼-头联合凝视转移模型，该模型认为VOR是唯一与眼跳相互作用的凝视稳定机制。其次，与目前认为主动头部运动不是由脑干神经元明确编码的假设相反，我们发现了一组对主动和被动头部运动都有反应的脑干前庭头部(VH)神经元。这些神经元编码主动的头部速度指令，在主动的头部运动中取代前庭感觉输入。第三，与Robinson提出的运动神经元放电率和眼动之间存在固定关系的眼动植物假说相反，我们发现在联合眼头注视转移后，AGS期间外展神经元的放电率远低于它们在VOR期间的反应所预测的。综上所述，这三个结果表明，当前的凝视控制模型是在使用单个动眼运动子系统的头部固定模型中发展起来的，不足以理解自然条件下涉及主动头部运动和多个动眼运动子系统的凝视控制。本研究的目的是通过表征VH神经元的作用和联系，以及在眼头联合运动过程中激动剂和拮抗剂眼外肌(EOM)运动神经元的活动，来阐明AGS的神经基础。

 DESCRIPTION (provided by applicant): In humans and other animals with foveate visual systems, eye movement is essential for clear vision, visual information processing, and cognition. The overarching goal of our work is to elucidate the neural mechanisms of eye movement control in order to understand the etiology of oculomotor disorders (e.g., nystagmus, strabismus, etc.) in neurological diseases, and to develop differential diagnoses and effective treatments. The oculomotor system has multiple subsystems performing two basic functions: shifting gaze to acquire a new target of interest and stabilizing gaze on the target against head or target motion. We here propose to study the neural mechanisms of gaze stabilization against self-generated, or active, head movement. The Aims of the proposal are motivated by three recent findings of ours that challenge current models of gaze control. First, we trained monkeys to make active head movements while maintaining stable gaze and found that compensatory eye movement against active head movement is not mediated by the vestibulo-ocular reflex (VOR), which is driven by vestibular sensory signals with a latency of ~7ms. Instead, it is mediated by a previously unrecognized active gaze stabilization (AGS) response, which is driven by corollary discharge of active head motor commands with zero latency with respect to active head rotation. We further showed that adaptive changes in VOR do not transfer to AGS, indicating that AGS is not only independent of the VOR, but also supersedes it during active head rotation. As a novel gaze stabilization mechanism, AGS challenges current models of combined eye-head gaze shifts that treat VOR as the sole gaze stabilizing mechanism interacting with saccades. Second, against the current assumption that active head movement is not explicitly encoded by brainstem neurons, we identified a group of brainstem vestibular-head (VH) neurons that respond to both active and passive head movements. These neurons encode active head velocity commands that supersede vestibular sensory input during active head movement. Third, contrary to the Ocular Plant Hypothesis proposed by Robinson, which assumes a fixed relationship between a motoneuron firing rate and eye movement, we found that following combined eye-head gaze shifts, the abducens neurons firing rate during AGS were much lower than that predicted by their responses during VOR. Taken together, these three results imply that current models of gaze control, developed in head-fixed models using an individual oculomotor subsystem, are insufficient to understand gaze control in natural conditions involving active head movement and multiple oculomotor subsystems. The Aims of the proposal are to elucidate the neural basis of AGS by characterizing the role and connections of VH neurons and the activity of motoneurons of the agonist/antagonist extraocular muscles (EOM) during combined eye-head movements.