EYE-MOVEMENTS IN MONKEYS WITH LOCAL DOPAMINE DEPLETION IN THE CAUDATE-NUCLEUS .1. DEFICITS IN SPONTANEOUS SACCADES

The basal ganglia contribute to the suppression and initiation of sacc adic eye movements through the inhibitory connection from the substant ia nigra pars reticulata (SNr) to the superior colliculus. This mechan ism consists of serial and parallel connections, which are mostly inhi bitory and GABAergic. Dopamine is known to exert powerful modulatory e ffects on the basal ganglia function, but its nature and mechanism are still unclear, especially in relation to voluntary behavior. The purp ose of this series of investigation was to study the role of dopamine in the control of saccadic eye movements. We examined, in the monkey, whether and how the deficiency of the nigrostriatal dopaminergic inner vation affects saccadic eye movements. The present article is focused on spontaneous saccades that the monkey made with no incentive to obta in reward; the next paper will describe task-specific saccades. Using an osmotic minipump we infused 1-methyl-4-phenyl-1,2,3,6-tetrahydropyr idine (MPTP) unilaterally into the head-body junction of the caudate n ucleus of monkeys where presaccadic neurons were clustered. Tyrosine h ydroxylase activity, visualized using an immunohistochemical method, d ecreased locally around the injection site with some effects extending into the ipsilateral putamen and locally in the ipsilateral substanti a nigra. Changes of eye movements started to appear 3-5 d after starti ng the infusion. Spontaneous saccades became less frequent. The area s canned by the saccades became narrower and shifted to the hemifield ip silateral to the infusion site. The saccade amplitudes and peak veloci ties decreased; durations were prolonged. These effects were more prom inent for saccades directed toward the side contralateral to the infus ion site. These monkeys showed no obvious skeletomotor symptoms. These results suggest that the local deprivation of the dopaminergic innerv ation in the caudate nucleus facilitates neuronal activity of the SNr leading to suppression of saccadic eye movements.