ACTIVE FILTERING IN THE COCHLEA

描述（由申请人提供）：最近的实验证据表明，哺乳动物耳蜗的外毛细胞（OHC）作为机电放大器的一部分，可将听力灵敏度提高100倍。拟议研究的长期目标是证实这一假设，并澄清我们对潜在机制的理解。本提案的目标是：确定Corti器官的哪些特性负责耳蜗频率图，确定OHCs如何放大行波，确定耳蜗隔墙的运动如何与IHC立体纤毛运动耦合，确定耳声发射如何与耳蜗隔墙运动相关，并更好地理解声损伤的机制。为了实现这些目标，我们计划建立耳蜗的定量解剖模型，测量Corti器官的细胞和细胞外元素的机械阻抗，成像Corti器官元素在切除耳蜗中响应电和机械刺激的运动，并在活体动物中进行生理实验。我们所提出的实验结果，连同我们和其他人以前的实验结果，将借助计算模型加以解释。将使用两种模型：微观力学模型和宏观力学模型。计算模型将尽可能以物理为基础，并将包括对Corti器官，基底膜和被膜，毛细胞机电转导和QHC运动以及内毛细胞生理学的机械特性的具体描述。

DESCRIPTION (provided by applicant): Recent experimental evidence suggests that the outer hair cells (OHC) of the mammalian cochlea act as part of an electromechanical amplifier that increases hearing sensitivity one-hundred fold. The long term goal of the proposed research is to confirm this hypothesis and to clarify our understanding of the underlying mechanisms. The goals of this proposal are: to determine which properties of the organ of Corti are responsible for the cochlear frequency map, to establish how the OHCs amplify the traveling wave, to determine how the motion of the cochlear partition is coupled to IHC stereocilia motion, to establish how otoacoustic emissions relate to cochlear partition motion, and to develop a better understanding of the mechanisms of acoustic trauma. To achieve these goals we plan to develop quantitative anatomical models of the cochlea, to measure the mechanical impedance of the cellular and extracellular elements of the organ of Corti, to image the motion of the elements of the organ of Corti in response to electrical and mechanical stimulation in excised cochleas, and to conduct physiological experiments in live animals. The results of the proposed experiments together with previous experiments by ourselves and others will be interpreted with the aid of computational models. Two types of models will be used: micromechanical and macromechanical. The computational models will be as physically based as possible and will include specific descriptions of the mechanical properties of the organ of Corti, basilar membrane and tectorial membrane, hair cell mechanoelectric transduction and QHC motility, and inner hair cell physiology.