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[电刺激大鼠束旁核对其丘脑底核和腹内侧核神经元活动的影响]

[Effects of electrical stimulation of the parafascicular nucleus on the neuronal activities of the subthalamic nucleus and the ventromedial nucleus in rats].

作者信息

Lin Fan-Kai, Xin Yan, Gao Dong-Ming, Xiong Zhe, Chen Jian-Guo

机构信息

Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

出版信息

Sheng Li Xue Bao. 2007 Feb 25;59(1):79-85.

Abstract

The present study was designed to investigate the function and mechanism of high-frequency stimulation (HFS) of the parafascicular nucleus (PF) used as a therapeutic approach for Parkinson's disease (PD). PD rat model was built by injecting 6-hydroxydopamine (6-OHDA) into the substartia nigra pars compacta of adult male Sprague-Dawley rats. Using the ethological methods, we examined the effect of electrical stimulation of PF on the apomorphine-induced rotational behavior in PD rats. Moreover, Electrophysiological recordings were made in rats to investigate the effects of electrical stimulation of PF on the neuronal activities of the subthalamic nucleus (STN) and the ventromedial nucleus (VM). Our results showed that one week after HFS (130 Hz, 0.4 mA, 5 s) of PF, there was significant improvement in apomorphine-induced rotational behavior in PD rats. HFS of PF caused an inhibition of the majority of neurons (84%) recorded in the STN in PD rats. The majority of cells recorded in the VM of the thalamus responded to the HFS with an increase in their unitary discharge activity (81%). These effects were in a frequency-dependent manner. Only stimulus frequencies above 50 Hz were effective. Furthermore, employing microelectrophoresis, we demonstrated that glutamatergic and GABAergic afferent nerve fibers converged on the same STN neurons. These results show that the HFS of PF induces a reduction of the excitatory glutamatergic output from the PF which in turn results in deactivation of STN neurons. The reduction in tonic inhibitory drive from the basal ganglia induces a disinhibition of activity in the VM, a motor thalamic nucleus. In conclusion, the results suggest that HFS of PF may produce a therapeutic effect in PD rats, which is mediated by the nuclei of PF, STN and VM.

摘要

本研究旨在探讨将束旁核(PF)高频刺激(HFS)用作帕金森病(PD)治疗方法的功能及机制。通过向成年雄性Sprague-Dawley大鼠黑质致密部注射6-羟基多巴胺(6-OHDA)建立PD大鼠模型。我们采用行为学方法,研究了PF电刺激对PD大鼠阿扑吗啡诱导的旋转行为的影响。此外,在大鼠中进行电生理记录,以研究PF电刺激对丘脑底核(STN)和腹内侧核(VM)神经元活动的影响。我们的结果显示,PF进行HFS(130Hz,0.4mA,5s)一周后,PD大鼠阿扑吗啡诱导的旋转行为有显著改善。PF的HFS导致PD大鼠STN中记录的大多数神经元(84%)受到抑制。丘脑VM中记录的大多数细胞对HFS的反应是其单位放电活动增加(81%)。这些效应呈频率依赖性。仅频率高于50Hz的刺激有效。此外,通过微电泳,我们证明谷氨酸能和γ-氨基丁酸能传入神经纤维汇聚于同一STN神经元。这些结果表明,PF的HFS导致PF兴奋性谷氨酸能输出减少,进而导致STN神经元失活。基底神经节紧张性抑制驱动的减少导致运动丘脑核VM的活动去抑制。总之,结果表明PF的HFS可能对PD大鼠产生治疗作用,这是由PF、STN和VM核介导的。

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