Visuomotor functions of ascending pathways to frontal cortex

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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.