[show abstract][hide abstract] ABSTRACT: 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.
Proceedings of the National Academy of Sciences 11/2012; · 9.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: It has been predicted that a nonfunctional prestin in the mammalian cochlea would produce a basilar membrane response at lower characteristic frequency, as we see in the prestin knock-out mouse, but with a reduced sensitivity that would reflect an enhanced coupling between basilar membrane and reticular lamina and inner hair cell stereocilia. We demonstrate here that this is the case in measurements from the 499 mouse where prestin in the lateral membrane of the outer hair cells is present but effectively silenced.
[show abstract][hide abstract] ABSTRACT: Our current understanding of the mating game for many mosquito species is that males aggregate in noisy mating swarms and listen with their Johnston's organs (JOs) for the deeper flight tones of approaching females, to which they are attracted. As has been demonstrated, at least for the most intensely studied vector species, the mechanical resonance of the flagellum and the frequency range of the female's JO is far below that of the male's flight tones. Therefore, it has been assumed that females do not use hearing to detect the presence of males. Here we reveal that this may not be the case, and that the JOs of female Culex quinquefasciatus are exquisitely tuned to low frequency distortion products in the vibrations of the antenna due to a nonlinear interaction between her own flight tones and those of a nearby male. She can hear male flight tones by virtue of, and not despite, hearing her own flight tones.
[show abstract][hide abstract] ABSTRACT: We demonstrate that in Otoa−∕− mice, in which the inner-ear-specific protein otoancorin is absent, excitation of the outer hair cells and cochlear amplification is normal. This finding is remarkable because the tectorial membrane (TM), although remaining functionally attached to the outer hair cell bundles, is completely detached from the spiral limbus. Therefore, as in ancestral vertebrate auditory organs, where inertia provides the excitatory force to the hair cells, it is the inertia of the TM that must be important for exciting the outer hair cells, setting the sensitivity of their transducer conductance, and determining the precise timing of cochlear amplification.
[show abstract][hide abstract] ABSTRACT: The visco-elastic properties of the tectorial membrane (TM) can be
determined by measuring the propagation velocity of travelling waves
over a range of frequencies. This study presents a new method using
laser interferometry and compares the TM's material properties (sheer
storage modulus, G' and viscosity, ɛ) at basal and
apical locations in wild-type mice and basal locations of three mutant
groups (TectaY1870C/+, Tectb-/- and
Otoa-/-). The G' and ɛ values calculated
for the wild-type mice are similar to estimates derived using other
methods whereas the mutant groups all exhibit slower wave propagation
velocities and reduced longitudinal coupling.
[show abstract][hide abstract] ABSTRACT: The round window membrane (RW) functions as a pressure relief valve in conventional hearing allowing structures of the middle ear to move. Investigations in recent years have shown that middle ear implants can be used to stimulate the cochlea via the RW. Isolated clinical uses of this technique have been applied but more thorough theoretical and empirical studies are required. Using guinea pigs as test subjects we have investigated physiological effects of RW stimulation using a simulation of active middle ear prosthesis, a cylindrical neodymium iron boron disk magnet placed upon the RW which can be stimulated by an electromagnetic coil positioned in close proximity to the magnet.
[show abstract][hide abstract] ABSTRACT: The sensory hair cells of amniote hearing organs are usually distributed in tonotopic array from low to high frequencies and are very sensitively and sharply tuned to acoustic stimulation. Frequency tuning and tonotopicity of non-mammalian auditory hair cells is due largely to intrinsic properties of the hair cells , but frequency tuning and tonotopic organisation of the mammalian cochlea has an extrinsic basis in the basilar membrane (BM); a spiralling ribbon of collagen-rich extracellular matrix that decreases in stiffness from the high-frequency base of the cochlea to the low-frequency apex [2,3]. Sensitive frequency tuning is due to amplification, which specifically boosts low-level input to the mechanosensitive hair cells at their tonotopic location to overcome viscous damping [1-3]. In non-mammalian hearing organs, at least, amplification is attributed to calcium-mediated hair bundle motion . In the mammalian cochlea, amplification is the remit of the sensory-motor outer hair cells (OHCs), located within the organ of Corti to exercise maximum mechanical effect on the motion of the BM and transmit cochlear responses to the adjacent sensory inner hair cells (IHCs) and, consequently, to the auditory nerve [1-3] (Figure 1A). OHCs behave like piezoelectric actuators, developing forces along their long axis in response to changes in membrane potential . These forces are due to voltage-dependent conformational changes in the motor molecule prestin, which is densely distributed in the OHC lateral membranes .
