Molecular mechanism of prestin electromotive signal amplification.

Hearing involves two fundamental processes: mechano-electrical transduction and signal amplification. Despite decades of studies, the molecular bases for both remain elusive. Here, we show how prestin, the electromotive molecule of outer hair cells (OHCs) that senses both voltage and membrane tension, mediates signal amplification by coupling conformational changes to alterations in membrane surface area. Cryoelectron microscopy (cryo-EM) structures of human prestin bound with chloride or salicylate at a common "anion site" adopt contracted or expanded states, respectively. Prestin is ensconced within a perimeter of well-ordered lipids, through which it induces dramatic deformation in the membrane and couples protein conformational changes to the bulk membrane. Together with computational studies, we illustrate how the anion site is allosterically coupled to changes in the transmembrane domain cross-sectional area and the surrounding membrane. These studies provide insight into OHC electromotility by providing a structure-based mechanism of the membrane motor prestin.

Revisiting the Potency of Tbx2 Expression in Transforming Outer Hair Cells into Inner Hair Cells at Multiple Ages In Vivo.

The mouse auditory organ cochlea contains two types of sound receptors: inner hair cells (IHCs) and outer hair cells (OHCs). Tbx2 is expressed in IHCs but repressed in OHCs, and neonatal OHCs that misexpress Tbx2 transdifferentiate into IHC-like cells. However, the extent of this switch from OHCs to IHC-like cells and the underlying molecular mechanism remain poorly understood. Furthermore, whether Tbx2 can transform fully mature adult OHCs into IHC-like cells is unknown. Here, our single-cell transcriptomic analysis revealed that in neonatal OHCs misexpressing Tbx2, 85.6% of IHC genes, including Slc17a8, are upregulated, but only 38.6% of OHC genes, including Ikzf2 and Slc26a5, are downregulated. This suggests that Tbx2 cannot fully reprogram neonatal OHCs into IHCs. Moreover, Tbx2 also failed to completely reprogram cochlear progenitors into IHCs. Lastly, restoring Ikzf2 expression alleviated the abnormalities detected in Tbx2+ OHCs, which supports the notion that Ikzf2 repression by Tbx2 contributes to the transdifferentiation of OHCs into IHC-like cells. Our study evaluates the effects of ectopic Tbx2 expression on OHC lineage development at distinct stages of either male or female mice and provides molecular insights into how Tbx2 disrupts the gene expression profile of OHCs. This research also lays the groundwork for future studies on OHC regeneration.

Optogenetics Reveals Roles for Supporting Cells in Force Transmission to and From Outer Hair Cells in the Mouse Cochlea.

Outer hair cells (OHCs) of the organ of Corti (OoC), acting as bidirectional cellular mechanoelectrical transducers, generate, receive, and exchange forces with other major elements of the cochlear partition, including the sensory inner hair cells (IHCs). Force exchange is mediated via a supporting cell scaffold, including Deiters' (DC) and outer pillar cells (OPC), to enable the sensitivity and exquisite frequency selectivity of the mammalian cochlea and to transmit its responses to the auditory nerve. To selectively activate DCs and OPCs in male and female mice, we conditionally expressed in them a hyperpolarizing halorhodopsin (HOP), a light-gated inward chloride ion pump, and measured extracellular receptor potentials (ERPs) and their DC component (ERPDCs) from the cortilymph, which fills the OoC fluid spaces, and compared the responses with similar potentials from HOP-/- littermates. The compound action potentials (CAP) of the auditory nerve were measured as an indication of IHC activity and transmission of cochlear responses to the CNS. HOP light-activated hyperpolarization of DCs and OPCs suppressed cochlear amplification through changing the timing of its feedback, altered basilar membrane (BM) responses to tones at all measured levels and frequencies, and reduced IHC excitation. HOP activation findings reported here complement recent studies that revealed channelrhodopsin activation depolarized DCs and OPCs and effectively bypassed, rather than blocked, the control of OHC mechanical and electrical responses to sound and their contribution to timed and directed electromechanical feedback to the mammalian cochlea. Moreover, our findings identify DCs and OPCs as potential targets for the treatment of noise-induced hearing loss.

