MIDBRAIN CIRCUITRY FOR NEURONAL CONTROL OF GAZE

用于注视神经元控制的中脑电路

• 批准号: 8117489
• 负责人: Paul J May
• 金额: $ 34.5万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8117489
• 关键词: Address; Amblyopia; Behavior; Beryllium; Brain; Cell Nucleus; Cells; Characteristics; Clinical; Contralateral; Dendrites; Electron Microscope; Electrons; Etiology; Eye; Fatigue; Fiber; Goals; Grant; Health; Immunohistochemistry; Interneurons; Investigation; Ipsilateral; Label; Macaca; Maintenance; Medial; Microscopic; Midbrain structure; Monkeys; Motor Neurons; Movement; Muscle Fibers; Neurons; Neuropeptides; Nucleus fastigii; Oculomotor nucleus; Pathway interactions; Pattern; Physiological; Play; Population; Positioning Attribute; Proprioception; Pupil; Regulation; Resistance; Reticular Formation; Role; Saccades; Series; Side; Source; Strabismus; Stress; Structure; Synapses; System; Techniques; Tectum Mesencephali; Testing; Time; Tracer; Triad Acrylic Resin; Vision; Work; base; cell type; gamma-Aminobutyric Acid; gaze; insight; lens; medial rectus muscle; neuronal circuitry; orbit muscle; research study; response; superior colliculus Corpora quadrigemina; urocortin

Description (provided by applicant): This study investigates the circuitry of neurons in the perioculomotor region, which subserve the components of the near response and ocular orientation, and which may be important in the etiology of strabismus and amblyopia. The aims are directed at determining the premotor inputs to the preganglionic parasympathetic motor neurons that control the lens and pupil, and the motor neurons that control the multiply innervated muscle fibers (MIFs) in the extraocular muscles. MIFs are highly fatigue resistant and tonically active. They help adjust the pulley system, and are associated with palisade endings that may subserve ocular proprioception. Consequently, they may play a role in controlling normal eye orientation, and eye misalignment in strabismus. The preganglionic and MIF motor neuron groups are found in the perioculomotor region. This region also contains interneurons including those that utilize the neuropeptide urocortin, which is believed to play a role in stress behaviors. In order to define the circuitry that underlies the control of the lens, pupil and MIF fibers in the extraocular muscles, we must identify the premotor inputs to each. The proposed experiments will determine which of these elements is targeted by three of the known inputs to the perioculomotor region: the central mesencephalic reticular formation (cMRF), which may contain both saccade-related and vergence-related neurons, the fastigial nucleus, which is believed to modulate near triad responses in an adaptive manner, and the superior colliculus, which has a well known role in saccadic eye movements, but might play a role in the near response, as well. The proposal contains 4 inter-related neuroanatomical aims carried out in macaque monkeys. They feature experiments that combine anterograde tracers with either retrograde or immunohistochemical cell identification, and feature both LM and EM analysis. Aim 1 is directed at determining the ultrastructural differences between MIF and SIF motor neurons. Examples of the two groups, retrogradely labeled from the medial rectus muscle, will be examined with the electron microscope in order to determine what differences in their synaptic arrangements underlie their functional differences. Aim 2 will test whether the cMRF contacts medial and superior rectus MIF and SIF motor neurons and preganglionic motor neurons. The pattern of connections will provide insight into whether the cMRF perioculomotor projection is concerned with vergence or conjugate gaze, or has even wider functions. Aim 3 will test the hypothesis that the fastigial nucleus is directly manipulating the motoneurons responsible for the near response. Aim 4 tests whether the tectal projection to the perioculomotor region is part of its conjugate function, with the dendrites of vertical gaze motor neurons being its target, or is a pathway that modulates components of the near response. PUBLIC HEALTH RELEVANCE Work towards cures for strabismus and amblyopia are among the prime goals of the NEI, but one of the great difficulties we have in addressing these clinical problems is a lack of understanding of their underlying mechanisms, and specifically a poor understanding of the neuronal circuits that control lens focus or that adjust and maintain the proper eye alignment. The aims of this grant are directed at determining the premotor inputs to the preganglionic parasympathetic motor neurons that control the lens and pupil, and the motor neurons that control the multiply innervated muscle fibers (MIFs) in the extraocular muscles, which may be important for sensing and adjusting the long term orientation of the eyes. The proposed experiments are the first to directly test which brain structures supply input to these motor neurons.

描述（由申请人提供）：本研究调查了眼运动周围区域的神经元回路，该回路促进了近处反应和眼定向的组成部分，并且在斜视和弱视的病因学中可能很重要。目的是确定控制晶状体和瞳孔的节前副交感运动神经元以及控制眼外肌中的多神经支配肌纤维（MIF）的运动神经元的运动前输入。 MIF 具有高度抗疲劳性和滋补活性。它们有助于调整滑轮系统，并与可能有助于眼睛本体感觉的栅栏末端相关。因此，它们可能在控制正常眼睛定向和斜视时眼睛错位方面发挥作用。节前运动神经元群和 MIF 运动神经元群位于眼运动周围区域。该区域还包含中间神经元，包括利用神经肽尿皮质素的中间神经元，据信该神经肽在压力行为中发挥作用。为了定义控制眼外肌中晶状体、瞳孔和 MIF 纤维的电路，我们必须识别每个神经元的运动前输入。拟议的实验将确定这些元素中的哪一个是运动周围区域的三个已知输入的目标：中央中脑网状结构（cMRF），它可能包含眼跳相关和聚散相关的神经元，顶核，它是据信以适应性方式调节近三联征反应，以及上丘，其在眼球扫视运动中具有众所周知的作用，但也可能在近距反应中发挥作用。该提案包含在猕猴身上进行的 4 个相互关联的神经解剖学目标。它们的特点是将顺行示踪剂与逆行或免疫组织化学细胞识别相结合的实验，并具有 LM 和 EM 分析。目标 1 旨在确定 MIF 和 SIF 运动神经元之间的超微结构差异。将用电子显微镜检查从内直肌逆行标记的两组样本，以确定其突触排列的差异是其功能差异的基础。目标 2 将测试 cMRF 是否接触内侧和上直肌 MIF 和 SIF 运动神经元以及节前运动神经元。连接模式将让我们深入了解 cMRF 眼运动投影是否与聚散或共轭凝视有关，或者具有更广泛的功能。目标 3 将检验顶核直接操纵负责近响应的运动神经元的假设。目标 4 测试顶盖投射到眼运动周围区域是否是其共轭功能的一部分（以垂直凝视运动神经元的树突为目标），或者是调节近处反应成分的途径。公共卫生相关性 治愈斜视和弱视的工作是 NEI 的首要目标之一，但我们在解决这些临床问题时遇到的最大困难之一是缺乏对其潜在机制的了解，特别是对神经元的了解不足控制镜头焦点或调整和保持正确的眼睛对准的电路。这项资助的目的是确定控制晶状体和瞳孔的节前副交感运动神经元的运动前输入，以及控制眼外肌中多神经支配肌纤维（MIF）的运动神经元，这对于感知可能很重要并调整眼睛的长期方向。所提出的实验是第一个直接测试哪些大脑结构向这些运动神经元提供输入的实验。