NEURAL MODULATION OF HEARING LOSSES INDUCED BY LOUD SOUND

来自职业和娱乐来源的巨大声音是对听力最常见的威胁，可导致暂时听力损失（如在嘈杂的酒吧或音乐会度过一个晚上后可能经历的）或永久性听力损失（如在嘈杂的工作环境中长时间或多次发出巨大声音后）。降噪方案不是总是可行的，就是不能有效地应用。一个平行的策略是研究可能改善听力损伤的生物机制，以优化这种机制。我建议以澳大利亚开创性的工作为基础，研究从大脑到内耳的神经系统如何调节由大声声音引起的听力损失（内耳是最容易受到大声声音伤害的部位）。早期的研究表明，这些神经可以防止由短时间的大声声音引起的损伤，这导致了国际上对这种保护的功能应用的兴趣，以减少人类遭受的听力损伤。然而，我最近的工作表明，神经对类似于普通创伤或在类似于普通创伤的条件下发生的大声声音具有复杂的保护和加剧作用。它们甚至会因声音过大而加剧听力损失，尤其是当双耳（双侧）的听力灵敏度不平衡时，这种情况与人类相似。这些发现使得延迟功能应用至关重要，直到神经发挥的全部作用被理解。我建议阐明这些神经对大声声音的新的复杂影响。具体目标是：(1)了解这些途径对人类所遇到的大声声音的影响；(2)研究慢性不平衡的双侧听力敏感性如何改变神经的作用，以及它们何时从保护性变为加重性；(3)引证非创伤性声音如何影响由于后来的大声声音而导致的听力损失以及这些神经所起的作用。

Loud sounds, from occupational and recreational sources, are the most common threat to hearing and can result in temporary hearing losses (as might be experienced after an evening at a noisy pub or concert) or permanent hearing losses (after prolonged or multiple loud sounds, as for example in a noisy work environment). Noise reduction programs are either not always possible or effectively applied. A parallel strategy is the study of biological mechanisms that may ameliorate hearing damage, with a view to optimising such mechanisms. I propose to build on seminal Australian work to examine how one such system, nerves from the brain to the inner ear (the site of most damage from loud sounds), modulates hearing losses caused by loud sounds. Early studies indicated these nerves could protect from damage induced by short-lasting loud sound and this has led to international interest in functional applications of such protection to reduce hearing damage suffered by humans. However, my recent work indicates the nerves exert complex protective and exacerbative effects to loud sounds similar to common trauma or occurring under conditions similar to common trauma. They even exacerbate hearing losses due to loud sound, especially when there is an imbalance in hearing sensitivity in the two ears (bilateral) similar to what is common in humans. These findings make it critical that functional application be delayed until the full range of effects exerted by the nerves is understood. I propose to elucidate the novel complex effects of these nerves to loud sound. Specific aims are: (1) To understand effects of these pathways to loud sounds like those encountered by humans, (2) To investigate how chronic imbalanced bilateral hearing sensitivity, like that common in humans, alters effects of the nerves and when they change from being protective to exacerbative, (3) To adduce how an atraumatic sound affects hearing losses due to later loud sound and the role played by these nerves.