Norepinephrine protects against cochlear outer hair cell damage and noise-induced hearing loss via α2A-adrenergic receptor.

BACKGROUND: The cochlear sympathetic system plays a key role in auditory function and susceptibility to noise-induced hearing loss (NIHL). The formation of reactive oxygen species (ROS) is a well-documented process in NIHL. In this study, we aimed at investigating the effects of a superior cervical ganglionectomy (SCGx) on NIHL in Sprague-Dawley rats. METHODS: We explored the effects of unilateral and bilateral Superior Cervical Ganglion (SCG) ablation in the eight-ten weeks old Sprague-Dawley rats of both sexes on NIHL. Auditory function was evaluated by auditory brainstem response (ABR) testing and Distortion product otoacoustic emissions (DPOAEs). Outer hair cells (OHCs) counts and the expression of α2A-adrenergic receptor (AR) in the rat cochlea using immunofluorescence analysis. Cells culture and treatment, CCK-8 assay, Flow cytometry staining and analysis, and western blotting were to explore the mechanisms of SCG fibers may have a protective role in NIHL. RESULTS: We found that neither bilateral nor unilateral SCGx protected the cochlea against noise exposure. In HEI-OC1 cells, H2O2-induced oxidative damage and cell death were inhibited by the application of norepinephrine (NE). NE may prevent ROS-induced oxidative stress in OHCs and NIHL through the α2A-AR. CONCLUSION: These results demonstrated that sympathetic innervation mildly affected cochlear susceptibility to acoustic trauma by reducing oxidative damage in OHCs through the α2A-AR. NE may be a potential therapeutic strategy for NIHL prevention.

Differential outcomes of high-fat diet on age-related rescaling of cochlear frequency place coding.

Auditory frequency coding is place-specific, which depends on the mechanical coupling of the basilar membrane-outer hair cell (OHC)-tectorial membrane network. Prestin-based OHC electromotility improves cochlear frequency selectivity and sensitivity. Cochlear amplification determines the frequency coding wherein discrete sound frequencies find a 'best' place along the cochlear length. Loss of OHC is the leading cause of age-related hearing loss (ARHL) and is the most common cause of sensorineural hearing loss and compromised speech perception. Lipid interaction with Prestin impacts OHC function. It has been established that high-fat diet (HFD) is associated with ARHL. To determine whether genetic background and metabolism preserve cochlear frequency place coding, we examined the effect of HFD in C57BL/6J (B6) and CBA/CaJ (CBA) on ARHL.We found a significant rescuing effect on ARHL in aged B6 HFD cohort. Prestin levels and cell sizes were better maintained in the experimental B6-HFD group. We also found that distortion product otoacoustic emission (DPOAE) group delay measurement was preserved, which suggested stable frequency place coding. In contrast, the response to HFD in the CBA cohort was modest with no appreciable benefit to hearing threshold. Notably, group delay was shortened with age along with the control. In addition, the frequency dependent OHC nonlinear capacitance gradient was most pronounced at young age but decreased with age. Cochlear RNA-seq analysis revealed differential TRPV1 expression and lipid homeostasis. Activation of TRPV1 and downregulation of arachidonic acid led to downregulation of inflammatory response in B6 HFD, which protects the cochlea from ARHL. The genetic background and metabolic state-derived changes in OHC morphology and function collectively contribute to a redefined cochlear frequency place coding and improved age-related pitch perception.

In vivo CRISPR-Cas9-mediated DNA chop identifies a cochlear outer hair cell-specific enhancer.

