Andrei N. Lukashkin

Sharpened cochlear tuning in a mouse with a genetically modified tectorial membrane

Frequency tuning in the cochlea is determined by the passive mechanical properties of the basilar membrane and active feedback from the outer hair cells, sensory-effector cells that detect and amplify sound-induced basilar membrane motions. The sensory hair bundles of the outer hair cells are imbedded in the tectorial membrane, a sheet of extracellular matrix that overlies the cochleas sensory epithelium. The tectorial membrane contains radially organized collagen fibrils that are imbedded in an unusual striated-sheet matrix formed by two glycoproteins, α-tectorin (Tecta) and β-tectorin (Tectb). In Tectb−/− mice the structure of the striated-sheet matrix is disrupted. Although these mice have a low-frequency hearing loss, basilar-membrane and neural tuning are both significantly enhanced in the high-frequency regions of the cochlea, with little loss in sensitivity. These findings can be attributed to a reduction in the acting mass of the tectorial membrane and reveal a new function for this structure in controlling interactions along the cochlea.

A deafness mutation isolates a second role for the tectorial membrane in hearing

α-tectorin (encoded by Tecta) is a component of the tectorial membrane, an extracellular matrix of the cochlea. In humans, the Y1870C missense mutation in TECTA causes a 50- to 80-dB hearing loss. In transgenic mice with the Y1870C mutation in Tecta, the tectorial membranes matrix structure is disrupted, and its adhesion zone is reduced in thickness. These abnormalities do not seriously influence the tectorial membranes known role in ensuring that cochlear feedback is optimal, because the sensitivity and frequency tuning of the mechanical responses of the cochlea are little changed. However, neural thresholds are elevated, neural tuning is broadened, and a sharp decrease in sensitivity is seen at the tip of the neural tuning curve. Thus, using TectaY1870C/+ mice, we have genetically isolated a second major role for the tectorial membrane in hearing: it enables the motion of the basilar membrane to optimally drive the inner hair cells at their best frequency.

A descriptive model of the receptor potential nonlinearities generated by the hair cell mechanoelectrical transducer

This paper describes a model for generating the hair cell receptor potential based on a second-order Boltzmann function. The model includes only the resistive elements of the hair cell membranes with batteries across them and the series resistance of the external return path of the transducer current through the tissue of the cochlea. The model provides a qualitative description of signal processing by the hair cell transducer and shows that the nonlinearity of the hair cell transducer can give rise to nonlinear phenomena, such as intermodulation distortion products and two-tone suppression with patterns similar to those which have been recorded from the peripheral auditory system. Particular outcomes of the model are the demonstration that two-tone suppression depends not on the saturation of the receptor current, but on the behaviour of the hair cell transducer function close to the operating point. The model also shows that there is non-monotonic growth and phase change for any spectral component, but not for the fundamental of the receptor potential.

Outer hair cell somatic, not hair bundle, motility is the basis of the cochlear amplifier

Sensitivity, dynamic range and frequency tuning of the cochlea are attributed to amplification involving outer hair cell stereocilia and/or somatic motility. We measured acoustically and electrically elicited basilar membrane displacements from the cochleae of wild-type and TectaΔENT/ΔENT mice, in which stereocilia are unable to contribute to amplification near threshold. Electrically elicited responses from TectaΔENT/ΔENT mice were markedly similar to acoustically and electrically elicited responses from wild-type mice. We conclude that somatic, and not stereocilia, motility is the basis of cochlear amplification.

Analysis of the f2−f1 and 2 f1−f2 distortion components generated by the hair cell mechanoelectrical transducer: Dependence on the amplitudes of the primaries and feedback gain

This paper describes the pattern of f2−f1 and 2 f1−f2 components at the output of the nonlinear hair cell mechanoelectrical transducer when the input consists of two sinusoidal signals. The mechanoelectrical transducer was represented by a second-order Boltzmann function. It is shown that some experimental observations, which have been cited to prove the existence of two discrete sources of distortion product otoacoustic emissions in the cochlea, can be produced by a single nonlinearity. These observations include the pattern of magnitude and phase “notches” in the growth functions of the distortion product otoacoustic emissions when measured in the two-dimensional space of the amplitudes of the two primaries. A single saturating nonlinearity also explains the distinctive response of the distortion product otoacoustic emissions to the decreasing gain of the cochlear amplifier. A possible basis for the differences in distortion product otoacoustic emissions, which have been measured in humans and rodents, ...

The tectorial membrane: one slice of a complex cochlear sandwich.

Purpose of reviewThe review is both timely and relevant, as recent findings have shown the tectorial membrane plays a more dynamic role in hearing than hitherto suspected, and that many forms of deafness can result from mutations in tectorial membrane proteins. Recent findingsMain themes covered are the molecular composition, the structural organization and properties of the tectorial membrane, the role of the tectorial membrane as a second resonator and a structure within which there is significant longitudinal coupling, and how mutations in tectorial membrane proteins cause deafness in mice and men. ConclusionFindings from experimental models imply that the tectorial membrane plays multiple, critical roles in hearing. These include coupling elements along the length of the cochlea, supporting a travelling wave and ensuring the gain and timing of cochlear feedback are optimal. The clinical findings suggest stable, moderate-to-severe forms of hereditary hearing loss may be diagnostic of a mutation in TECTA, a gene encoding one of the major, noncollagenous proteins of the tectorial membrane.

