Structure-Function Analysis of C-Group Motoneurons

描述(申请人提供)：完全的视觉功能依赖于视觉和眼球运动的协调动作来引导我们的视线，从而使感兴趣的物体被成像在每只眼睛的中心凹上。为了获得最大的视觉敏锐度和深度知觉，我们必须能够将眼睛稳定地盯着静止或移动的目标。如果正常的神经不能发育或因损伤而受损，可能会导致婴儿或后天的眼睛不对准(斜视)。事实上，在美国出生的儿童中，每年至少有3%被诊断出斜视。早期适当的斜视治疗是预防视功能丧失的关键。然而，斜视的治疗仍然具有挑战性，部分原因是我们对疾病的病因缺乏明确的了解。在一些斜视患者中，眼睛的错位很可能是由于个别眼部肌肉或肌肉间隔的紧张性神经调节不当所致。最终，眼球对齐、凝视和眼球运动取决于对不同眼外肌(EOM)和肌肉间隔的动眼神经支配的质量。最近的解剖学研究，包括我们各自实验室的一些研究表明，至少有两类不同的运动神经元分布于眼眶层和眼球层。一类(例如，A基团)提供内斑末端以单独支配EOM纤维(SIF)。另一类(如C基团和S基团)提供葡萄末端来繁衍支配EOM纤维(MIF)。重要的是，运动前结构中调制这些不同类别动眼神经元的信号来源有明显的差异。我们的研究将比较和对比不同类型运动神经元(C组和A组)的功能组织和相对作用，这些运动神经元主要驱动眼眶或全球肌肉纤维。我们将测试这一假设，即通过不同肌肉间隔的动作可以实现适当的眼睛对齐，这些肌肉间隔直接插入眼睛(全局层)或通过插入最近发现的眼外肌滑轮间接作用。我们将验证这一假设，即C组运动神经元在维持眼球对准、凝视和聚焦方面发挥着重要作用。我们将通过对猴子进行神经生理学研究来实现这一点，这些猴子被训练成注视和跟踪移动的目标。我们还将进行免费的神经解剖学研究，以完善我们对这些不同类别运动神经元的一些运动前信号源的理解。完成我们的研究可以显著提高我们对正常和病理性眼球对齐、凝视和眼球运动的理解。 公共卫生相关性：治疗和治愈发育性或获得性斜视需要提高我们对大脑如何控制眼球对齐、凝视和眼球运动的了解。我们的研究将考察不同类别的动眼神经元在上述功能中的相对作用，这些神经元支配不同的眼肌室。

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.