| 1. |
- Videhult Pierre, Pernilla, et al.
(författare)
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Self-reported hearing difficulties, main income sources, and socio-economic status; a cross-sectional population-based study in Sweden
- 2012
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hearing difficulties constitute the most common cause of disability globally. Yet, studies on people with hearing difficulties regarding socio-economic status (SES), work, long-term unemployment, sickness absence, and disability pension are scarce. The aim of the present study was to investigate the main income sources of men and women of working ages with and without self-reported hearing difficulties and associations with gender, age, SES, type of living area, and country of birth.METHODS: A cross-sectional population-based study, using information on self-reported hearing difficulties and SES of 19 045 subjects aged 20-64 years participating in Statistics Sweden's annual Living Conditions Surveys in any of the years 2004 through 2008. The information was linked to a nationwide database containing data on demographics and income sources. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated, using binary logistic regression analysis.RESULTS: Hearing difficulties increased with age and were more common in men (age-adjusted OR: 1.42 (95% CI: 1.30-1.56)) with an overall prevalence of 13.1% in men and 9.8% in women. Using working men as reference, the OR of having hearing difficulties was 1.23 (0.94-1.60) in men with unemployment benefits and 1.36 (1.13-1.65) in men with sickness benefits or disability pension, when adjusting for age and SES. The corresponding figures in women were 1.59 (1.17-2.16) and 1.73 (1.46-2.06). The OR of having sickness benefits or disability pension in subjects with hearing difficulties was 1.36 (1.12-1.64) in men and 1.70 (1.43-2.01) in women, when adjusting for age and SES and using men and women with no hearing difficulties as reference.CONCLUSIONS: Hearing difficulties were more prevalent in men. After adjustment with age and SES as well as with type of living area and country of birth, a significant association with unemployment benefits was found only in women, and the associations with long-term sickness absence and disability pension tended to be stronger in women.
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| 2. |
- Bagger-Sjoback, Dan, et al.
(författare)
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High-frequency hearing, tinnitus, and patient satisfaction with stapedotomy: A randomized prospective study
- 2015
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Ingår i: Scientific Reports. - : Nature Publishing Group: Open Access Journals - Option C / Nature Publishing Group. - 2045-2322. ; 5:13341
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Tidskriftsartikel (refereegranskat)abstract
- Otosclerosis is a common disorder that leads to conductive hearing loss. Most patients with otosclerosis also have tinnitus, and surgical treatment is known to improve hearing as well as tinnitus. Some patients however experience worsening of tinnitus after the operation, but there are no known factors that allow surgeons to predict who will be at risk. In this prospective observational study on 133 patients undergoing stapedotomy, we show that postoperative air conduction thresholds at very high stimulus frequencies predict improvement of tinnitus, as assessed with proportional odds logistic regression models. Young patients were significantly more likely to experience reduction of tinnitus and patients whose tinnitus became better were also more satisfied with the outcome of the operation. These findings have practical importance for patients and their surgeons. Young patients can be advised that surgery is likely to be beneficial for their tinnitus, but a less positive message should be conveyed to older patients.
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| 3. |
- Bagger-Sjöbäck, Dan, et al.
(författare)
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A Randomised, Double Blind Trial of N-Acetylcysteine for Hearing Protection during Stapes Surgery
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- Background Otosclerosis is a disorder that impairs middle ear function, leading to conductive hearing loss. Surgical treatment results in large improvement of hearing at low sound frequencies, but high-frequency hearing often suffers. A likely reason for this is that inner ear sensory cells are damaged by surgical trauma and loud sounds generated during the operation. Animal studies have shown that antioxidants such as N-Acetylcysteine can protect the inner ear from noise, surgical trauma, and some ototoxic substances, but it is not known if this works in humans. This trial was performed to determine whether antioxidants improve surgical results at high frequencies. Methods We performed a randomized, double-blind and placebo-controlled parallel group clinical trial at three Swedish university clinics. Using block-stratified randomization, 156 adult patients undergoing stapedotomy were assigned to intravenous N-Acetylcysteine (150 mg/kg body weight) or matching placebo (1:1 ratio), starting one hour before surgery. The primary outcome was the hearing threshold at 6 and 8 kHz; secondary outcomes included the severity of tinnitus and vertigo. Findings One year after surgery, high-frequency hearing had improved 2.7 +/- 3.8 dB in the placebo group (67 patients analysed) and 2.4 +/- 3.7 dB in the treated group (72 patients; means +/- 95% confidence interval, p = 0.54; linear mixed model). Surgery improved tinnitus, but there was no significant intergroup difference. Post-operative balance disturbance was common but improved during the first year, without significant difference between groups. Four patients receiving N-Acetylcysteine experienced mild side effects such as nausea and vomiting. Conclusions N-Acetylcysteine has no effect on hearing thresholds, tinnitus, or balance disturbance after stapedotomy.
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| 4. |
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| 5. |
- Brownell, William E, et al.
(författare)
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Membrane cholesterol modulates cochlear electromechanics
- 2011
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Ingår i: Pflügers Archiv. - : Springer Science and Business Media LLC. - 0031-6768 .- 1432-2013. ; 461:6, s. 677-686
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Tidskriftsartikel (refereegranskat)abstract
- Changing the concentration of cholesterol in the plasma membrane of isolated outer hair cells modulates electromotility and prestin-associated charge movement, suggesting that a similar manipulation would alter cochlear mechanics. We examined cochlear function before and after depletion of membrane cholesterol with methyl-β-cyclodextrin (MβCD) in an excised guinea pig temporal bone preparation. The mechanical response of the cochlear partition to acoustic and/or electrical stimulation was monitored using laser interferometry and time-resolved confocal microscopy. The electromechanical response in untreated preparations was asymmetric with greater displacements in response to positive currents. Exposure to MβCD increased the magnitude and asymmetry of the response, without changing the frequency tuning of sound-evoked mechanical responses or cochlear microphonic potentials. Sodium salicylate reversibly blocked the enhanced electromechanical response in cholesterol depleted preparations. The increase of sound-evoked vibrations during positive current injection was enhanced following MβCD in some preparations. Imaging was used to assess cellular integrity which remained unchanged after several hours of exposure to MβCD in several preparations. The enhanced electromechanical response reflects an increase in outer hair cell electromotility and may reveal features of cholesterol distribution and trafficking in outer hair cells.
