皮层-纹状体通路在耳鸣发病机制中的调控作用研究

Tinnitus is one of the major health problems worldwide affecting 10-15 percent of population. To date, functional MRI studies have indicated that corticostriatal pathways might play an important role in the perception of tinnitus. But the specific mechanism is not clear. Our group has found that local inhibition of the corticostriatal system with lidocaine can down regulate the increased neural activity and dopamine level caused by sodium salicylate. To address this issue, we intend to apply neurotropic virus to trace the synaptic connections between those two neural networks. After that, we chronically deliver sodium salicylate(SS) to induce tinnitus in rats and confirm it with conventional behavioral model. We then record the change of neural activity and biological molecules in the two system pre- and post- SS treatment and verify the result with physical and drug intervention. Through the above process, we would find the synaptic connections between the corticostriatal pathways and the classical auditory pathways and the neurotransmitters function in the network, which would help to figure out the developing mechanism of tinnitus and offer some guidance for precise clinical treatment of the disorder.

耳鸣在人群的发生率为10%-15%，是世界性的重大健康问题之一。功能磁共振研究提示皮层-纹状体通路可能在耳鸣的发生中起着重要的作用，但具体机制不清。我们前期研究发现，局部干预皮层-纹状体通路中的伏隔核可下调耳鸣过程中的听皮层神经兴奋性和多巴胺的变化。因此,本研究拟采用嗜神经病毒跨突触追踪技术明确经典听觉通路与皮层-纹状体通路之间的神经网络联系。同时，采用经典方法建立注射水杨酸钠诱导耳鸣的大鼠模型,采用电生理学及活体电化学分析等方法，动态同步观察耳鸣前后及局部物理和药物干预前后皮层-纹状体通路与听觉通路间神经电活动与神经递质/调质与动物行为学（出现耳鸣）的时间相位上的对应关系，明确皮层-纹状体通路在耳鸣产生中与经典听觉通路间的神经网络联系，为阐明耳鸣的发生机制提供理论基础，进而为临床耳鸣治疗提供了更为精准的靶点参考。

耳鸣在人群的发生率为10%-15%，是世界性的重大健康问题之一。本研究采用经典方法建立注射水杨酸钠诱导耳鸣的大鼠模型,采用电生理学及活体电化学分析等方法，动态同步观察耳鸣前后及局部物理和药物干预前后皮层-纹状体通路与听觉通路间神经电活动与神经递质/调质与动物行为学（出现 耳鸣）的时间相位上的对应关系，明确皮层-纹状体通路在耳鸣产生中与经典听觉通路间的神经网络联系，为阐明耳鸣的发生机制提供理论基础，进而为临床耳鸣治疗提供了更为 精准的靶点参考。本研究不仅在耳鸣分子机制的基础研究方面具有重要意义，而且在耳鸣的临床治疗方面也具有重要指导作用