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Title:: In Vivo Monitoring L-DOPA-Induced Glutamate Flux and Electrophysiological Signals with a Microelectrode Array

作者:: 范心怡1; 2 ; 张松1; 2; 宋轶琳1; 徐辉任1; 2; 肖桂花1; 2; 杨丽丽1; 2; 蔡新霞1; 2; 1. 中国科学院电子学研究所传感技术联合国家重点实验室，北京 100190； 2. 中国科学院大学，北京 100190

Author(s):: Fan Xinyi1; 2; Zhang Song1; 2; Song Yilin1; Xu Huiren1; 2; Xiao Guihua1; 2; Yang Lili1; 2 ; Cai Xinxia 1; 2; 1. State Key Laboratory of Transducer Technology, Institute of Electronics, Chinese Academy of Sciences, Beijing 100190, China; 2. University of Chinese Academy of Sciences, Beijing 100190, China

Keywords:: micro-electro-mechanical-system (MEMS); implantable microelectrode array (MEA); 3; 4-dihydroxyphenyl-L-alanine(L-DOPA); glutamate; spike; local field potential (LFP)

摘要:: 左旋多巴（L-DOPA）是帕金森症的主要治疗药物之一，长期使用具有神经毒性，其作用机理复杂.为了研究LDOPA对大脑纹状体谷氨酸神经通路在体神经元的影响，采用微机电系统（MEMS）技术制备了一种16通道植入式微电极阵列（MEA）芯片，其上集成了直径10 μm的电生理、电化学双模信号检测位点，能够实时记录脑内神经递质谷氨酸和动作电位（spike）、局部场电位（LFP）等神经电信号的同步变化.将这种MEA植入大鼠纹状体，在皮层施加L-DOPA（100 μL，2 mmol/L）刺激后，随着纹状体内谷氨酸浓度的迅速增加，神经元spike发放频率和LFP低频段功率同步衰减.实验结果从神经元层次在体验证了L-DOPA的神经毒性，可为帕金森症治疗药理研究提供线索.

Abstract:: 3,4-dihydroxyphenyl-L-alanine(L-DOPA) remains one of the major therapeutic drugs for Parkinson’s disease, whereas long-term use is neurotoxic and its mechanism is complex . In order to study the effect of L-DOPA on neuronal neurons in the striatum of the brain, a 16-channel implanted microelectrode array（MEA） was fabricated by micro-electro-mechanical-system (MEMS), which integrates electrophysiological and electrochemical dual-mode signal detection sites with a diameter of 10 μm. It can record the glutamate and spike, local field potential (LFP) synchronization of neuronal electrical signals. The MEA was implanted into the striatum of rats. During these multi-modal recordings, L-DOPA (2 mmol/L, 100 μL) increased the extracellular glutamate levels as well as the firing rate and LFP initially, while the neural activity was suppressed. Results reveal the noxious effect of L-DOPA and may provide clues to the therapy of Parkinson’s disease.