Dynamic Basal Ganglia Saccade Networks

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DESCRIPTION (provided by applicant): Clinical data strongly implicate the basal ganglia, including the striatum, in the control of saccadic eye movements. For example, saccade deficits occur both in Parkinson's disease and in Huntington's disease. Experimental evidence also points to the critical role of the striatum and basal ganglia circuits in oculomotor control. The striatum has prominent saccade-related activity, and this region receives projections from oculomotor-related areas of the neocortex including the frontal eye fields, the supplementary eye fields and the caudal dorsolateral prefrontal cortex. The oculomotor zone of the striatum itself projects to the substantia nigra pars reticulata which in turn projects to, and inhibits the superior colliculus and inhibits saccades thereby. This basal ganglia pathway is used as a prime example of the release functions of the basal ganglia. We propose an experimental program to study in Maccaca mulatta the response properties of the oculomotor striatum and oculomotor cortical areas during learning and subsequent performance of a series of tasks including visually-guided sequential saccade tasks. We have developed chronic, multi-electrode recording methods for use as macaques perform a battery of saccade tasks. We will test 3 hypotheses in 3 Aims. In Aim 1, we hypothesize that many of the response properties of neurons in the oculomotor zone of the striatum and corresponding cortical regions are built up by experience. We will record during acquisition of a defined set of tasks to test this hypothesis. In Aim 2, we hypothesize that sequence-selective activity will occur in the basal ganglia as macaques perform reaching tasks. To test this hypothesis, we will train macaques on a touch screen reaching task under ocular fixation. In Aim 3, we hypothesize that spontaneously produced sequences of saccades will be represented in the brain by sequence-selective activity. We will test these hypotheses by recording from multiple electrodes implanted in the striatum and cortex as macaques perform saccade and arm reaching tasks. We aim to maximize the usefulness of the data collected for understanding oculomotor control exerted by these highly clinically important pathways in health and disease. The basal ganglia are critical for normal movements including sequential movements. Repetitive movement disorders are a hallmark of basal ganglia dysfunction. Our goal is to illuminate mechanisms disordered in these disabling human conditions.