Why do mammals have a flexible three-bone ossicular chain?

描述（由申请人提供）：哺乳动物中耳在四足动物（哺乳动物、两栖动物、爬行动物和鸟类）中是独特的，因为它包含三个不同的听小骨（锤骨、砧骨和镫骨），这三个听小骨在鼓膜和耳蜗之间形成间接的且通常是柔性的耦合路径，其中大部分听小骨质量集中在远离耳蜗入口轴的地方。这与非哺乳动物四足动物的中耳明显不同，在非哺乳动物的四足动物中，鼓膜运动通过杆状鼻小柱结构或多或少以直线传递到耳蜗。关于这种特殊的中耳排列的功能后果和可能的优点，已经提出了许多理论，特别是考虑到哺乳动物能够听到比非哺乳动物高得多的频率（>100 kHz与<12 kHz），这些理论的范围从允许听小骨在较高频率下采用较低惯性振动模式;提供增加的灵活性以保护耳蜗免受耳道中的高静压或脉冲刺激;涉及利用离轴质量分布和关节柔韧性来减少响应于来自自身的颅骨振动而传递到耳蜗的听骨惯性的量，由于发声、呼吸、泵血等而产生的声音，从而使更多的注意力集中在对生存至关重要的外部声音上。在该提案中，将通过测量空气和骨传导刺激引起的三维运动以及耳道中正负静压引起的三维位移，测试哺乳动物听骨链的功能;和建模，制作完整中耳的解剖学上精确的基于CT的3D模型，并精确表示听骨，关节的灵活性和可选的线圈耳蜗模型测试骨传导反应的结合。测量将进行，模型的基础上，人类，猫和小鼠的颞骨，与他们的：1）天然听骨链，以及与修改后的版本，2）改变其自然的运动自由融合一个 或两个听骨关节，以及3）通过用柱状假体直接连接锤骨长突与镫骨的底板或头来替代砧骨，消除其间接耦合路径和离轴质量分布。测量结果和所得模型将用于比较检查中耳结构在以下方面的作用：1）从耳道到耳蜗的声音传输，特别是在较高频率下; 2）耳蜗的保护;以及3）声音通过骨传导传输到耳蜗。在三个建议的科学和临床上重要的哺乳动物物种的比较将有助于澄清任何功能的变化所造成的哺乳动物中耳解剖结构的差异，而建议的听骨链修饰的比较将允许澄清的功能意义的结构特征独特的哺乳动物中耳。测量和模型与假体取代砧骨可能会导致额外的新思路，以改善中耳重建手术的临床结果。

DESCRIPTION (provided by applicant): The mammalian middle ear is unique among tetrapods (mammals, amphibians, reptiles, and birds), in that it contains three distinct ossicles (the malleus, incus, and stapes) that form an indirect and usually flexible coupling path between the eardrum and cochlea, for which the majority of the ossicular mass is concentrated away from the cochlear entry axis. This differs markedly from the middle ears of non-mammalian tetrapods, in which eardrum motions are transmitted to the cochlea more or less in a straight line via a rod-like columella structure. Many theories have been presented as to the functional consequences and possible advantages of this peculiar middle-ear arrangement, especially considering that mammals are capable of hearing to much higher frequencies than non-mammals (>100 kHz vs. <12 kHz), and these theories range from allowing the ossicles to adopt lower-inertia vibrational modes at higher frequencies; to providing added flexibility to protect th cochlea against high static pressures in the ear canal or impulsive stimuli; to leveraging the off-axis mass distribution and joint flexibility to reduce the amount of ossicular inertia transmitted o the cochlea in response to skull vibrations from self-generated sounds due to vocalizations, breathing, pumping blood, etc., and thus allowing more attention to be focused on the external sounds critical for survival. In this proposal, the functioning of the mammalian ossicular chain will be tested, using measurements of 3D motion due to air and bone-conducted stimuli and 3D displacements due to positive and negative static pressure in the ear canal; and modeled, producing anatomically accurate �CT-based 3D models of the full middle ear with accurate representations of ossicular-joint flexibility and the optional incorporation of a coiled cochlear model for testing bone-conduction responses. The measurements will be performed, and models based, on human, cat, and mouse temporal bones, with their: 1) natural ossicular chains, as well as with modified versions that 2) alter its natural freedom of motion by fusing one or both ossicular joints, and that 3) remove its indirect coupling path and off-axis mass distribution by replacing the incus with a columella-like prosthesis directly connecting the long process of the malleus to the footplate or head of the stapes. The measurements and resulting models will be used to comparatively examine the role of middle-ear structure on: 1) sound transmission from the ear canal to the cochlea, especially at higher frequencies; 2) protection of the cochlea; and 3) the transmission of sound to the cochlea via bone conduction. Comparisons across the three proposed scientifically and clinically important mammalian species will help to clarify any functional changes caused by differences in mammalian middle-ear anatomy, while comparisons across the proposed ossicular chain modifications will allow clarification of the functional implications of the structural features unique to mammalian middle ears. The measurements and models with a prosthesis replacing the incus may additionally lead to new ideas for improving the clinical outcomes of middle-ear reconstruction surgeries.