Current biology: CB 09/2011; 21(18):R682-3. · 10.99 Impact Factor
[show abstract][hide abstract] ABSTRACT: The mammalian inner ear contains sense organs responsible for detecting sound, gravity and linear acceleration, and angular acceleration. Of these organs, the cochlea is involved in hearing, while the sacculus and utriculus serve to detect linear acceleration. Recent evidence from birds and mammals, including humans, has shown that the sacculus, a hearing organ in many lower vertebrates, has retained some of its ancestral acoustic sensitivity. Here we provide not only more evidence for the retained acoustic sensitivity of the sacculus, but we also found that acoustic stimulation of the sacculus has behavioral significance in mammals. We show that the amplitude of an elicited auditory startle response is greater when the startle stimuli are presented simultaneously with a low-frequency masker, including masker tones that are outside the sensitivity range of the cochlea. Masker-enhanced auditory startle responses were also observed in otoconia-absent Nox3 mice, which lack otoconia but have no obvious cochlea pathology. However, masker enhancement was not observed in otoconia-absent Nox3 mice if the low-frequency masker tones were outside the sensitivity range of the cochlea. This last observation confirms that otoconial organs, most likely the sacculus, contribute to behavioral responses to low-frequency sounds in mice.
Journal of the Association for Research in Otolaryngology 12/2010; 11(4):725-32. · 2.95 Impact Factor
[show abstract][hide abstract] ABSTRACT: Mosquitoes are more sensitive to sound than any other insect due to the remarkable properties of their antennae and Johnston's organ at the base of each antenna. Male mosquitoes detect and locate female mosquitoes by hearing the female's flight tone, but until recently we had no idea that females also respond to male flight tones. Our investigation of a novel mechanism of sex recognition in Toxorhynchites brevipalpis revealed that male and female mosquitoes actively respond to the flight tones of other flying mosquitoes by altering their own wing-beat frequencies. Male-female pairs converge on a shared harmonic of their respective fundamental flight tones, whereas same sex pairs diverge. Most frequency matching occurs at frequencies beyond the detection range of the Johnston's organ but within the range of mechanical responsiveness of the antennae. We have shown that this is possible because the Johnston's organ is tuned to, and able to detect difference tones in, the harmonics of antennal vibrations which are generated by the combined input of flight tones from both mosquitoes. Acoustic distortion in hearing organs exists usually as an interesting epiphenomenon. Mosquitoes, however, appear to use it as a sensory cue that enables male-female pairs to communicate through a signal that depends on auditory interactions between them. Frequency matching may also provide a means of species recognition. Morphologically identical but reproductively isolated molecular forms of Anopheles gambiae fly in the same mating swarms, but rarely hybridize. Extended frequency matching occurs almost exclusively between males and females of the same molecular form, suggesting that this behavior is associated with observed assortative mating.
Journal of the Association for Research in Otolaryngology 10/2010; 11(4):527-40. · 2.95 Impact Factor
[show abstract][hide abstract] ABSTRACT: The design principles and specific proteins of the dynein-tubulin motor, which powers the flagella and cilia of eukaryotes, have been conserved throughout the evolution of life from algae to humans. Cilia and flagella can support both motile and sensory functions independently, or sometimes in parallel to each other. In this paper we show that this dual sensory-motile role of eukaryotic cilia is preserved in the most sensitive of all invertebrate hearing organs, the Johnston's organ of the mosquito. The Johnston's organ displays spontaneous oscillations, which have been identified as being a characteristic of amplification in the ears of mosquitoes and Drosophila. In the auditory organs of Drosophila and vertebrates, the molecular basis of amplification has been attributed to the gating and adaptation of the mechanoelectrical transducer channels themselves. On the basis of their temperature-dependence and sensitivity to colchicine, we attribute the molecular basis of spontaneous oscillations by the Johnston's organ of the mosquito Culex quinquefasciatus, to the dynein-tubulin motor of the ciliated sensillae. If, as has been claimed for insect and vertebrate hearing organs, spontaneous oscillations epitomize amplification, then in the mosquito ear, this process is independent of mechanotransduction.
