How Close Should the Outer Hair Cell RC Roll-Off Frequency Be to the Characteristic Frequency?

Recent experiments have shown a much larger conductance in outer hair cells, the central components of the mammalian cochlear amplifier. The report used only the cell's linear capacitance, which together with increased conductance, raised the cell's RC corner frequency so that voltage-dependent motility was better able to amplify high-frequency sounds. We construct transfer functions for a simple model of a high characteristic frequency (CF) local cochlear resonance. These show that voltage roll-off does not occur above the RC corner. Instead, it is countered by high-pass filtering that is intrinsic to the mammal's electromechanical resonance. Thus, the RC corner of a short outer hair cell used for high-frequency amplification does not have to be close to the CF, but depending on the drag, raised only above 0.1 CF. This high-pass filter, built in to the mammalian amplifier, allows for sharp frequency selectivity at very high CF.     

Cochlear mechanics: no shout but a twist in the absence of prestin

Mammalian hearing is boosted by mechanically active auditory receptor cells, the outer hair cells which amplify the actions of incoming sounds. Recent evidence indicates that the molecular motor that drives this amplification, prestin, may do more than boogie.     

Consequences of Location-Dependent Organ of Corti Micro-Mechanics

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.     

Structure of the inner ear of bluefin tuna Thunnus thynnus

The ears of five large bluefin tuna Thunnus thynnus were examined by light and scanning electron microscopy (SEM). The gross structure of the ear is similar to that in other fishes. The ears, however, appear to be held more rigidly in place than in other species through the presence of an extensive connective tissue between the membranous ear and the surrounding bone. Moreover, unlike other fishes, the semicircular canals and otolithic end organs have thick cartilaginous walls and there is a dense matrix surrounding the otoliths rather than a more watery fluid found in other species. SEM revealed that the saccular epithelium has a 'standard' hair cell orientation pattern. The hair cell orientation patterns in the lagena and utricle resemble those found in most other fishes. Ciliary bundle density and length vary in different epithelial regions and each ear had >2 × 10⁶ sensory cells. The morphological results support the hypothesis that bluefin tuna probably do not detect sounds to much over 1000 Hz (if that high) and that only very loud anthropogenic sounds have the potential to affect hearing in this species.     

Multifrequency forcing of a Hopf oscillator model of the inner ear

In response to a sound stimulus, the inner ear emits sounds called otoacoustic emissions. While the exact mechanism for the production of otoacoustic emissions is not known, active motion of individual hair cells is thought to play a role. Two possible sources for otoacoustic emissions, both localized within individual hair cells, include somatic motility and hair bundle motility. Because physiological models of each of these systems are thought to be poised near a Hopf bifurcation, the dynamics of each can be described by the normal form for a system near a Hopf bifurcation. Here we demonstrate that experimental results from three-frequency suppression experiments can be predicted based on the response of an array of noninteracting Hopf oscillators tuned at different frequencies. This supports the idea that active motion of individual hair cells contributes to active processing of sounds in the ear. Interestingly, the model suggests an explanation for differing results recorded in mammals and nonmammals.     

Sensors, motors, and tuning in the cochlea: interacting cells could form a surface acoustic wave resonator

The outer hair cells of the cochlea occur in three distinct and geometrically precise rows and, unusually, display both sensing and motor properties. As well as sensing sound, outer hair cells (OHCs) undergo cycle-by-cycle length changes in response to stimulation. OHCs are central to the way in which the cochlea processes and amplifies sounds, but how they do so is presently unknown. In explanation, this paper proposes that outer hair cells act like a single-port surface acoustic wave (SAW) resonator in which the interdigital electrodes--the three distinctive rows--exhibit the required electromechanical and mechanoelectrical properties. Thus, frequency analysis in the cochlea might occur through sympathetic resonance of a bank of interacting cells whose microscopic separation largely determines the resonance frequency. In this way, the cochlea could be tuned from 20 Hz at the apex, where the spacing is largest, to 20 kHz at the base, where it is smallest. A suitable candidate for a wave that could mediate such a short-wavelength interaction--a 'squirting wave' known in ultrasonics--has recently been described. Such a SAW resonator could thereby underlie the 'cochlear amplifier'--the device whose action is evident to auditory science but whose identity has not yet been established.     

