Active and Nonlinear Models for Cochlear Mechanics

项目概要： 流体流动刺激耳蜗的内毛细胞（IHC）的毛束（HB），打开机械传导通路。 IHC的电换能器（MET）通道。产生的电流使细胞体去极化， 神经递质释放，最终，听觉神经刺激。耳蜗的活动机制， 通过外毛细胞（OHC）的运动性，既调节了IHC HB的微流体激发， 非线性压缩然而，OHC体细胞和HB运动性对这种最终流体的相对影响是不确定的。 耳蜗中的受力还有待最终确定。此外，免疫组化HB的表达方式 物理激励，无论是通过流体的剪切运动的影响，还是通过引起的压力差 脉动流还有待确定。该补助金的具体目标是开发数学模型， 这些现象，并通过与现有实验的比较来严格测试这些假设， 我们的合作者设计可行的新实验来测试我们的预测。除了预测 耳蜗的反应，我们强调的重要性，确定噪声存在于系统时，没有 刺激存在;一种计算，设置可以感知的最低声音（因为信号必须超过 噪音）-模型的另一个测试。 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， 耳蜗对外部声刺激和内部电刺激的反应。如果成功，这 模型将增强我们对耳蜗故障机制的理解，回答重要问题， 耳蜗的形态学元素以及为什么会失败。这样的理解将提高非侵入性 将听力诊断为反应异常可与特定的病理联系起来。此外，作为我们的 模型可以预测电放大和声放大的相互作用。最后，了解 耳蜗如何处理整个频谱上的声音将有助于我们了解 信号在耳蜗中被处理（例如语音和音乐），并且这种理解可以导致更好地理解。 语音处理算法或耳蜗植入电刺激方法。

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 neurotransmiter 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.