This proposal is concerned with the mechanical and electrical properties of cells in the organ of Corti and how those properties influence the ability of the organ to process sounds. In particular, the experiments are designed to determine how the outer hair cells (OHCs) function in vivo to control the vibration of the basilar membrane and cellular structure of the organ. It is thought that OHCs use their inherent motile ability to amplify sound-evoked vibration of the neurosensory structures in the cochlea. This process is called cochlear amplification. However, it is not known how OHCs accomplish this amplification, a property critical to normal hearing because it provides both for the great sensitivity of the ear and for the acuity needed to understand speech in a noisy environment. The amplifier mechanism must work within a system of mechanical and electrical filters.
In Aim 1 we test the hypothesis that the stereocillia of OHCs act as a critical mechanical filter that has not yet been studied. The amplifier must also generate power and it is clear OHCs have cellular or subcellular motor activity that may provide the power.
In Aim 2 we will determine whether cochlear amplification requires forces produced by the stereocilia (via so called fast adaptation) of OHCs or prestin motor molecules in the baso-lateral membrane of the OHC or both. The manipulation of endolymphatic calcium is key to the Aim 1 and 2 experiments. Finally, cochlear amplification can only come about with the proper (but as yet unknown) micromechanical motions of the system of cells that make up the organ of Corti.
In Aim 3 we study the micro or cellular mechanics of the organ of Corti (in yivo) using custom designed measurement instrumentation based on low coherence optical interferometry. We investigate the mechanical processing of sound that occurs with activity of the OHCs and the resulting stimulation of the stereocilia of inner hair cells. Knowledge of OHCs and organ of Corti mechanics is essential to our understanding of the normal and pathophysiologial function of the cochlea. Data derived in these studies are critically needed for appropriate mathematical modeling of the inner ear and in turn such models provide the only way to completely understand its complex mechanics.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC000141-32
Application #
7755396
Study Section
Auditory System Study Section (AUD)
Program Officer
Donahue, Amy
Project Start
1979-04-01
Project End
2012-01-31
Budget Start
2010-02-01
Budget End
2011-01-31
Support Year
32
Fiscal Year
2010
Total Cost
$530,854
Indirect Cost
Name
Oregon Health and Science University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Wu, Tao; Ramamoorthy, Sripriya; Wilson, Teresa et al. (2016) Optogenetic Control of Mouse Outer Hair Cells. Biophys J 110:493-502
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
Ramamoorthy, Sripriya; Zhang, Yuan; Petrie, Tracy et al. (2016) Minimally invasive surgical method to detect sound processing in the cochlear apex by optical coherence tomography. J Biomed Opt 21:25003
Shi, Xiaorui; Zhang, Fei; Urdang, Zachary et al. (2014) Thin and open vessel windows for intra-vital fluorescence imaging of murine cochlear blood flow. Hear Res 313:38-46
Ramamoorthy, Sripriya; Zha, Dingjun; Chen, Fangyi et al. (2014) Filtering of acoustic signals within the hearing organ. J Neurosci 34:9051-8
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
Subhash, Hrebesh M; Choudhury, Niloy; Chen, Fangyi et al. (2013) Depth-resolved dual-beamlet vibrometry based on Fourier domain low coherence interferometry. J Biomed Opt 18:036003
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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