Force transmission in the organ of Corti micromachine.
ABSTRACT: Auditory discrimination is limited by the performance of the cochlea whose acute sensitivity and frequency tuning are underpinned by electromechanical feedback from the outer hair cells. Two processes may underlie this feedback: voltage-driven contractility of the outer hair cell body and active motion of the hair bundle. Either process must exert its mechanical effect via deformation of the organ of Corti, a complex assembly of sensory and supporting cells riding on the basilar membrane. Using finite element analysis, we present a three-dimensional model to illustrate deformation of the organ of Corti by the two active processes. The model used available measurements of the properties of structural components in low-frequency and high-frequency regions of the rodent cochlea. The simulations agreed well with measurements of the cochlear partition stiffness, the longitudinal space constant for point deflection, and the deformation of the organ of Corti for current injection, as well as displaying a 20-fold increase in passive resonant frequency from apex to base. The radial stiffness of the tectorial membrane attachment was found to be a crucial element in the mechanical feedback. Despite a substantial difference in the maximum force generated by hair bundle and somatic motility, the two mechanisms induced comparable amplitudes of motion of the basilar membrane but differed in the polarity of their feedback on hair bundle position. Compared to the hair bundle motor, the somatic motor was more effective in deforming the organ of Corti than in displacing the basilar membrane.
Project description:The cochlea performs frequency analysis and amplification of sounds. The graded stiffness of the basilar membrane along the cochlear length underlies the frequency-location relationship of the mammalian cochlea. The somatic motility of outer hair cell is central for cochlear amplification. Despite two to three orders of magnitude change in the basilar membrane stiffness, the force capacity of the outer hair cell's somatic motility, is nearly invariant over the cochlear length. It is puzzling how actuators with a constant force capacity can operate under such a wide stiffness range. We hypothesize that the organ of Corti sets the mechanical conditions so that the outer hair cell's somatic motility effectively interacts with the media of traveling waves-the basilar membrane and the tectorial membrane. To test this hypothesis, a computational model of the gerbil cochlea was developed that incorporates organ of Corti structural mechanics, cochlear fluid dynamics, and hair cell electro-physiology. The model simulations showed that the micro-mechanical responses of the organ of Corti are different along the cochlear length. For example, the top surface of the organ of Corti vibrated more than the bottom surface at the basal (high frequency) location, but the amplitude ratio was reversed at the apical (low frequency) location. Unlike the basilar membrane stiffness varying by a factor of 1700 along the cochlear length, the stiffness of the organ of Corti complex felt by the outer hair cell remained between 1.5 and 0.4 times the outer hair cell stiffness. The Y-shaped structure in the organ of Corti formed by outer hair cell, Deiters cell and its phalange was the primary determinant of the elastic reactance imposed on the outer hair cells. The stiffness and geometry of the Deiters cell and its phalange affected cochlear amplification differently depending on the location.
Project description:<h4>Unlabelled</h4>The exquisite sensitivity and frequency discrimination of mammalian hearing underlie the ability to understand complex speech in noise. This requires force generation by cochlear outer hair cells (OHCs) to amplify the basilar membrane traveling wave; however, it is unclear how amplification is achieved with sharp frequency tuning. Here we investigated the origin of tuning by measuring sound-induced 2-D vibrations within the mouse organ of Corti in vivo Our goal was to determine the transfer function relating the radial shear between the structures that deflect the OHC bundle, the tectorial membrane and reticular lamina, to the transverse motion of the basilar membrane. We found that, after normalizing their responses to the vibration of the basilar membrane, the radial vibrations of the tectorial membrane and reticular lamina were tuned. The radial tuning peaked at a higher frequency than transverse basilar membrane tuning in the passive, postmortem condition. The radial tuning was similar in dead mice, indicating that this reflected passive, not active, mechanics. These findings were exaggerated in Tecta(C1509G/C1509G) mice, where the tectorial membrane is detached from OHC stereocilia, arguing that the tuning of radial vibrations within the hair cell epithelium is distinct from tectorial membrane tuning. Together, these results reveal a passive, frequency-dependent contribution to cochlear filtering that is independent of basilar membrane filtering. These data argue that passive mechanics within the organ of Corti sharpen frequency selectivity by defining which OHCs enhance the vibration of the basilar membrane, thereby tuning the gain of cochlear amplification.<h4>Significance statement</h4>Outer hair cells amplify the traveling wave within the mammalian cochlea. The resultant gain and frequency sharpening are necessary for speech discrimination, particularly in the presence of background noise. Here we measured the 2-D motion of the organ of Corti in mice and found that the structures that stimulate the outer hair cell stereocilia, the tectorial membrane and reticular lamina, were sharply tuned in the radial direction. Radial tuning was similar in dead mice and in mice lacking a tectorial membrane. This suggests that radial tuning comes from passive mechanics within the hair cell epithelium, and that these mechanics, at least in part, may tune the gain of cochlear amplification.
