Human Cochlear Structure & Function

项目总结 虽然耳蜗的内部工作负责听力的最基本方面，包括听力 在灵敏度和频率调谐方面，我们对人类耳蜗力学的直接知识是有限的。这种信息的缺乏 迫使研究人员依赖动物实验来推断人类的耳蜗行为，根据 假设耳蜗区(CP)，包括基底膜(BM)和Corti器官的运动 (OOC)，人类和实验动物之间是相似的。然而，我们最近发现了令人惊讶的差异 与实验动物相比，人类CP的解剖学和运动学。动物体内的骨髓附着在狭窄的固定骨骼上 结构，骨性螺旋椎板(OSL)，并解释了几乎所有的CP运动。相比之下，人类的OSL 更宽，可移动，并通过新发现的软组织结构连接到BM，我们将其命名为CP “桥”。这座桥在实验室动物中是不存在的，它和BM一样宽，振动也一样多。 再加上OSL本身是移动的，因此BM只占Cp运动总量的一小部分 人类。这些新发现的人类CP解剖和运动方面挑战了长期以来的假设，即 在哺乳动物中，耳蜗机能被认为是相似的。 因为CP结构，如OSL、桥和覆盖膜(TM)附着到 角膜缘在人类中都是可移动的，但在实验动物中不是，我们假设OOC结构的运动， 包括网状板和TM，在人类中是不同的，从而改变了驱动转导过程的输入 在内毛细胞和外毛细胞的发束。为了测试这一点，光学相干层析成像(OCT)将允许我们 在非常新鲜的人身体标本上，原位测定各种CP结构的解剖和相对运动。我们 还将使用各种不同的方法来研究和阐明人类CP中力学和解剖学之间的关系 表征CP形态、结构结构和材料组成的技术。 我们将进一步测试我们的假设，通过开发包含了 测量解剖学和CP力学。由于我们的测量来自于死后的耳朵，它们不能揭示 活动进程。然而，我们的模型可以根据预测的活体动物结果来近似活动行为 考虑到这些结构的相似解剖结构，在功能上与人类相似。由此产生的模型将进行测试 并与来自心理声学数据的已知人类调谐能力进行了验证，为未来的应用打开了大门 其中可以以前所未有的逼真度模拟人类耳蜗的病理、操作和治疗。 这项研究将极大地促进我们对人类CP的结构如何共同作用的理解 毛细胞形成的换能器的输入。它还将使我们更好地了解其适用性和 动物实验在人类听力研究中的局限性，并更好地利用动物模型进行科学研究。 此外，所提出的计算模型将对听力现象的科学研究和 未来在听力疾病的理解、诊断和治疗方面的改进。

PROJECT SUMMARY Although the inner workings of the cochlea are responsible for the most fundamental aspects of hearing, including hearing sensitivity and frequency tuning, our direct knowledge of human cochlear mechanics is limited. This lack of information has forced researchers to rely on animal experiments to make inferences about cochlear behavior in humans, under the assumption that the motions of the cochlear partition (CP), including the basilar membrane (BM) and the organ of Corti (OoC), are similar between humans and laboratory animals. However, we have recently found surprising differences in human CP anatomy and motion as compared to laboratory animals. The BM in animals is attached to a narrow fixed bony structure, the osseous spiral lamina (OSL), and accounts for almost all of the CP motion. In contrast, the OSL in humans is much wider, is mobile, and connects to the BM via a newly identified soft-tissue structure that we have named the CP “bridge”. The bridge, which is non-existent in laboratory animals, is as wide as and vibrates as much as the BM. Combined with the fact that the OSL itself is mobile, the BM therefore only accounts for a fraction of total CP motion in humans. These newly discovered aspects of human CP anatomy and motion challenge the long-held assumption that cochlear mechanics can be regarded as similar across mammals. Because CP structures such as the OSL, bridge, and location where the tectorial membrane (TM) attaches to the limbus are all mobile in humans but not in laboratory animals, we hypothesize that the motions of the OoC structures, including the reticular lamina and TM, are different in humans, thereby altering the input driving the transduction process at the hair bundles of the inner and outer hair cells. To test this, Optical Coherence Tomography (OCT) will allow us to determine the anatomy and relative motion of various CP structures in situ in very fresh human cadaveric specimens. We will also investigate and elucidate the relationships between mechanics and anatomy in the human CP using a variety of techniques to characterize the morphometry, structural architecture, and material composition of the CP. We will further test our hypothesis by developing finite-element models of the human cochlea that incorporate the measured anatomy and CP mechanics. As our measurements are from postmortem ears, they cannot reveal the effects of active processes. However, our models can approximate active behavior based on live-animal results, which are predicted to be functionally similar to human given the similar anatomies of these structures. The resulting models will be tested and validated against known human tuning capabilities from psychoacoustic data, opening the door to future applications in which human cochlear pathologies, manipulations, and treatments can be simulated with unprecedented fidelity. This research will greatly advance our understanding of how the structures of the human CP work together to define the inputs to the transducers formed by the hair cells. It will also enable us to better understand the applicability and limitations of animal experiments in the study of human hearing, and to better utilize animal models for scientific inquiry. Moreover, the proposed computational models will be valuable both for scientific investigation of hearing phenomena and for future improvements in the understanding, diagnosis and treatment of hearing disease.