The primary goal of the proposed research project is to identify the vestibular-related cerebellar zones of the nodulus. Both anatomical and physiological investigations will be employed to define the structural organization and the functional utility of each zone. Four nodulus zones that are related to vestibular system function are hypothesized based upon previously published data and that obtained as preliminary results. Each zone will initially be defined anatomically according to the climbing fiber input from different regions of the inferior olive, then further characterized according to input from different regions of the vestibular nuclei. Functional identification of the nodulus zones will be performed using extracellular recordings from Purkinje cells, microstimulation during behavioral tasks, and 2- deoxyglucose uptake during vestibular and/or visual stimulation. The first specific aim seeks to determine if cerebellar zones exist in the monkey nodulus. Both anterograde and retrograde neural tracers will be used to identify the nodulus zones, with injection sites being guided by previous electrophysiological mapping. Nodulus efferents will be traced using BDA injected into the Purkinje cell layer. Afferents to the nodulus from different regions in the vestibular nuclei will be identified using double label experiments of fluorescent dyes. Electrophysiological recordings of Purkinje cell responses to specific vestibular and visual stimulations that differ according the axis plane of reference will be obtained both in alert and anesthetized monkeys.
The second aim attempts to determine if the monkey nodulus zones are functionally organized, with the specific function for each zone being related to its? structural substrate. Electrical microstimulation of different regions in the nodulus will be delivered during nystagmus produced by specific vestibular and visual excitations in order to determine which nodulus region mediates the behavior. The effects upon blood pressure and heart rate will be examined during identical nodulus microstimulation in order to identify the zone related to autonomic function. As an additional characterization, 2- deoxyglucose uptake by nodulus neurons being stimulated by specific vestibular and visual tasks designed to discriminate different functional zones will be examined.
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