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

描述(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)中是独一无二的，因为它包含三个不同的听骨(锤骨、砧骨和砧骨)，这三个听骨在鼓膜和耳蜗之间形成了一个间接的、通常是灵活的耦合路径，其中大部分听骨块集中在远离耳蜗入口轴的地方。这与非哺乳动物的四足动物的中耳明显不同，在四足动物的中耳中，鼓膜的运动或多或少是通过杆状的小柱结构以直线的方式传递到耳蜗处。关于这种特殊的中耳布置的功能后果和可能的优势，已经提出了许多理论，特别是考虑到哺乳动物的听力频率比非哺乳动物高得多(100 khz比12 khz)，这些理论的范围从允许听小骨在较高频率采用低惯性振动模式；到提供额外的灵活性以保护耳蜗免受耳道内的高静态压力或脉冲刺激的影响；利用离轴质量分布和关节灵活性，以减少因发声、呼吸、泵血等引起的头骨振动而传递到耳蜗处的听小骨惯性量，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。在这项提案中，将测试哺乳动物听骨链的功能，使用测量空气和骨传导刺激引起的3D运动以及由于耳道内正负静压引起的3D位移；并进行建模，产生基于CT的解剖精确的全中耳3D模型，准确表示听骨关节灵活性，并可选择加入螺旋耳蜗模型来测试骨传导反应。测量和模型将基于人类、猫和小鼠的颞骨，它们有：1)自然的听骨链，以及2)通过融合一个改变其自然运动自由的改良版本 或双侧听骨关节，3)用柱状假体直接将锤骨的长突连接到踝骨的底板或距骨头部，以消除其间接耦合路径和离轴质量分布。这些测量结果和由此产生的模型将被用来比较研究中耳结构在以下方面的作用：1)从耳道到耳蜗的声音传递，特别是在更高的频率上；2)保护耳蜗；以及3)通过骨传导将声音传递到耳蜗处。对三个拟议的具有科学和临床重要性的哺乳动物物种的比较将有助于澄清哺乳动物中耳解剖结构的差异所造成的任何功能变化，而跨拟议的听骨链修饰的比较将有助于澄清哺乳动物中耳特有的结构特征的功能含义。用假体取代砧骨的测量和模型可能会为改善中耳重建手术的临床结果带来新的想法。

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.