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| 6. |
- Burwood, George, et al.
(författare)
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Best frequencies and temporal delays are similar across the low-frequency regions of the guinea pig cochlea
- 2022
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Ingår i: Science Advances. - : AMER ASSOC ADVANCEMENT SCIENCE. - 2375-2548. ; 8:38
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Tidskriftsartikel (refereegranskat)abstract
- The cochlea maps tones with different frequencies to distinct anatomical locations. For instance, a faint 5000-hertz tone produces brisk responses at a place approximately 8 millimeters into the 18-millimeter-long guinea pig cochlea, but little response elsewhere. This place code pervades the auditory pathways, where neurons have "best frequencies" determined by their connections to the sensory cells in the hearing organ. However, frequency selectivity in cochlear regions encoding low-frequency sounds has not been systematically studied. Here, we show that low-frequency hearing works according to a unique principle that does not involve a place code. Instead, sound-evoked responses and temporal delays are similar across the low-frequency regions of the cochlea. These findings are a break from theories considered proven for 100 years and have broad implications for understanding information processing in the brainstem and cortex and for optimizing the stimulus delivery in auditory implants.
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| 7. |
- Burwood, G., et al.
(författare)
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Outer hair cell driven reticular lamina mechanical distortion in living cochleae
- 2022
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Ingår i: Hearing Research. - : ELSEVIER. - 0378-5955 .- 1878-5891. ; 423
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Tidskriftsartikel (refereegranskat)abstract
- Cochlear distortions afford researchers and clinicians a glimpse into the conditions and properties of inner ear signal processing mechanisms. Until recently, our examination of these distortions has been limited to measuring the vibration of the basilar membrane or recording acoustic distortion output in the ear canal. Despite its importance, the generation mechanism of cochlear distortion remains a substantial task to understand. The ability to measure the vibration of the reticular lamina in rodent models is a recent experimental advance. Surprising mechanical properties have been revealed. These properties merit both discussion in context with our current understanding of distortion, and appraisal of the significance of new interpretations of cochlear mechanics. This review focusses on some of the recent data from our research groups and discusses the implications of these data on our understanding of vocalization processing in the periphery, and their influence upon future experimental directions. (C) 2021 Elsevier B.V. All rights reserved.
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| 8. |
- Burwood, George W. S., et al.
(författare)
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Revealing the morphology and function of the cochlea and middle ear with optical coherence tomography
- 2019
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Ingår i: QUANTITATIVE IMAGING IN MEDICINE AND SURGERY. - : AME PUBL CO. - 2223-4292 .- 2223-4306. ; 9:5, s. 858-881
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Forskningsöversikt (refereegranskat)abstract
- Optical coherence tomography (OCT) has revolutionized physiological studies of the hearing organ, the vibration and morphology of which can now be measured without opening the surrounding bone. In this review, we provide an overview of OCT as used in the otological research, describing advances and different techniques in vibrometry, angiography, and structural imaging.
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| 9. |
- Chen, Fangyi, et al.
(författare)
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A differentially amplified motion in the ear for near-threshold sound detection
- 2011
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Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 14:6, s. 770-774
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Tidskriftsartikel (refereegranskat)abstract
- The ear is a remarkably sensitive pressure fluctuation detector. In guinea pigs, behavioral measurements indicate a minimum detectable sound pressure of ∼20 μPa at 16 kHz. Such faint sounds produce 0.1-nm basilar membrane displacements, a distance smaller than conformational transitions in ion channels. It seems that noise within the auditory system would swamp such tiny motions, making weak sounds imperceptible. Here we propose a new mechanism contributing to a resolution of this problem and validate it through direct measurement. We hypothesized that vibration at the apical side of hair cells is enhanced compared with that at the commonly measured basilar membrane side. Using in vivo optical coherence tomography, we demonstrated that apical-side vibrations peaked at a higher frequency, had different timing and were enhanced compared with those at the basilar membrane. These effects depend nonlinearly on the stimulus sound pressure level. The timing difference and enhancement of vibrations are important for explaining how the noise problem is circumvented.
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| 10. |
- Ciganovic, Nikola, et al.
(författare)
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Static length changes of cochlear outer hair cells can tune low-frequency hearing
- 2018
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Ingår i: PloS Computational Biology. - : PUBLIC LIBRARY SCIENCE. - 1553-734X .- 1553-7358. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The cochlea not only transduces sound-induced vibration into neural spikes, it also amplifies weak sound to boost its detection. Actuators of this active process are sensory outer hair cells in the organ of Corti, whereas the inner hair cells transduce the resulting motion into electric signals that propagate via the auditory nerve to the brain. However, how the outer hair cells modulate the stimulus to the inner hair cells remains unclear. Here, we combine theoretical modeling and experimental measurements near the cochlear apex to study the way in which length changes of the outer hair cells deform the organ of Corti. We develop a geometry-based kinematic model of the apical organ of Corti that reproduces salient, yet counter-intuitive features of the organs motion. Our analysis further uncovers a mechanism by which a static length change of the outer hair cells can sensitively tune the signal transmitted to the sensory inner hair cells. When the outer hair cells are in an elongated state, stimulation of inner hair cells is largely inhibited, whereas outer hair cell contraction leads to a substantial enhancement of sound-evoked motion near the hair bundles. This novel mechanism for regulating the sensitivity of the hearing organ applies to the low frequencies that are most important for the perception of speech and music. We suggest that the proposed mechanism might underlie frequency discrimination at low auditory frequencies, as well as our ability to selectively attend auditory signals in noisy surroundings.
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| 11. |
- Dash-Wagh, Suvarna, et al.
