Neural mechanisms of active gaze stabilization (AGS) in monkeys

猴子主动凝视稳定（AGS）的神经机制

• 批准号: 9756158
• 负责人: Paul J May
• 金额: $ 32.41万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9756158
• 关键词: Agonist; Animal Model; Animals; Axon; Brain Stem; Cell Nucleus; Clinical; Cognition; Diagnosis; Differential Diagnosis; Disease; Doctor of Philosophy; Etiology; Exhibits; Eye; Eye Movements; Future; Goals; Head; Head Movements; Human; Individual; Inferior; Interneurons; Investigation; Knowledge; Lateral; Medial; Mediating; Modeling; Monkeys; Motion; Motor; Motor Neurons; Muscimol; Nerve; Neurons; Output; Pathologic Nystagmus; Plants; Play; Positioning Attribute; Role; Rotation; Saccades; Sensory; Signal Transduction; Source; Strabismus; Sum; System; Testing; Therapeutic Intervention; Training; Translations; Vision; Visual system structure; Work; abducens nucleus; anatomical tracing; effective therapy; fovea centralis; gaze; improved; information processing; interest; microstimulation; nerve supply; nervous system disorder; neuromechanism; neurophysiology; novel; oculomotor; orbit muscle; public health relevance; relating to nervous system; response; sensory input; vestibulo-ocular reflex; visual information

 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.

 描述（由申请人提供）：在具有中央凹视觉系统的人类和其他动物中，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。了解神经系统疾病中动眼神经疾病（例如眼球震颤、斜视等）的病因，并制定鉴别诊断和有效的治疗方法。具有执行两个基本功能的多个子系统：移动注视以获取新的感兴趣目标以及稳定目标上的注视以防止头部或目标运动我们在此建议研究注视稳定以防止自生或主动头部运动的神经机制。该提案的目的是受到我们最近的三个发现的启发，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眼睛调节的。这前庭眼反射 (VOR)，由延迟约 7 毫秒的前庭感觉信号驱动，而是由先前未被识别的主动凝视稳定 (AGS) 反应介导，该反应由主动头部运动命令的必然放电驱动。我们进一步表明，VOR 的自适应变化不会转移到 AGS，这表明 AGS 不仅独立于 VOR，而且在主动头部旋转期间取代了 VOR。作为一种新颖的凝视稳定机制，AGS 挑战了当前将 VOR 视为与眼跳相互作用的唯一凝视稳定机制的模型。 ，我们确定了一组对主动和被动头部运动做出反应的脑干前庭头部（VH）神经元，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。根据 Robinson 提出的眼植物假说，该假说假设运动神经元放电率和眼球运动之间存在固定关系，我们发现在眼头注视组合转移后，AGS 期间外展神经元的放电率远低于其反应预测的值总而言之，这三个结果意味着当前的凝视控制模型（使用单独的动眼神经子系统在头部固定模型中开发）不足以理解涉及主动头部运动和多个运动的自然条件下的控制。该提案的目的是通过描述 VH 神经元的作用和连接以及眼头联合运动期间激动/拮抗眼外肌 (EOM) 运动神经元的活动来阐明 AGS 的神经基础。