The basal ganglia have been strongly implicated in the control of saccadic eye movements on the basis of clinical and experimental studies. Oculomotor defects occur in patients with extrapyramidal disorders such as Parkinson's and Huntington's disease, and lesions or inactivation of the striatum and other basal ganglia nuclei can produce such defects experimentally. The oculomotor zone of the striatum is centered in the caudate nucleus. This nucleus projects to the substantia nigra, pars reticulata (SNr), which in turn projects to the superior colliculus. Evidence suggests that this circuit is a release circuit for saccades. The oculomotor zone has been investigated intensively with conventional single unit recording methods in highly over-trained macaques. The results of these experiments suggest that single units in the oculomotor zone of the caudate nucleus have response properties that resemble those in saccade-related regions of the frontal cortex, including the frontal eye field (FEF), the supplementary eye field (SEF) and the dorsolateral prefrontal cortex (DLPFC). These include responses in visually guided and memory-guided tasks and in sequential saccade tasks. Nothing is yet known, however, about the ensemble activity of saccade-related neurons in the oculomotor zone of the striatum (OMZ-S), or its cortico-basal ganglia loops with the FEF, SEF and DLPFC. Nor is it known how activity is modulated in the oculomotor zone and its associated cortical loops as monkeys acquire procedural learning tasks, behavior thought to be a core function of the basal ganglia. We hypothesize that during learning neurons in the oculomotor zone of the striatum will show progressively more task-related activity and that during the overtraining period population-level coding will emerge in this oculomotor zone. We further hypothesize that temporally coordinated patterns of activity will emerge in cortico-basal ganglia loops during learning and that these will be detectable using chronic multi-unit recording methods. We propose experiments based on preliminary studies to record chronically in 1-2 week bouts from initially naive macaques as they learn procedural saccade tasks. Using multiple tetrodes, stereotrodes and conventional electrodes, we Propose to study multi-unit neural activity in the oculomotor zone of the striatum during acquisition (Aim 1), to study the functional local network architecture of the oculomotor zone during performance (Aim 2), and to study activity in cortico-basal ganglia loops with simultaneous ensemble recordings in the oculomotor zone of the striatum together with the FEF, SEF and DLPFC (Aim 3). The results obtained will have significance for understanding forebrain oculomotor control circuits and for understanding oculomotor defects in extrapyramidal disorders.
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