Cochlear outer hair cells (OHCs) are essential for hearing. A short, OHC-specific enhancer is necessary but not yet available for gene therapeutic applications in OHC damage. Such damage is a major cause of deafness. Prestin is a motor protein exclusively expressed in OHCs. We hypothesized that the cis-regulatory DNA fragment deletion of Slc26a5 would affect its expression. We tested this hypothesis by conducting CRISPR/Cas9-mediated large DNA fragment deletion of mouse Slc26a5 intron regions. First, starting from a ~13 kbp fragment, step-by-step, we narrowed down the sequence to a 1.4 kbp segment. By deleting either a 13 kbp or 1.4 kbp fragment, we observed delayed Prestin expression. Second, we showed that 1.4 kbp was an OHC-specific enhancer because enhanced green fluorescent protein (EGFP) was highly and specifically expressed in OHCs in a transgenic mouse where EGFP was driven by the 1.4 kbp segment. More importantly, specific EGFP was also driven by its homologous 398 bp fragment in human Slc26a5. This suggests that the enhancer is likely to be evolutionarily conserved across different species.

Mild hearing loss in C57BL6/J mice after exposure to antiretroviral compounds during gestation and nursing.

OBJECTIVE: There is evidence of ototoxicity from antiretrovirals (ARVs), and ARV therapy in pregnant/nursing mothers can expose offspring to these compounds. The current work modelled whether exposure to ARVs in utero and during nursing altered the functioning of the auditory system in offspring mice. DESIGN: The females of seven breeding pairs of C57BL6/J mice were given daily doses of ARVs lamivudine and tenofovir disoproxil fumarate by oral gavage during gestation and nursing. Three breeder females were given equivalent volumes of water as controls. At wean age (3 weeks after birth), the offspring mice were tested with auditory brainstem responses (ABRs). At the conclusion of the experiment, the offspring mice's cochleae were examined for hair cell counts. STUDY SAMPLE: Ten breeder female C57BL6/J mice and 69 offspring mice. RESULTS: The offspring mice exposed to ARVs during development showed higher ABR thresholds than the control offspring. No differences were found in supra-threshold ABRs. There was no evidence of missing hair cells. CONCLUSIONS: Hearing impairment may be a possible consequence of exposure to ARVs during gestation and development. Because the threshold differences were not large, if they are occurring in humans, it is unlikely they would be identified in any hearing screening tests.

Outer Hair Cell Glutamate Signaling through Type II Spiral Ganglion Afferents Activates Neurons in the Cochlear Nucleus in Response to Nondamaging Sounds.

Cochlear outer hair cells (OHCs) are known to uniquely participate in auditory processing through their electromotility, and like inner hair cells, are also capable of releasing vesicular glutamate onto spiral ganglion (SG) neurons: in this case, onto the sparse Type II SG neurons. However, unlike glutamate signaling at the inner hair cell-Type I SG neuron synapse, which is robust across a wide spectrum of sound intensities, glutamate signaling at the OHC-Type II SG neuron synapse is weaker and has been hypothesized to occur only at intense, possibly damaging sound levels. Here, we tested the ability of the OHC-Type II SG pathway to signal to the brain in response to moderate, nondamaging sound (80 dB SPL) as well as to intense sound (115 dB SPL). First, we determined the VGluTs associated with OHC signaling and then confirmed the loss of glutamatergic synaptic transmission from OHCs to Type II SG neurons in KO mice using dendritic patch-clamp recordings. Next, we generated genetic mouse lines in which vesicular glutamate release occurs selectively from OHCs, and then assessed c-Fos expression in the cochlear nucleus in response to sound. From these analyses, we show, for the first time, that glutamatergic signaling at the OHC-Type II SG neuron synapse is capable of activating cochlear nucleus neurons, even at moderate sound levels.SIGNIFICANCE STATEMENT Evidence suggests that cochlear outer hair cells (OHCs) release glutamate onto Type II spiral ganglion neurons only when exposed to loud sound, and that Type II neurons are activated by tissue damage. Knowing whether moderate level sound, without tissue damage, activates this pathway has functional implications for this fundamental auditory pathway. We first determined that OHCs rely largely on VGluT3 for synaptic glutamate release. We then used a genetically modified mouse line in which OHCs, but not inner hair cells, release vesicular glutamate to demonstrate that moderate sound exposure activates cochlear nucleus neurons via the OHC-Type II spiral ganglion pathway. Together, these data indicate that glutamate signaling at the OHC-Type II afferent synapse participates in auditory function at moderate sound levels.

