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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC000141-35
Application #
8511596
Study Section
Auditory System Study Section (AUD)
Program Officer
Cyr, Janet
Project Start
1979-04-01
Project End
2016-06-30
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
35
Fiscal Year
2013
Total Cost
$355,401
Indirect Cost
$111,790
Name
Oregon Health and Science University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Chen, Fangyi; Zha, Dingjun; Yang, Xiaojie et al. (2018) Hydromechanical Structure of the Cochlea Supports the Backward Traveling Wave in the Cochlea In Vivo. Neural Plast 2018:7502648
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

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