(författare)
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Intracellular Delivery of Short Interfering RNA in Rat Organ of Corti Using a Cell-penetrating Peptide PepFect6
- 2012
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Ingår i: Molecular Therapy Nucleic Acids. - : Elsevier BV. - 2162-2531. ; 1:e61
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Tidskriftsartikel (refereegranskat)abstract
- RNA interference (RNAi) using short interfering RNA (siRNA) is an attractive therapeutic approach for treatment of dominant-negative mutations. Some rare missense dominant-negative mutations lead to congenital-hearing impairments. A variety of viral vectors have been tested with variable efficacy for modulating gene expression in inner ear. However, there is concern regarding their safety for clinical use. Here, we report a novel cell-penetrating peptide (CPP)-based nonviral approach for delivering siRNA into inner ear tissue using organotypic cultures as model system. PepFect6 (PF6), a variant of stearyl-TP10, was specially designed for improved delivery of siRNA by facilitating endosomal release. We show that PF6 was internalized by all cells without inducing cytotoxicity in cochlear cultures. PF6/siRNA nanoparticles lead to knockdown of target genes, a housekeeping gene and supporting cell-specific connexin 26. Interestingly, application of PF6/connexin 26 siRNA exhibited knockdown of both connexin 26 and 30 mRNA and their absence led to impaired intercellular communication as demonstrated by reduced transfer of calcein among the PF6/connexin 26-siRNA-treated cells. Thus, we conclude that PF6 is an efficient nonviral vector for delivery of siRNA, which can be applied as a tool for the development of siRNA-based therapeutic applications for hearing impairments.
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| 12. |
- Duan, Maoli, et al.
(författare)
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Imaging of the guinea pig cochlea following round window gadolinium application
- 2004
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Ingår i: NeuroReport. - : Wolters Kluwer. - 0959-4965 .- 1473-558X. ; 15:12, s. 1927-1930
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Tidskriftsartikel (refereegranskat)abstract
- Precise, non-invasive determination of the aetiology and site of pathology of inner ear disorders is difficult. The aim of this study was to describe an alternative method for inner ear visualization, based on local application of the paramagnetic contrast agent gadolinium. Using a 4.7 T MRI scanner, high contrast images of all four cochlear turns were obtained 3.5 h after placing gadolinium on the round window membrane. Gadolinium cleared from the cochlea within 96 h. Auditory brainstem response measurements performed on a separate group of animals showed no significant threshold shifts after the application, indicating that gadolinium is non-toxic to the guinea pig cochlea.
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| 13. |
- Felix, Richard A, et al.
(författare)
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Sound rhythms are encoded by postinhibitory rebound spiking in the superior paraolivary nucleus
- 2011
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 31:35, s. 12566-12578
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Tidskriftsartikel (refereegranskat)abstract
- The superior paraolivary nucleus (SPON) is a prominent structure in the auditory brainstem. In contrast to the principal superior olivary nuclei with identified roles in processing binaural sound localization cues, the role of the SPON in hearing is not well understood. A combined in vitro and in vivo approach was used to investigate the cellular properties of SPON neurons in the mouse. Patch-clamp recordings in brain slices revealed that brief and well timed postinhibitory rebound spiking, generated by the interaction of two subthreshold-activated ion currents, is a hallmark of SPON neurons. The I(h) current determines the timing of the rebound, whereas the T-type Ca(2+) current boosts the rebound to spike threshold. This precisely timed rebound spiking provides a physiological explanation for the sensitivity of SPON neurons to sinusoidally amplitude-modulated (SAM) tones in vivo, where peaks in the sound envelope drive inhibitory inputs and SPON neurons fire action potentials during the waveform troughs. Consistent with this notion, SPON neurons display intrinsic tuning to frequency-modulated sinusoidal currents (1-15Hz) in vitro and discharge with strong synchrony to SAMs with modulation frequencies between 1 and 20 Hz in vivo. The results of this study suggest that the SPON is particularly well suited to encode rhythmic sound patterns. Such temporal periodicity information is likely important for detection of communication cues, such as the acoustic envelopes of animal vocalizations and speech signals.
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| 14. |
- Flock, Å., et al.
(författare)
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Methods for integrating fluorimetry in the study of hearing organ structure and function
- 1997
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Ingår i: Hearing Research. - : Elsevier. - 0378-5955 .- 1878-5891. ; 106:1-2, s. 29-38
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Tidskriftsartikel (refereegranskat)abstract
- The measurement of function in the intact organ of Corti has up to now been achieved by three methods: electrophysiology, mechanical measurement and biochemical analysis. The two former methods have supplied information at the level of single identified cells. We have used a fourth method, optical fluorimetry, to measure hair cell function at the cellular level in the intact organ of Corti. Here we describe the methods involved in fluorescence labelling and video-enhanced microscopy in combination with electrophysiological recording of cochlear microphonic (CM) and summating potentials (SP). The guinea pig temporal bone containing an intact ear drum, ossicular chain and cochlea can be maintained in the isolated state by perfusion of the scala tympani with oxygenated tissue culture medium. Substances added to the perfusate readily diffuse through the basilar membrane into the organ of Corti. In this way cells in the organ can be stained by a number of fluorescent probes which label different structures and functions. Here we have used two dyes which label mitochondria and fluoresce with an intensity proportional to metabolic activity. By simultaneous measurement of CM and SP the functional state of the organ can be monitored.
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| 15. |
- Flock, Å., et al.
