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: 9117504
• 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 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9117504
• 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; Health; 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; base; effective therapy; fovea centralis; gaze; improved; information processing; interest; microstimulation; nerve supply; nervous system disorder; neuromechanism; neurophysiology; novel; oculomotor; orbit muscle; 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（由适用提供）：在人类和其他具有视觉系统的动物中，眼动对于清晰的视觉，视觉信息处理和认知至关重要。我们工作的总体目标是阐明眼动控制的神经元机制，以了解神经系统疾病中动眼疾病的病因（例如，眼球震颤，斜视，斜视等），并开发差异诊断和有效的治疗方法。眼动系统具有多个子系统，执行了两个基本功能：转移目光以获取新的目标目标，并稳定目标，以针对头部或目标运动。我们在这里建议研究针对自我生成或积极的头部运动的凝视稳定的神经机制。该提案的目的是由我们最近的三个发现挑战当前凝视控制模式的促进的动机。首先，我们训练了猴子在保持稳定的凝视的同时进行积极的头部运动，发现反对主动头部运动的补偿性眼动并非由前庭纤维反射（VOR）介导，后者是由前庭感觉信号驱动的，潜伏期约为7ms。取而代之的是，它是由先前未认识到的主动凝视稳定（AGS）响应介导的，该响应是由有效的头部电动机命令的推出，相对于主动头部旋转而零潜伏期。我们进一步表明，VOR的自适应变化不会转移到AGS上，表明AG不仅与VOR无关，而且在主动头部旋转过程中也取代了AG。作为一种新颖的凝视稳定机制，AGS挑战了当前的眼头凝视转移模型，这些模型将VOR视为唯一的凝视稳定机制与扫视相互作用。其次，根据当前的假设，即主动运动没有被脑干神经元明确编码，我们确定了一组脑干前庭头（VH）神经元，这些神经元对主动和被动头部运动响应。这些神经元编码主动速度命令，这些命令取代了主动头运动过程中前庭感觉输入。第三，与罗宾逊提出的眼工植物假设形成对比，罗宾逊假设运动神经元的发射速率和眼动之间存在固定的关系，我们发现，随着眼头视线移动的结合，AGS期间的神经元发射率远低于其在VOR期间的反应所预测的。综上所述，这三个结果表明，使用单个眼动子亚系统在头部固定模型中开发的目前的凝视控制模型不足以理解涉及主动头部运动和多个动眼运动子系统的自然条件下的凝视控制。该提案的目的是通过表征VH神经元的作用和连接以及在综合的眼头运动中激动剂/拮抗剂外肌肉（EOM）的运动神经元的活性来阐明AG的神经元基础。