Properties Of Outer Hair Cells Research Articles

Differential deletion of GDNF in the auditory system leads to altered sound responsiveness.

Glial-derived neurotrophic factor (GDNF) has been proposed as a potent neurotrophic factor with the potential to cure neurodegenerative diseases. In the cochlea, GDNF has been detected in auditory neurons and sensory receptor cells and its expression is upregulated upon trauma. Moreover, the application of GDNF in different animal models of deafness has shown its capacity to prevent hearing loss and promoted its future use in therapeutic trials in humans. In the present study we have examined the endogenous requirement of GDNF during auditory development in mice. Using a lacZ knockin allele we have confirmed the expression of GDNF in the cochlea including its sensory regions during development. Global inactivation of GDNF throughout the hearing system using a Foxg1-Cre line causes perinatal lethality but reveals no apparent defects during formation of the cochlea. Using TrkC-Cre and Atoh1-Cre lines, we were able to generate viable mutants lacking GDNF in auditory neurons or both auditory neurons and sensory hair cells. These mutants show normal frequency-dependent auditory thresholds. However, mechanoelectrical response properties of outer hair cells (OHCs) in TrkC-Cre GDNF mutants are altered at low thresholds. Furthermore, auditory brainstem wave analysis shows an abnormal increase of wave I. On the other hand, Atoh1-Cre GDNF mutants show normal OHC function but their auditory brainstem wave pattern is reduced at the levels of wave I, III and IV. These results show that GDNF expression during the development is required to maintain functional hearing at different levels of the auditory system.

Scientist and data architect collaborate to curate and archive an inner ear electrophysiology data collection.

In the past scientists reported summaries of their findings; they did not provide their original data collections. Many stakeholders (e.g., funding agencies) are now requesting that such data be made publicly available. This mandate is being adopted to facilitate further discovery, and to mitigate waste and deficits in the research process. At the same time, the necessary infrastructure for data curation (e.g., repositories) has been evolving. The current target is to make research products FAIR (Findable, Accessible, Interoperable, Reusable), resulting in data that are curated and archived to be both human and machine compatible. However, most scientists have little training in data curation. Specifically, they are ill-equipped to annotate their data collections at a level that facilitates discoverability, aggregation, and broad reuse in a context separate from their creation or sub-field. To circumvent these deficits data architects may collaborate with scientists to transform and curate data. This paper’s example of a data collection describes the electrical properties of outer hair cells isolated from the mammalian cochlea. The data is expressed with a variant of The Ontology for Biomedical Investigations (OBI), mirrored to provide the metadata and nested data architecture used within the Hierarchical Data Format version 5 (HDF5) format. Each digital specimen is displayed in a tree configuration (like directories in a computer) and consists of six main branches based on the ontology classes. The data collections, scripts, and ontological OWL file (OBI based Inner Ear Electrophysiology (OBI_IEE)) are deposited in three repositories. We discuss the impediments to producing such data collections for public use, and the tools and processes required for effective implementation. This work illustrates the impact that small collaborations can have on the curation of our publicly-funded collections, and is particularly salient for fields where data is sparse, throughput is low, and sacrifice of animals is required for discovery.

Investigation of the 2f1−f2 and 2f2−f1 distortion product otoacoustic emissions using a computational model of the gerbil ear

