Experimental_Theoretical_Studies_of_Cochlear_Mechanisms

点击翻译按钮获取中文摘要

Abstract Based on its strategic location, the tectorial membrane (TM) has long been believed to play an essential role in hearing, but the important cochlear mechanisms remain unclear. We propose research to improve our understanding of the functional role of the TM in determining (1) the remarkable properties of normal hearing — including its exquisite sensitivity and frequency selectivity — as well as (2) the hearing loss associated with genetic mutations of the TM and other cochlear pathologies. The proposed research is organized with three related aims. Aim 1: We propose to characterize TM material properties that determine local interactions between the TM, hair bundles, and surrounding fluid. We will measure the poroelastic and electrokinetic properties of the TM that interact with the hair bundles at micro- and nano-scales. Aim 2: We propose to measure radial and transverse modes of TM motion that stimulate motions of inner and outer hair cells. Recent studies have challenged the conventional notion that hair bundle motions are generated exclusively by shearing motions of the TM (and subtectorial fluid) relative to the reticular lamina. In addition to radial modes of motion (e.g., resonance models), complex linkages between transverse and radial modes of TM motion are thought to be significant, especially for low-frequency stimulation of inner hair cells. Aim 3: We propose to characterize TM traveling waves and tuning in humans compared to mice, gerbils and guinea pigs. While the cross-sectional structure of the mammal cochlea is highly conserved across species, the sensitivity and frequency selectivity of hearing differs greatly. Recently, the sharp frequency tuning in Tectb-/- mutant mice relative to wild-type mice has been linked to differences in longitudinal coupling via TM traveling waves. We propose to test the generality of the relation between wave properties and tuning across mammalian species, including humans. We will measure TM material properties (e.g., shearing stiffness and viscous moduli), morphology (e.g., width, thickness, number and orientation of radial fibers), and TM wave properties in mice, gerbils, guinea pigs, and humans. Results from these three aims will increase our understanding of the cochlear mechanisms that underlie both normal and abnormal hearing. This knowledge has important practical applications for the delineation of inner-ear disorders (and concomitant suggestions for treatment) and for the design of speech-processing devices such as cochlear implants, hearing aids, and speech-recognition systems.