Cochlear amplification, outer hair cells and prestin

Mechanical amplification of acoustic signals is apparently a common feature of vertebrate auditory organs. In non-mammalian vertebrates amplification is produced by stereociliary processes, related to the mechanotransducer channel complex and probably to the phenomenon of fast adaptation. The extended frequency range of the mammalian cochlea has probably co-evolved with a novel hair cell type, the outer hair cell and its constituent membrane protein, prestin. Cylindrical outer hair cells are motile and their somatic length changes are voltage driven and powered by prestin. One of the central outstanding problems in mammalian cochlear neurobiology is the relation between the two amplification processes.     

Hair cell heterogeneity and ultrasonic hearing: recent advances in understanding fish hearing

The past decade has seen a wealth of new data on the auditory capabilities and mechanisms of fishes. We now have a significantly better appreciation of the structure and function of the auditory system in fishes with regard to their peripheral and central anatomy, physiology, behaviour, sound source localization and hearing capabilities. This paper deals with two of the newest of these findings, hair cell heterogeneity and the detection of ultrasound. As a result of this recent work, we now know that fishes have several different types of sensory hair cells in both the ear and lateral line and there is a growing body of evidence to suggest that these hair cell types arose very early in the evolution of the octavolateralis system. There is also some evidence to suggest that the differences in the hair cell types have functional implications for the way the ear and lateral line of fishes detect and process stimuli. Behavioural studies have shown that, whereas most fishes can only detect sound to 1-3 kHz, several species of the genus Alosa (Clupeiformes, i.e. herrings and their relatives) can detect sounds up to 180 kHz (or even higher). It is suggested that this capability evolved so that these fishes can detect one of their major predators, echolocating dolphins. The mechanism for ultrasound detection remains obscure, though it is hypothesized that the highly derived utricle of the inner ear in these species is involved.     

Prestin-based outer hair cell motility is necessary for mammalian cochlear amplification

It is a central tenet of cochlear neurobiology that mammalian ears rely on a local, mechanical amplification process for their high sensitivity and sharp frequency selectivity. While it is generally agreed that outer hair cells provide the amplification, two mechanisms have been proposed: stereociliary motility and somatic motility. The latter is driven by the motor protein prestin. Electrophysiological phenotyping of a prestin knockout mouse intimated that somatic motility is the amplifier. However, outer hair cells of knockout mice have significantly altered mechanical properties, making this mouse model unsatisfactory. Here, we study a mouse model without alteration to outer hair cell and organ of Corti mechanics or to mechanoelectric transduction, but with diminished prestin function. These animals have knockout-like behavior, demonstrating that prestin-based electromotility is required for cochlear amplification.     

Hair cell BK channels interact with RACK1, and PKC increases its expression on the cell surface by indirect phosphorylation

Large conductance (BK) calcium activated potassium channels (Slo) are ubiquitous and implicated in a number of human diseases including hypertension and epilepsy. BK channels consist of a pore forming α-subunit (Slo) and a number of accessory subunits. In hair cells of nonmammalian vertebrates these channels play a critical role in electrical resonance, a mechanism of frequency selectivity. Hair cell BK channel clusters on the surface and currents increase along the tonotopic axis and contribute significantly to the responsiveness of these hair cells to sounds of high frequency. In contrast, messenger RNA levels encoding the Slo gene show an opposite decrease in high frequency hair cells. To understand the molecular events underlying this paradox, we used a yeast two-hybrid screen to isolate binding partners of Slo. We identified Rack1 as a Slo binding partner and demonstrate that PKC activation increases Slo surface expression. We also establish that increased Slo recycling of endocytosed Slo is at least partially responsible for the increased surface expression of Slo. Moreover, analysis of several PKC phosphorylation site mutants confirms that the effects of PKC on Slo surface expression are likely indirect. Finally, we show that Slo clusters on the surface of hair cells are also increased by increased PKC activity and may contribute to the increasing amounts of channel clusters on the surface of high-frequency hair cells.     

About functional evolution of peripheral part of the auditory system

Functional evolution of the peripheral part of the auditory system is considered. The key point of the appearance of a possibility of analysis of sound waved is formation in the course of evolution of cells with protoplasmic processes (sensillae)—the hair cells—that are transformed into auditory receptors. The fundamental moment is the emergence in evolution of the specialized ionic medium (endolymph) surrounding the auditory receptors. This medium is necessary for generation of receptor potential due to mechanical deformations of the auditory receptor. The characteristic feature of functional evolution of the peripheral part of the auditory system is the many-time repetition in the course of evolution of the main devices to detect and to distinguish sounds. This indicates recapitulation in evolution not only of the central parts of the brain (including central regions of the auditory system), but also of its peripheral part.     