In this work, a three-dimensional computational model of the gerbil ear is used to investigate the generation of the 2f1−f2 and 2f2−f1 distortion product otoacoustic emissions (DPOAEs). In order to predict both the distortion and reflection sources, cochlear roughness is modeled by introducing random inhomogeneities in the outer hair cell properties. The model was used to simulate the generation of DPOAEs in response to a two-tone stimulus for various primary stimulus levels and frequency ratios. As in published experiments, the 2f1−f2 DPOAEs are mostly dominated by the distortion component while the 2f2−f1 DPOAEs are dominated by the reflection component; furthermore, the influence of the levels and frequency ratio of the primaries are consistent with measurements. Analysis of the intracochlear response shows that the distortion component has the highest magnitude at all longitudinal locations for the 2f1−f2 distortion product (DP) while the distortion component only dominates close to the DP best place in the case of the 2f2−f1 DP. Decomposition of the intracochlear DPs into forward and reverse waves demonstrates that the 2f1−f2 DP generates reverse waves for both the distortion and reflection components; however, a reverse wave is only generated for the reflection component in the case of the 2f2−f1 DP. As in experiments in the gerbil, the group delay of the reflection component of the DPOAE is between 1× and 2× the forward group delay, which is consistent with the propagation of DP towards the stapes as slow reverse waves.

Optimal Electrical Properties of Outer Hair Cells Ensure Cochlear Amplification

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.

Viscoelastic properties of outer hair cells

Viscoelastic properties of outer hair cells

The Efferent System or Olivocochlear Function Bundle - Fine Regulator and Protector of Hearing Perception

The efferent system of the ear possesses several distinct functions, in particular noise protection, mediation of selective attention and improvement of signal to noise ratio. It also supports adaptation and frequency selectivity by modification of the micromechanical properties of outer hair cells. There are many differences in anatomy and physiology between the medial and lateral olivocochlear system suggesting that they are functionally separate systems. The efferent system is affected by inner ear stressors, e.g. noise, ototoxic drugs, and might play a key role in tinnitus generation and maintenance. The anatomy, physiology and its realtionships to inner ear pathologies are discussed in this review article.

Modelling the human cochlea

One of the salient features of the human cochlea is the incredible dynamic range it possesses—the loudest bearable sound is 10,000,000 times greater than the softest detectable sound; this is in part due to an active process. More than twelve thousand hairlike cells known as outer hair cells are believed to expand and contract in time to amplify cochlear motions. However, the cochlea's response is more than just the sum of its parts: the local properties of outer hair cells can have unexpected consequences for the global behavior of the system. One such consequence is the existence of otoacoustic emissions (OAEs), sounds that (sometimes spontaneously!) propagate out of the cochlea to be detected in the ear canal. In this doctoral thesis, a classical, lumped-element model is used to study the cochlea and to simulate click-evoked and spontaneous OAEs. The original parameter values describing the microscopic structures of the cochlea are re-tuned to match several key features of the cochlear response in humans. The frequency domain model is also recast in a formulation known as state space; this permits the calculation of linear instabilities given random perturbations in the cochlea which are predicted to produce spontaneous OAEs.Full text available at http://eprints.soton.ac.uk/64535/

The influence of cholesterol on the motility of cochlear outer hair cells and the motor protein prestin

Conclusions: We provide evidence that cholesterol reduces electromotility in a dose-dependent matter. The data show that cholesterol modulates electromotility mainly by influencing the motor protein prestin, less by affecting the passive membrane properties. Objectives: Elevated serum cholesterol is linked to inner ear disorders and may influence hearing by altering membrane properties of outer hair cells (OHCs) and by affecting the motor protein prestin. In this study we wanted to determine whether cholesterol modulates the electromotility of OHCs and if this modulation results from effects on the membrane properties or on the motor protein prestin. Materials and methods: The motile responses of 12 isolated OHCs were investigated at increasing concentrations of 0, 0.1, and 1 mM extracellular cholesterol using the patch clamp technique and continuous video image analysis. To study effects on prestin, experiments were performed in 12 cells with half activated protein function and concentrations of 0 and 1 mM cholesterol. Results: Cholesterol at a concentration of 0.1 mM had no effect on motility. A concentration of 1 mM reduced maximal evoked shortening significantly by 29% in the depolarizing and by 9% in the hyperpolarizing direction. Investigating half activated motor proteins, 1 mM cholesterol reduced movements significantly by 18%, elongations decreased nonsignificantly by 5%.