(författare)
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Supporting cells contribute to control of hearing sensitivity
- 1999
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Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 19:11, s. 4498-4507
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Tidskriftsartikel (refereegranskat)abstract
- The mammalian hearing organ, the organ of Corti, was studied in an in vitro preparation of the guinea pig temporal bone. As in vivo, the hearing organ responded with an electrical potential, the cochlear microphonic potential, when stimulated with a test tone. After exposure to intense sound, the response to the test tone was reduced. The electrical response either recovered within 10-20 min or remained permanently reduced, thus corresponding to a temporary or sustained loss of sensitivity. Using laser scanning confocal microscopy, stimulus-induced changes of the cellular structure of the hearing organ were simultaneously studied. The cells in the organ were labeled with two fluorescent probes, a membrane dye and a cytoplasm dye, showing enzymatic activity in living cells. Confocal microscopy images were collected and compared before and after intense sound exposure. The results were as follows. (1) The organ of Corti could be divided into two different structural entities in terms of their susceptibility to damage: an inner, structurally stable region comprised of the inner hair cell with its supporting cells and the inner and outer pillar cells; and an outer region that exhibited dynamic structural changes and consisted of the outer hair cells and the third Deiters' cell with its attached Hensen's cells. (2) Exposure to intense sound caused the Deiters' cells and Hensen's cells to move in toward the center of the cochlear turn. (3) This event coincided with a reduced sensitivity to the test tone (i.e., reduced cochlear microphonic potential). (4) The displacement and sensitivity loss could be reversible. It is concluded that these observations have relevance for understanding the mechanisms behind hearing loss after noise exposure and that the supporting cells take an active part in protection against trauma during high-intensity sound exposure.
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| 16. |
- Fridberger, Anders, 1966-, et al.
(författare)
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Acoustic overstimulation increases outer hair cell Ca2+ concentrations and causes dynamic contractions of the hearing organ
- 1998
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 95:12, s. 7127-7132
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Tidskriftsartikel (refereegranskat)abstract
- The dynamic responses of the hearing organ to acoustic overstimulation were investigated using the guinea pig isolated temporal bone preparation. The organ was loaded with the fluorescent Ca2+ indicator Fluo-3, and the cochlear electric responses to low-level tones were recorded through a microelectrode in the scala media. After overstimulation, the amplitude of the cochlear potentials decreased significantly. In some cases, rapid recovery was seen with the potentials returning to their initial amplitude. In 12 of 14 cases in which overstimulation gave a decrease in the cochlear responses, significant elevations of the cytoplasmic [Ca2+] in the outer hair cells were seen. [Ca2+] increases appeared immediately after terminating the overstimulation, with partial recovery taking place in the ensuing 30 min in some preparations. Such [Ca2+] changes were not seen in preparations that were stimulated at levels that did not cause an amplitude change in the cochlear potentials. The overstimulation also gave rise to a contraction, evident as a decrease of the width of the organ of Corti. The average contraction in 10 preparations was 9 microm (SE 2 microm). Partial or complete recovery was seen within 30-45 min after the overstimulation. The [Ca2+] changes and the contraction are likely to produce major functional alterations and consequently are suggested to be a factor contributing strongly to the loss of function seen after exposure to loud sounds.
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| 17. |
- Fridberger, Anders, 1966-, et al.
(författare)
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Acute mechanical overstimulation of isolated outer hair cells causes changes in intracellular calcium levels without shape changes
- 1996
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Ingår i: Acta Oto-Laryngologica. - : Informa Healthcare. - 0001-6489 .- 1651-2251. ; 116:1, s. 17-24
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Tidskriftsartikel (refereegranskat)abstract
- Impaired auditory function following acoustic overstimulation, or noise, is mainly reported to be accompanied by cellular changes such as damage to the sensory hair bundles, but changes in the cell bodies of the outer hair cells have also been described. To investigate more closely the immediate cellular responses to overstimulation, isolated guinea pig outer hair cells were subjected to a 200 Hz oscillating water jet producing intense mechanical stimulation. The water jet was aimed at the cell body of the isolated outer hair cell. Cell shape changes were studied using video microscopy, and intracellular calcium concentration changes were monitored by means of the fluorescent calcium indicator Fluo-3. Cells exposed to a high-intensity stimulus showed surprisingly small light-microscopical alterations. The cytoplasmic calcium concentration increased in most cells, although some cells appeared very resistant to the mechanical stress. No correlation could be found be tween the calcium concentration changes and the cell length. The changes in calcium concentration reported here are suggested to be involved in the long-term pathogenesis of noise-induced hair cell damage.
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| 18. |
- Fridberger, Anders, 1966-, et al.
(författare)
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Alterations of basilar membrane response phase and velocity after acoustic overstimulation
- 2002
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Ingår i: Hearing Research. - : Elsevier. - 0378-5955 .- 1878-5891. ; 167:1-2, s. 214-222
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the physiology of noise-induced hearing loss, the sound-induced vibrations of the basilar membrane (BM) of the inner ear were measured in living anesthetized guinea pigs before and after intense sound exposure. The vibrations were measured using a laser Doppler velocimeter after placing reflective glass beads on the BM. Pseudo-random noise waveforms containing frequencies between 4 and 24 kHz were used to generate velocity tuning curves. Before overstimulation, sharp response peaks were seen at stimulus frequencies between 15 and 17 kHz, consistent with the expected best frequency of the recording location. The response to low level stimuli lagged the high level ones by up to 90 degrees at the characteristic frequency. Following exposure to loud sound, the BM vibrations showed a pronounced reduction in amplitude, primarily at low stimulus levels, and the best frequency moved to approximately 12 kHz. At higher levels, the reduction was either absent or much smaller. In addition to the amplitude changes, increased phase lags were seen at frequencies near the characteristic frequency. In animals with more severe exposures, response phases were altered also at frequencies showing no change of the amplitude. The phase was independent of stimulus level after severe exposures.
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| 19. |
- Fridberger, Anders, 1966-, et al.
(författare)
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An in vitro model for acoustic overstimulation
- 1998
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Ingår i: Acta Oto-Laryngologica. - : Informa Healthcare. - 0001-6489 .- 1651-2251. ; 118:3, s. 352-361
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Tidskriftsartikel (refereegranskat)abstract
- Although many studies have been performed on the effects of acoustic overstimulation on the inner ear, our knowledge about the cellular processes underlying reduced hearing sensitivity and auditory cell death is still limited. In order to further our understanding of cellular processes occurring in conjunction with acoustic trauma, we designed an in vitro model to study the effects of overstimulation directly on sensory hair cells isolated from the low-frequency part of the guinea pig cochlea. The isolated outer hair cells were subjected to pressure jets delivered by a glass micropipette positioned close to the cell, in order to mimic the pressure changes occurring in the intact inner ear during sound stimulation. A second micropipette coupled to a piezoresistive pressure transducer was used as a probe measuring the pressure at precise locations at and around the cell. In a previous study, we found that such stimulation gave rise to increases in the intracellular calcium concentration. The present study characterizes the stimulus, describes the computer-controlled setup used for calibration, and gives examples of different modes of overstimulation at the cellular level. The peak pressure that could be generated using the pressure jet was around 325 Pa, or 144 dB (re 20 microPa) at 140 Hz. The pressure jet elicited large mechanical vibrations of the cell bodies of isolated cells. The vibration mode of the cells often changed over time, implying that the stimulation caused changes of the cellular stiffness. However, most cells appeared quite resistant to the high intensity mechanical stimulation.
