Active and Nonlinear Models for Cochlear Mechanics

项目总结： 流体流刺激耳蜗内毛细胞的毛束(HB)打开机械连接。 IHC的电气换能器(MET)通道。由此产生的电流使细胞体感应去极化 神经递质的释放，最终，听觉神经刺激。耳蜗的活动机械，被驱动 通过外毛细胞(OHC)的运动，两者都调节了IHC HBs的微流体兴奋，并为 非线性压缩。然而，OHC体细胞和Hb运动对最终流体的相对影响 强迫进入耳蜗还没有最终确定。此外，IHC HBs的方式 物理激励的，无论是由于流体的剪切运动的影响还是由压力差引起的 脉动流还有待确定。这笔赠款的具体目标是开发数学模型 这些现象，并通过与现有实验和工作的比较，严格检验这些假说 我们的合作者设计了可行的新实验来验证我们的预测。除了预测 对于耳蜗的反应，我们强调了在没有 存在刺激；设置可感知的最低声音的计算(因为信号必须超过 噪音)-对模型的又一次测试。 这项研究的首要目标是开发一个完整的流体-机械-电气模型，该模型描述了 耳蜗对外部声学和内部电刺激的反应。如果成功，这将是 模型将增强我们对耳蜗失效机制的理解，回答以下重要问题 到耳蜗会失效的形态元素及其原因。这样的理解将改善非侵入性 听力反应异常的诊断可以与特定的病理联系起来。此外，作为我们的 模型可以预测电声放大的相互作用。最后，了解一下 如何在整个频谱上听起来耳蜗声将帮助我们理解有多重要的类别 信号是在耳蜗中处理的(如语音和音乐)，这种理解可以带来更好的 语音处理算法或人工耳蜗电刺激方法。

PROJECT SUMMARY: Fluid flow stimulates the hair bundles (HB) of the inner hair cells (IHC) of the cochlea opening the mechano- electric transducer (MET) channels of the IHCs. The resulting current depolarizes the cell body inducing neurotransmitter release and, ultimately, auditory nerve stimulation. The active machinery of the cochlea, driven by motility of outer hair cells (OHC), both tunes the microfluidic excitation of the IHC HBs and provides for nonlinear compression. However, the relative influence of OHC somatic and HB motility on this final fluidic forcing in the cochlea has yet to be conclusively determined. Further, the manner in which the IHC HBs are physically excited, whether by the influence of shear motion of the fluid or by a pressure difference induced pulsatile flow has yet to be determined. The specific aims of this grant are to develop mathematical models of these phenomenon and rigorously test these hypotheses via comparison to existing experiments and work with our collaborators to devise feasible new experiments to test our predictions. In addition to predicting the response of the cochlea, we emphasize the importance of determine the noise present in the system when no stimulus is present; a computation that sets the lowest sound that can be sensed (as the signal must exceed the noise) – another test of the models. The overarching goal of this research is to develop a complete fluid-mechanical-electrical model that describes the response of the cochlea to both external acoustic and internal electrical stimulation. If successful, this model will enhance our understanding of failure mechanisms in the cochlea, answering important questions as to the morphological elements of the cochlea that fail and why. Such understanding will improve noninvasive diagnosis of hearing as abnormalities in the response can be linked to specific pathologies. Further, as our model can predict the interaction of electrical and acoustic amplification. Finally, having an understanding of how the cochlea process sound over the entire spectrum will help us to understand how important classes of signals are processed in the cochlea (such as speech and music) and such understanding can lead to better speech processing algorithms or cochlear implant electrical stimulation approaches.