Visuomotor functions of ascending pathways to frontal cortex

描述（由申请人提供）：大脑神经元回路的研究对于确定视觉系统如何发挥功能以及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如何合作以保护视觉和控制眼球运动。一个显著的视觉扫视区域是额叶眼区（FEF），其在皮层下投射以促成扫视产生。然而，FEF也接受来自皮质下结构的通路的上行输入，包括上级丘（SC）、黑质网状部（SNr）和齿状核（DN）。这些上升路径的功能是什么？我们以前表明，SC-FEF途径传达有关扫视（必然放电）的反馈，但对SNr-FEF和DN-FEF途径知之甚少。SNr是基底神经节的输出节点，基底神经节是进行自主运动所必需的系统，而DN是小脑的输出节点，小脑对于进行视觉引导运动更关键。因此，我们预测，SNr-FEF和DN-FEF途径发挥不同的作用，使自愿和视觉引导扫视。本提案的总体目标是确定SNr-FEF和DN-FEF途径的功能。第一个具体的目标是记录识别出的神经元在每个通路中的情况，并确定它们编码的信号。我们假设SNr-FEF和DN-FEF通路分别优先传递与自愿和视觉引导扫视相关的活动。第二个目标是可逆性地研究每个通路，并通过研究扫视缺陷来推断其行为功能。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扫视。第三个目标是可逆性地阻断每个通路，并通过研究FEF活性的变化来推断其回路水平的功能。我们假设SNr-FEF途径导致FEF活动伴随自愿扫视，而DN-FEF途径导致FEF活动伴随视觉引导扫视。这项研究的总体结果，结合我们以前的工作，将建立三个平行的途径上升到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.