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MPTP诱导的帕金森病猴苍白球神经元对纹状体刺激的反应。

Responses of pallidal neurons to striatal stimulation in monkeys with MPTP-induced parkinsonism.

作者信息

Tremblay L, Filion M, Bédard P J

机构信息

Centre de Recherche en Neurobiologie, Université Laval, Que, Canada.

出版信息

Brain Res. 1989 Sep 25;498(1):17-33. doi: 10.1016/0006-8993(89)90395-8.

DOI:10.1016/0006-8993(89)90395-8
PMID:2790469
Abstract

Extracellular single unit activity was recorded from neurons of the internal (GPi) and external (GPe) pallidal segments, and from 'border cells' (Bor) which are part of the nucleus basalis, in 2 cynomolgus monkeys rendered parkinsonian by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). Cell counts showed that at least 90% of the nigral neurons of the compacta-type were degenerated. Electrical stimulation was applied to 3 sites bilaterally in the striatum: one in the caudate nucleus and 2 in the putamen. The results were compared to those obtained in intact monkeys. In the parkinsonians, more neurons of the 3 types responded to ipsilateral stimulation. The difference was even greater for contralateral responses, except in the case of Bor neurons. Greater proportions of the 3 types of neurons also responded to 2 and 3 sites and showed convergent responses to both the caudate nucleus and the putamen. The magnitude of the responses was larger. These results are in accordance with the excessive and unselective responses of the same neurons to passive limb movement, obtained in the same animals and described previously. The electrical stimulation allowed more detailed analyses of the responses. The major change in the responses of GPi and Bor neurons was the more frequent and larger late inhibitions, whereas the excitations were larger in GPe neurons. Long lasting oscillatory responses occurred frequently in the parkinsonians, mainly in GPi, and at frequencies close to the tremor displayed by the animals. Responses beginning with early inhibition were displayed by neurons located in the center of the pallidal zone of influence of each striatal stimulation site, as in intact animals, but in the GPi of the parkinsonians they were less frequently curtailed by excitation. Moreover, in the parkinsonians, the zones of influence were larger in both GPi and GPe, mainly because of the expansion of their periphery, where responses began with excitation and had lower thresholds than in intact animals. The dopamine agonist apomorphine normalized the responses in the parkinsonians. Thus, both the temporal and spatial magnitudes of inhibitions and excitations are abnormal at the output of the basal ganglia in parkinsonism.

摘要

在2只经1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导产生帕金森病的食蟹猴中,记录苍白球内侧部(GPi)、外侧部(GPe)神经元以及基底核“边界细胞”(Bor)的细胞外单单位活动。细胞计数显示,至少90%的致密型黑质神经元发生退变。双侧纹状体的3个部位接受电刺激:1个在尾状核,2个在壳核。将结果与在正常猴子中获得的结果进行比较。在帕金森病模型猴中,这3种类型的更多神经元对同侧刺激有反应。除了Bor神经元外,对侧反应的差异更大。这3种类型的神经元中,更大比例的神经元也对2个和3个刺激部位有反应,并对尾状核和壳核均表现出汇聚反应。反应的幅度更大。这些结果与在相同动物中先前描述的同一神经元对被动肢体运动的过度且无选择性反应一致。电刺激使得对反应的分析更加详细。GPi和Bor神经元反应的主要变化是更频繁且更大的晚期抑制,而GPe神经元的兴奋更大。在帕金森病模型猴中,持续的振荡反应频繁出现,主要在GPi,且频率接近动物表现出的震颤频率。与正常动物一样,位于每个纹状体刺激部位苍白球影响区中心的神经元表现出以早期抑制开始的反应,但在帕金森病模型猴的GPi中,它们较少被兴奋所终止。此外,在帕金森病模型猴中,GPi和GPe的影响区都更大,主要是因为其周边区域扩大,在该区域反应以兴奋开始且阈值低于正常动物。多巴胺激动剂阿扑吗啡使帕金森病模型猴的反应恢复正常。因此,帕金森病中基底神经节输出时抑制和兴奋的时间和空间幅度均异常。

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