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| 20. |
- Fridberger, Anders
(författare)
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Hair cell and organ of corti responses to normal and intense acoustic stimulation
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The principal aims of the studies described in this thesis were to develop an in vitro model for studying acoustic overstimulation at the cellular level, to define the electrical and mechanical response characteristics of the perfused temporal bone preparation, and to investigate the effects of intense sound stimulation on the calcium levels of the hair cells in the intact hearing organ. In the in vitro model for acoustic overstimulation, isolated cochlear outer hair cells were subjected to a pressure jet emanating from a glass micropipette aimed at the cell body. The pressure jet was generated by the vibrating shaft of a minishaker, hydraulically coupled to the micropipette. Such stimulation was found to cause increases of the cytoplasmic calcium concentration in most auditory sensory cells. The calcium changes were sustained, and no evidence of recovery of the elevated levels were seen after the termination of the stimulus. A system was also developed to measure the pressures delivered to the cells. This system was based on a piezoresistive pressure transducer connected to a glass micropipette brought into the immediate vicinity of cells subjected to the pressure jet, allowing highly localized pressure changes to be measured. The peak pressure that could be generated by the stimulus system was found to be 144 dB SPL. Taking the middle ear transfer function into account, this level would correspond to approximately 120 dB SPL at the tympanic membrane during normal sound stimulation. Using laser heterodyne interferometry, the sound-induced vibrations of the low-frequency regions of the inner ear were investigated. The responses of the perfused isolated temporal bone preparation was found to be similar to that of living animals, both in terms of sharpness of tuning and the presence of nonlinearities. These characteristics were also reflected in the extracellularly recorded receptor potentials of the hair cells. The mechanical and electrical responses of the low-frequency regions of the cochlea were substantially different from the high-frequency regions, however. Methods were developed to load the organ of Corti with fluorescent dyes and to measure the fluorescence after various experimental manipulations, using video-enhanced microscopy. The fluorescence images were further processed off-line, using a computerized algorithm, to remove out-of-focus information. When the isolated temporal bone preparation was subjected to acoustic overstimulation, large increases of the calcium concentration of the outer hair cells were seen. In addition, overstimulation caused contractions of the hearing organ that were reversible after the termination of the stimulus. Both the calcium changes and the contraction response could be expected to have severe effects on the function of the inner ear.
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| 21. |
- Fridberger, Anders, 1966-, et al.
(författare)
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Imaging hair cell transduction at the speed of sound : dynamic behavior of mammalian stereocilia
- 2006
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 103:6, s. 1918-1923
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Tidskriftsartikel (refereegranskat)abstract
- The cochlea contains two types of sensory cells, the inner and outer hair cells. Sound-evoked deflection of outer hair cell stereocilia leads to fast force production that will enhance auditory sensitivity up to 1,000-fold. In contrast, inner hair cells are thought to have a purely receptive function. Deflection of their stereocilia produces receptor potentials, transmitter release, and action potentials in the auditory nerve. Here, we describe a method for rapid confocal imaging. The method was used to image stereocilia during simultaneous sound stimulation in an in vitro preparation of the guinea pig cochlea. We show that inner hair cell stereocilia move because they interact with the fluid surrounding the hair bundles, but stereocilia deflection occurs at a different phase of the stimulus than is generally expected. In outer hair cells, stereocilia deflections were approximately 1/3 of the reticular lamina displacement. Smaller deflections were found in inner hair cells. The ratio between stereocilia deflection and reticular lamina displacement is important for auditory function, because it determines the stimulus applied to transduction channels. The low ratio measured here suggests that amplification of hair-bundle movements may be necessary in vivo to preserve transduction fidelity at low stimulus levels. In the case of the inner hair cells, this finding would represent a departure from traditional views on their function.
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| 22. |
- Fridberger, Anders, 1966-, et al.
(författare)
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Internal shearing within the hearing organ evoked by basilar membrane motion
- 2002
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Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 22:22, s. 9850-9857
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Tidskriftsartikel (refereegranskat)abstract
- The vibration of the hearing organ that occurs during sound stimulation is based on mechanical interactions between different cellular structures inside the organ of Corti. The exact nature of these interactions is unclear and subject to debate. In this study, dynamic structural changes were produced by stepwise alterations of scala tympani pressure in an in vitro preparation of the guinea pig temporal bone. Confocal images were acquired at each level of pressure. In this way, the motion of several structures could be observed simultaneously with high resolution in a nearly intact system. Images were analyzed using a novel wavelet-based optical flow estimation algorithm. Under these conditions, the reticular lamina moved as a stiff plate with a center of rotation in the region of the inner hair cells. Despite being enclosed in several types of supporting cells, the inner hair cells, together with the adjacent inner pillar cells, moved in a manner signifying high compliance. The outer hair cells displayed radial motion indicative of cellular bending. Together, these results show that shearing motion occurs between several parts of the organ, and that structural relationships within the organ change dynamically during displacement of the basilar membrane.
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| 23. |
- Fridberger, Anders, 1966-, et al.
