Motor unit diversity in horizontal eye movement control

水平眼球运动控制中运动单位的多样性

• 批准号: 8400817
• 负责人: Paul Douglas Gamlin
• 金额: $ 51.68万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8400817
• 关键词: Address; Anatomy; Animals; Brain; Characteristics; Contact Lenses; Data; Development; Diagnostic radiologic examination; Diplopia; Electric Stimulation; Electrodes; Eye; Eye Movements; Face; Fatigue; Fiber; Generations; Histology; Image; Implant; Individual; Isometric Exercise; Knowledge; Lateral; Lead; Lesion; Location; Macaca; Macaca mulatta; Magnetic Resonance Imaging; Measurement; Measures; Medial; Methods; Modeling; Monkeys; Motor; Motor Neurons; Movement; Muscle; Muscle Fibers; Nerve; Neurons; Ocular Motility Disorders; Operative Surgical Procedures; Pharmaceutical Preparations; Phase; Physiological; Physiology; Plants; Positioning Attribute; Primates; Procedures; Property; Protein Isoforms; Recruitment Activity; Reporting; Research Personnel; Retinal; Role; Saccades; Signal Transduction; Site; Smooth Pursuit; Specificity; Speed; Staging; Strabismus; Suction; System; Techniques; Tendon structure; Testing; Time; Transducers; Vision; design; gaze; instrument; interest; motor control; nerve supply; neuromuscular; neuromuscular system; neuroregulation; nonhuman primate; novel; oculomotor; orbit muscle; relating to nervous system

DESCRIPTION (provided by applicant): The oculomotor control system of foveate animals such as primates faces very diverse demands depending on the eye movement task. During some periods of time, the brain must precisely control the extraocular muscles so the eyes steadily fixate and stabilize the retinal image; during other periods, it must control the extraocular muscles to move the eyes rapidly from one position to another (saccades), or track objects of interest at widely differing speeds (smooth pursuit), or precisely change the viewing angle of the two eyes (vergence). It is currently assumed that these eye movements are produced through common pools of motor units (a "motor unit" is a motor neuron and its muscle fibers), recruited irrespective of task. But there is clear anatomic and histological evidence of motor unit diversity with physiological evidence of differential inputs from the oculomotor subsystems. Also, by directly measuring eye muscle forces using muscle force transducers (MFTs) and finding that they could not be predicted from neural innervation, we recently demonstrated that the simple concept of a final common motor path is incorrect ("missing force paradox"), and that this notion likely has impaired our understanding of the neuromuscular control of eye movements. In non-human primates, we propose to investigate how motor units with distinct characteristics and locations are recruited differentially for different horizontal ee motor tasks (saccades, smooth pursuit, and vergence) and task phases (phasic and tonic). We will identify lateral and medial rectus motoneurons using antidromic activation and spike-triggered averaging of electromyograms (STA-EMG), and measure motor unit functional properties using spike-triggered averaging of the muscle force transducer signal (STA-MFT), a new method we have recently validated. We will precisely localize motoneurons with X-ray images registered to MRI and histology, and fully characterize motor unit activity during these horizontal eye movements. Better understanding of eye motor control should lead to better treatment of eye movement disorders, such as strabismus. Drugs that modify eye muscle properties, elsewhere under development, show promise as simple, inexpensive office procedures able to effect corrections not possible with strabismus surgery. Our STA- MFT technique would be suitable to study the fiber type specific functionality of pharmacologically-modified motor units in alert animals. Relevance The novel techniques used in this proposal will allow us, for the first time, to study long-overlooked task specificities in the neuromuscular systems that stabilize and move our eyes for effective vision. These studies should result in more effective and less costly treatments for strabismus and other eye movement disorders that are of a neuromuscular origin. PUBLIC HEALTH RELEVANCE: Accurate binocular alignment of the eyes on targets at different distances requires precise horizontal eye movements. Individuals with deficits in such eye movements are often strabismic and report diplopia (double-vision). We hypothesize that physiologically distinct motor unit types contribute differentially to the dynamic and static components of different horizontal eye movements. We will characterize such motor units in alert, behaving animals during different horizontal eye movements and hence test our hypothesis.

描述（由申请人提供）：视眼运动任务而定，诸如灵长类的中央凹动物的眼控制系统面临非常多样化的需求。在某些时期，大脑必须精确地控制眼外肌，使眼睛稳定地注视和稳定视网膜图像;在其他时期，它必须控制眼外肌将眼睛从一个位置快速移动到另一个位置（扫视），或以不同的速度跟踪感兴趣的物体（平滑追踪），或精确地改变两只眼睛的视角（聚散）。目前认为，这些眼球运动是通过共同的运动单元池（“运动单元”是运动神经元及其肌肉纤维）产生的，与任务无关。但是，有明确的解剖学和组织学证据表明运动单位的多样性，以及来自眼神经子系统的不同输入的生理学证据。此外，通过使用肌肉力量传感器（MFTs）直接测量眼肌肉力量，并发现它们不能从神经支配中预测，我们最近证明了最终共同运动路径的简单概念是不正确的（“缺失力量悖论”），并且这种概念可能损害了我们对眼运动的神经肌肉控制的理解。 在非人类灵长类动物中，我们建议调查不同的水平ee运动任务（眼跳，顺利的追求，和聚散）和任务阶段（相位和紧张）的不同特点和位置的运动单位招募。我们将使用逆向激活和尖峰触发平均肌电图（STA-EMG）识别外直肌和内直肌运动神经元，并使用尖峰触发平均肌肉力传感器信号（STA-MFT）测量运动单位功能特性，这是我们最近验证的一种新方法。我们将精确定位运动神经元与X射线图像配准到MRI和组织学，并充分表征运动单位的活动，在这些水平眼球运动。 更好地理解眼球运动控制应该导致更好地治疗眼球运动障碍，如斜视。其他地方正在开发的改变眼肌特性的药物，显示出简单、廉价的办公室程序，能够实现斜视手术无法实现的矫正。我们的STA-MFT技术将适合于研究警觉动物中药理学修饰的运动单位的纤维类型特异性功能。相关性在这项提案中使用的新技术将使我们能够第一次研究长期被忽视的神经肌肉系统的任务特异性，这些系统稳定和移动我们的眼睛以获得有效的视觉。这些研究将为斜视和其他源于神经肌肉的眼球运动障碍提供更有效、更便宜的治疗方法。 公共卫生相关性：在不同距离的目标上准确的双眼对准需要精确的水平眼球运动。在这种眼球运动中有缺陷的人通常会斜视并报告复视（复视）。我们假设，生理上不同的运动单位类型有助于不同的水平眼球运动的动态和静态成分。我们将描述这些运动单位在警觉，行为动物在不同的水平眼球运动，从而测试我们的假设。