Active and Nonlinear Models for Cochlear Mechanics

描述（由申请人提供）：液体流动刺激耳蜗内毛细胞（IHC）的毛束（HB），打开IHC的机电换能器（MET）通道。由此产生的电流使细胞体去极化，诱导神经递质释放，并最终刺激听神经。由外毛细胞（OHC）的运动驱动的耳蜗主动机制，既调节了IHC HBs的微流体激励，又提供了非线性压缩。然而，OHC体运动和HB运动对耳蜗内最终流体强迫的相对影响尚未确定，激发IHC HB的微流体流动也尚未确定。该资助的具体目的是通过开发亚覆盖空间流动的微流体表示来开发IHC HB刺激模型，并将这些模型与耳蜗的宏观模型耦合。在具体的目标2中，我们试图确定对Corti器官的活跃OHC力和对IHC HB的流体力的tonotic依赖性和联合效应。本研究的首要目标是建立一个完整的流体-机械-电模型，描述耳蜗对外部声学和内部电刺激的反应。如果成功，这个模型将增强我们对耳蜗失败机制的理解，回答关于耳蜗失败的形态学因素及其原因的重要问题。这将提高听力的非侵入性诊断，因为反应措施中的异常可以与特定病理联系起来。此外，由于我们的模型可以预测电刺激和声刺激的相互作用，它将能够预测声电联合假体的效果(如将

DESCRIPTION (provided by applicant): 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 apportioned nor has the microfluidi flow that excites the IHC HB. The specific aims of this grant are to develop models of IHC HB stimulation by developing a microfluidic representation of the flow in the subtectorial space and coupling these models to the macroscopic model of the cochlea. In specific aim 2 we seek to determine the tonotopic dependence and combined effect of active OHC forces on the organ of Corti and of the fluidic forces on the IHC HB. 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. This will improve noninvasive diagnosis of hearing as abnormalities in the response measures can be linked to specific pathologies. Further, as our model can predict the interaction of electrical and acoustic stimulus it will enable a prediction of the effect of a combined acoustic-electric prosthesis (such as would be used in schemes where some residual hearing is still present). Finally, a mathematical model of the cochlear response to 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) which can lead to better speech processing algorithms or cochlear implant electrical stimulation paradigms.