Project description:In the mammalian cochlea, small vibrations of the sensory epithelium are amplified due to active electro-mechanical feedback of the outer hair cells. The level of amplification is greater in the base than in the apex of the cochlea. Theoretical studies have used longitudinally varying active feedback properties to reproduce the location-dependent amplification. The active feedback force has been considered to be proportional to the basilar membrane displacement or velocity. An underlying assumption was that organ of Corti mechanics are governed by rigid body kinematics. However, recent progress in vibration measurement techniques reveals that organ of Corti mechanics are too complicated to be fully represented with rigid body kinematics. In this study, two components of the active feedback are considered explicitly-organ of Corti mechanics, and outer hair cell electro-mechanics. Physiological properties for the outer hair cells were incorporated, such as the active force gain, mechano-transduction properties, and membrane RC time constant. Instead of a kinematical model, a fully deformable 3D finite element model was used. We show that the organ of Corti mechanics dictate the longitudinal trend of cochlear amplification. Specifically, our results suggest that two mechanical conditions are responsible for location-dependent cochlear amplification. First, the phase of the outer hair cell's somatic force with respect to its elongation rate varies along the cochlear length. Second, the local stiffness of the organ of Corti complex felt by individual outer hair cells varies along the cochlear length. We describe how these two mechanical conditions result in greater amplification toward the base of the cochlea.
Project description:The cochlear cavity is filled with viscous fluids, and it is partitioned by a viscoelastic structure called the organ of Corti complex. Acoustic energy propagates toward the apex of the cochlea through vibrations of the organ of Corti complex. The dimensions of the vibrating structures range from a few hundred (e.g., the basilar membrane) to a few micrometers (e.g., the stereocilia bundle). Vibrations of microstructures in viscous fluid are subjected to energy dissipation. Because the viscous dissipation is considered to be detrimental to the function of hearing-sound amplification and frequency tuning-the cochlea uses cellular actuators to overcome the dissipation. Compared to extensive investigations on the cellular actuators, the dissipating mechanisms have not been given appropriate attention, and there is little consensus on damping models. For example, many theoretical studies use an inviscid fluid approximation and lump the viscous effect to viscous damping components. Others neglect viscous dissipation in the organ of Corti but consider fluid viscosity. We have developed a computational model of the cochlea that incorporates viscous fluid dynamics, organ of Corti microstructural mechanics, and electrophysiology of the outer hair cells. The model is validated by comparing with existing measurements, such as the viscoelastic response of the tectorial membrane, and the cochlear input impedance. Using the model, we investigated how dissipation components in the cochlea affect its function. We found that the majority of acoustic energy dissipation of the cochlea occurs within the organ of Corti complex, not in the scalar fluids. Our model suggests that an appropriate dissipation can enhance the tuning quality by reducing the spread of energy provided by the outer hair cells' somatic motility.
Project description:In this article, a nonlinear mathematical model is developed based on the physiology of the cochlea of the guinea pig. The three-dimensional intracochlear fluid dynamics are coupled to a micromechanical model of the organ of Corti and to electrical potentials in the cochlear ducts and outer hair cells (OHC). OHC somatic electromotility is modeled by linearized piezoelectric relations whereas the OHC hair-bundle mechanoelectrical transduction current is modeled as a nonlinear function of the hair-bundle deflection. The steady-state response of the cochlea to a single tone is simulated in the frequency domain using an alternating frequency time scheme. Compressive nonlinearity, harmonic distortion, and DC shift on the basilar membrane (BM), tectorial membrane (TM), and OHC potentials are predicted using a single set of parameters. The predictions of the model are verified by comparing simulations to available in vivo experimental data for basal cochlear mechanics. In particular, the model predicts more amplification on the reticular lamina (RL) side of the cochlear partition than on the BM, which replicates recent measurements. Moreover, small harmonic distortion and DC shifts are predicted on the BM, whereas more significant harmonic distortion and DC shifts are predicted in the RL and TM displacements and in the OHC potentials.
Project description:The high sensitivity and wide bandwidth of mammalian hearing are thought to derive from an active process involving the somatic and hair-bundle motility of the thousands of outer hair cells uniquely found in mammalian cochleae. To better understand this, a biophysical three-dimensional cochlear fluid model was developed for gerbil, chinchilla, cat, and human, featuring an active "push-pull" cochlear amplifier mechanism based on the cytoarchitecture of the organ of Corti and using the time-averaged Lagrangian method. Cochlear responses are simulated and compared with in vivo physiological measurements for the basilar membrane (BM) velocity, V(BM), frequency tuning of the BM vibration, and Q?? values representing the sharpness of the cochlear tuning curves. The V(BM) simulation results for gerbil and chinchilla are consistent with in vivo cochlea measurements. Simulated mechanical tuning curves based on maintaining a constant V(BM) value agree with neural-tuning threshold measurements better than those based on a constant displacement value, which implies that the inner hair cells are more sensitive to V(BM) than to BM displacement. The Q?? values of the V(BM) tuning curve agree well with those of cochlear neurons across species, and appear to be related in part to the width of the basilar membrane.