About functional evolution of peripheral part of the auditory system

Functional evolution of the peripheral part of the auditory system is considered. The key point of the appearance of a possibility of analysis of sound waves is formation in the course of evolution of cells with protoplasmic processes (sensillae)--the hair cells--that are transformed into auditory receptors. The fundamental moment is the emergence in evolution of the specialized ionic medium (endolymph) surrounding the auditory receptors. This medium is necessary for generation of receptor potential due to mechanical deformations of the auditory receptor. The characteristic feature of functional evolution of the peripheral part of the auditory system is the many-time repetition in the course of evolution of the main devices to detect and to distinguish sounds. This indicates recapitulation in evolution not only of the central parts of the brain (including central regions of the auditory system), but also of its peripheral part.     

Localization of the cochlear amplifier in living sensitive ears

Background

To detect soft sounds, the mammalian cochlea increases its sensitivity by amplifying incoming sounds up to one thousand times. Although the cochlear amplifier is thought to be a local cellular process at an area basal to the response peak on the spiral basilar membrane, its location has not been demonstrated experimentally.

Methodology and Principal Findings

Using a sensitive laser interferometer to measure sub-nanometer vibrations at two locations along the basilar membrane in sensitive gerbil cochleae, here we show that the cochlea can boost soft sound-induced vibrations as much as 50 dB/mm at an area proximal to the response peak on the basilar membrane. The observed amplification works maximally at low sound levels and at frequencies immediately below the peak-response frequency of the measured apical location. The amplification decreases more than 65 dB/mm as sound levels increases.

Conclusions and Significance

We conclude that the cochlea amplifier resides at a small longitudinal region basal to the response peak in the sensitive cochlea. These data provides critical information for advancing our knowledge on cochlear mechanisms responsible for the remarkable hearing sensitivity, frequency selectivity and dynamic range.     

Friction from Transduction Channels’ Gating Affects Spontaneous Hair-Bundle Oscillations

Hair cells of the inner ear can power spontaneous oscillations of their mechanosensory hair bundle, resulting in amplification of weak inputs near the characteristic frequency of oscillation. Recently, dynamic force measurements have revealed that delayed gating of the mechanosensitive ion channels responsible for mechanoelectrical transduction produces a friction force on the hair bundle. The significance of this intrinsic source of dissipation for the dynamical process underlying active hair-bundle motility has remained elusive. The aim of this work is to determine the role of friction in spontaneous hair-bundle oscillations. To this end, we characterized key oscillation properties over a large ensemble of individual hair cells and measured how viscosity of the endolymph that bathes the hair bundles affects these properties. We found that hair-bundle movements were too slow to be impeded by viscous drag only. Moreover, the oscillation frequency was only marginally affected by increasing endolymph viscosity by up to 30-fold. Stochastic simulations could capture the observed behaviors by adding a contribution to friction that was 3?8-fold larger than viscous drag. The extra friction could be attributed to delayed changes in tip-link tension as the result of the finite activation kinetics of the transduction channels. We exploited our analysis of hair-bundle dynamics to infer the channel activation time, which was ～1 ms. This timescale was two orders-of-magnitude shorter than the oscillation period. However, because the channel activation time was significantly longer than the timescale of mechanical relaxation of the hair bundle, channel kinetics affected hair-bundle dynamics. Our results suggest that friction from channel gating affects the waveform of oscillation and that the channel activation time can tune the characteristic frequency of the hair cell. We conclude that the kinetics of transduction channels’ gating plays a fundamental role in the dynamic process that shapes spontaneous hair-bundle oscillations.     

A mechanism for active hearing

The remarkable sensitivity, frequency selectivity, and nonlinearity of the cochlea have been attributed to the putative 'cochlear amplifier', which consumes metabolic energy to amplify the cochlear mechanical response to sounds. Recent studies have demonstrated that outer hair cells actively generate force using somatic electromotility and active hair-bundle motion. However, the expected power gain of the cochlear amplifier has not been demonstrated experimentally, and the measured location of cochlear nonlinearity is inconsistent with the predicted location of the cochlear amplifier. We instead propose a 'cochlear transformer' mechanism to interpret cochlear performance.     

