Based on its strategic location, the tectorial membrane (TM) has long been believed to play an essential role in hearing, but the important cochlear mechanisms remain unclear. We propose research to improve our understanding of the functional role of the TM in determining (1) the remarkable properties of normal hearing ? including its exquisite sensitivity and frequency selectivity ? as well as (2) the hearing loss associated with genetic mutations of the TM and other cochlear pathologies. The proposed research is organized with three related aims.
Aim 1 : We propose to characterize TM material properties that determine local interactions between the TM, hair bundles, and surrounding ?uid. We will measure the poroelastic and electrokinetic properties of the TM that interact with the hair bundles at micro- and nano-scales.
Aim 2 : We propose to measure radial and transverse modes of TM motion that stimulate motions of inner and outer hair cells. Recent studies have challenged the conventional notion that hair bundle motions are generated exclusively by shearing motions of the TM (and subtectorial ?uid) relative to the reticular lamina. In addition to radial modes of motion (e.g., resonance models), complex linkages between transverse and radial modes of TM motion are thought to be signi?cant, especially for low-frequency stimulation of inner hair cells.
Aim 3 : We propose to characterize TM traveling waves and tuning in humans compared to mice, gerbils and guinea pigs. While the cross-sectional structure of the mammal cochlea is highly conserved across species, the sensitivity and frequency selectivity of hearing di?ers greatly. Recently, the sharp frequency tuning in Tectb-/- mutant mice relative to wild-type mice has been linked to di?erences in longitudinal coupling via TM traveling waves. We propose to test the generality of the relation between wave properties and tuning across mammalian species, including humans. We will measure TM material properties (e.g., shearing sti?ness and viscous moduli), morphology (e.g., width, thickness, number and orientation of radial ?bers), and TM wave properties in mice, gerbils, guinea pigs, and humans. Results from these three aims will increase our understanding of the cochlear mechanisms that underlie both normal and abnormal hearing. This knowledge has important practical applications for the delineation of inner-ear disorders (and concomitant suggestions for treatment) and for the design of speech-processing devices such as cochlear implants, hearing aids, and speech-recognition systems.

Public Health Relevance

Statement Our ability to communicate with each other and to navigate through acoustically rich environments depends on the detection and analysis of sounds by the inner ear. Numerous genetic studies have shown that the tectorial membrane plays a key role in shaping this analysis, but little is known about the underlying mechanisms. The proposed research to clarify these mechanisms will improve our understanding of both normal and impaired hearing and will be important for the design of speech-processing devices such as cochlear implants, hearing aids, and speech-communication and speech-recognition systems.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC000238-33
Application #
9419788
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Cyr, Janet
Project Start
1984-06-01
Project End
2021-11-30
Budget Start
2017-12-01
Budget End
2018-11-30
Support Year
33
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Type
Organized Research Units
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02142
Sellon, Jonathan B; Ghaffari, Roozbeh; Freeman, Dennis M (2017) Geometric Requirements for Tectorial Membrane Traveling Waves in the Presence of Cochlear Loads. Biophys J 112:1059-1062
Wadhwa, Neal; Chen, Justin G; Sellon, Jonathan B et al. (2017) Motion microscopy for visualizing and quantifying small motions. Proc Natl Acad Sci U S A 114:11639-11644
Farrahi, Shirin; Ghaffari, Roozbeh; Sellon, Jonathan B et al. (2016) Tectorial Membrane Traveling Waves Underlie Sharp Auditory Tuning in Humans. Biophys J 111:921-4
Sellon, Jonathan B; Farrahi, Shirin; Ghaffari, Roozbeh et al. (2015) Longitudinal spread of mechanical excitation through tectorial membrane traveling waves. Proc Natl Acad Sci U S A 112:12968-73
Sellon, Jonathan B; Ghaffari, Roozbeh; Farrahi, Shirin et al. (2014) Porosity controls spread of excitation in tectorial membrane traveling waves. Biophys J 106:1406-13
Ghaffari, Roozbeh; Page, Scott L; Farrahi, Shirin et al. (2013) Electrokinetic properties of the mammalian tectorial membrane. Proc Natl Acad Sci U S A 110:4279-84
Masaki, Kinuko; Ghaffari, Roozbeh; Gu, Jianwen Wendy et al. (2010) Tectorial membrane material properties in Tecta(Y)(1870C/+) heterozygous mice. Biophys J 99:3274-81
Ghaffari, Roozbeh; Aranyosi, Alexander J; Richardson, Guy P et al. (2010) Tectorial membrane travelling waves underlie abnormal hearing in Tectb mutant mice. Nat Commun 1:96
Masaki, Kinuko; Gu, Jianwen Wendy; Ghaffari, Roozbeh et al. (2009) Col11a2 deletion reveals the molecular basis for tectorial membrane mechanical anisotropy. Biophys J 96:4717-24
Gu, Jianwen Wendy; Hemmert, Werner; Freeman, Dennis M et al. (2008) Frequency-dependent shear impedance of the tectorial membrane. Biophys J 95:2529-38

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