Sound pressure produces force across the mammalian cochlear partition, ultimately creating a vibratory traveling wave that propagates longitudinally up the cochlear duct. The key feature distinguishing this process from the non-mammalian cochlea is amplification, whereby forces produced by thousands of outer hair cells (OHCs) sharpen and amplify the traveling wave. Our overarching objective is to understand how the complex biomechanics of the 3D multi-cellular and acellular arrangement that forms the organ of Corti work together to create cochlear amplification. Specifically, we will determine how this process, which stems from the broadly- tuned basilar membrane, creates sharp frequency tuning and high sensitivity. This question is significant on a basic science level because these biophysical processes underlie the ability to hear sounds just above the Brownian motion of molecules in air with an exquisite frequency resolution. This question remains unsolved and is clinically important because hearing loss is typically due to loss of cochlear amplification. Our central hypothesis is that the mechanical properties of the organ of Corti provide additional filtering beyond that provided by the passive mechanics of the basilar membrane and surrounding fluid, and that this modulates OHC force production to give rise to the observed sensitivity and sharp frequency tuning. To test the hypothesis, we have developed an innovative technology, termed Volumetric Optical Coherence Tomography Vibrometry (VOCTV). Besides permitting traditional basilar membrane motion measurements in vivo, VOCTV also permits the measurement of sound-induced vibrations throughout the organ of Corti. We propose to use VOCTV to study the interactions between components of the organ of Corti and assess how they relate to cochlear amplification within the apical turn of the mouse cochlea.
In Aim 1, we propose to measure transverse and radial vibratory motions within the apical turn of the wild- type mouse cochlea in vivo for the first time. We will use 3D localization to compare the responses of different organ of Corti structures, assessing both the frequency response and the gain of cochlear amplification.
In Aim 2, we propose to measure vibratory motions within the apical turn of several transgenic mouse strains that have molecular changes designed to selectively alter of organ of Corti mechanics. Through this approach, we will probe the mechanical contributions of prestin-based electromotility, stereociliary bundle mechanics, tectorial membrane traveling waves, and hair cell/supporting cell patterning. Together, these data will be interpreted so as to test our hypothesis. If our hypothesis is true, sharply-tuned differential motion within the organ of Corti is necessary to generate the sensitivity and sharp tuning of the mammalian cochlea.

Public Health Relevance

Mammals hear when the highly-organized organ of Corti vibrates in response to sound pressure waves and stimulates hair cells. Herein, we propose image these vibrations non-invasively and understand how these structures work together to create high auditory sensitivity and sharp frequency tuning. This question remains unsolved and is clinically important because while hearing aids can compensate for the loss of sensitivity, we have no treatments for the loss of frequency tuning.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
1R01DC014450-01
Application #
8859866
Study Section
Auditory System Study Section (AUD)
Program Officer
Cyr, Janet
Project Start
2015-05-01
Project End
2020-04-30
Budget Start
2015-05-01
Budget End
2016-04-30
Support Year
1
Fiscal Year
2015
Total Cost
$346,834
Indirect Cost
$131,365
Name
Stanford University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94304
Lee, Hee Yoon; Raphael, Patrick D; Xia, Anping et al. (2016) Two-Dimensional Cochlear Micromechanics Measured In Vivo Demonstrate Radial Tuning within the Mouse Organ of Corti. J Neurosci 36:8160-73
Jawadi, Zina; Applegate, Brian E; Oghalai, John S (2016) Optical Coherence Tomography to Measure Sound-Induced Motions Within the Mouse Organ of Corti In Vivo. Methods Mol Biol 1427:449-62
Xia, Anping; Liu, Xiaofang; Raphael, Patrick D et al. (2016) Hair cell force generation does not amplify or tune vibrations within the chicken basilar papilla. Nat Commun 7:13133
Kim, Sangmin; Raphael, Patrick D; Oghalai, John S et al. (2016) High-speed spectral calibration by complex FIR filter in phase-sensitive optical coherence tomography. Biomed Opt Express 7:1430-44
Zeng, Wei-Zheng; Grillet, Nicolas; Dewey, James B et al. (2016) Neuroplastin Isoform Np55 Is Expressed in the Stereocilia of Outer Hair Cells and Required for Normal Outer Hair Cell Function. J Neurosci 36:9201-16
Lee, Hee Yoon; Raphael, Patrick D; Park, Jesung et al. (2015) Noninvasive in vivo imaging reveals differences between tectorial membrane and basilar membrane traveling waves in the mouse cochlea. Proc Natl Acad Sci U S A 112:3128-33
Song, Yohan; Xia, Anping; Lee, Hee Yoon et al. (2015) Activity-dependent regulation of prestin expression in mouse outer hair cells. J Neurophysiol 113:3531-42