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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(picro-toxin,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。
Changes in the plasticity of dopaminergic neurons in the ventral tegmental area (VTA) directly affect the functions of the relevant brain regions such as the reward system. At present, the studies on the plasticity of dopaminergic neurons in VTA mainly focus on the synaptic plasticity, and the research on the excitability plasticity of dopaminergic neuron somatic cells has not been reported yet. The purpose of this experiment was to investigate the effect of high-frequency stimulation on the excitability and plasticity of dopaminergic neuronal cell bodies. GABAA receptor blocker picro-toxin (PTX), glutamate AMPA receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione -7-nitroquinoxaline-2,3-dione, CNQX), DL-2-amino-5-phosphonopentanoic acid ) Perfused rat VTA dopaminergic neurons and blocked the neuronal synapse connection. The excised slices of the brain slices were used to observe whether excitability of dopaminergic neurons was changed after high frequency stimulation of the somatic cells. The results showed that after high frequency stimulation, the input impedance of VTA dopaminergic neurons increased, the base intensity decreased, the discharge frequency increased, and the excitability of cells increased over time. At the same time, the total cell current was significantly decreased after induced by high-frequency stimulation, and the hyperpolarization-activated mixed cation flow (Ih) also decreased. These results suggest that high-frequency stimulation of VTA dopaminergic neuron long-term excitability increased, the mechanism involved in neuronal membrane current changes.