(författare)
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Local mechanical stimulation of the hearing organ by laser irradiation
- 2006
-
Ingår i: NeuroReport. - : Ovid Technologies (Wolters Kluwer Health). - 0959-4965 .- 1473-558X. ; 17:1, s. 33-37
-
Tidskriftsartikel (refereegranskat)abstract
- Light produces force when interacting with matter. Such radiation pressure may be used to accelerate small objects along the beam path of a laser. Here, we demonstrate that a moderately powerful laser can deliver enough force to locally stimulate the hearing organ, in the absence of conventional sound. Damped mechanical oscillations are observed following brief laser pulses, implying that the organ of Corti is locally resonant. This new method will be helpful for probing the mechanical properties of the hearing organ, which have crucial importance for the ear's ability to detect sound.
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| 24. |
- Fridberger, Anders, 1966-, et al.
(författare)
-
Loud sound-induced changes in cochlear mechanics
- 2002
-
Ingår i: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 88:5, s. 2341-2348
-
Tidskriftsartikel (refereegranskat)abstract
- To investigate the inner ear response to intense sound and the mechanisms behind temporary threshold shifts, anesthetized guinea pigs were exposed to tones at 100-112 dB SPL. Basilar membrane vibration was measured using laser velocimetry, and the cochlear microphonic potential, compound action potential of the auditory nerve, and local electric AC potentials in the organ of Corti were used as additional indicators of cochlear function. After exposure to a 12-kHz intense tone, basilar membrane vibrations in response to probe tones at the characteristic frequency of the recording location (17 kHz) were transiently reduced. This reduction recovered over the course of 50 ms in most cases. Organ of Corti AC potentials were also reduced and recovered with a time course similar to the basilar membrane. When using a probe tone at either 1 or 4 kHz, organ of Corti AC potentials were unaffected by loud sound, indicating that transducer channels remained intact. In most experiments, both the basilar membrane and the cochlear microphonic response to the 12-kHz overstimulation was constant throughout the duration of the intense stimulus, despite a large loss of cochlear sensitivity. It is concluded that the reduction of basilar membrane velocity that followed loud sound was caused by changes in cochlear amplification and that the cochlear response to intense stimulation is determined by the passive mechanical properties of the inner ear structures.
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| 25. |
- Fridberger, Anders, 1966-, et al.
(författare)
-
Measuring hearing organ vibration patterns with confocal microscopy and optical flow
- 2004
-
Ingår i: Biophysical Journal. - : Cell Press. - 0006-3495 .- 1542-0086. ; 86:1, s. 535-543
-
Tidskriftsartikel (refereegranskat)abstract
- A new method for visualizing vibrating structures is described. The system provides a means to capture very fast repeating events by relatively minor modi. cations to a standard confocal microscope. An acousto-optic modulator was inserted in the beam path, generating brief pulses of laser light. Images were formed by summing consecutive frames until every pixel of the resulting image had been exposed to a laser pulse. Images were analyzed using a new method for optical flow computation; it was validated through introducing artificial displacements in confocal images. Displacements in the range of 0.8 to 4 pixels were measured with 5% error or better. The lower limit for reliable motion detection was 20% of the pixel size. These methods were used for investigating the motion pattern of the vibrating hearing organ. In contrast to standard theory, we show that the organ of Corti possesses several degrees of freedom during sound-evoked vibration. Outer hair cells showed motion indicative of deformation. After acoustic overstimulation, supporting cells contracted. This slowly developing structural change was visualized during simultaneous intense sound stimulation and its speed measured with the optical flow technique.
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| 26. |
- Fridberger, Anders, 1966-, et al.
(författare)
-
Organ of Corti potentials and the motion of the basilar membrane
- 2004
-
Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 24:45, s. 10057-10063
-
Tidskriftsartikel (refereegranskat)abstract
- During sound stimulation, receptor potentials are generated within the sensory hair cells of the cochlea. Prevailing theory states that outer hair cells use the potential-sensitive motor protein prestin to convert receptor potentials into fast alterations of cellular length or stiffness that boost hearing sensitivity almost 1000-fold. However, receptor potentials are attenuated by the filter formed by the capacitance and resistance of the membrane of the cell. This attenuation would limit cellular motility at high stimulus frequencies, rendering the above scheme ineffective. Therefore, Dallos and Evans (1995a) proposed that extracellular potential changes within the organ of Corti could drive cellular motor proteins. These extracellular potentials are not filtered by the membrane. To test this theory, both electric potentials inside the organ of Corti and basilar membrane vibration were measured in response to acoustic stimulation. Vibrations were measured at sites very close to those interrogated by the recording electrode using laser interferometry. Close comparison of the measured electrical and mechanical tuning curves and time waveforms and their phase relationships revealed that those extracellular potentials indeed could drive outer hair cell motors. However, to achieve the sharp frequency tuning that characterizes the basilar membrane, additional mechanical processing must occur inside the organ of Corti.
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| 27. |
- Fridberger, Anders, 1966-, et al.
(författare)
-
Pressure-induced basilar membrane position shifts and the stimulus-evoked potentials in the low-frequency region of the guinea pig cochlea
- 1997
-
Ingår i: Acta Physiologica Scandinavica. - 0001-6772 .- 1365-201X. ; 161:2, s. 239-252
-
Tidskriftsartikel (refereegranskat)abstract
- We have used the guinea pig isolated temporal bone preparation to investigate changes in the non-linear properties of the tone-evoked cochlear potentials during reversible step displacements of the basilar membrane towards either the scala tympani or the scala vestibuli. The position shifts were produced by changing the hydrostatic pressure in the scala tympani. The pressures involved were calculated from measurements of the fluid flow through the system, and the cochlear DC impedance calculated (1.5 x 10(11) kg m-4 s-1, n = 10). Confocal microscopic visualization of the organ of Corti showed that pressure increases in the scala tympani caused alterations of the position of the reticular lamina and stereocilia bundles. For low pressures, there was a sigmoidal relation between the DC pressure applied to the scala tympani (and thus the position shift of the organ of Corti) and the amplitude of the summating potential. The cochlear microphonic potential also showed a pronounced dependence on the applied pressure: pressure changes altered the amplitude of the fundamental as well as its harmonics. In addition, the sound pressure level at which the responses began to saturate was increased, implying a transition towards a linear behaviour. An increase of the phase lag of the cochlear microphonic potential was seen when the basilar membrane was shifted towards the scala vestibuli. We have also measured the intracochlear DC pressure using piezoresistive pressure transducers. The results are discussed in terms of changes in the non-linear properties of cochlear transduction. In addition, the implications of these results for the pathophysiology and diagnosis of Meniérè's disease are discussed.
