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胞体高频刺激诱导VTA多巴胺能神经元兴奋性的长时程增强

魏春玲, 刘志强, 刘一辉^*, 任维

陕西师范大学现代教学技术教育部重点实验室，生命科学学院，西安 710062

摘要

中脑腹侧背盖区(ventral tegmental area, VTA)多巴胺能神经元的可塑性变化直接影响着奖赏系统等相关脑区的功能。目前对于VTA多巴胺能神经元可塑性的研究主要集中在突触的可塑性，而对多巴胺能神经元胞体兴奋性可塑性的研究还未见报道。本实验旨在研究高频刺激对多巴胺能神经元胞体兴奋性可塑性的影响。采用GABAA受体阻断剂印防己毒素(picrotoxin, PTX)、谷氨酸AMPA受体阻断剂6-氰基-7-硝基喹喔啉-2,3-二酮(6-Cyano-7-nitroquinoxaline-2,3-dione, CNQX)、谷氨酸NMDA受体阻断剂DL-2-氨基-5-膦酰基戊酸(DL-2-amino-5-phosphonopentanoic acid, AP-5)灌流大鼠VTA多巴胺能神经元，阻断神经元突触联系，用离体脑片膜片钳技术观察高频刺激胞体后多巴胺能神经元胞体兴奋性是否发生改变。结果显示，高频刺激后，大鼠VTA多巴胺能神经元的输入阻抗增加，基强度降低，放电频率增加，细胞的兴奋性长时程增强。同时，高频刺激诱导后全细胞电流显著减小，超极化激活的混合阳离子流(Ih)也减小。以上结果提示，高频刺激使VTA多巴胺能神经元兴奋性发生长时程的增强，其机制涉及神经元膜电流的变化。

关键词： 中脑腹侧背盖区; 多巴胺能神经元; 神经元兴奋性; 兴奋性可塑性

分类号：Q42

[High-frequency stimulation on soma induces long-term potentiation of intrinsic excitability in VTA dopamine neurons.] [Article in Chinese]

Wei Chun-Ling, Liu Zhi-Qiang, LIU Yi-Hui^*, REN Wei

Key Laboratory of MOE for Modern Teaching Technology and College of Life Science, Shaanxi Normal University, Xi’an 710062, China

Abstract

Ventral tegmental area (VTA) is an important relay station of signal transmission in the reward system. The plasticity of VTA dopaminergic neurons directly influences actions of other regions of the reward system. Studies concerning the plasticity of VTA dopaminergic neurons focus mainly on synaptic plasticity, while much less attention has been given to the plasticity of intrinsic excitability of the neurons. The aim of the present study was to investigate the effect of high-frequency stimulation (HFS) on the plasticity of excitability of VTA neuron. Whole-cell patch-clamping was performed on VTA dopaminergic neurons in midbrain slices bathed with PTX, AP-5 and CNQX, and HFS was introduced to cell soma. The result showed that, after HFS induction the pharmacologically isolated neurons showed increased input resistance and firing frequency, as well as decreased rheobase. Meanwhile, the steady-state whole-cell current decreased, and the hyperpolarization-activated current (I(h)) decreased. These results suggest that HFS on soma induces a long-term potentiation of excitability in VTA dopaminergic neurons, and the underlying mechanism involves the changes of membrane current.

Key words: ventral tegmental area; dopaminergic neurons; neuronal excitability; plasticity of excitability

收稿日期：2012-05-04　　录用日期：2012-08-07

通讯作者：刘一辉　　E-mail: liu.y.hui@gmail.com

引用本文：

魏春玲, 刘志强, 刘一辉, 任维. 胞体高频刺激诱导VTA多巴胺能神经元兴奋性的长时程增强[J]. 生理学报 2013; 65 (1): 55-60.

Wei Chun-Ling, Liu Zhi-Qiang, LIU Yi-Hui, REN Wei. [High-frequency stimulation on soma induces long-term potentiation of intrinsic excitability in VTA dopamine neurons.] [Article in Chinese]. Acta Physiol Sin 2013; 65 (1): 55-60 (in Chinese with English abstract).