Neural Control of a Complex Oculomotor Plant

描述(申请人提供)：意义：近40年的动眼神经生理学一直建立在一个强大的简化概念的基础上，即动眼神经核、它们的脑神经和眼外肌(EOMS)构成一个简单、均匀的最终公共路径(FCP)，其中控制几种类型的眼动的超核信号匿名组合。因此，令人惊讶的是，如果FCP假说是正确的，那么使用直接肌肉力量测量和磁共振成像(MRI)对集中眼球运动的研究未能证实来自早期良好复制的运动神经元(MN)研究的预测。这一假设现在似乎站不住脚，动眼植物探索其长期被忽视的功能丰富的时机已经成熟。超核疾病大多无法治疗，而定位于动眼神经外周的功能可能很容易受到药物、手术和遗传操作的影响。与目前可用于治疗斜视和相关疾病的肌肉动作的粗略操作相比，了解相关的运动神经元和肌肉纤维特化将使实现微妙变化成为可能。 研究：我们的第一个总体目标是描绘FCP假说的失败：(1)我们将通过记录已识别的外展MN并同时测量收敛处的LR力来强有力地验证“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力和内直肌(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，这是一项在人类身上进行的MRI研究，在收敛中没有发现眼球后退，并将使用“金珠基准”(GBF)来扩展它，以可视化眼眶内容物。(4)使用我们的肌力传感器(MFT)，我们将确定LR和MR力是否与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描述动眼植物的复杂关节。(5)我们将确定LR路径长度的减少是否抵消了MN研究预测的与收敛相关的收缩力量的增加。(6)我们将微刺激MN并使用GBF来可视化球体、滑轮和其他组织的运动，(7)确定MN的招募顺序是否随收敛状态而变化，以及(8)肌力是否随固定精度而变化。(9)我们将利用多电极刺激和MFTs研究体内EOM单位的总和。

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.