MIDBRAIN CIRCUITRY FOR NEURONAL CONTROL OF GAZE

 描述（由申请人提供）：本项目将研究控制聚散、透镜调节和瞳孔收缩的近三联体动作的运动前神经元的输入和生理;斜视和弱视病因学中的关键动作。它将：1.提供了第一个详细的解剖演示电路的基础聚散功能; 2.表征一组新的近三联体前运动神经元的功能和连接，以及3.测试目前眼动控制的竞争模型。这些结果将有助于我们更好地理解获得立体视觉的机制。在3-D空间中的两种相反的眼动控制模型提供了上下文。其中一个可以追溯到Hering，他认为共轭和聚散眼球运动信号是在运动神经元的水平上叠加在一起的。另一种可以追溯到亥姆霍兹，他认为每只眼睛的运动都是独立控制的，共轭和聚散运动代表了意志协调的学习模式。我们将描述的生理反应，并确定两个群体的神经元的输入：peroculptum聚散细胞被认为是位于上眼区（SOA）和一组新发现的运动前神经元位于中央中脑网状结构（CMRF）。这两个群体接触的节前运动神经元在Edinger-Westphal核（EWpg），控制透镜和瞳孔，和内直肌运动神经元活跃的聚散，表明在近三联体控制的功能。该研究将确定眼周聚散细胞和/或前运动cMRF神经元是否被尾侧、扫视相关的丘、吻侧丘（其包含在注视和聚散期间活跃的细胞）或额眼场（FEF）聚散区靶向。在猕猴中进行的5个相互关联的目标利用清醒行为动物的生理记录、常规神经元示踪剂和常规和重组病毒的跨神经元转运。目的1比较眼周聚散细胞和运动前区cMRF神经元的精确解剖位置。目的2将通过使用跨神经元追踪来测试Hering和Helmhotz模型，以确定这两个群体或脑桥中的运动前神经元在解剖学上是否具有眼特异性。目的3记录将测试的假设，只有前运动cMRF神经元控制的近三联体在分离性扫视。目的4将探讨这两个人群的顶盖投影模式是否支持这样的功能分工。目的5将联合收割机的生理和解剖的方法来问同样的问题，关于FEF输入。该项目所提供的对眼动控制回路和细胞功能的极大增强的理解将为改善眼动控制和协调健康和疾病的概念提供关键基础。

 DESCRIPTION (provided by applicant): This project will investigate the inputs and physiology of premotor neurons controlling the near triad actions of vergence, lens accommodation and pupillary constriction; critical actions in the etiology of strabismus and amblyopia. It will: 1. provide the first detailed anatomical demonstration of the circuits underlying vergence functions; 2. characterize the function and connections of a novel set of near triad premotor neurons, and 3. test competing current models of eye movement control. The results will confer a better understanding of the mechanisms for obtaining stereoscopic vision. Two opposing models of eye movement control in 3-D space provide the context. One traces its lineage to Hering, who believed that conjugate and vergence eye movement signals were added together at the level of the motoneuron. The other traces its heritage to Helmhotz, who believed that the movement of each eye is independently controlled, and that conjugate and vergence movements represent learned patterns of volitional coordination. We will characterize the physiological responses and determine the inputs to two populations of neurons: perioculomotor vergence cells believed to lie in the supraoculomotor area (SOA) and a newly discovered set of premotor neurons located in the central mesencephalic reticular formation (cMRF). These two populations contact the preganglionic motoneurons in the Edinger-Westphal nucleus (EWpg) that control the lens and pupil, and medial rectus motoneurons active in vergence, indicating a function in near triad control. The study will determine whether the perioculomotor vergence cells and/or premotor cMRF neurons are targeted by the caudal, saccade-related component of the colliculus, the rostral colliculus, which contains cells active during fixation and vergence, or the frontal eye fields (FEF) vergence zone. The 5 inter-related aims carried out in macaque monkeys utilize physiological recording in awake behaving animals, conventional neuronal tracers and transneuronal transport of conventional and recombinant viruses. Aim 1 will compare the precise anatomical location of perioculomotor vergence cells and premotor cMRF neurons. Aim 2 will test the Hering and Helmhotz models by using transneuronal tracing to determine whether these two populations or premotor neurons in the pons are anatomically eye- specific. Aim 3 recordings will test the hypothesis that only the premotor cMRF neurons control the near triad during disjunctive saccades. Aim 4 will examine whether the pattern of tectal projections to these two populations supports such a functional division. Aim 5 will combine physiological and anatomical approaches to ask the same question about FEF inputs. The dramatically augmented understanding of eye movement control circuits and cell function afforded by this project will provide a critical basis for improved concepts of eye movement control and coordination in health and disease.