Distortion product otoacoustic mapping measured pre- and post-loud sound exposures.

OBJECTIVE: Sampling distortion product otoacoustic emissions (DPOAEs) at multiple f2/f1 ratios and f2 frequency values produces a DPOAE "map." This study examined the efficacy of DPOAE mapping compared with pure tone audiometry and standard DPOAEs for detecting noise effects in subjects exposed to loud sound. DESIGN: A map significance score was developed as a single measure of map change. Significance scores were evaluated before and after exposure to: loud music (LM), controlled noise (CN), and firing range noise (FR) in three separate sets of subjects. Scores were compared to audiometry and standard DPOAE results in the LM study. STUDY SAMPLE: The LM and CN exposure studies involved 22, and 20 healthy young subjects respectively with normal hearing. Eight Marines were studied before and after FR exposure. RESULTS: After LM exposure, audiometry showed significant changes at 1, 2, 4, and 6 kHz. Standard DPOAE measures were also significantly different at several frequencies. Map significance scores detected changes more effectively and showed the distribution of DPOAE alterations. CONCLUSIONS: Map significance scores detected changes after noise exposure more reliably than audiometry and standard DPOAEs. Additionally, maps showed a diffuse response to sound exposure perhaps explaining why individual DP-grams appear less sensitive.

Altered Outer Hair Cell Mitochondrial and Subsurface Cisternae Connectomics Are Candidate Mechanisms for Hearing Loss in Mice.

Organelle crosstalk is vital for cellular functions. The propinquity of mitochondria, ER, and plasma membrane promote regulation of multiple functions, which include intracellular Ca2+ flux, and cellular biogenesis. Although the purposes of apposing mitochondria and ER have been described, an understanding of altered organelle connectomics related to disease states is emerging. Since inner ear outer hair cell (OHC) degeneration is a common trait of age-related hearing loss, the objective of this study was to investigate whether the structural and functional coupling of mitochondria with subsurface cisternae (SSC) was affected by aging. We applied functional and structural probes to equal numbers of male and female mice with a hearing phenotype akin to human aging. We discovered the polarization of cristae and crista junctions in mitochondria tethered to the SSC in OHCs. Aging was associated with SSC stress and decoupling of mitochondria with the SSC, mitochondrial fission/fusion imbalance, a remarkable reduction in mitochondrial and cytoplasmic Ca2+ levels, reduced K+-induced Ca2+ uptake, and marked plasticity of cristae membranes. A model of structure-based ATP production predicts profound energy stress in older OHCs. This report provides data suggesting that altered membrane organelle connectomics may result in progressive hearing loss.

Characterisation of the static offset in the travelling wave in the cochlear basal turn.

In mammals, audition is triggered by travelling waves that are evoked by acoustic stimuli in the cochlear partition, a structure containing sensory hair cells and a basilar membrane. When the cochlea is stimulated by a pure tone of low frequency, a static offset occurs in the vibration in the apical turn. In the high-frequency region at the cochlear base, multi-tone stimuli induce a quadratic distortion product in the vibrations that suggests the presence of an offset. However, vibrations below 100 Hz, including a static offset, have not been directly measured there. We therefore constructed an interferometer for detecting motion at low frequencies including 0 Hz. We applied the interferometer to record vibrations from the cochlear base of guinea pigs in response to pure tones. When the animals were exposed to sound at an intensity of 70 dB or higher, we recorded a static offset of the sinusoidally vibrating cochlear partition by more than 1 nm towards the scala vestibuli. The offset's magnitude grew monotonically as the stimuli intensified. When stimulus frequency was varied, the response peaked around the best frequency, the frequency that maximised the vibration amplitude at threshold sound pressure. These characteristics are consistent with those found in the low-frequency region and are therefore likely common across the cochlea. The offset diminished markedly when the somatic motility of mechanosensitive outer hair cells, the force-generating machinery that amplifies the sinusoidal vibrations, was pharmacologically blocked. Therefore, the partition offset appears to be linked to the electromotile contraction of outer hair cells.

