IN VITRO STUDIES OF COCHLEAR NEUROBIOLOGY

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By common consensus, outer hair cells (OHCs) are the key requisites of the mammalian cochlea's ability to process sound with high sensitivity and exquisite frequency resolution over a wide frequency range. OHC deficit, arising from environmental insults, disease or from the aging process, tends to be the initial cause of most sensorineural hearing loss. Such loss may affect as many as 20 million Americans. The existence of local mechanical feedback within the mammalian cochlea is now well accepted. In this scheme inner hair cells (IHC) are the true sensory receptors of the ear and, transmit auditory information to the central nervous system. In contrast, outer hair cells (OHC) are assumed not to have significant (auditory) receptor function but a major role as effector (motor) elements in a mechanical feedback loop which ultimately controls the input to IHCs. This feedback represents the cochlear amplification process. Shape changes (motility) of OHCs are assumed to be mechanism whereby energy is fed back to the vibrating cochlear partition. An array of experiments is proposed to assess and quantify various motile properties of isolated outer hair cells. Both electrically induced (electromotility) and ciliary displacement induced (mechanomotility) somatic shape change responses are studied. In addition, alterations in ciliary bundle responsiveness, related to membrane potential changes and somatic motile responses, are examined. Techniques developed in our Laboratory permit these measurements to he made in a simulated in vivo environment, at nanometer resolution, and over and exceeding the full audio bandwidth. The purpose of these studies is to elucidate the biophysics of cellular and ciliary motility as possible bases of the cochlear amplifier and to understand OHC function.