Visuomotor functions of ascending pathways to frontal cortex

描述（由申请人提供）：对大脑中神经元回路的研究对于确定视觉系统如何运作以及它在疾病状态下如何受损至关重要。这项应用的长期目标是确定灵长类动物大脑中的结构是如何合作来服务视觉和控制眼球运动的。大脑皮层一个突出的视跳跃性区域是额叶视野（FEF），它向皮层下投射，促进眼跳跃性的产生。然而，FEF也接受来自皮层下结构的上行输入，包括上丘（SC）、网状黑质（SNr）和齿状核（DN）。这些提升路径的功能是什么？我们之前已经表明SC-FEF通路传递了关于扫视的反馈（必然放电），但相对而言，我们对SNr-FEF和DN-FEF通路知之甚少。SNr是基底神经节的输出节点，这是进行自主运动所必需的系统，而DN是小脑的输出节点，这对于进行视觉引导的运动更为关键。因此，我们预测SNr-FEF和DN-FEF通路在自发扫视和视觉引导扫视中起着不同的作用。本提案的总体目标是确定SNr-FEF和DN-FEF通路的功能。第一个具体目标是记录每条通路中已识别的神经元，并确定它们编码的信号。我们假设SNr-FEF和DN-FEF通路分别传递与自主扫视和视觉引导扫视相关的活动。第二个目标是通过研究跳眼缺陷来可逆地灭活每个通路并推断其行为功能。我们假设SNr-FEF通路有助于产生或监测自愿扫视，而DN-FEF通路有助于产生或监测视觉引导的扫视。第三个目标是通过研究FEF活动的变化，可逆地使每个通路失活，并推断其回路水平的功能。我们假设SNr-FEF通路导致自发性扫视的FEF活动，而DN-FEF通路导致视觉引导的扫视的FEF活动。本研究的总体结果，结合我们之前的工作，将建立三个平行路径上升到FEF的功能。

DESCRIPTION (provided by applicant): The study of neuronal circuits in the brain is essential for determining how the visual system functions and how it becomes impaired in disease states. The long-term goal of this application is to determine how structures in the primate brain cooperate to subserve vision and control eye movements. One prominent visuosaccadic region of cortex is the frontal eye field (FEF), which projects subcortically to contribute to saccade generation. Yet the FEF also receives ascending input from pathways originating in subcortical structures including the superior colliculus (SC), the substantia nigra pars reticulata (SNr), and the dentate nucleus (DN). What are the functions of these ascending pathways? We showed previously that the SC-FEF pathway conveys feedback about saccades (corollary discharge), but relatively little is known about the SNr-FEF and DN-FEF pathways. The SNr is an output node of the basal ganglia, a system necessary for making voluntary movements, while the DN is an output node of the cerebellum, which is more critical for making visually-guided movements. Hence we predict that the SNr-FEF and DN-FEF pathways play differential roles related to making voluntary and visually-guided saccades. The overall goal of this proposal is to determine the functions of the SNr-FEF and DN-FEF pathways. The first specific aim is to record from identified neurons throughout each pathway and determine the signals they encode. We hypothesize that the SNr-FEF and DN-FEF pathways convey activity preferentially correlated with voluntary and visually-guided saccades, respectively. The second aim is to reversibly inactivate each pathway and infer its behavioral function by studying saccadic deficits. We hypothesize that the SNr-FEF pathway contributes to generating or monitoring voluntary saccades while the DN-FEF pathway contributes to generating or monitoring visually-guided saccades. The third aim is to reversibly inactivate each pathway and infer its circuit-level function by studying changes in FEF activity. We hypothesize that the SNr-FEF pathway causes FEF activity accompanying voluntary saccades while the DN-FEF pathway causes FEF activity accompanying visually-guided saccades. The overall result of this study, taken together with our previous work, will be to establish the functions of three parallel pathways ascending to the FEF.