Effect of different blood groups on tympanometric findings and acoustic reflex thresholds.

PURPOSE: The blood group can have an effect on the auditory system, and it is suggested that it could be an indicator of noise-induced hearing loss. There could be changes in the immittance findings, too, in adults having different blood groups. The present study attempted to determine if there are any differences in tympanometric results (admittance, peak pressure, gradient, resonance frequency, and ear canal volume) and acoustic reflex thresholds (ART) at 500, 1000, 2000 and 4000 Hz between individuals with different blood groups (A positive, B positive, O positive and AB positive). METHODS: Eighty normal hearing adults between the age of 18 and 27 years were considered for the study. They were divided into 20 participants, each with blood groups A, B, AB, and O. The immittance findings were recorded from all the participants of the study. RESULTS: The results showed that the resonance frequency was slightly higher in blood group O compared to other blood groups. Also, the acoustic reflex thresholds were slightly elevated at all frequencies (ipsilateral and contralateral) for individuals with blood group O. CONCLUSIONS: The results of the study suggest possible reduced outer hair cells in persons with blood group O. This could have resulted in elevated acoustic reflex thresholds.

Hair cell and neural contributions to the cochlear summating potential.

The cochlear summating potential (SP) to a tone is a baseline shift that persists for the duration of the burst. It is often considered the most enigmatic of cochlear potentials because its magnitude and polarity vary across frequency and level and its origins are uncertain. In this study, we used pharmacology to isolate sources of the SP originating from the gerbil cochlea. Animals either had the full complement of outer and inner hair cells (OHCs and IHCs) and an intact auditory nerve or had systemic treatment with furosemide and kanamycin (FK) to remove the outer hair cells. Responses to tone bursts were recorded from the round window before and after the neurotoxin kainic acid (KA) was applied. IHC responses were then isolated from the post-KA responses in FK animals, neural responses were isolated from the subtraction of post-KA from pre-KA responses in NH animals, and OHC responses were isolated by subtraction of post-KA responses in FK animals from post-KA responses in normal hearing (NH) animals. All three sources contributed to the SP; OHCs with a negative polarity and IHCs and the auditory nerve with positive polarity. Thus the recorded SP in NH animals is a sum of contributions from different sources, contributing to the variety of magnitudes and polarities seen across frequency and intensity. When this information was applied to observations of the SP recorded from the round window in human cochlear implant subjects, a strong neural contribution to the SP was confirmed in humans as well as gerbils. NEW & NOTEWORTHY Of the various potentials produced by the cochlea, the summating potential (SP) is typically described as the most enigmatic. Using combinations of ototoxins and neurotoxins, we show contributions to the SP from the auditory nerve and from inner and outer hair cells, which differ in polarity and vary in size across frequency and level. This complexity of sources helps to explain the enigmatic nature of the SP.

Reticular lamina and basilar membrane vibrations in living mouse cochleae.

It is commonly believed that the exceptional sensitivity of mammalian hearing depends on outer hair cells which generate forces for amplifying sound-induced basilar membrane vibrations, yet how cellular forces amplify vibrations is poorly understood. In this study, by measuring subnanometer vibrations directly from the reticular lamina at the apical ends of outer hair cells and from the basilar membrane using a custom-built heterodyne low-coherence interferometer, we demonstrate in living mouse cochleae that the sound-induced reticular lamina vibration is substantially larger than the basilar membrane vibration not only at the best frequency but surprisingly also at low frequencies. The phase relation of reticular lamina to basilar membrane vibration changes with frequency by up to 180 degrees from ∼135 degrees at low frequencies to ∼-45 degrees at the best frequency. The magnitude and phase differences between reticular lamina and basilar membrane vibrations are absent in postmortem cochleae. These results indicate that outer hair cells do not amplify the basilar membrane vibration directly through a local feedback as commonly expected; instead, they actively vibrate the reticular lamina over a broad frequency range. The outer hair cell-driven reticular lamina vibration collaboratively interacts with the basilar membrane traveling wave primarily through the cochlear fluid, which boosts peak responses at the best-frequency location and consequently enhances hearing sensitivity and frequency selectivity.