Effects of Chlorpromazine on Mechanical Properties of the Outer Hair Cell Plasma Membrane

An optical tweezers system was used to characterize the effects of chlorpromazine (CPZ) on the mechanical properties of the mammalian outer hair cell (OHC) through the formation of plasma membrane tethers. Such tethers exhibited force relaxation when held at a constant length for several minutes. We used a second-order generalized Kelvin body to model tether-force behavior from which several mechanical parameters were then calculated including stiffness, viscosity-associated measures, and force relaxation time constants. The results of the analysis portray a two-part relaxation process characterized by significantly different rates of force decay, which we propose is due to the local reorganization of lipids within the tether and the flow of external lipid into the tether. We found that CPZ’s effect was limited to the latter phenomenon since only the second phase of relaxation was significantly affected by the drug. This finding coupled with an observed large reduction in overall tether forces implies a common basis for the drug’s effects, the plasma membrane-cytoskeleton interaction. The CPZ-induced changes in tether viscoelastic behavior suggest that alterations in the mechanical properties of the OHC lateral wall could play a role in the modulation of OHC electromotility by CPZ.

Mechanical properties of sensory and supporting cells in the organ of Corti of the guinea pig cochlea ? study by atomic force microscopy

Mammalian hearing is refined by amplification of the motion of the cochlear partition. To understand the cochlear amplification, mechanical models of the cochlea have been used. When the dynamic behavior of the cochlea is analyzed by a model, elastic properties of the cells in the organ of Corti must be determined in advance. Recently, elastic properties of outer hair cells (OHCs) and pillar cells have been elucidated. However, those of other cells have not yet been clarified. Therefore, in this study, using an atomic force microscope (AFM), elastic properties of Hensen's cells, Deiters' cells and inner hair cells (IHCs) in the apical turn and those in the basal and second turns were estimated. As a result, slopes indicative of cell elastic properties were (8.9 ± 5.8) × 103 m−1 for Hensen's cells (n=30), (5.5 ± 5.3) × 103 m−1 for Deiters' cells (n=20) and (3.8 ± 2.6) × 103 m−1 for IHCs (n=20), and Young's modulus were 0.69 ± 0.45 kPa for Hensen's cells and 0.29 ± 0.20 kPa for IHCs. There was no significant difference between elastic properties of each type of cell in the apical turn and those in the basal and second turns. However, it was found that there is a significant difference between Young's moduli of cells estimated in this study and those of the OHCs and pillar cells reported previously.

Mechanical properties of sensory and supporting cells in the organ of Corti of the guinea pig cochlea – study by atomic force microscopy

Mammalian hearing is refined by amplification of the motion of the cochlear partition. To understand the cochlear amplification, mechanical models of the cochlea have been used. When the dynamic behavior of the cochlea is analyzed by a model, elastic properties of the cells in the organ of Corti must be determined in advance. Recently, elastic properties of outer hair cells (OHCs) and pillar cells have been elucidated. However, those of other cells have not yet been clarified. Therefore, in this study, using an atomic force microscope (AFM), elastic properties of Hensen's cells, Deiters' cells and inner hair cells (IHCs) in the apical turn and those in the basal and second turns were estimated. As a result, slopes indicative of cell elastic properties were (8.9 ± 5.8) × 10 3 m −1 for Hensen's cells ( n=30), (5.5 ± 5.3) × 10 3 m −1 for Deiters' cells ( n=20) and (3.8 ± 2.6) × 10 3 m −1 for IHCs ( n=20), and Young's modulus were 0.69 ± 0.45 kPa for Hensen's cells and 0.29 ± 0.20 kPa for IHCs. There was no significant difference between elastic properties of each type of cell in the apical turn and those in the basal and second turns. However, it was found that there is a significant difference between Young's moduli of cells estimated in this study and those of the OHCs and pillar cells reported previously.

