噪声影响听觉及记忆的中枢机制研究

People in modern societies are continuously bombarded by environmental noise with various temporal patterns and intensity levels (but mostly moderate levels at ~60-80 dB SPL) in their daily life. While it has been demonstrated in animal models that loud noise (for example, >105 dB SPL) impairs both peripheral and central functions of the auditory system, behavioral and physiological impacts of chronic exposure to moderate-level noise in adults to date are not well studied. In this proposal, we will first examine noise-degraded multi-parametric responses of auditory cortical neurons in levels of neural circuits and synapses, by exposing adult rats to moderate-level (~65 dB SPL) noise for 2 months. Neural basis underlying noise-induced changes in memory will then be examined in the hippocampus and the prefrontal cortex, two usual candidates contributing to regulation of memory. We will finally examine the effects of perceptual training on noise-induced alterations in auditory function and memory, by using behavioral, electrophysiological, and immunohistochemical methods. These proposed studies shall illustrate potentially destructive consequences of even moderate-level noise exposure for auditory function and memory of older children and adults. Since noise-exposure safety regulations have long been based on noise intensity levels that generate permanent damage to the inner ear, these studies shall also highlight the importance of more completely defining these possible hitherto-unappreciated hazards of noise pollution which cannot be detected on the standard audiogram, in modern human environments. Lastly, these studies shall indicate a therapeutic potential of perceptual training for normalizing noise-impaired auditory function and memory during adulthood.

噪声污染不仅影响听觉，还引发机体其它健康问题。现代社会人们时刻暴露于其中的多为~60-80 dB SPL中等强度的生活、交通及办公环境噪声。和高强度噪声不同，这些中等强度噪声并不显著影响听觉的外周器官因而被认为是“相对安全”的，其对成年人健康的影响因此经常被忽视。本项目拟以成年大鼠为动物模型，在申请者已有研究基础上进一步结合行为学、电生理学及分子生物学等技术研究成年期中等强度(~65 dB SPL)噪声暴露影响听觉及记忆的几个重要问题：1.噪声暴露效应的听觉皮层多模态、神经网络及突触分子机制；2.噪声影响记忆的神经及突触分子机制；3.知觉训练对噪声暴露效应的逆转作用及其机制。这些研究将有助了解噪声影响成年听觉及记忆的中枢机制，并为重新审视一直被忽视的中等强度噪声对成年人健康的影响提供全新视角。研究还将为创新性地通过知觉训练诱导脑可塑性以逆转噪声暴露引致的成年听觉及记忆功能异常提供理论依据。

噪声污染不仅影响听觉，还引发机体其它健康问题，但相关的神经机制目前还不十分清楚。本项目以Sprague-Dawley（SD）大鼠为实验模型，研究中等强度噪声暴露影响听觉及学习记忆的行为表征及其神经机制。结果发现：1）噪声暴露虽未改变外周听觉功能，但显著降低暴露动物的声分辨能力，且其初级听皮层神经元对声刺激的调谐反应减弱。这些行为及神经元水平的变化和噪声引起的听皮层兴奋-抑制平衡紊乱有关。2）噪声暴露在不改变基础运动量及焦虑水平的前提下，显著降低暴露动物海马相关的学习记忆能力并减弱海马的长时程增强效应，这和噪声暴露引起的海马突触后CaMKII的活性及AMPA受体数量的变化有关。3）听知觉训练诱导可塑性可在一定程度逆转噪声诱导的海马LTP变化。这些研究结果有助了解噪声影响成年听觉及记忆的中枢机制，并为重新审视一直被忽视的中等强度噪声对人类健康的影响提供了全新视角。

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