Olivocochlear Efferent Systems and Cochlear Physiology

描述（由申请人提供）：我们的目标是了解外毛细胞（OHC）如何产生哺乳动物听觉的高灵敏度。在了解孤立的OHC的特性方面已经取得了很大的进展，但是关于OHC如何在完整的耳蜗中工作还有一些基本的问题没有回答。内侧橄榄耳蜗（MOC）传出神经元支配OHC，并为理解OHC机制提供了重要工具。为了研究OHCs在体内的机械效应，我们将测量基底膜（BM）运动和中枢神经（AN）放电模式以及通过电刺激MOC传出神经在这些反应中产生的变化。 我们最近的工作提供了强有力的证据，证明存在第二个行波沿着耳蜗，一个波，可能耦合OHC运动BM运动。拟议的工作将表征这第二波的性质及其与经典横向行波的关系。这将在（1）远低于局部特征频率（CF）的频率下完成，其中刚度主导机械响应，并且可以在没有由耳蜗放大产生的并发症的情况下研究两个行波的影响，以及（2）在接近CF的频率下完成，其中耳蜗放大器具有其主要影响。我们和其他人的工作表明，MOC刺激的“缓慢效应”是由于OHC刚度的降低。这种刚度变化将被用来确定OHC刚度如何影响耳蜗特性，如CF，并测试OHC压电理论，该理论可以解释OHC体细胞运动如何在高于OHC膜截止频率的频率下有效。所提出的工作的结果将有助于充实出一个新的图片耳蜗力学。力学是耳蜗功能的一个关键领域，它会被许多影响听力的病理所破坏。了解耳蜗力学，以及OHC在耳蜗力学中的作用，对于听力的几乎所有方面的进步都是至关重要的。

DESCRIPTION (provided by applicant): Our goal is to understand how outer hair cells (OHCs) produce the high sensitivity of mammalian hearing. Great progress has been made in understanding the properties of isolated OHCs, but there are fundamental unanswered questions about how OHCs work in intact cochleas. Medial olivocochlear (MOC) efferent neurons innervate OHCs and provide an important tool for understanding OHC-based mechanisms. To study the mechanical effects of OHCs in vivo, we will measure basilar-membrane (BM) motion and auditory-nerve (AN) firing patterns and the changes produced in these responses by electrical stimulation of MOC efferents. Our recent work provides strong evidence for the existence of a second traveling wave along the cochlea, a wave that may couple OHC motility to BM motion. The proposed work will characterize the properties of this second wave and its relationship to the classic transverse traveling wave. This wil be done (1) at frequencies well below the local characteristic frequency (CF), where stiffness dominates the mechanical response and the effects of the two traveling waves can be studied without the complications produced by cochlear amplification, and (2) at frequencies near CF where the cochlear amplifier has its primary effects. Our work, and that of others, has shown that the "slow effect" of MOC stimulation is due to a decrease in OHC stiffness. This stiffness change will be exploited to determine how OHC stiffness affects cochlear properties such as CF, and to test the OHC piezoelectric theory, a theory that may account for how OHC somatic motility can be effective at frequencies above the OHC membrane cut-off frequency. The results of the proposed work will help to flesh out a new picture of cochlear mechanics. Mechanics is a key area of cochlear function that is disrupted by many of the pathologies that affect hearing. Understanding cochlear mechanics, and the role of OHCs in cochlear mechanics, is essential for progress in almost all aspects of hearing.