Differences in the suppression of distortion product otoacoustic emissions by contralateral white noise between patients with acute or chronic tinnitus.

OBJECTIVE: The mechanisms underlying the shift from acute tinnitus to chronic remain obscure. An association between tinnitus and medial olivocochlear bundle (MOCB) reflex dysfunction has been hypothesised by several studies. The differences between participants with acute and chronic tinnitus have not yet been investigated. DESIGN: Participants were examined with distortion product otoacoustic emissions (DPOAEs) suppression elicited by contralateral white noise. They were compared in terms of frequency regions with non-recordable DPOAEs, suppression amplitudes and the presence of DPOAE enhancement. STUDY SAMPLE: Eighteen participants with acute tinnitus, 40 age-matched adults with chronic tinnitus and 17 controls were included. All participants (aged 34.7 ± 9.6years; mean ± Standard deviation) had normal hearing. Tinnitus was bilateral in 22 participants and unilateral in 36. RESULTS: Ears with chronic tinnitus presented significantly lower DPOAE suppression amplitudes than ears with acute tinnitus (p < 0.0001). Both acute and chronic tinnitus ears present a high prevalence of enhancement, significantly different from controls (p < 0.0001, p = 0.0002, respectively). Non-recordable DPOAEs were significantly more frequent in the chronic than in the acute tinnitus and control groups (p < 0.0001). CONCLUSIONS: The differences between study groups indicate that when tinnitus becomes chronic, DPOAEs suppression presents changes that might reveal corresponding steps in tinnitus pathophysiology. Treatment implications are discussed.

Repair of traumatized mammalian hair cells via sea anemone repair proteins.

Mammalian hair cells possess only a limited ability to repair damage after trauma. In contrast, sea anemones show a marked capability to repair damaged hair bundles by means of secreted repair proteins (RPs). Previously, it was found that recovery of traumatized hair cells in blind cavefish was enhanced by anemone-derived RPs; therefore, the ability of anemone RPs to assist recovery of damaged hair cells in mammals was tested here. After a 1 h incubation in RP-enriched culture media, uptake of FM1-43 by experimentally traumatized murine cochlear hair cells was restored to levels comparable to those exhibited by healthy controls. In addition, RP-treated explants had significantly more normally structured hair bundles than time-matched traumatized control explants. Collectively, these results indicate that anemone-derived RPs assist in restoring normal function and structure of experimentally traumatized hair cells of the mouse cochlea.

Responses of the Human Inner Ear to Low-Frequency Sound.

The perceptual insensitivity to low frequency (LF) sound in humans has led to an underestimation of the physiological impact of LF exposure on the inner ear. It is known, however, that intense, LF sound causes cyclic changes of indicators of inner ear function after LF stimulus offset, for which the term "Bounce" phenomenon has been coined.Here, we show that the mechanical amplification of hair cells (OHCs) is significantly affected after the presentation of LF sound. First, we show the Bounce phenomenon in slow level changes of quadratic, but not cubic, distortion product otoacoustic emissions (DPOAEs). Second, Bouncing in response to LF sound is seen in slow, oscillating frequency and correlated level changes of spontaneous otoacoustic emissions (SOAEs). Surprisingly, LF sound can induce new SOAEs which can persist for tens of seconds. Further, we show that the Bounce persists under free-field conditions, i.e. without an in-ear probe occluding the auditory meatus. Finally, we show that the Bounce is affected by contralateral acoustic stimulation synchronised to the ipsilateral LF sound. These findings clearly demonstrate that the origin of the Bounce lies in the modulation of cochlear amplifier gain. We conclude that activity changes of OHCs are the source of the Bounce, most likely caused by a temporary disturbance of OHC calcium homeostasis. In the light of these findings, the effects of long-duration, anthropogenic LF sound on the human inner ear require further research.

