Experimental - Theoretical Studies of Cochlear Mechanisms

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It is increasingly clear that the extraordinary acoustical sensitivity and frequency selectivity that are hallmarks of our sense of hearing arise from micromechanical mechanisms. Genetic manipulations have shown that the tectorial membrane (TM) plays an essential role in this process. But that role remains enigmatic, in large part because of the paucity of direct measurements of TM properties. We propose research to improve our understanding of the role of the TM with studies in three related categories, [a.] We propose to measure material properties of the TM to determine their molecular basis and functional significance. We will combine mechanical, chemical, osmotic and electrical measurements of the TM to characterize its material properties as a function of longitudinal position in the cochlea. These material properties will provide a quantitative basis for understanding the functional role of the TM in normal hearing, [b.] We propose to measure effects of genetic mutations on material properties of the TM. Several human genetic disorders of hearing result from mutations of TM proteins. Measurements of the material properties of TMs from mouse models of these disorders will provide a better understanding of the physical basis of the human disorders of hearing, and will elucidate the molecular basis of the material properties of the TM. [c.] We propose to measure coupling of the TM to other cochlear structures in an isolated, but intact cochlea. We will apply displacements to the stapes and measure the resulting motions of the TM and hair bundles of inner and outer hair cells. These measurements will provide direct tests of hypotheses about the role of the TM in cochlear mechanics. The practical benefits of this knowledge should include more precise delineation of inner ear disorders, suggestions for treatment, development of prosthetic devices, and>incorporation of knowledge of inner-ear processing into the design of systems for processing speech.... :¿¿