[Spontaneous saccades in MPTP-induced hemi-parkinsonian monkeys]

The basal ganglia play an important role in the control of saccadic eye movements. Parkinsonian patients have deficits in saccade initiation; the deficits are more prominent in memory-guided saccade than in visually guided saccade (Hikosaka et al, 1987). These results show that deficiency of nigrostriatal dopaminergic system affects the neural mechanism of saccadic eye movements in the basal ganglia. In order to investigate this hypothesis, we studied saccadic eye movements in MPTP-induced hemiparkinsonian monkeys. We made two models of parkinsonism using two monkeys: 1) unilateral intra-carotid injection of MPTP, and 2) intracaudate injection of MPTP using osmotic minipump. We recorded saccadic eye movements using the magnetic search coil method. After experiments, monkeys were sacrificed and investigated by histological procedures. Following the intracarotid injection, we observed hypokinesia and rigidity in the arm and leg contralateral to the injection. Eye position was shifted to the ipsilateral side and the frequency of saccades towards the contralateral side was reduced. Following the intracaudate injection, we observed hypokinesia and rigidity in the contralateral arm and leg and circling behavior towards the contralateral side. In both monkeys, the saccade amplitude and peak velocity towards contralateral side were reduced. We considered three mechanisms that might account for these results. First, dopaminergic denervation due to MPTP in the caudate nucleus may suppress the activity of neurons projecting to the pars reticulata of the substantia nigra. Second, nigra cell activity may be tonically elevated through an indirect pathway via the external pallidum and the subthalamic nucleus. Third, MPTP may enhance nigra cell activity through dendro-dendritic connections from the pars compacta to the pars reticulata in the substantia nigra.