噪声暴露后大鼠听皮层兴奋性及抑制性系统的改变

Noise exposure can induce tinnitus besides hearing loss, and, up to now, there is no effective treatment for tinnitus. In recent years, most researchers hold the opinion that the neural basis of tinnitus is the change of balance of inhibition and excitation in central auditory loop, which caused hyperexcitability in the central auditory system and eventually tinnitus occurs, but the underlying structure is not clear, especially in the level of receptors. In our previous study, we found that the number of GABAergic inhibitory neurons was changed and the change is dynamic during different stages after noise exposure. So we conclude that the change of inhibitory neurotransimission after noise exposure is one of the structure bases for generation of tinnitus, but we don't know whether there is any change in inbitory receptors, and whether there is any involvement of exictatory system remains unknown. In the present project, we want to use in vivo recording, patch clamp recording and in vitro field potential recording combined with morphological method to study the change of inbhibitory and excitatory system in auditory cortex, so that we can clarify the underying neural mechanism of tinnitus, and hopefully contribute to the develpoment of tinnitus therapeutic methods.

噪声暴露不仅可导致听力下降，还会诱发耳鸣，但目前临床上缺乏有效治疗耳鸣的手段。目前许多学者都支持这样的观点：听觉外周损伤后,由于外周传入减少，听觉中枢兴奋增强或抑制减弱，引起听觉中枢超兴奋，可能是耳鸣产生的原因，但具体机制特别是受体水平的结构基础还不清楚。申请人前期研究结果表明，大鼠听皮层抑制性神经元的数量在噪声暴露后在不同的阶段发生了动态的改变。因此我们推测，在噪声暴露后听觉中枢抑制性系统的改变可能是耳鸣产生的结构基础之一，虽然我们看到抑制性神经元数量本身发生了改变，但抑制性受体的功能是否有改变还不清楚，并且兴奋性系统是否参与了耳鸣产生也不清楚。本课题拟通过在体电生理记录、脑片膜片钳及离体场电位记录的方法，结合形态学等方法，利用噪声暴露制作大鼠耳鸣模型，研究耳鸣动物听皮层兴奋性以及抑制性突触传递的改变，以阐述耳鸣产生的潜在作用机制，这将有助于寻找有效的耳鸣治疗方案。

本研究建立了噪声暴露耳蜗受损的动物模型，在大鼠单耳噪声暴露后可观察到暴露侧听阈升高，而非暴露耳听阈没有变化。利用琥珀酸脱氢酶染色方法观察噪声暴露侧耳蜗毛细胞受损，染色结果显示暴露侧毛细胞受损严重，而保护侧毛细胞几乎不受影响，说明噪声暴露耳蜗受损动物模型建立成功。通过对听皮层PV神经元数量的检查发现，与对照组相比，双侧听皮层可检测到的PV神经元数量在暴露后都升高，而暴露耳同侧的可检测到的神经元数量高于暴露耳对侧。蛋白质免疫印迹法定量分析发现在暴露耳同侧听皮层PV蛋白的水平更高。这些发现说明在噪声暴露大鼠PV神经元的活性高，提示可能是噪声暴露后为了维持大脑的平衡状态而启动的一种补偿机制，为耳鸣的产生提供了理论依据。电生理数据表明听皮层中的创伤后发育变化以及除了去抑制之外可能涉及升高的兴奋活动与单耳听力相关的可塑性。我们提出，在不同情况下，新的轴突投射，去抑制和升高的兴奋活动有助于单耳听力相关的可塑性。