Auditory Mechanics and Cochlear Amplification 2020 Sound input to the cochlea causes a frequency-sorted wave-pattern of sensory tissue motion that conveys sound information to the auditory neurons, leading to hearing. A currently untreatable aspect of hearing impairment is the deterioration of the cochlea's ability to sharply separate sound by frequency. The cochlea's healthy frequency tuning is largely provided by the cochlear amplifier, an outer-hair-cell-driven, place-frequency-localized electromechanical feedback mechanism that is both powerful and fragile. This project's aims 1-3 explore the cell/structure basis of cochlear amplification. The studies use intracochlear sensors and a cutting-edge imaging and vibrometry technology, spectral-domain optical-coherence-tomography (SD-OCT). Localized measurements of mechanical and electrical responses at and within the cochlea's sensory tissue will be made both in healthy normal and in modified cochleae. Gerbils and guinea pigs are used and critical aspects of cochlear amplification are compared in the two species in aim 2.
In aim 1, measurements are made in cochleae before and after intracochlear injection of substances that will modify tectorial membrane (TM) mechanics. Because it governs transduction in hair cells, the TM plays a profound role in cochlear amplification; our studies test hypotheses that are based on cochlear models and measurements in isolated TMs and in TM-mutant mice.
Aim 3 makes use of SD-OCT's penetrating abilities to test previously untestable fluid-mechanical properties of the organ of Corti.
Aim 4 explores the transmission of sound to the cochlea by the middle ear, and how this transmission is modified by feedback from the middle ear muscle, tensor tympani. In preliminary work, tensor tympani modified transmission in a subtle, frequency-dependent manner that could be involved in focusing on particular sound sources, for example during communication. Experiments in which tensor tympani is tensed with voltage pulses will determine how the muscle affects the transmitted sound signal.

Public Health Relevance

Auditory Mechanics and Cochlear Amplification 2020 The ear's ability to discriminate frequencies is fundamental to hearing; this ability is based in the cochlear amplifier, a cell-based, electromechanical engine that is both powerful and fragile. The cochlear amplifier degrades due to aging, illness, from exposure to loud sounds, and following some treatments for infection and cancer. This project uses purpose-built sensors and sensing techniques to probe the constellation of factors that is required for healthy cochlear amplification, and to understand how the amplifier fails -- in order to advance our ability to treat hearing loss and to devise strategies to reduce it.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
2R01DC015362-06
Application #
10110733
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Cyr, Janet
Project Start
2016-03-01
Project End
2026-02-28
Budget Start
2021-03-01
Budget End
2022-02-28
Support Year
6
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Lin, Nathan C; Hendon, Christine P; Olson, Elizabeth S (2017) Signal competition in optical coherence tomography and its relevance for cochlear vibrometry. J Acoust Soc Am 141:395
Milazzo, Mario; Fallah, Elika; Carapezza, Michael et al. (2017) The path of a click stimulus from ear canal to umbo. Hear Res 346:1-13
Wang, Yi; Olson, Elizabeth S (2016) Cochlear perfusion with a viscous fluid. Hear Res 337:1-11
Dong, Wei; Olson, Elizabeth S (2016) Two-Tone Suppression of Simultaneous Electrical and Mechanical Responses in the Cochlea. Biophys J 111:1805-1815