TectaY1870C/+ mice with alterations in the structure and porosity of the tectorial membrane display large numbers of spontaneous emissions

Cheatham, Mary Ann; Ahmad, Aisha; Dallos, Peter; Richardson, Guy P.

doi:10.1063/1.5038461

Cited by 3 publications

(8 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our conclusions regarding the enhancement of SOAEs when TM viscoelasticity is reduced are remarkably similar to observations of increased occurrence of SOAEs in genetically modified mice 36,38 : for example, while SOAEs are uncommon in WT mice (only ∼8.2% emit SOAEs), about 52% of Tecta Y 1870 C /+ mice emit SOAEs 38 . In the Tecta Y 1870 C /+ mice, the TM has reduced shear viscosity and reduced shear stiffness 42,43 due to the increased porosity of the TM and the total loss of the striated sheet matrix.…”

Section: Discussionsupporting

confidence: 88%

“…While our model predictions provide compelling evidence that reducing TM viscoelastic coupling enhances the generation of SOAEs, it does not capture all of the experimental observations regarding SOAE generation in TM mutant mice. For example, the model does not give a mechanism for the increased occurrence of low frequency SOAEs in Tecta Y 1870 C /+ mice 38 . The limited validity of the model at the apex of the cochlea, where OHCs are predicted to have a nearly negligible influence on the BM response to sound (see Supplementary Fig.…”

Section: Discussionmentioning

confidence: 95%

“…Our model predicts that if the mutation only affects the TM shear modulus, Tectb KO mice should emit slightly more SOAEs than WT mice, which is consistent with measurements by Cheatham et al . 38 .…”

Section: Discussionmentioning

confidence: 99%

“…The theoretical results from this paper, and the previous experiments in transgenic mice by Cheatham et al . 36–38 , suggest that another important function of the TM is to prevent the emergence of limit cycles oscillations of large amplitudes.…”

Section: Discussionmentioning

confidence: 99%

“…Mutations of the genes that encode the TM proteins affect important characteristics of cochlear function, such as the sensitivity 33,34 and tuning 35 of the cochlear response to sound. Interestingly, recent experiments in transgenic mice have also shown that altering the properties, structure and morphology of the TM tends to enhance the generation of SOAEs 36–38 . This could imply that the TM helps maintain cochlear stability and prevent the generation of too many spontaneous oscillations.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Reducing tectorial membrane viscoelasticity enhances spontaneous otoacoustic emissions and compromises the detection of low level sound

Bowling

Lemons

Meaud

2019

Sci Rep

View full text Add to dashboard Cite

The mammalian cochlea is able to detect faint sounds due to the presence of an active nonlinear feedback mechanism that boosts cochlear vibrations of low amplitude. Because of this feedback, self-sustained oscillations called spontaneous otoacoustic emissions (SOAEs) can often be measured in the ear canal. Recent experiments in genetically modified mice have demonstrated that mutations of the genes expressed in the tectorial membrane (TM), an extracellular matrix located in the cochlea, can significantly enhance the generation of SOAEs. Multiple untested mechanisms have been proposed to explain these unexpected results. In this work, a physiologically motivated computational model of a mammalian species commonly studied in auditory research, the gerbil, is used to demonstrate that altering the viscoelastic properties of the TM tends to affect the linear stability of the cochlea, SOAE generation and the cochlear response to low amplitude stimuli. These results suggest that changes in TM properties might be the underlying cause for SOAE enhancement in some mutant mice. Furthermore, these theoretical findings imply that the TM contributes to keeping the mammalian cochlea near an oscillatory instability, which promotes high sensitivity and the detection of low level stimuli.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Reducing tectorial membrane viscoelasticity enhances spontaneous otoacoustic emissions and compromises the detection of low level sound

