Neural mechanisms of active gaze stabilization (AGS) in monkeys

 描述（由申请人提供）：在人类和其他具有中央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至关重要。我们工作的首要目标是阐明眼球运动控制的神经机制，以了解眼病的病因（例如，眼球震颤、斜视等）在神经系统疾病，并开发鉴别诊断和有效的治疗。眼动系统具有执行两个基本功能的多个子系统：转移注视以获取新的感兴趣目标，以及针对头部或目标运动稳定对目标的注视。在这里，我们建议研究的神经机制的凝视稳定对自我产生的，或主动，头部运动。该提案的目的是由我们最近的三项发现激发的，这些发现挑战了当前的凝视控制模型。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，并发现针对主动头部运动的补偿性眼球运动不是由前庭眼反射（VOR）介导的，该反射由前庭感觉信号驱动，潜伏期约为7 ms。相反，它是由先前未识别的主动凝视稳定（AGS）反应介导的，该反应由相对于主动头部旋转具有零延迟的主动头部运动命令的必然放电驱动。我们进一步表明，VOR的适应性变化不转移到AGS，表明AGS不仅是独立的VOR，但也取代它在积极的头部旋转。作为一种新颖的注视稳定机制，AGS挑战了当前将VOR视为与扫视交互的唯一注视稳定机制的眼-头组合注视移位模型。其次，针对目前的假设，主动头部运动不是明确编码的脑干神经元，我们确定了一组脑干前庭头（VH）神经元，积极和被动的头部运动。这些神经元编码主动头部速度命令，在主动头部运动期间取代前庭感觉输入。第三，与罗宾逊提出的眼植物假说相反，该假说假设运动神经元放电率和眼球运动之间存在固定的关系，我们发现，在眼-头注视移位后，AGS期间外展神经元的放电率远低于VOR期间它们的反应所预测的。两者合计，这三个结果意味着，目前的模型的凝视控制，在头部固定的模型，使用一个单独的眼动子系统，是不足以理解的凝视控制在自然条件下，涉及主动头部运动和多个眼动子系统。该提案的目的是阐明AGS的神经基础，通过表征VH神经元的作用和连接以及激动剂/拮抗剂眼外肌（EOM）运动神经元在联合眼头运动期间的活动。

 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.