A goal of the cochlear physiology laboratory is to understand how the components of the organ of Corti enhance the sound induced vibration of the basilar membrane, a process known as cochlear amplification (CA). Two questions of broad interest are to be studied;how do the outer hair cells transmit force to activate the CA and what is the mechanical role of the tectorial membrane in CA? Standard techniques are clearly insufficient for answering these questions, so new and innovative methodology will be used. The Fourier Domain Optical (Low) Coherence Tomography (FDOCT) system that we developed gives unique possibilities for studying CA. Using this method;we propose to determine how the complex motion of the organ of the Corti, powered by OHC forces, results in mechanical stimulation of the inner hair cell stereocilia. This is the critical first step in hearing, the stiulation of inner hair cells. We also propose to determine whether the tectorial membrane has a mechanical resonance relevant to organ of Corti function. This is fundamental to understanding how the displacement of the stereocilia hair bundles on outer hair cells can have the proper timing to make effective any force that they actively produce. We also study a controversial question about where along the length of the organ of Corti is OHC power applied to result in traveling wave amplification, sharp tuning, sensitivity and nonlinearity. The distribution of outer hair cell activity is fundamental to knowing how the traveling wave propagates and how otoacoustic emissions are created. The spatial distribution of the CA is studied with FDOCT, innovative optogenetic methodology, and mathematical modeling. We will create a mouse model that has the expression of a light sensitive ion channel in the OHCs. Local and targeted application of light will modulate the CA and reveal it's spatial extent along the length of the cochlear duct.
Normal hearing depends upon the sound amplifying action of sensory outer hair cells in the cochlea while incorrect function or loss of the cells is the cause f the majority of hearing loss. Within the organ of Corti, the cells operate mechanically and electrically to increase the sound caused vibration of the organ. This proposal will learn what the cells mechanically do that results in sensitive and normal hearing.
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|Krey, Jocelyn F; Drummond, Meghan; Foster, Sarah et al. (2016) Annexin A5 is the Most Abundant Membrane-Associated Protein in Stereocilia but is Dispensable for Hair-Bundle Development and Function. Sci Rep 6:27221|
|Warren, Rebecca L; Ramamoorthy, Sripriya; Ciganovi?, Nikola et al. (2016) Minimal basilar membrane motion in low-frequency hearing. Proc Natl Acad Sci U S A 113:E4304-10|
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|Ramamoorthy, Sripriya; Wilson, Teresa M; Wu, Tao et al. (2013) Non-uniform distribution of outer hair cell transmembrane potential induced by extracellular electric field. Biophys J 105:2666-75|
|Ren, Tianying; Zheng, Jiefu; He, Wenxuan et al. (2013) MEASUREMENT OF AMPLITUDE AND DELAY OF STIMULUS FREQUENCY OTOACOUSTIC EMISSIONS. J Otol 8:57-62|
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|Zha, Dingjun; Chen, Fangyi; Ramamoorthy, Sripriya et al. (2012) In vivo outer hair cell length changes expose the active process in the cochlea. PLoS One 7:e32757|
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