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正常和震颤型1-甲基-4-苯基-1,2,3,6-四氢吡啶黑长尾猴帕金森病模型中苍白球神经元自发放电的放电模式及相关性

Firing patterns and correlations of spontaneous discharge of pallidal neurons in the normal and the tremulous 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine vervet model of parkinsonism.

作者信息

Raz A, Vaadia E, Bergman H

机构信息

Department of Physiology, The Hebrew University-Hadassah Medical School, Jerusalem, 91120, Israel.

出版信息

J Neurosci. 2000 Nov 15;20(22):8559-71. doi: 10.1523/JNEUROSCI.20-22-08559.2000.

Abstract

To investigate the role of the basal ganglia in parkinsonian tremor, we recorded hand tremor and simultaneous activity of several neurons in the external and internal segments of the globus pallidus (GPe and GPi) in two vervet monkeys, before and after systemic treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and development of parkinsonism with tremor of 5 and 11 Hz. In healthy monkeys, only 11% (20/174) of the GPe cells and 3% (1/29) of the GPi cells displayed significant 3-19 Hz oscillations. After MPTP treatment, 39% (107/271) of the GPe cells and 43% (26/61) of the GPi cells developed significant oscillations. Oscillation frequencies of single cells after MPTP treatment were bimodally distributed around 7 and 13 Hz. For 10% of the oscillatory cells that were recorded during tremor periods, there was a significant tendency for the tremor and neuronal oscillations to appear simultaneously. Cross-correlation analysis revealed a very low level of correlated activity between pallidal neurons in the normal state; 95.6% (477/499) of the pairs were not correlated, and oscillatory cross-correlograms were found in only 1% (5/499) of the pairs. After MPTP treatment, the correlations increased dramatically, and 40% (432/1080) of the cross-correlograms had significant oscillations, centered around 13-14 Hz. Phase shifts of the cross-correlograms of GPe pairs, but not of GPi, were clustered around 0 degrees. The results illustrate that MPTP treatment changes the pattern of activity and synchronization in the GPe and GPi. These changes are related to the symptoms of Parkinson's disease and especially to the parkinsonian tremor.

摘要

为研究基底神经节在帕金森震颤中的作用,我们在两只黑长尾猴身上记录了手部震颤以及苍白球外侧部和内侧部(GPe和GPi)多个神经元的同步活动,记录时间为全身注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)前后,以及出现5赫兹和11赫兹震颤的帕金森病发展过程中。在健康猴子中,只有11%(20/174)的GPe细胞和3%(1/29)的GPi细胞表现出显著的3 - 19赫兹振荡。MPTP治疗后,39%(107/271)的GPe细胞和43%(26/61)的GPi细胞出现了显著振荡。MPTP治疗后单细胞的振荡频率在7赫兹和13赫兹左右呈双峰分布。在震颤期记录的10%的振荡细胞中,震颤和神经元振荡有显著的同时出现趋势。互相关分析显示,正常状态下苍白球神经元之间的相关活动水平非常低;95.6%(477/499)的配对不相关,只有1%(5/499)的配对出现振荡互相关图。MPTP治疗后,相关性显著增加,40%(432/1080)的互相关图有显著振荡,中心频率在13 - 14赫兹左右。GPe配对的互相关图的相位偏移集中在0度左右,而GPi的则不然。结果表明,MPTP治疗改变了GPe和GPi的活动模式和同步性。这些变化与帕金森病的症状特别是帕金森震颤有关。

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