A variety of experiments are designed to examine the operation of the two types of sensory receptor cells of the mammalian hearing organ: inner hair cells and outer hair cells. It is now known that inner hair cells communicate auditory information to the brain, whereas outer hair cells modify the mechanical environment in the cochlea thereby producing amplification. In this work electrical responses to sound are recorded intracellularly from hair cells and extracellularly for their immediate environment in the organ of Corti of anesthetized guinea pigs. A significant portion of the proposed work is aimed at an investigation of the connections between single outer hair cell receptor potentials (their electrical response to sound) and gross extracellular electrical responses. It is proposed that the latter may influence the amplification process at high frequencies. Further, contemporary descriptions are sought of cochlear electroanatomy (its electrical impedance pattern), particularly at high frequencies, and of the organ of Corti proper. Finally, we aim to continue studies designed to evaluate cochlear nonlinear processes (two-tone suppression, low-frequency biasing, combination tone and harmonic production) as reflected in receptor potentials and as influenced by longitudinal location along the cochlear spiral. Aside from its intrinsic interest in describing cochlear nonlinear processing, much of this work is also used diagnostically to evaluate inner versus outer hair cell function and the sources of extracellular responses. A subset of these studies is aimed at finally resolving the long-standing discrepancy in the production of intracellular tonic receptor potentials, generated by outer hair cells in the high versus low frequency regions of the cochlea.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
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Hearing Research Study Section (HAR)
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Northwestern University at Chicago
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Schools of Arts and Sciences
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Wiwatpanit, Teerawat; Lorenzen, Sarah M; CantĂș, Jorge A et al. (2018) Trans-differentiation of outer hair cells into inner hair cells in the absence of INSM1. Nature 563:691-695
Takahashi, Satoe; Sun, Willy; Zhou, Yingjie et al. (2018) Prestin Contributes to Membrane Compartmentalization and Is Required for Normal Innervation of Outer Hair Cells. Front Cell Neurosci 12:211
Wiwatpanit, Teerawat; Remis, Natalie N; Ahmad, Aisha et al. (2018) Codeficiency of Lysosomal Mucolipins 3 and 1 in Cochlear Hair Cells Diminishes Outer Hair Cell Longevity and Accelerates Age-Related Hearing Loss. J Neurosci 38:3177-3189
Xu, Yingyue; Cheatham, Mary Ann; Siegel, Jonathan H (2017) Identifying the Origin of Effects of Contralateral Noise on Transient Evoked Otoacoustic Emissions in Unanesthetized Mice. J Assoc Res Otolaryngol 18:543-553
Takahashi, Satoe; Homma, Kazuaki; Zhou, Yingjie et al. (2016) Susceptibility of outer hair cells to cholesterol chelator 2-hydroxypropyl-?-cyclodextrine is prestin-dependent. Sci Rep 6:21973
Takahashi, Satoe; Cheatham, Mary Ann; Zheng, Jing et al. (2016) The R130S mutation significantly affects the function of prestin, the outer hair cell motor protein. J Mol Med (Berl) 94:1053-62
Cheatham, Mary Ann; Ahmad, Aisha; Zhou, Yingjie et al. (2016) Increased Spontaneous Otoacoustic Emissions in Mice with a Detached Tectorial Membrane. J Assoc Res Otolaryngol 17:81-8
Cheatham, Mary Ann; Edge, Roxanne M; Homma, Kazuaki et al. (2015) Prestin-Dependence of Outer Hair Cell Survival and Partial Rescue of Outer Hair Cell Loss in PrestinV499G/Y501H Knockin Mice. PLoS One 10:e0145428
Keller, Jacob Pearson; Homma, Kazuaki; Duan, Chongwen et al. (2014) Functional regulation of the SLC26-family protein prestin by calcium/calmodulin. J Neurosci 34:1325-32
Homma, Kazuaki; Duan, Chongwen; Zheng, Jing et al. (2013) The V499G/Y501H mutation impairs fast motor kinetics of prestin and has significance for defining functional independence of individual prestin subunits. J Biol Chem 288:2452-63

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