Motor unit diversity in horizontal eye movement control

描述（由申请人提供）：灵长类等注视窝动物的眼动控制系统根据眼动任务的不同面临着非常多样化的需求。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，它必须控制眼外肌肉使眼睛快速地从一个位置移动到另一个位置（扫视），或者以不同的速度跟踪感兴趣的物体（平滑追踪），或者精确地改变两只眼睛的视角（收敛）。目前的假设是，这些眼球运动是通过共同的运动单元池产生的（一个“运动单元”是一个运动神经元和它的肌肉纤维），与任务无关。但有明确的解剖和组织学证据表明运动单元多样性，生理证据表明来自动眼肌子系统的不同输入。此外，通过使用肌肉力传感器（mft）直接测量眼肌力，并发现它们无法从神经支配中预测，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（“缺失力悖论”），并且这个概念可能损害了我们对眼球运动的神经肌肉控制的理解。在非人类灵长类动物中，我们建议研究具有不同特征和位置的运动单元如何在不同的水平眼动运动任务（扫视、平滑追求和收敛）和任务阶段（相性和强直性）中被不同地招募。我们将使用反反激活和肌电图（STA-EMG）的峰触发平均来识别外侧和内侧直肌运动神经元，并使用肌力传感器信号（STA-MFT）的峰触发平均来测量运动单元的功能特性，这是我们最近验证的一种新方法。我们将通过MRI和组织学记录的x射线图像精确定位运动神经元，并充分表征这些水平眼运动期间的运动单元活动。更好地了解眼运动控制将有助于更好地治疗眼运动障碍，如斜视。其他正在开发的改变眼部肌肉特性的药物有望成为简单、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技术将适用于研究警觉性动物的药物修饰运动单元的纤维类型特异性功能。这项提案中使用的新技术将使我们第一次能够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由神经肌肉引起的眼动障碍提供更有效、成本更低的治疗方法。

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.