A101 ヒートストレスがマウス外有毛細胞の機械的特性に及ぼす影響(A1-1 細胞工学1)

A101 ヒートストレスがマウス外有毛細胞の機械的特性に及ぼす影響(A1-1 細胞工学1)

Elastic moduli of the piezoelectric cochlear outer hair cell membrane

The outer hair cell is a specialized cell in the mammalian cochlea, believed to amplify incoming sound waves. This amplification is associated with the outer hair cell's electromotility, a unique cellular phenomenon of voltage-dependent length changes. Outer hair cell properties can be described in terms of the piezoelectric relationships, and the elastic moduli are a key part of them. We revisit the problem of estimating the elastic moduli of the outer hair cell composite membrane (wall) where two methods have previously been proposed. We analyze the two methods, while taking into account experimental ranges of the measured parameters. We have shown that cell stiffness is the critical parameter that determines the difference between the method predictions, and we have found a range of stiffness where the results are reasonably close. The elastic moduli corresponding to this range can be recommended for estimation of the characteristics of the piezoelectric model.

Regulation of outer hair cell cytoskeletal stiffness by intracellular Ca 2+: underlying mechanism and implications for cochlear mechanics

Two Ca 2+-dependent mechanisms have been proposed to regulate the mechanical properties of outer hair cells (OHCs), the sensory–motor receptors of the mammalian cochlea. One involves the efferent neurotransmitter, acetylcholine, decreasing OHC axial stiffness. The other depends on elevation of intracellular free Ca 2+ concentration ([Ca 2+] i) resulting in OHC elongation, a process known as Ca 2+-dependent slow motility. Here we provide evidence that both these phenomena share a common mechanism. In whole-cell patch-clamp conditions, a fast increase of [Ca 2+] i by UV-photolysis of caged Ca 2+ or by extracellular application of Ca 2+-ionophore, ionomycin, produced relatively slow (time constant ∼20 s) cell elongation. When OHCs were partially collapsed by applying minimal negative pressure through the patch pipette, elevation of the [Ca 2+] i up to millimole levels (estimated by Fura-2) was unable to restore the cylindrical shape of the OHC. Stiffness measurements with vibrating elastic probes showed that the increase of [Ca 2+] i causes a decrease of OHC axial stiffness, with time course similar to that of the Ca 2+-dependent elongation, without developing any measurable force. We concluded that, contrary to a previous proposal, Ca 2+-induced OHC elongation is unlikely to be driven by circumferential contraction of the lateral wall, but is more likely a passive mechanical reaction of the turgid OHC to Ca 2+-induced decrease of axial stiffness. This may be the key phenomenon for controlling gain and operating point of the cochlear amplifier.

Behavioral investigation of some possible effects of the central olivocochlear pathways in transgenic mice

This study investigated the auditory behaviors of transgenic mice with deletions of α9 nicotinic acetylcholine receptor subunits. In the normal mammalian cochlea, the mechanical properties of outer hair cells are modified by the release of acetylcholine from olivocochlear efferent terminals. Electrophysiological correlates of this efferent feedback have not been demonstrated in α9 knockout mice, presumably because they are mediated by α9 receptors. Previous studies have associated lesions of olivocochlear pathways with hearing impairments in background noise. The prediction that α9 knockout mice would show similar deficits was tested by collecting psychophysical thresholds for tone detection and intensity discrimination from knockout mice, within-strain control subjects, and CBA/CaJ mice. Comparable performance was observed for the subject groups in quiet and in continuous background noise. The preservation of auditory function in α9 knockout mice suggests that central efferent pathways work in combination with the peripheral olivocochlear system to enhance hearing in noise, and may compensate for profound manipulations of peripheral feedback in highly routine testing procedures. An intriguing possibility is that these central mechanisms include the brainstem collaterals of olivocochlear neurons since their post-synaptic targets do not express α9 receptors and therefore are likely to maintain their effects in α9 knockout mice.

1445 外有毛細胞の伸縮運動に及ぼす細胞側壁の機械的特性の影響

1445 外有毛細胞の伸縮運動に及ぼす細胞側壁の機械的特性の影響

Solution of the inverse problem for a linear cochlear model: a tonotopic cochlear amplifier.