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| 28. |
- Fridberger, Anders, 1966-, et al.
(författare)
-
Sound-induced differential motion within the hearing organ
- 2003
-
Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 6:5, s. 446-448
-
Tidskriftsartikel (refereegranskat)abstract
- Hearing depends on the transformation of sound-induced basilar membrane vibration into deflection of stereocilia1 on the sensory hair cells, but the nature of these mechanical transformations is unclear. Using new techniques to visualize and measure sound-induced vibration deep inside the moving organ of Corti, we found that two functionally crucial structures, the basilar membrane and the reticular lamina, have different centers of rotation, leading to shearing motion and rapid deformation for the mechanoreceptive outer hair cells. Structural relations within the organ of Corti are much more dynamic than previously thought, which clarifies how outer hair cell molecular motors can have such a powerful effect.
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| 29. |
- Fridberger, Anders, 1966-, et al.
(författare)
-
Three-dimensional structure of outer hair cell pillars
- 2009
-
Ingår i: Acta Oto-Laryngologica. - : Informa Healthcare. - 0001-6489 .- 1651-2251. ; 129:9, s. 940-945
-
Tidskriftsartikel (refereegranskat)abstract
- Conclusions. Electron tomography was used to generate three-dimensional reconstructions of the pillars that connect the cell membrane with the cytoskeleton of the outer hair cell. Results are consistent with the hypothesis that pillars are important for mechanically linking the membrane with the cytoskeleton.Objective: To make a qualitative assessment of the morphology of the sub-membrane pillars of cochlear outer hair cells.Materials and methods. Guinea pig cochleae were fixed and prepared for electron microscopy using protocols described previously. Sections were imaged on an electron microscope equipped with a goniometer. The specimens were tilted through a range of 120°, and an image was acquired at each tilt angle. Filtered back-projection was used to generate three-dimensional reconstructions.Results. Twelve individual pillars were successfully reconstructed. Pillars often connect to the cell membrane through a thin segment, and to the cytoskeleton through a forking structure that may form a central cavity.
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| 30. |
- Fridberger, Anders, et al.
(författare)
-
What Shapes the Stimulus to the Inner Hair Cell?: A Moderated Discussion
- 2015
-
Ingår i: MECHANICS OF HEARING: PROTEIN TO PERCEPTION. - : AMER INST PHYSICS. - 9780735413504
-
Konferensbidrag (refereegranskat)abstract
- The following is an edited transcript of a recorded discussion session on the topic of "What Shapes the Stimulus to the Inner Hair Cell?". The discussion, moderated by the authors, took place at the 12th International Workshop on the Mechanics of Hearing held at Cape Sounio, Greece, in June 2014. All participants knew that the session was being recorded. In view of both the spontaneous nature of the discussion and the editing, however, this transcript may not represent the considered or final views of the participants, and may not represent a consensus of experts in the field. The reader is advised to consult additional independent publications.
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| 31. |
- Grosh, Karl, et al.
(författare)
-
Light-Induced Basilar Membrane Vibrations in the Sensitive Cochlea
- 2015
-
Ingår i: MECHANICS OF HEARING: PROTEIN TO PERCEPTION. - : AMER INST PHYSICS. - 9780735413504
-
Konferensbidrag (refereegranskat)abstract
- The exceptional sensitivity of mammalian hearing organ is attributed to an outer hair cell-mediated active process, where forces produced by sensory cells boost sound-induced vibrations, making soft sounds audible. This process is thought to be local, with each section of the hearing organ capable of amplifying sound-evoked movement, and nearly instantaneous, since amplification can work for sounds at frequencies up to 100 kHz in some species. To test these precepts, we developed a method for focally stimulating the living hearing organ with light. Light pulses caused intense and highly damped mechanical responses followed by traveling waves that developed with considerable delay. The delayed response was identical to movements evoked by click-like sounds. A physiologically based mathematical model shows that such waves engage the active process, enhancing hearing sensitivity. The experiments and the theoretical analysis show that the active process is neither local nor instantaneous, but requires mechanical waves traveling from the cochlear base toward its apex.
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| 32. |
- Hakizimana, Pierre, et al.
(författare)
-
Effects of salicylate on sound-evoked outer hair cell stereocilia deflections
- 2015
-
Ingår i: Pflügers Archiv. - : Springer Berlin/Heidelberg. - 0031-6768 .- 1432-2013. ; 467:9, s. 2021-2029
-
Tidskriftsartikel (refereegranskat)abstract
- Hearing depends on sound-evoked deflections of the stereocilia that protrude from the sensory hair cells in the inner ear. Although sound provides an important force driving stereocilia, forces generated through mechanically sensitive ion channels and through the motor protein prestin have been shown to influence stereocilia motion in solitary hair cells. While a possible influence of prestin on mechanically sensitive ion channels has not been systematically investigated, a decrease in transducer currents is evident in solitary hair cells when prestin is blocked with salicylate, raising the question of whether a reduced prestin activity or salicylate itself affected the mechanotransduction apparatus. We used two- and three-dimensional time-resolved confocal imaging to visualize outer hair cell stereocilia during sound stimulation in the apical turn of cochlear explant preparations from the guinea pig. Surprisingly, following application of salicylate, outer hair cell stereocilia deflections increased, while cochlear microphonic potentials decreased. However, when prestin activity was altered with the chloride ionophore tributyltin, both the cochlear microphonic potential and the stereocilia deflection amplitude decreased. Neither positive nor negative current stimulation abolished the bundle movements in the presence of salicylate, indicating that the observed effects did not depend on the endocochlear potential. These data suggest that salicylate may alter the mechanical properties of stereocilia, decreasing their bending stiffness.
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| 33. |
- Hakizimana, Pierre, 1976-, et al.
