When Parkinson's disease (P.D.) patients are asked to follow (or track) a moving visual target with the eye, deficits are revealed in the EOG which parallel the primary motor symptoms of akinesia, bradykinesia and hypokinesia observable in their skeletal muscle activities. This project is directed, first, at characterizing eye tracking in monkeys before and after treatments which produce a Parkinson-like syndrome, and comparing their post-treatment performance to that of P.D. patients in similar situations. We are asking whether oculomotor performance can provide a simple, easy to measure, but quantitative indicator of the primary P.D. symptoms in the monkey models. Such a behavioral model would be useful in evaluating the effectiveness of various therapeutic strategies. Our model of choice involves a new drug (NMPTP) which produces a syndrome in both man and monkeys which resembles closely that seen in idiopathic Parkinsonism. Brain damage produced by injection of NMPTP appears localized, at least at this writing, to the pars compacta of the substantia nigra. As a check on the selectivity of NMPTP damage, and for other reasons concerned with the still limited experience with this model, we will also study another group of monkeys in which localized nigral lesions are produced by Ibotenic acid. General motor behavior as well as oculomotor performance will be compared between groups.
The second aim of this project is to examine neuronal correlates of oculomotor dysfunction in the monkey P.D. models. As a site of first inquiry we have selected the superior colliculus, which receives a massive GABAergic projection from the substantia nigra. It is expected that single unit responses related to saccadic eye tracking will be especially affected after the monkeys have been rendered Parkinsonian, compared to pre-treatment measures in the same animals. These studies should begin to inform us regarding the specific neuronal control mechanisms which contribute to akinesia, bradykinesia and hypokinesia when disease affects the basal ganglia.
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| Brooks-Eidelberg, B A; Adler, G (1992) A frontal cortical potential associated with saccades in humans. Exp Brain Res 89:441-6 |
| Brooks, B A; Eidelberg, E; Morgan, W W (1987) Behavioral and biochemical studies in monkeys made hemiparkinsonian by MPTP. Brain Res 419:329-32 |