The extraordinary fine-tuning characteristic of normal mammalian hearing is attributed to physiological mechanisms collectively known as the cochlear amplifier (CA), which amplifies and sharpens the basilar membrane (BM) vibration response to incoming acoustic pressure oscillations. Electromechanical properties of outer hair cells (OHCs) are believed to be the critical component of the CA, but its "circuitry" as yet remains unknown. Here, the required frequency-space response characteristics of the CA are computationally determined when typical in vivo tuning data are introduced as input to a linear hydroelastic cochlear model whose cross-sectional dynamics are represented by two coupled vibrational degrees of freedom. It is assumed that the CA senses motion at the tectorial membrane (TM) reticular lamina (RL) and applies proportional, equal, and opposite forces to the BM and the RL. The results show the CA to be tonotopically tuned, meaning it conforms to a space-frequency similarity principle like other cochlear dynamical responses. This requires that the active mechanism use information distributed along the cochlear partition. The physiological mechanism responsible for such behavior remains unknown, but here the computed CA characteristics can be qualitatively reproduced by a circuit spanning the length of the cochlea. This does not preclude other mechanisms, but is intended to motivate closer experimental investigation of extracellular and intercellular ionic flow pathways.

Acoustic trauma causes reversible stiffness changes in auditory sensory cells

A common cause of hearing impairment is exposure to loud noise. Recent research has demonstrated that the auditory mechanosensory cells are essential for normal hearing sensitivity and frequency selectivity. However, little is known about the effect of noise exposure on the mechanical properties of the auditory sensory cells. Here we report a significant reduction in the stiffness and cell length of the outer hair cells after impulse noise exposure, suggesting that mechanical changes at the cellular level are involved in noise-induced hearing loss. There is a recovery of the cellular stiffness and cell length over a two-week period, indicating an activation of cellular repair mechanisms for restoring the auditory function following noise trauma. The reduced stiffness observed at the cellular level is likely to be the cause for the downward shift of the characteristic frequency seen following acoustic trauma. The deterioration and the recovery of the mechanical properties of outer hair cells may form important underlying factors in all kinds of noise-induced hearing loss.

Relationship between stiffness, internal cell pressure and shape of outer hair cells isolated from the guinea-pig hearing organ.

The mechanical properties of outer hair cells are of importance for normal hearing, and it has been shown that damage of the cells can lead to a reduction in the hearing sensitivity. In this study, we measured the stiffness of isolated outer hair cells in hyper- and hypotonic conditions, and examined the change in stiffness in relation to the corresponding changes in internal cell pressure and cell shape. The results showed that the axial stiffness of isolated outer hair cells (30-90 microns in length, 8-12 microns in diameter), ranging from 0.13-5.39 mN m-1, was inversely related to cell length. Exposure to hyper- and hypotonic external media with a small percentage change in osmolality caused a similar magnitude of change in cell length and cell diameter, but an average 60% change in cell stiffness. Therefore, a moderate osmotic change in the external medium can lead to a significant alteration in cell stiffness. The findings thus indicate an important contribution of internal cell pressure to cell stiffness.

Evolution of transient evoked otoacoustic emissions in preterm newborns: A preliminary study

Transient evoked otoacoustic emissions (TEOEs) were recorded in a cohort study of preterm neonates in order to study their basic properties as a function of gestational age. Their main properties were: (1) TEOEs spectrum did not vary with age; it was analogous to those of full term; (2) there was no statistically significant variation of the TEOEs amplitude with age. The maturation of outer hair cell properties appears to be complete at a gestational age of 29 weeks. Because a number of infants at risk for hearing loss are preterm babies, screening for TEOEs has to be performed in the neonatal care unit. To improve the accuracy and efficiency of the test, screening should take place as close to hospital discharge as possible, with the optimum time at 35 gestational weeks.