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低频电刺激大鼠脚桥核对丘脑腹外侧核神经元自发放电的影响及其机制

刘焕, 林宇涵, 程九华, 蔡越, 於进文, 马进, 高东明^*

第四军医大学航空航天医学教育部重点实验室，航空航天生理学教研室，西安 710032；辽宁医学院生理学教研室，锦州 121001

摘要

本文旨在观察低频电刺激脚桥核(pedunculopontine nucleus, PPN)对帕金森病(Parkinson’s disease, PD)模型大鼠丘脑腹外侧核(ventrolateral thalamic nucleus, VL)神经元自发放电活动的影响，以探讨低频电刺激PPN改善PD症状的作用机制。通过纹状体内注射6-羟多巴胺制备PD大鼠模型。采用在体细胞外记录、电刺激及微电泳方法，观察低频电刺激PPN、微电泳乙酰胆碱(acetylcholine, ACh)及其M型受体阻断剂阿托品(atropine, ATR)、γ-氨基丁酸(γ-aminobutyric acid, GABA)及其A型受体阻断剂荷包牡丹碱(bicuculline, BIC)对大鼠VL神经元放电频率的影响。结果显示，低频电刺激PPN可使正常大鼠和PD大鼠VL神经元自发放电频率增加。微电泳ACh对VL神经元具有兴奋和抑制两种作用，而微电泳ATR则主要抑制VL神经元，即使对被ACh抑制的神经元也产生抑制作用。微电泳GABA抑制VL神经元，而微电泳BIC则兴奋VL神经元。另外，在微电泳ACh的过程中微电泳GABA，被ACh兴奋或抑制的VL神经元放电频率明显降低。在ATR抑制作用的基础上低频电刺激PPN则不能使VL神经元放电频率增加。以上结果提示，胆碱能和GABA能传入纤维可能会聚于同一VL神经元，并对其具有紧张性作用。低频电刺激PPN可能使该核团投射至VL的胆碱能纤维释放ACh增加，从而通过突触前负反馈调节抑制投射至基底节输出核VL的GABA能通路，释放丘脑–皮层投射，使相应运动皮层活动提高而改善PD症状。

关键词： 帕金森病; 脚桥核; 丘脑腹外侧核; 微电泳; 低频电刺激

分类号：R338.8

[Effects and mechanism of low frequency stimulation of pedunculopontine nucleus on spontaneous discharges of ventrolateral thalamic nucleus in rats.] [Article in Chinese]

LIU Huan, LIN Yu-Han, CHENG Jiu-Hua, CAI Yue, YU Jin-Wen, MA Jin, GAO Dong-Ming^*

Key Laboratory of Aerospace Medicine, Ministry of Education； Department of Aerospace Physiology, the Fourth Military Medical University, Xi’an 710032, China； Department of Physiology, Liaoning Medical College, Jinzhou 121001, China

Abstract

Parkinson’s disease is a progressive neurodegenerative disorder characterized clinically by rigidity, akinesia, resting tremor and postural instability. It has recently been suggested that low frequency stimulation of the pedunculopontine nucleus (PPN) has a role in the therapy for Parkinsonism, particularly in gait disorder and postural instability. However, there is limited information about the mechanism of low frequency stimulation of the PPN on Parkinson’s disease. The present study was to investigate the effect and mechanism of low frequency stimulation of the PPN on the firing rate of the ventrolateral thalamic nucleus (VL) in a rat model with unilateral 6-hydroxydopamine lesioning of the substantia nigra pars compacta. In vivo extracellular recording and microiontophoresis were adopted. The results showed that the firing rate of 60.71% VL neurons in normal rats and 59.57% VL neurons in 6-hydroxydopamine lesioned rats increased with low frequency stimulation of the PPN. Using microiontophoresis to VL neurons, we found the firing rate in VL neurons responded with either an increase or decrease in application of acetylcholine (ACh) in normal rats, whereas with a predominant decrease in M receptor antagonist atropine. Furthermore, the VL neurons were mainly inhibited by application of γ-aminobutyric acid (GABA) and excited by GABAA receptor antagonist bicuculline. Importantly, the VL neurons responding to ACh were also inhibited by application of GABA. We also found that the excitatory response of the VL neurons to the low frequency stimulation of the PPN was significantly reversed by microiontophoresis of atropine. These results demonstrate that cholinergic and GABAergic afferent nerve fibers may converge on the same VL neurons and they are involved in the effects of low frequency stimulation of the PPN, with ACh combining M2 receptors on the presynaptic membrane of GABAergic afferents, which will inhibit the release of GABA in the VL and then improve the symptoms of Parkinson’s disease.

Key words: Parkinson’s disease; pedunculopontine nucleus; ventrolateral thalamic nucleus; microiontophoresis; low frequency stimulation

收稿日期：2011-01-21　　录用日期：2011-05-10

通讯作者：高东明　　E-mail: jzgaodm@163.com

引用本文：

刘焕, 林宇涵, 程九华, 蔡越, 於进文, 马进, 高东明. 低频电刺激大鼠脚桥核对丘脑腹外侧核神经元自发放电的影响及其机制[J]. 生理学报 2011; 63 (4): 311.

LIU Huan, LIN Yu-Han, CHENG Jiu-Hua, CAI Yue, YU Jin-Wen, MA Jin, GAO Dong-Ming. [Effects and mechanism of low frequency stimulation of pedunculopontine nucleus on spontaneous discharges of ventrolateral thalamic nucleus in rats.] [Article in Chinese]. Acta Physiol Sin 2011; 63 (4): 311 (in Chinese with English abstract).