Project description:The gene causative for the human nonsyndromic recessive form of deafness DFNB22 encodes otoancorin, a 120-kDa inner ear-specific protein that is expressed on the surface of the spiral limbus in the cochlea. Gene targeting in ES cells was used to create an EGFP knock-in, otoancorin KO (Otoa(EGFP/EGFP)) mouse. In the Otoa(EGFP/EGFP) mouse, the tectorial membrane (TM), a ribbon-like strip of ECM that is normally anchored by one edge to the spiral limbus and lies over the organ of Corti, retains its general form, and remains in close proximity to the organ of Corti, but is detached from the limbal surface. Measurements of cochlear microphonic potentials, distortion product otoacoustic emissions, and basilar membrane motion indicate that the TM remains functionally attached to the electromotile, sensorimotor outer hair cells of the organ of Corti, and that the amplification and frequency tuning of the basilar membrane responses to sounds are almost normal. The compound action potential masker tuning curves, a measure of the tuning of the sensory inner hair cells, are also sharply tuned, but the thresholds of the compound action potentials, a measure of inner hair cell sensitivity, are significantly elevated. These results indicate that the hearing loss in patients with Otoa mutations is caused by a defect in inner hair cell stimulation, and reveal the limbal attachment of the TM plays a critical role in this process.
Project description:This study presents the initial assessment for a new approach to frequency selectivity aimed at mimicking the function of the basilar membrane within the human cochlea. The term cochlea tonotopy refers to the passive frequency selectivity and a transformation from the acoustic wave into a frequency signal assisted by the hair cells in the organ of Corti. While high-frequency sound waves vibrate near the base of the cochlea (near the oval windows), low-frequency waves vibrate near the apex (at the maximum distance from the base), which suggests the existence of continuous frequency selectivity. Over the past few decades, frequency selectivity using artificial membranes has been utilized in acoustic transducers by mimicking cochlea tonotopy using cantilever-beam arrays with defined physical parameters such as length and thickness. Unlike the conventional cantilever-beam array type, the travelling wave propagation based-mechanoluminescence (ML) membrane made of ZnS:Cu- polydimethylsiloxane (ZnS:Cu-PDMS) composite that we describe here provides new frequency selectivity more similar to that demonstrated by the human membrane. Here, we explored the potential of the ML membrane to deliver new frequency selectivity by using a non-contact image sensor to measure visualized frequencies. We report that the ML basilar membrane can provide effective visualization of the distribution of strain rate associated with the position of maximal amplitude of the travelling wave.
Project description:The human cochlea transforms sound waves into electrical signals in the acoustic nerve fibers with high acuity. This transformation occurs via vibrating anisotropic membranes (basilar and tectorial membranes) and frequency-specific hair cell receptors. Frequency-positions can be mapped within the cochlea to create a tonotopic chart which fits an almost-exponential function with lowest frequencies positioned apically and highest frequencies positioned at the cochlear base (Bekesy 1960, Greenwood 1961). To date, models of frequency positions have been based on a two-dimensional analysis with inaccurate representations of the cochlear hook region. In the present study, the first three-dimensional frequency analysis of the cochlea using dendritic mapping to obtain accurate tonotopic maps of the human basilar membrane/organ of Corti and the spiral ganglion was performed. A novel imaging technique, synchrotron radiation phase-contrast imaging, was used and a spiral ganglion frequency function was estimated by nonlinear least squares fitting a Greenwood-like function (F?=?A (10<sup>ax</sup> - K)) to the data. The three-dimensional tonotopic data presented herein has large implications for validating electrode position and creating customized frequency maps for cochlear implant recipients.
Project description:The organ of Corti (OC) is the auditory epithelium of the mammalian cochlea comprising sensory hair cells and supporting cells riding on the basilar membrane. The outer hair cells (OHCs) are cellular actuators that amplify small sound-induced vibrations for transmission to the inner hair cells. We developed a finite element model of the OC that incorporates the complex OC geometry and force generation by OHCs originating from active hair bundle motion due to gating of the transducer channels and somatic contractility due to the membrane protein prestin. The model also incorporates realistic OHC electrical properties. It explains the complex vibration modes of the OC and reproduces recent measurements of the phase difference between the top and the bottom surface vibrations of the OC. Simulations of an individual OHC show that the OHC somatic motility lags the hair bundle displacement by ?90 degrees. Prestin-driven contractions of the OHCs cause the top and bottom surfaces of the OC to move in opposite directions. Combined with the OC mechanics, this results in ?90 degrees phase difference between the OC top and bottom surface vibration. An appropriate electrical time constant for the OHC membrane is necessary to achieve the phase relationship between OC vibrations and OHC actuations. When the OHC electrical frequency characteristics are too high or too low, the OHCs do not exert force with the correct phase to the OC mechanics so that they cannot amplify. We conclude that the components of OHC forward and reverse transduction are crucial for setting the phase relations needed for amplification.