Neural Control of a Complex Oculomotor Plant

描述（由申请人提供）： 意义：近 40 年的动眼生理学一直基于强大的简化概念，即动眼神经核、颅神经和眼外肌 (EOM) 构成了一个简单、同质的最终共同路径 (FCP)，其中控制多种类型眼球运动的超核信号匿名组合。 因此，如果 FCP 假设是正确的，使用直接肌肉力测量和磁共振成像 (MRI) 进行的眼球聚散运动研究未能证实早期重复良好的运动神经元 (MN) 研究得出的预测，这是令人惊讶的。 这一假设现在看来站不住脚，而动眼植物已经成熟，可以探索其长期被忽视的功能丰富性。 超核疾病大多难以治疗，而定位于动眼神经周围的功能可能很容易受到药理学、手术和遗传操作的影响。 与目前可用于治疗斜视和相关疾病的肌肉动作的粗略操作相比，对相关运动神经元和肌纤维专门化的了解将有可能实现微妙的变化。 研究：我们的第一个总体目标是描绘 FCP 假设的失败：（1）我们将通过记录已识别的外展肌 MN 并同时测量聚散中的 LR 力来有力地验证“缺失的外直肌（LR）力悖论”，继续（2）区分 MN 速率-位置曲线的斜率和 Y 截距的变化，并研究 LR 和内直肌（MR）会聚力在水平凝视平面上的变化。 (3) 我们将在猴子身上复制一项人类 MRI 研究，发现收敛时没有地球回缩，并将使用“金珠基准”(GBF) 来扩展它以可视化轨道内容。 (4) 使用我们的肌肉力传感器 (MFT)，我们将确定 LR 和 MR 力是否与通过 GBF 观察到的全球平移、肌肉路径和结缔组织运动一致。 我们的第二个总体目标是表征动眼植物的复杂关节。 (5) 我们将确定 LR 路径长度的减小是否抵消了 MN 研究预测的与收敛相关的收缩力的增加。 （6）我们将微刺激 MN 并使用 GBF 来可视化地球、滑轮和其他组织运动，（7）确定 MN 募集顺序是否随聚散状态变化，以及（8）肌肉力量是否随注视精度变化。 (9) 我们将使用多电极刺激和 MFT 在体内研究 EOM 单位求和。

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.