Structure-Function Analysis of C-Group Motoneurons

描述（由申请人提供）：完整的视觉功能依赖于视觉和眼球运动的协调作用来引导我们的视线，以便每只眼睛的中央凹都能成像感兴趣的物体。为了获得最大的视觉敏锐度和深度感知，我们必须能够在静止或移动的目标上保持眼睛稳定。如果正常的神经支配不能发育或受到损伤，可能导致婴儿或获得性眼睛错位（斜视）。事实上，每年在美国出生的儿童中至少有3%被诊断患有斜视。早期和适当的治疗斜视是必不可少的，以防止视力丧失。然而，斜视的治疗仍然具有挑战性，部分原因是我们对该病的病因缺乏明确的了解。在一些斜视中，眼睛的不对准很可能是由于个别眼部肌肉或肌肉室的张力神经支配校准不当所致。最终，眼球对准、凝视和眼球运动取决于不同眼外肌（EOM）和肌室的动眼神经支配质量。最近的解剖工作，包括我们各自实验室的一些工作，表明至少有两种不同的运动神经元支配眼膜的眶层和全局层。一类（如a -群）提供斑块末梢单神经支配EOM纤维（SIFs）。另一类（如C-和s -组）提供en-葡萄末梢，以繁殖神经支配的EOM纤维（MIFs）。重要的是，运动前结构的信号来源有明显的差异，而运动前结构调节着这些不同种类的动眼神经细胞。我们的研究将比较和对比不同类型的运动神经元（C-和a -组）的功能组织和相对作用，这些运动神经元主要驱动轨道或全局肌纤维。我们将测试这一假设，即适当的眼睛对齐可以通过不同的肌肉室的作用来实现，这些肌肉室直接插入眼睛（全局层）或通过插入最近发现的眼外肌滑轮间接起作用。我们将检验c群运动神经元在维持眼睛对准、凝视和收敛方面起主要作用的假设。我们将通过对猴子进行神经生理学研究来实现这一目标。我们还将进行补充的神经解剖学研究，以完善我们对这些不同类别的运动神经元的一些运动前信号来源的理解。完成我们的研究可以显著提高我们对正常和病理眼睛对准、凝视和眼球运动的理解。

DESCRIPTION (provided by applicant): Full visual function depends on the coordinated action of vision and eye movements to direct our line of sight so that an object of interest will be imaged on the fovea of each eye. To achieve maximum visual acuity and depth perception, we must be able to hold our eyes steady on a stationary or moving target. If normal innervation fails to develop or is compromised by injury, infantile or acquired misalignment of the eyes (strabismus) could result. In fact, at least 3% of children born in the United States are diagnosed with strabismus every year. Early and appropriate treatment of strabismus is essential to prevent loss of visual function. However, treatment of strabismus remains challenging, partly because we lack a definitive understanding of the etiology of the disease. It is likely that misalignment of the eyes in some strabismics is due to improperly calibrated tonic innervation of individual eye muscles or muscle compartments. Ultimately, eye alignment, gaze- holding and eye movements depend on the quality of oculomotor innervation to different extra-ocular muscles (EOM) and muscle compartments. Recent anatomical work, including some from our respective laboratories, shows that there are at least two separate classes of motoneurons that innervate orbital and global layers of EOM. One class (e.g., A-groups) provides en-plaque endings to singly innervate EOM fibers (SIFs). The other class (e.g., C- and S-groups) provides en-grape endings to multiply innervate EOM fibers (MIFs). Importantly, there are clear differences in the sources of signals in pre-motor structures, which modulate these different classes of oculomotor neurons. Our studies will compare and contrast the functional organization and relative roles of different classes of motoneurons (C- and A-groups) that primarily drive either orbital or global muscle fibers. We will test the hypothesis that proper eye alignment could be achieved by the action of different muscle compartments, which have direct insertion on the eye (global layer) or act indirectly by inserting on the recently discovered extraocular muscle pulleys. We will test the hypothesis that C-group motoneurons play a major role in maintaining eye alignment, gaze-holding and vergence. We will accomplish this by conducting neurophysiological studies in monkeys trained to fixate and track moving targets. We will also conduct complimentary neuroanatomical studies to refine our understanding of some of the premotor sources of signals to these different classes of motor neurons. Completion of our studies could significantly advance our understanding of normal and pathological eye alignment, gaze-holding and eye movements. PUBLIC HEALTH RELEVANCE: Treatment and cure of developmental or acquired strabismus requires advancing our knowledge about how the brain controls eye alignment, gaze-holding and eye movements. Our studies will examine the relative roles of different classes of oculomotor neurons that innervate different eye muscle compartments in the above functions.