MIDBRAIN CIRCUITRY FOR NEURONAL CONTROL OF GAZE

 描述(申请人提供)：本项目将研究运动前神经元的输入和生理学，控制近视、晶状体调节和瞳孔收缩的三联反应；斜视和弱视的病因中的关键作用。它将：1.提供第一个关于融合功能的电路的详细的解剖学演示；2.描述一组新的近三联运动前运动神经元的功能和连接；以及3.测试眼动控制的竞争电流模型。这一结果将有助于更好地理解获得立体视觉的机制。3D空间中眼动控制的两种截然相反的模型提供了背景。其中一个可以追溯到海林，他认为共轭和会聚的眼动信号是在运动神经元水平上加在一起的。另一种则追溯到赫姆霍兹，他认为每只眼睛的运动都是独立控制的，共轭和会聚运动代表了意志协调的习得模式。我们将描述生理反应的特征，并确定两类神经元的输入：据信位于动眼上区(SOA)的动周收敛细胞和位于中央中脑网状结构(CMRF)的一组新发现的运动前神经元。这两个群体接触到控制晶状体和瞳孔的Edinger-Westphal核(EWpg)的节前运动神经元和活跃的内直肌运动神经元，表明其在近三联征控制中发挥作用。这项研究将确定运动周围收敛细胞和/或运动前cMRF神经元是否被小丘的尾部扫视相关成分、包含注视和聚焦时活跃细胞的吻侧小丘或前额眼场(FEF)聚集区作为靶点。在猕猴身上实现的5个相互关联的目标利用了清醒行为动物的生理记录、常规神经元示踪剂以及常规和重组病毒的跨神经元传输。目的1比较动眼周围聚集细胞和运动前cMRF神经元的精确解剖位置。Aim 2将通过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上是否具有眼部特异性。目的3录音将验证这一假设，即只有运动前cmrf神经元在分离性眼跳过程中控制近三联征。目标4将研究这两个人群的顶盖投射模式是否支持这种功能划分。目标5将结合生理学和解剖学方法，对FEF输入提出同样的问题。该项目极大地增强了对眼动控制电路和细胞功能的了解，将为改进健康和疾病中眼动控制和协调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.