Structure-Function Analysis of C-Group Motoneurons

描述（由申请人提供）：完整的视觉功能取决于视觉和眼球运动的协调作用，以引导我们的视线，从而使感兴趣的物体在每只眼睛的中央凹上成像。为了达到最大的视觉敏锐度和深度感知，我们必须能够保持我们的眼睛稳定在一个静止或移动的目标。如果正常的神经支配不能发展或受到伤害，婴儿或后天的眼睛错位（斜视）可能会导致。事实上，每年至少有3%在美国出生的儿童被诊断为斜视。斜视的早期和适当的治疗对于防止视功能丧失至关重要。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。在某些斜视中，眼睛的错位可能是由于个别眼睛肌肉或肌肉隔室的不正确校准的紧张性神经支配。最终，眼睛对准、凝视保持和眼睛运动取决于不同眼外肌（EOM）和肌肉隔室的眼神经支配的质量。最近的解剖工作，包括一些从我们各自的实验室，表明至少有两个独立的类运动神经元，支配眶层和全球层的眼外肌。一个类（例如，A-组）提供en-plaque末梢以单独地神经支配眼外肌纤维（SIF）。另一类（例如，C-和S-组）提供葡萄状终末以倍增神经支配眼外肌纤维（MIFs）。重要的是，前运动结构中的信号源存在明显差异，这些信号源调节这些不同类别的眼神经元。我们的研究将比较和对比不同类别的运动神经元（C组和A组）的功能组织和相对作用，主要驱动眼眶或全球肌纤维。我们将测试的假设，正确的眼睛对齐，可以通过不同的肌肉隔室，其中有直接插入眼睛（全球层）或插入最近发现的眼外肌滑轮间接作用的行动。我们将测试的假设，即C组运动神经元在维持眼睛对齐，凝视和聚散发挥了重要作用。我们将通过对猴子进行神经生理学研究来实现这一目标，这些猴子被训练来注视和跟踪移动目标。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型运动神经元的信号前运动源的理解。我们的研究的完成可以显着推进我们的正常和病理眼对齐，凝视和眼球运动的理解。 公共卫生相关性：发育性或后天性斜视的治疗和治愈需要我们进一步了解大脑如何控制眼睛对准，凝视和眼球运动。我们的研究将探讨不同类别的眼神经元，支配不同的眼肌区室在上述功能的相对作用。

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.