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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。
The aim of this study was to investigate the effect of low frequency electrical stimulation of pedunculopontine nucleus (PPN) on spontaneous discharges of ventrolateral thalamic nucleus (VL) neurons in Parkinson’s disease (PD) model in rats Mechanism of Low Frequency Electrical Stimulation of PPN on PD Symptoms. PD rat model was prepared by intracerebral injection of 6-hydroxydopamine. The effects of low frequency electrical stimulation of PPN, acetylcholine (ACh) and its M receptor antagonist atropine (ATR), γ-aminobutyric acid γ-aminobutyric acid (GABA) and its type A receptor antagonist bicuculline (BIC) on the firing rate of VL neurons in rats. The results showed that low frequency electrical stimulation PPN can make the normal rats and PD rats VL neurons spontaneous firing frequency increased. Microelectrophoresis ACh has two functions of VL neuron excitation and inhibition, while the microelectrophoresis ATR mainly inhibit VL neurons, even inhibit ACh-inhibited neurons. Microelectrophoresis GABA inhibits VL neurons, whereas microelectrophoresis BIC excites VL neurons. In addition, in the process of micro-electrophoresis ACh GABA microelectrodes, ACh excited or inhibited VL neurons discharge frequency was significantly reduced. Based on the inhibition of ATR, low-frequency electrical stimulation of PPN failed to increase the firing rate of VL neurons. These results suggest that cholinergic and GABA-afferent fibers may be clustered in the same VL neurons and have a tonic effect on them. Low-frequency electrical stimulation of PPN may cause the nucleus to cholinergic fibers of the VL releasing ACh, thereby inhibiting the projection of the GABAergic pathway to the basal ganglia output nucleus VL by presynaptic negative feedback regulation, releasing the thalamic-cortical projections, Increased motor cortex to improve PD symptoms.