Bowling

Lemons

Meaud

2019

Sci Rep

View full text Add to dashboard Cite

show abstract

Anisotropic Material Properties of Wild-Type and Tectb−/− Tectorial Membranes

Lemons

Sellon

Boatti

et al. 2019

Biophysical Journal

View full text Add to dashboard Cite

The tectorial membrane (TM) is an extracellular matrix that is directly coupled with the mechanoelectrical receptors responsible for sensory transduction and amplification. As such, the TM is often hypothesized to play a key role in the remarkable sensory abilities of the mammalian cochlea. Genetic studies targeting TM proteins have shown that changes in TM structure dramatically affect cochlear function in mice. Precise information about the mechanical properties of the TMs of wild-type and mutant mice at audio frequencies is required to elucidate the role of the TM and to understand how these genetic mutations affect cochlear mechanics. In this study, images of isolated TM segments are used to determine both the radial and longitudinal motions of the TM in response to a harmonic radial excitation. The resulting longitudinally propagating radial displacement and highly spatially dependent longitudinal displacement are modeled using finite-element models that take into account the anisotropy and finite dimensions of TMs. An automated, least-square fitting algorithm is used to find the anisotropic material properties of wild-type and Tectb À/À mice at audio frequencies. Within the auditory frequency range, it is found that the TM is a highly viscoelastic and anisotropic structure with significantly higher stiffness in the direction of the collagen fibers. Although no decrease in the stiffness in the fiber direction is observed, the stiffness of the TM in shear and in the transverse direction is found to be significantly reduced in Tectb À/À mice. As a result, TMs of the mutant mice tend to be significantly more anisotropic within the frequency range examined in this study. The effects of the Tectb À/À mutation on the TM's anisotropic material properties may be responsible for the changes in cochlear tuning and sensitivity that have been previously reported for these mice.

show abstract

Spontaneous Otoacoustic Emissions inTecta^Y1870C/+Mice Reflect Changes in Cochlear Amplification and How It Is Controlled by the Tectorial Membrane

Cheatham

Zhou

Goodyear

et al. 2018

eNeuro

View full text Add to dashboard Cite

Spontaneous otoacoustic emissions (SOAEs) recorded from the ear canal in the absence of sound reflect cochlear amplification, an outer hair cell (OHC) process required for the extraordinary sensitivity and frequency selectivity of mammalian hearing. Although wild-type mice rarely emit, those with mutations that influence the tectorial membrane (TM) show an incidence of SOAEs similar to that in humans. In this report, we characterized mice with a missense mutation in Tecta, a gene required for the formation of the striated-sheet matrix within the core of the TM. Mice heterozygous for the Y1870C mutation (TectaY1870C/+) are prolific emitters, despite a moderate hearing loss. Additionally, Kimura’s membrane, into which the OHC stereocilia insert, separates from the main body of the TM, except at apical cochlear locations. Multimodal SOAEs are also observed in TectaY1870C/+ mice where energy is present at frequencies that are integer multiples of a lower-frequency SOAE (the primary). Second-harmonic SOAEs, at twice the frequency of a lower-frequency primary, are the most frequently observed. These secondary SOAEs are found in spatial regions where stimulus-evoked OAEs are small or in the noise floor. Introduction of high-level suppressors just above the primary SOAE frequency reduce or eliminate both primary and second-harmonic SOAEs. In contrast, second-harmonic SOAEs are not affected by suppressors, either above or below the second-harmonic SOAE frequency, even when they are much larger in amplitude. Hence, second-harmonic SOAEs do not appear to be spatially separated from their primaries, a finding that has implications for cochlear mechanics and the consequences of changes to TM structure.

show abstract

TectaY1870C/+ mice with alterations in the structure and porosity of the tectorial membrane display large numbers of spontaneous emissions

Cited by 3 publications

References 17 publications

Reducing tectorial membrane viscoelasticity enhances spontaneous otoacoustic emissions and compromises the detection of low level sound

Reducing tectorial membrane viscoelasticity enhances spontaneous otoacoustic emissions and compromises the detection of low level sound

Anisotropic Material Properties of Wild-Type and Tectb−/− Tectorial Membranes

Spontaneous Otoacoustic Emissions inTecta^Y1870C/+Mice Reflect Changes in Cochlear Amplification and How It Is Controlled by the Tectorial Membrane

Contact Info

Product

Resources

About

TectaY1870C/+ mice with alterations in the structure and porosity of the tectorial membrane display large numbers of spontaneous emissions

Cited by 3 publications

References 17 publications

Reducing tectorial membrane viscoelasticity enhances spontaneous otoacoustic emissions and compromises the detection of low level sound

Reducing tectorial membrane viscoelasticity enhances spontaneous otoacoustic emissions and compromises the detection of low level sound

Anisotropic Material Properties of Wild-Type and Tectb−/− Tectorial Membranes

Spontaneous Otoacoustic Emissions inTectaY1870C/+Mice Reflect Changes in Cochlear Amplification and How It Is Controlled by the Tectorial Membrane

Contact Info

Product

Resources

About

Spontaneous Otoacoustic Emissions inTecta^Y1870C/+Mice Reflect Changes in Cochlear Amplification and How It Is Controlled by the Tectorial Membrane