Intracochlear measures of active cochlear mechanics

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DESCRIPTION (provided by applicant): Two fundamental facts of mammalian auditory processing are: (1) the frequency selectivity that exists in the auditory nerve is due to mechanical preprocessing in the cochlea and (2) the mechanics of the cochlea are highly nonlinear. Cochlear nonlinearity works to boost the mechanical response at low sound pressure levels at frequencies close to the location's best frequency. Thus, cochlear nonlinearity is central to the cochlea's frequency selectivity. In ears in which the mechanics are damaged (through overstimulation, some chemotherapies, and simply aging) nonlinearity is reduced or eliminated, leading to severe loss of hearing acuity. Much remains to be learned about the micromechanical actions and interactions that produce cochlear nonlinearity, termed the "cochlear amplifier." Mouse models in which cellular and acellular cochlear components are altered through genetic engineering have been developed and are already being used to advance our understanding of cochlear mechanics. However, historically mice were not used for cochlear mechanics and robust normative data is lacking. We propose to measure normal intracochlear pressures and motions in mice upon acoustic stimulation. These are the basic responses to normal stimulation. We will also measure pressures and motions upon electrical current stimulation, which is similar and in some ways complementary to acoustic stimulation, and has been used already in modified mouse studies with interesting results. Upon establishing robust normative results we plan to go on, in future projects, to study mice with genetically modified cochlear components. PUBLIC HEALTH RELEVANCE: Healthy hearing relies upon mechanical boosting of the response within the inner ear (cochlea). In ears in which cochlear mechanics are damaged due to overstimulation, chemotherapies or simply aging the boosting is reduced or eliminated, leading to hearing loss. With the advent of genetic engineering, mouse models are being developed in which specific components of the cochlea are modified. This leads to many possibilities to explore the workings of the healthy cochlea and the ways to repair a damaged cochlea. In this project, the foundation for such advances is laid by measuring the mechanical responses of the cochleae of normal mice.