Characterization of transcriptomes of cochlear inner and outer hair cells.

Inner hair cells (IHCs) and outer hair cells (OHCs) are the two types of sensory receptor cells that are critical for hearing in the mammalian cochlea. IHCs and OHCs have different morphology and function. The genetic mechanisms that define their morphological and functional specializations are essentially unknown. The transcriptome reflects the genes that are being actively expressed in a cell and holds the key to understanding the molecular mechanisms of the biological properties of the cell. Using DNA microarray, we examined the transcriptome of 2000 individually collected IHCs and OHCs from adult mouse cochleae. We show that 16,647 and 17,711 transcripts are expressed in IHCs and OHCs, respectively. Of those genes, ∼73% are known genes, 22% are uncharacterized sequences, and 5.0% are noncoding RNAs in both populations. A total of 16,117 transcripts are expressed in both populations. Uniquely and differentially expressed genes account for <15% of all genes in either cell type. The top 10 differentially expressed genes include Slc17a8, Dnajc5b, Slc1a3, Atp2a3, Osbpl6, Slc7a14, Bcl2, Bin1, Prkd1, and Map4k4 in IHCs and Slc26a5, C1ql1, Strc, Dnm3, Plbd1, Lbh, Olfm1, Plce1, Tectb, and Ankrd22 in OHCs. We analyzed commonly and differentially expressed genes with the focus on genes related to hair cell specializations in the apical, basolateral, and synaptic membranes. Eighty-three percent of the known deafness-related genes are expressed in hair cells. We also analyzed genes involved in cell-cycle regulation. Our dataset holds an extraordinary trove of information about the molecular mechanisms underlying hair cell morphology, function, pathology, and cell-cycle control.

Filtering of acoustic signals within the hearing organ.

The detection of sound by the mammalian hearing organ involves a complex mechanical interplay among different cell types. The inner hair cells, which are the primary sensory receptors, are stimulated by the structural vibrations of the entire organ of Corti. The outer hair cells are thought to modulate these sound-evoked vibrations to enhance hearing sensitivity and frequency resolution, but it remains unclear whether other structures also contribute to frequency tuning. In the current study, sound-evoked vibrations were measured at the stereociliary side of inner and outer hair cells and their surrounding supporting cells, using optical coherence tomography interferometry in living anesthetized guinea pigs. Our measurements demonstrate the presence of multiple vibration modes as well as significant differences in frequency tuning and response phase among different cell types. In particular, the frequency tuning at the inner hair cells differs from other cell types, causing the locus of maximum inner hair cell activation to be shifted toward the apex of the cochlea compared with the outer hair cells. These observations show that additional processing and filtering of acoustic signals occur within the organ of Corti before inner hair cell excitation, representing a departure from established theories.

Use of Otoacoustic Emissions (OAE) to detect sub-clinical inner ear damage in divers of the Indian Navy.

BACKGROUND: Professional Divers are at a high risk of Sensorineural Hearing Impairment. Divers may sustain sub-clinical hearing loss that is not identified on pure tone audiometry (PTA). Otoacoustic Emissions (OAE) reflect the functional status of the Outer Hair Cells. OAE testing constitutes the only non-invasive means of objective cochlear investigation and may be a more sensitive measure than PTA in identifying sub-clinical hearing loss. METHODS: This cross-sectional study was performed to determine utility of Otoacoustic Emissions testing in detecting sub-clinical Inner Ear damage in divers of Indian Navy. Transient Evoked Otoacoustic Emissions (TEOAE) levels were measured in 50 audiologically asymptomatic ship divers of Indian Navy and compared with control group comprising of 50 normal hearing individuals. RESULTS: No statistically significant differences were observed between the study and control group. Also no correlation was observed between diving years and TEOAE levels. There was no correlation greater than -0.49 between diving years and TEOAE SNR. CONCLUSIONS: We concluded that TEOAE levels are not a sensitive tool in identifying ships divers without any history of noise exposure at risk for developing hearing loss.