联系作者：林凡凯，男，30岁，博士研究生。Tel: 0086-027-83691760; E-mail: linzi_lfk@sina.com
通讯作者：陈建国，男，42岁，博士，教授。
*Corresponding author. Tel: 86-27-83692636; Fax: 86-27-83692608; E-mail: chenj@mails.tjmu.edu.cn
This work was supported by grants from the National Science Fund for Distinguished Young Scholars in China (No. 30425024) and the National Basic Research Program of China (973 Program) (No. 2007CB507404).
电刺激大鼠束旁核对底丘脑核和丘脑腹内侧核神经元的影响
林凡凯1，辛 艳2 ，高东明3，熊 哲1，陈建国1,*
1华中科技大学同济医学院药理学系，武汉 430030；2沈阳药科大学中药学院，沈阳110016；3 辽宁医学院生理学教研室，锦州 121001
摘 要：本工作旨在探讨电刺激束旁核(parafascicular nucleus, PF)对帕金森模型(Parkinson’s disease, PD)大鼠神经行为的改善作用及其机制。实验中采用行为学方法观察了电刺激PF对大鼠阿朴吗啡诱发的旋转行为的作用，并应用体细胞外记录法观察电刺激PF对大鼠底丘脑核(subthalamic nucleus, STN)及丘脑腹内侧核(ventromedial nucleus, VM)神经元放电的影响。结果发现，高频电刺激(130 Hz, 0.4 mA) PF一周明显改善PD大鼠旋转行为。细胞外放电记录显示，高频电刺激PF使PD大鼠STN神经元自发放电减少，且该作用具有频率依赖性。另外，高频电刺激PF可使VM神经元兴奋，该作用也是频率依赖性的。我们在实验中同时观察到微电泳γ-氨基丁酸(γ-amino butyric acid, GABA)和谷氨酸受体拮抗剂MK-801使STN神经元放电频率减少或完全抑制。微电泳谷氨酸(glutamic acid, Glu)和GABA受体拮抗剂印防己毒素(picrotoxin, Pic) 则使神经元放电频率增加。以上结果表明GABA能和Glu能传入纤维可会聚于同一STN神经元，并对后者有紧张性作用。高频刺激PF，使该核团到STN神经元的Glu能兴奋性输出减少，导致STN的失活。这一作用通过基底神经节的间接通路，最终去抑制释放了丘脑运动核团VM的活性。本研究提示高频刺激PF是通过经PF，STN和VM的神经通路而发挥对PD大鼠神经行为的改善作用的。
关键词：束旁核；底丘脑核；丘脑腹内侧核；电刺激；微电泳
中图分类号：R338.2
Effects of electrical stimulation of the parafascicular nucleus on the neuronal activities of the subthalamic nucleus and the ventromedial nucleus in rats
LIN Fan-Kai1 , XIN Yan2, GAO Dong-Ming3, XIONG Zhe1, CHEN Jian-Guo1,*
1 Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030; 2School of Traditional Chinese Materia Medica,3Shenyang Pharmaceutical University, Shenyan 110016; 3 Department of Physiology, Liaoning Medical College, Jinzhou 121001
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. Using the ethological methods, we examined the effect of electrical stimulation of PF on the apomorphine-induced rotational behavior in 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) of PF, there was significant improvement of apomorphine-induced rotational behavior in rats with 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta. HFS of PF caused an inhibition of the majority of neurons (84%) recorded in the STN in the 6-OHDA lesioned 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 stimulation frequencies over 50 Hz were effective. Furthermore, employing microelectrophoresis, we demonstrated that glutamatergic and GABAergic afferent nerve fibers convergence 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 the 6-OHDA lesioned rats, which is mediated by the nuclei of PF, STN and VM.