MIDBRAIN CIRCUITRY FOR NEURONAL CONTROL OF GAZE

用于注视神经元控制的中脑电路

• 批准号: 7918043
• 负责人: Paul J May
• 金额: $ 35.94万
• 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/7918043
• 关键词: Address; Amblyopia; Be++ element; Behavior; Beryllium; Brain; Cell Nucleus; Cells; Characteristics; Clinical; Contralateral; Dendrites; Electron Microscope; Electrons; Etiology; Eye; Fatigue; Fiber; Goals; Grant; 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; public health relevance; 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）：这项研究研究了核能周围区域的神经元的回路，这些神经元可以介绍近反应和眼取向的成分，并且在斜视和amblyopia的病因中可能很重要。目的旨在确定控制晶状体和瞳孔的前副交感神经运动神经元的前输入，以及控制多个神经支配的肌肉纤维（MIF）的运动神经元。 MIF具有高度疲劳性耐酸性和色调活性。它们有助于调整皮带轮系统，并与帕利塞德的末端有关，这些末端可能会产生眼部本体感受。因此，它们可能在控制正常的眼睛方向以及斜视中的眼对准方面发挥作用。在糖块骨周围区域发现了神经节前和MIF运动神经元组。该区域还包含中间神经元，其中包括利用神经肽尿果素的中间神经元，据信这在压力行为中起作用。为了定义对镜头，瞳孔和MIF纤维控制的电路，我们必须确定每种镜头的前者输入。 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在Saccadic的眼球运动中，但也可能在近反应中发挥作用。该提案包含4个相互关联的神经解剖学目的，该目标在猕猴中进行。它们具有实验，这些实验将顺行示踪剂与逆行或免疫组织化学细胞鉴定相结合，并具有LM和EM分析。 AIM 1旨在确定MIF和SIF运动神经元之间的超微结构差异。将使用电子显微镜检查两组的示例，并从内侧直肌肌肉逆转来检查，以确定其突触排列的差异是其功能差异的基础。 AIM 2将测试CMRF接触内侧和上直肌MIF和SIF运动神经元以及Ganglionic运动神经元。连接的模式将提供有关CMRF周期投影与凝视或共轭凝视有关的洞察力，甚至具有更广泛的功能。 AIM 3将检验以下假设：快速核直接操纵负责接近响应的运动神经元。 AIM 4测试对周围环区域的直肠投影是其结合功能的一部分，而垂直注视运动神经元的树突是其靶标，还是一种调节近反应组件的途径。公共卫生相关性的工作旨在治愈斜视和弱视是NEI的主要目标之一，但是我们在解决这些临床问题方面遇到的巨大困难之一是缺乏对它们的基本机制的了解，特别是对神经元电路的不良理解，即控制镜头的关注或调整和维持适当的眼睛对象。这笔赠款的目的旨在确定控制镜头和学生的前副副交感神经运动神经元的前输入，以及控制多个神经支配的肌肉纤维（MIFS）的运动神经元，这对于长期以来的眼光感应和调整可能很重要。提出的实验是第一个直接测试哪种大脑结构为这些运动神经元提供输入的实验。