PROJECT SUMMARY: Rotation of the hair bundles (HB) of the inner hair cells (IHC) of the cochlea open the mechano-electric transducer (MET) channels of the IHCs. The resulting current depolarizes the cell body inducing neurotransmitter release and, ultimately, auditory nerve stimulation. The active machinery of the cochlea, driven by motility of outer hair cells (OHC), both tunes the excitation of the IHC HBs and provides for nonlinear compression. The first specific aim of the grant involves the quantification of cochlear vibrations when no sound is presented, to characterize noise floor and test the theory of the cochlear amplifier. The second aim is to predict the cochlear response to simple and complex acoustic signals and to determine the effect of attachment of IHC mechanically to the tectorial membrane. Particular emphasis is placed on testing rate-dependent effects in MET models (including adaptation) and in OHC electromechanics. The specific aims of this grant are to develop mathematical models of these phenomenon, to rigorously test these hypotheses via comparison to existing experiments, and to work with our collaborators to devise feasible new experiments to test our predictions. The overarching goal of this research is to develop a complete fluid-mechanical-electrical model that describes the response of the cochlea to both external acoustic stimulation. If successful, this model will enhance our understanding of failure mechanisms in the cochlea, answering important questions as to the morphological elements of the cochlea that fail and why. Such understanding will improve noninvasive diagnosis of hearing as abnormalities in the response can be linked to specific pathologies. Finally, having an understanding of how the cochlea process sound over the entire spectrum will help us to understand how important classes of signals are processed in the cochlea (such as speech and music) and such understanding can lead to better speech processing algorithms or cochlear implant electrical stimulation approaches.