Multiple roles for the tectorial membrane in the active cochlea

This review is concerned with experimental results that reveal multiple roles for the tectorial membrane in active signal processing in the mammalian cochlea. We discuss the dynamic mechanical properties of the tectorial membrane as a mechanical system with several degrees of freedom and how its different modes of movement can lead to hair-cell excitation. The role of the tectorial membrane in distributing energy along the cochlear partition and how it channels this energy to the inner hair cells is described.

Prestin's Role in Cochlear Frequency Tuning and Transmission of Mechanical Responses to Neural Excitation

The remarkable power amplifier [1] of the cochlea boosts low-level and compresses high-level vibrations of the basilar membrane (BM) [2]. By contributing maximally at the characteristic frequency (CF) of each point along its length, the amplifier ensures the exquisite sensitivity, narrow frequency tuning, and enormous dynamic range of the mammalian cochlea. The motor protein prestin in the outer hair cell (OHC) lateral membrane is a prime candidate for the cochlear power amplifier [3]. The other contender for this role is the ubiquitous calcium-mediated motility of the hair cell stereocilia, which has been demonstrated in vitro and is based on fast adaptation of the mechanoelectrical transduction channels [4, 5]. Absence of prestin [6] from OHCs results in a 40-60 dB reduction in cochlear neural sensitivity [7]. Here we show that sound-evoked BM vibrations in the high-frequency region of prestin(-/-) mice cochleae are, surprisingly, as sensitive as those of their prestin(+/+) siblings. The BM vibrations of prestin(-/-) mice are, however, broadly tuned to a frequency approximately a half octave below the CF of prestin(+/+) mice at similar BM locations. The peak sensitivity of prestin(+/+) BM tuning curves matches the neural thresholds. In contrast, prestin(-/-) BM tuning curves at their best frequency are >50 dB more sensitive than the neural responses. We propose that the absence of prestin from OHCs, and consequent reduction in stiffness of the cochlea partition, changes the passive impedance of the BM at high frequencies, including the CF. We conclude that prestin influences the cochlear partitions dynamic properties that permit transmission of its vibrations into neural excitation. Prestin is crucial for defining sharp and sensitive cochlear frequency tuning by reducing the sensitivity of the low-frequency tail of the tuning curve, although this necessitates a cochlear amplifier to determine the narrowly tuned tip.

Dependence of the DPOAE amplitude pattern on acoustical biasing of the cochlear partition.

Distortion product otoacoustic emissions (DPOAEs) were recorded from guinea pigs in response to simultaneous increases in the levels of high frequency primary tones in the presence of a low frequency biasing tone of 30 Hz at 120 dB SPL. The DPOAE amplitudes plotted as functions of the biasing tone phase angle show distinctive repeatable minima, which are identical to the amplitude notches observed for the distortion products at the output of a single saturating non-linearity. The number of the amplitude minima grows with increasing order of the DPOAE, a feature that is also reproduced by the model. The model of DPOAE generation due to a single saturating non-linearity does not explain the experimentally observed asymmetry of the response of the DPOAEs to rising and falling half cycles of the biasing tone. This asymmetry is attributed to a hypothetical mechanism, which adjusts the operating point of the outer hair cells mechanoelectrical transducer. Experimental data were consistent with a hypothesis that, for the parameters of stimulation used in this study, both lower and upper sideband DPOAEs are dominated by emission generated from a single and spatially localized place in the cochlea.

Origin of the bell-like dependence of the DPOAE amplitude on primary frequency ratio

For low and medium sound pressure levels (SPLs), the amplitude of the distortion product otoacoustic emission (DPOAE) recorded from guinea pigs at the 2f1-f2 frequency is maximal when f2/f1 approximately 1.23 and decreases for lower and higher f2/f1 ratios. The high-ratio slope of the DPOAE dependence on the ratio of the primary frequencies might be anticipated since the f1 amplitude at the f2 place is expected to decrease for higher f2/f1 ratios. The low-ratio slope of the dependence at low and medium SPLs of the primaries is actually one slope of a notch. The DPOAE amplitude recovers from the notch when the f2/f1 ratio is further reduced. In two-dimensional space formed by the f2/f1 ratio, and the levels of the primaries, the notch is continuous and has a level-dependent phase transition. The notch is identical to that seen in DPOAE growth functions. Similar notches and phase transitions were observed for high-order and high-frequency DPOAEs. Theoretical analysis reveals that a single saturating nonlinearity is capable of generating similar amplitude notch and phase transition when the f2/f1 ratio is decreased because of the increase in f1 amplitude at the DPOAE generation place (f2 place). The difference between the DPOAE recorded from guinea pigs and humans is discussed in terms of different position of the operating point of the DPOAE generating nonlinearity.