Proceedings of the Royal Society B: Biological Sciences 06/2010; 277(1688):1761-9. · 5.68 Impact Factor
[show abstract][hide abstract] ABSTRACT: Anopheles gambiae, responsible for the majority of malaria deaths annually, is a complex of seven species and several chromosomal/molecular forms. The complexity of malaria epidemiology and control is due in part to An. gambiae's remarkable genetic plasticity, enabling its adaptation to a range of human-influenced habitats. This leads to rapid ecological speciation when reproductive isolation mechanisms develop [1-6]. Although reproductive isolation is essential for speciation, little is known about how it occurs in sympatric populations of incipient species . We show that in such a population of "M" and "S" molecular forms, a novel mechanism of sexual recognition (male-female flight-tone matching [7-9]) also confers the capability of mate recognition, an essential precursor to assortative mating; frequency matching occurs more consistently in same-form pairs than in mixed-form pairs (p = 0.001). [corrected] Furthermore, the key to frequency matching is "difference tones" produced in the nonlinear vibrations of the antenna by the combined flight tones of a pair of mosquitoes and detected by the Johnston's organ. By altering their wing-beat frequencies to minimize these difference tones, mosquitoes can match flight-tone harmonic frequencies above their auditory range. This is the first description of close-range mating interactions in incipient An. gambiae species.
Current biology: CB 01/2010; 20(2):131-6. · 10.99 Impact Factor
[show abstract][hide abstract] ABSTRACT: Recent observations have changed our understanding of tectorial membrane function. Transgenic mice have shown that the tectorial
membrane is a structure that can influence the sensitivity and tuning properties of the cochlea in several ways. It ensures
that the gain and timing of cochlear feedback are optimal; that the hair bundles of the inner hair cells are driven efficiently
by the outer hair cells, and it may influence the extent to which different elements are coupled along the length of the cochlea.
KeywordsCochlea-Deafness genes-Hearing loss-TECTA-Tectorial membrane-Cochlear amplification
[show abstract][hide abstract] ABSTRACT: 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.
Hearing research 10/2009; 266(1-2):26-35. · 2.18 Impact Factor
[show abstract][hide abstract] ABSTRACT: Sexual recognition through wing-beat frequency matching was first demonstrated in Toxorhynchites brevipalpis, where wing-beat frequencies of males and females are similar. Here we show frequency matching in Culex quinquefasciatus, where the wing-beat frequencies of males and females differ considerably. The wing-beat frequencies converge not on the fundamental but on the nearest shared harmonic (usually female's third and male's second). Frequencies in this range are, however, too high to elicit phasic sensory-neural responses from the Johnston's organ (JO) or to drive the mosquito's motor neurons. Potential cues for frequency matching are difference tones produced by nonlinear mixing of male and female flight tones in the vibrations of the mosquito's antennae. Receptor potentials and neural-motor activity were recorded in response to difference tones produced when a mosquito was stimulated simultaneously by two tones at frequencies outside the phasic response range of the JO but within range of the antennal vibrations. We demonstrate sexual recognition through matching of flight-tone harmonics in Culex mosquitoes and suggest that difference tones are used as an error signal for frequency matching beyond the frequency range of the JO's sensory-neural range. This is the first report of acoustic distortion being exploited as a sensory cue, rather than existing as an epiphenomenon.
Current biology: CB 04/2009; 19(6):485-91. · 10.99 Impact Factor
[show abstract][hide abstract] ABSTRACT: The 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.
Main 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.
Findings 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.
Current opinion in otolaryngology & head and neck surgery 11/2008; 16(5):458-64.
[show abstract][hide abstract] ABSTRACT: 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 Tecta(DeltaENT/DeltaENT) mice, in which stereocilia are unable to contribute to amplification near threshold. Electrically elicited responses from Tecta(DeltaENT/DeltaENT) 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.
