Human Organ of Corti Micromechanics - There has been significant effort on measurements and modeling to decipher organ of Corti (OoC) micro- mechanics in laboratory animals. A parallel effort has been lacking for the human cochlea, but is now possible thanks to new motion measurements and imaging in fresh human temporal bones. Notable differences between human and animal cochlear partitions have been observed. These findings point to the need to study cochlear micro-mechanics in humans directly. The goal of the proposed project is to understand in human cochleae (1) the forward transduction that drives inner hair cell (IHC) and outer hair cell (OHC) stereocilia and (2) the reverse transduction that amplifies OoC motion via OHC electromotility. A novel finite element (FE) technique will be used to model thin slices of the cochlea, which makes it computationally feasible to incorporate anatomically accurate OoC cytoarchitecture and the details of surrounding structures. The high accuracy of the technique in capturing 3D motions was shown in recent publications. Slice FE models of the human basal high-frequency (1st) and middle frequency (2nd) turns will be built with detailed anatomy and material properties determined using OCT vibrometry data from locations along the human cochlear partition (Specific Aim 1). Each anatomical detail can lead to unknown mechanics that will be explored through specific hypotheses. We hypothesize (H1) that, due to the mobile bridge of the human cochlea, OHC stereocilia move in the inhibitory direction with BM upwards motion, which is opposite to that of the classical model derived for laboratory animals. We further hypothesize (H2) that IHC stereocilia are mainly driven by fluid flow in and out of the inner spiral sulcus due to sub-tectorial space height change, while OHC stereocilia are mainly driven by TM-RL shear motion, and that the exact combination of the two mechanisms for each type of hair cell will change with frequency. The different combinations of mechanisms will provide different gains and phases of stereocilia motion relative to BM transverse motion at different frequencies. We hypothesize (H3) that TM material properties and size will have an influence on the radial vibration modes of the TM, affecting both stereocilia gain and phase. The phase of OHC stereocilia motion is crucial in active feedback mechanism, while the gain of IHC stereocilia will directly affect the sensitivity and tuning of sound perception. Our hypotheses will be tested (Specific Aim 2) by observing the IHC and OHC stereocilia deflection angles in relation to TM-RL shear and sub-tectorial space height change, and their frequency dependency. The roles of the mobile OSL and bridge, and the TM size and material properties on IHC and OHC stereocilia drives will be tested by model parameter variations. Last, “reverse transduction” will be studied by simulating electrically-evoked responses of the OoC (Specific Aim 3) using the same model developed for the passive cochlea. Preliminary work towards a fully active slice model will also be done. OoC micro-mechanics is a crucial part of the puzzle for understanding the extraordinary tuning of human hearing. The proposed project will be the first to model passive and active OoC micro-mechanics in humans.