Development of frequency tuning in the auditory periphery.

The peripheral auditory organ, the cochlea, acts as a spectral analyzer resolving the frequency components of sound. During development the cochlea first responds to loud low-frequency sounds, and only gradually acquires the adult pattern of increased sensitivity and an expanded high-frequency range. This evolution of function may result in part from the gradual maturation of hair cell properties.     

Auditory processing of complex sounds: an overview.

The past 30 years has seen a remarkable development in our understanding of how the auditory system--particularly the peripheral system--processes complex sounds. Perhaps the most significant has been our understanding of the mechanisms underlying auditory frequency selectivity and their importance for normal and impaired auditory processing. Physiologically vulnerable cochlear filtering can account for many aspects of our normal and impaired psychophysical frequency selectivity with important consequences for the perception of complex sounds. For normal hearing, remarkable mechanisms in the organ of Corti, involving enhancement of mechanical tuning (in mammals probably by feedback of electro-mechanically generated energy from the hair cells), produce exquisite tuning, reflected in the tuning properties of cochlear nerve fibres. Recent comparisons of physiological (cochlear nerve) and psychophysical frequency selectivity in the same species indicate that the ear's overall frequency selectivity can be accounted for by this cochlear filtering, at least in bandwidth terms. Because this cochlear filtering is physiologically vulnerable, it deteriorates in deleterious conditions of the cochlea--hypoxia, disease, drugs, noise overexposure, mechanical disturbance--and is reflected in impaired psychophysical frequency selectivity. This is a fundamental feature of sensorineural hearing loss of cochlear origin, and is of diagnostic value. This cochlear filtering, particularly as reflected in the temporal patterns of cochlear fibres to complex sounds, is remarkably robust over a wide range of stimulus levels. Furthermore, cochlear filtering properties are a prime determinant of the 'place' and 'time' coding of frequency at the cochlear nerve level, both of which appear to be involved in pitch perception. The problem of how the place and time coding of complex sounds is effected over the ear's remarkably wide dynamic range is briefly addressed. In the auditory brainstem, particularly the dorsal cochlear nucleus, are inhibitory mechanisms responsible for enhancing the spectral and temporal contrasts in complex sounds. These mechanisms are now being dissected neuropharmacologically. At the cortical level, mechanisms are evident that are capable of abstracting biologically relevant features of complex sounds. Fundamental studies of how the auditory system encodes and processes complex sounds are vital to promising recent applications in the diagnosis and rehabilitation of the hearing impaired.     

New tunes from Corti's organ: the outer hair cell boogie rules

The amplification of acoustic stimuli is a feature of hair cells that evolved early on in vertebrates. Though standard stereocilia mechanisms to promote such amplification may persist in the mammal, an additional mechanism evolved to enhance high frequency sensation. Only in mammals, a special cell type, the outer hair cell, arose that possesses a remarkably fast somatic mechanical response, which probably endows the passive cochlea with a boost in sensitivity by a factor of 100 (40dB), at least. Experiments conducted over the past few years have shed light on many aspects of outer hair cell electromotility, including the molecular identification of the motor, the effects of a knockout, and underlying mechanisms of action. A review of this remarkable progress is attempted.     

The sensory and motor roles of auditory hair cells

Cochlear hair cells respond with phenomenal speed and sensitivity to sound vibrations that cause submicron deflections of their hair bundle. Outer hair cells are not only detectors, but also generate force to augment auditory sensitivity and frequency selectivity. Two mechanisms of force production have been proposed: contractions of the cell body or active motion of the hair bundle. Here, we describe recently identified proteins involved in the sensory and motor functions of auditory hair cells and present evidence for each force generator. Both motor mechanisms are probably needed to provide the high sensitivity and frequency discrimination of the mammalian cochlea.     

Silencing the cochlear amplifier by immobilizing prestin

Achieving the exquisite sensitivity and frequency selectivity of the mammalian ear requires active amplification of input sound. In this issue of Neuron, Dallos and colleagues demonstrate that the molecular motor prestin, which drives shape changes in the soma of mechanosensory hair cells, underlies mechanical feedback mechanisms for sound amplification in mammals.