Neural Control of a Complex Oculomotor Plant

复杂动眼植物的神经控制

• 批准号: 6737867
• 负责人: Joel M Miller
• 金额: $ 50.77万
• 依托单位: SMITH-KETTLEWELL EYE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-10 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6737867
• 关键词: Macaca mulatta; biomechanics; connective tissue; electrostimulus; eye movements; magnetic resonance imaging; motor neurons; muscle; muscle contraction; neuroregulation; oculomotor nerve; oculomotor nuclei

DESCRIPTION (provided by applicant): Significance: Almost 40 years of oculomotor physiology have been based on the powerful simplifying notion that the oculomotor nuclei, their cranial nerves, and the extraocular muscles (EOMs) constitute a simple, homogeneous Final Common Path (FCP), in which supernuclear signals controlling the several types of eye movement combine anonymously. It was, therefore, surprising when studies of vergence eye movement using direct muscle force measurements and magnetic resonance imaging (MRI) failed to confirm predictions that would follow from earlier, well-replicated motoneuron (MN) studies, if the FCP hypothesis were correct. This hypothesis now appears untenable, and the oculomotor plant ripe for exploration of its long-neglected functional richness. Supernuclear disorders are mostly inaccessible to treatment, whereas functions localized to the oculomotor periphery may be readily subject to pharmacologic, surgical and genetic manipulations. An understanding of related motoneuron and muscle fiber specializations would make it possible to effect subtle changes, compared to the gross manipulations of muscle action currently available to treat strabismus and related disorders. Studies: Our first overall aim is to delineate failures of the FCP hypothesis: (1) We will strongly verify the "missing lateral rectus (LR) force paradox" by recording identified abducens MNs and simultaneously measuring LR forces in vergence, continuing (2) to distinguish changes in slopes and Y-intercepts of MN rate-position curves, and to study the variation of LR and medial rectus (MR) convergence forces across the horizontal gaze plane. (3) We will replicate in monkeys, an MRI study in humans that found no globe retraction in convergence, and will extend it using "gold bead fiducials" (GBFs) to visualize orbital contents. (4) Using our muscle force transducers (MFTs) we will determine if LR and MR forces are consistent with globe translation, muscle paths and connective tissue movements observed with GBFs. Our second overall aim is to characterize complex articulations of the oculomotor plant. (5) We will determine if decreases in LR path length offset the convergence-related increase in contractile force predicted by the MN studies. (6) We will microstimulate MNs and use GBFs to visualize globe, pulley and other tissue movements, (7) determine if MN recruitment order varies with vergence state, and (8) if muscle forces vary with fixation accuracy. (9) We will study EOM unit summation in-vivo using multi-electrode stimulation and MFTs.

描述（由申请人提供）：意义：近40年的动眼肌生理学基于一个强有力的简化概念，即动眼肌核、它们的脑神经和眼外肌（EOMs）构成一个简单、均匀的最终共同路径（FCP），其中控制几种类型眼球运动的超核信号匿名地结合在一起。因此，如果FCP假说是正确的，那么使用直接肌肉力测量和磁共振成像（MRI）对眼球运动进行的研究未能证实先前得到充分复制的运动神经元（MN）研究的预测，这是令人惊讶的。这一假设现在看来是站不住脚的，动眼草已经成熟，可以探索其长期被忽视的功能丰富性了。超核疾病大多无法治疗，而定位于动眼肌周围的功能可能很容易受到药物，手术和遗传操作的影响。与目前用于治疗斜视和相关疾病的肌肉活动的粗大操作相比，了解相关的运动神经元和肌纤维特殊化将有可能实现细微的变化。