Usui S, Fukuda H, Hikosaka O
Department of Neurology, Juntendo University School of Medicine.
Rinsho Shinkeigaku. 1990 Nov;30(11):1181-9.
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.
基底神经节在眼球扫视运动的控制中起重要作用。帕金森病患者在扫视启动方面存在缺陷；这些缺陷在记忆引导的扫视中比在视觉引导的扫视中更为突出（日高坂等，1987）。这些结果表明，黑质纹状体多巴胺能系统的缺陷会影响基底神经节中眼球扫视运动的神经机制。为了研究这一假设，我们对MPTP诱导的偏侧帕金森病猴的眼球扫视运动进行了研究。我们用两只猴子制作了两种帕金森病模型：1）经颈内动脉单侧注射MPTP，2）使用渗透微型泵向尾状核内注射MPTP。我们使用磁性搜索线圈法记录眼球扫视运动。实验结束后，处死猴子并通过组织学程序进行研究。经颈内动脉注射后，我们观察到注射侧对侧的手臂和腿部出现运动迟缓及僵硬。眼球位置向同侧偏移，向对侧的扫视频率降低。向尾状核内注射后，我们观察到对侧手臂和腿部出现运动迟缓及僵硬，并出现向对侧的转圈行为。在两只猴子中，向对侧的扫视幅度和峰值速度均降低。我们考虑了三种可能解释这些结果的机制。第一，尾状核中MPTP导致的多巴胺能去神经支配可能会抑制投射到黑质网状部的神经元的活动。第二，黑质细胞的活动可能通过经由苍白球外侧部和丘脑底核的间接通路被持续性增强。第三，MPTP可能通过黑质致密部到黑质网状部的树突 - 树突连接增强黑质细胞的活动。
