Measuring and Modeling the Cochlear Organ-of-Corti Motions Responsible for Inner-and Outer-Hair-Cell Drives and Amplification

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Project Summary/Abstract Our knowledge of cochlear organ-of-Corti (OoC) mechanics is undergoing major rethinking. Recent findings show that the reticular lamina (RL) moves much more than the basilar membrane (BM) and with a different phase than previously thought. Our high-resolution optical-coherence-tomography (OCT) imaging and vibrometry measurements in the gerbil high-frequency basal region reveal that the RL at outer-hair-cell (OHC) row 3 (RL3) moves significantly more than at OHC row 1 (RL1). This new discovery suggests that the RL’s mosaic structure, comprised of the cuticular plates of the basally tilted OHCs and apically tilted phalangeal processes (PhPs) is not stiff, but rather bends and/or stretches. Our central hypothesis is that the PhP extensions of the Deiters’ cells (DCs) influence radial and longitudinal motion of the RL mosaic to provide the motion phase and/or magnitude at each OHC row required for cochlear amplification, and sensitive hearing. This hypothesis will be tested by measurements and models to determine if: (1) RL3 motion has a bigger radial component that increases the drive to the OHC3 stereocilia; (2) cytoarchitectural differences below the RL mosaic (e.g., the radial and longitudinal PhP angles) cause the radial and longitudinal motions to differ across the three OHC rows; (3) the outer-tunnel (OT) fluid space is part of a resonant system that has a substantial effect on RL radial motion; and (4) the OoC area changes the pressure in the scala media to produce amplification, and (5) how these motions influence the drive to inner-hair-cell (IHC) stereocilium bundles. A high-resolution, high-framerate OCT system (approx. 2.3-µm axial resolution) will be used to image and measure motions of the OoC in gerbils and mice. We will measure the transverse and radial motions and/or the radial and longitudinal motions of the BM, OHC–DC junctions, RL, OT, and tectorial membrane (TM) in response to acoustic stimulation at multiple sound levels; and will do so at cochlear locations corresponding approximately to 0.5-kHz (apical), 2-kHz (middle), and 45-kHz (basal) locations in gerbil, and 10-kHz (apical), 20-kHz (middle), and 60-kHz (basal) locations in mouse, to determine the applicability of our hypotheses. The measurements from the middle and apical turns in these two species will span much of the 0.02–20 kHz frequency range of human hearing. To translate the measured OoC motions into a detailed understanding of the mechanisms responsible for OHC and IHC stimulation, we will use our OCT images and measurements to build and test passive and active 3D finite-element models of gerbil and mouse cochleae. The models will incorporate, in a viscous-fluid environment, the detailed OoC microanatomy, including the radial and longitudinal PhP angles across the three rows, pillar cells, IHCs, and TM. The models will allow clear relationships to be established between cochlear function and the structure and material properties of the OoC. This work will combine experimental and modeling efforts to deepen our understanding of the complex mechanical interactions within the cochlea that produce amplification and sound transduction.