耳鸣过程中电生理与鼠脑内多巴胺释放相关性的活体研究

Tinnitus is a noise such as a ringing or buzzing that you can hear, but the noise does not come from outside your ear，which is a kind of diseases of great impact on the life and work of the patients. Dopamine is one of the most important neurotransmitters released from neurons. This project uses electrophysiological techniques combined with electrochemical methods to study the excitatory activity and neurotransmitter dopamine in rat brain of tinnitus model, and based on this, to study the relationship between them. The contents of this project include the development of a new principle and new method for selective determination dopamine based on its unique electrochemical properties. With the method, we will record electrochemical and electrophysiological signal at the same time to understand the relationship between neurotransmitter release and electrophysiological activity during the development of tinnitus. We will further investigate the mechanism underlying the simultaneous changes in dopamine release and in electrophysiological activity by monitoring the changes of the concentrations of glutamate, ascorbate and Zn2+ during the development of tinnitus. This project would be very useful for understanding the pathogenesis of tinnitus and could thus provides a molecular basis for the relationship between transmitter release and neuronal activity.

耳鸣是指在没有外部声源存在下，产生的一种主观听觉感受，是一种会对患者的生活和工作造成影响的病理症状。本项目针对耳鸣过程中信号转导通路研究，尤其是生理活性小分子变化规律与电生理信号之间关系尚不明确这一关键问题，结合分析化学和生命科学的最新研究进展，利用微纳结构和功能分子独特的电化学和光学性能，发展多巴胺的选择性测定新原理和新方法；发展可与电生理信号同时记录的多巴胺电化学测定新方法；在此基础上，研究耳鸣发生过程中神经递质释放与电生理信号之间的相互关系，进而结合其它生理活性分子（如谷氨酸、抗坏血酸、锌离子等）的变化规律，探索耳鸣过程中与谷氨酸毒性相关的信号转导过程的分子机制。这一研究的开展将为理解耳鸣发病过程中经元电活动与化学递质之间的相关性研究奠定基础。

本项目利用电化学与电生理方法，在活体层次研究了耳鸣过程中多巴胺递质的分子机制，深入理解这一分子机制与电生理信号所反映的神经元活动之间的关系，从而进一步探索调节多巴胺递质活动对神经元活动的影响。具体研究内容包括：1）电生理信号平台的建立，2）多巴胺化学信号的原位记录，3）电化学电生理信号的同时记录，4）耳鸣模型过程中电生理和电化学信号的同时记录。经过一年的探索和研究，前三部分的研究已经取得阶段性研究成果，第三部分的内容专利正在申请中，第四部分的研究已经开展了前期的探索工作，并取得了一些进展。