[show abstract][hide abstract] ABSTRACT: Electrically evoked otoacoustic emissions are sounds emitted from the inner ear when alternating current is injected into the cochlea. Their temporal structure consists of short- and long-delay components and they have been attributed to the motile responses of the sensory-motor outer hair cells of the cochlea. The nature of these motile responses is unresolved and may depend on either somatic motility, hair bundle motility, or both. The short-delay component persists after almost complete elimination of outer hair cells. Outer hair cells are thus not the sole generators of electrically evoked otoacoustic emissions. We used prestin knockout mice, in which the motor protein prestin is absent from the lateral walls of outer hair cells, and Tecta(Delta ENT/Delta ENT) mice, in which the tectorial membrane, a structure with which the hair bundles of outer hair cells normally interact, is vestigial and completely detached from the organ of Corti. The amplitudes and delay spectra of electrically evoked otoacoustic emissions from Tecta(Delta ENT/Delta ENT) and Tecta(+/+) mice are very similar. In comparison with prestin(+/+) mice, however, the short-delay component of the emission in prestin(-/-) mice is dramatically reduced and the long-delay component is completely absent. Emissions are completely suppressed in wild-type and Tecta(Delta ENT/Delta ENT) mice at low stimulus levels, when prestin-based motility is blocked by salicylate. We conclude that near threshold, the emissions are generated by prestin-based somatic motility.
Journal of Neurophysiology 05/2008; 99(4):1607-15. · 3.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: The remarkable power amplifier  of the cochlea boosts low-level and compresses high-level vibrations of the basilar membrane (BM) . 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 . 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  from OHCs results in a 40-60 dB reduction in cochlear neural sensitivity . 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 partition's 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.
Current Biology 03/2008; 18(3):200-2. · 9.49 Impact Factor
[show abstract][hide abstract] ABSTRACT: With notable exceptions such as the hair cells of the bullfrog amphibian papilla (Flock and Flock 1966), outer hair cells of the cochlea of the horseshoe bats (Rhinolophidae) and Hipposideros (Bruns and Schmieszek 1980; Vater et al. 1992), and the entire outer hair-cell region of the mole rat (Spalax ehrenbergi, Raphael et al. 1991), the mechanosensitive hair cells of the lateral line, vestibular system, and cochlea receive direct efferent innervation. The structure and synaptic physiology of the efferent synapses in each of these sensory systems, where the hair cells subserve different sensory modalities, are similar in many respects. Through the action of the efferent fibers on the hair cells, the central nervous system can control the outflow of information from these sensory epithelia to the central nervous system. This review is concerned with the cellular and molecular physiology of the postsynaptic action of the efferent synapses on hair cells and how these might interact with the inherently nonlinear cellular properties of the mechanotransducer conductance and the cochlear amplifier. The second part of the review discusses how efferent-induced changes in the nonlinear properties of hair cells may influence the mechanics of the cochlea, including their manifestation in distortion product otoacoustic emissions (DPOAEs). The cochlea efferent system has been extensively reviewed in recent years in this series (Guinan 1996; Smith and Spirou 2002), and this current review will deal with research more recent than this and with earlier research that relates to recent discoveries and concepts.
[show abstract][hide abstract] ABSTRACT: It was first suggested by Gold in 1948  that the exquisite sensitivity and frequency selectivity of the mammalian cochlea is due to an active process referred to as the cochlear amplifier. It is thought that this process works by pumping energy to augment the otherwise damped sound-induced vibrations of the basilar membrane [2-4], a mechanism known as negative damping. The existence of the cochlear amplifier has been inferred from comparing responses of sensitive and compromised cochleae  and observations of acoustic emissions [6, 7] and through mathematical modeling [8, 9]. However, power amplification has yet to be demonstrated directly. Here, we prove that energy is indeed produced in the cochlea on a cycle-by-cycle basis. By using laser interferometry , we show that the nonlinear component of basilar-membrane responses to sound stimulation leads the forces acting on the membrane. This is possible only in active systems with negative damping . Our finding provides the first direct evidence for power amplification in the mammalian cochlea. The finding also makes redundant current hypotheses of cochlear frequency sharpening and sensitization that are not based on negative damping.
Current Biology 09/2007; 17(15):1340-4. · 9.49 Impact Factor