(författare)
-
Inner hair cell stereocilia are embedded in the tectorial membrane
- 2021
-
Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Mammalian hearing depends on sound-evoked displacements of the stereocilia of inner hair cells (IHCs), which cause the endogenous mechanoelectrical transducer channels to conduct inward currents of cations including Ca2+. Due to their presumed lack of contacts with the overlaying tectorial membrane (TM), the putative stimulation mechanism for these stereocilia is by means of the viscous drag of the surrounding endolymph. However, despite numerous efforts to characterize the TM by electron microscopy and other techniques, the exact IHC stereocilia-TM relationship remains elusive. Here we show that Ca2+-rich filamentous structures, that we call Ca2+ ducts, connect the TM to the IHC stereocilia to enable mechanical stimulation by the TM while also ensuring the stereocilia access to TM Ca2+. Our results call for a reassessment of the stimulation mechanism for the IHC stereocilia and the TM role in hearing.
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| 34. |
- Hakizimana, Pierre, et al.
(författare)
-
Sound-induced length changes in outer hair cell stereocilia
- 2012
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 3
-
Tidskriftsartikel (refereegranskat)abstract
- Hearing relies on mechanical stimulation of stereocilia bundles on the sensory cells of the inner ear. When sound hits the ear, each stereocilium pivots about a neck-like taper near their base. More than three decades of research have established that sideways deflection of stereocilia is essential for converting mechanical stimuli into electrical signals. Here we show that mammalian outer hair cell stereocilia not only move sideways but also change length during sound stimulation. Currents that enter stereocilia through mechanically sensitive ion channels control the magnitude of both length changes and bundle deflections in a reciprocal manner: the smaller the length change, the larger is the bundle deflection. Thus, the transduction current is important for maintaining the resting mechanical properties of stereocilia. Hair cell stimulation is most effective when bundles are in a state that ensures minimal length change.
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| 35. |
- Hakizimana, Pierre, et al.
(författare)
-
Sound‐Evoked Length Changes of the Outer Hair Cell Stereocilia Bundle are Modulated by Endocochlear Currents
- 2011
-
Ingår i: WHAT FIRE IS IN MINE EARS: PROGRESS IN AUDITORY BIOMECHANICS: Proceedings of the 11th International Mechanics of Hearing Workshop. - : American Institute of Physics (AIP).
-
Konferensbidrag (refereegranskat)abstract
- The apical surface of vertebrate inner ear sensory cells is characterized by a bundle of giant microvilli commonly known as stereocilia. Stereocilia bend about a neck‐like thinning near their base and more than three decades of research has established that the direction and magnitude of sideways bundle deflection is the basis of the mechanoelectrical signalling that initiates sound perception. Aside from its ability to bend at the neck, the stereocilium is usually considered as a stiff inelastic rod. Here we show that the length of OHC stereocilia changes during sound transduction, demonstrating their axial compliance, and that the magnitude of the length change is modulated by currents that mimic in vivo endocochlear currents. A reciprocal relation between length change and bundle deflection is evident: the smaller the length changes, the larger the bundle deflection.
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| 36. |
- He, Wenxuan, et al.
(författare)
-
An outer hair cell-powered global hydromechanical mechanism for cochlear amplification
- 2022
-
Ingår i: Hearing Research. - : ELSEVIER. - 0378-5955 .- 1878-5891. ; 423
-
Forskningsöversikt (refereegranskat)abstract
- It is a common belief that the mammalian cochlea achieves its exquisite sensitivity, frequency selectiv-ity, and dynamic range through an outer hair cell-based active process, or cochlear amplification. As a sound-induced traveling wave propagates from the cochlear base toward the apex, outer hair cells at a narrow region amplify the low level sound-induced vibration through a local feedback mechanism. This widely accepted theory has been tested by measuring sound-induced sub-nanometer vibrations within the organ of Corti in the sensitive living cochleae using heterodyne low-coherence interferometry and optical coherence tomography. The aim of this short review is to summarize experimental findings on the cochlear active process by the authors group. Our data show that outer hair cells are able to gener-ate substantial forces for driving the cochlear partition at all audible frequencies in vivo. The acoustically induced reticular lamina vibration is larger and more broadly tuned than the basilar membrane vibration. The reticular lamina and basilar membrane vibrate approximately in opposite directions at low frequen-cies and in the same direction at the best frequency. The group delay of the reticular lamina is larger than that of the basilar membrane. The magnitude and phase differences between the reticular lamina and basilar membrane vibration are physiologically vulnerable. These results contradict predictions based on the local feedback mechanism but suggest a global hydromechanical mechanism for cochlear amplifi-cation. This article is part of the Special Issue Outer hair cell Edited by Joseph Santos-Sacchi and Kumar Navaratnam. (c) 2021 Elsevier B.V. All rights reserved.
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| 37. |
- He, Wenxuan, et al.
(författare)
-
Fast reverse propagation of sound in the living cochlea
- 2010
-
Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 98:11, s. 2497-2505
-
Tidskriftsartikel (refereegranskat)abstract
- The auditory sensory organ, the cochlea, not only detects but also generates sounds. Such sounds, otoacoustic emissions, are widely used for diagnosis of hearing disorders and to estimate cochlear nonlinearity. However, the fundamental question of how the otoacoustic emission exits the cochlea remains unanswered. In this study, emissions were provoked by two tones with a constant frequency ratio, and measured as vibrations at the basilar membrane and at the stapes, and as sound pressure in the ear canal. The propagation direction and delay of the emission were determined by measuring the phase difference between basilar membrane and stapes vibrations. These measurements show that cochlea-generated sound arrives at the stapes earlier than at the measured basilar membrane location. Data also show that basilar membrane vibration at the emission frequency is similar to that evoked by external tones. These results conflict with the backward-traveling-wave theory and suggest that at low and intermediate sound levels, the emission exits the cochlea predominantly through the cochlear fluids.
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| 38. |
- He, WX, et al.
(författare)
-
Reverse wave propagation in the cochlea
- 2008
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 105:7, s. 2729-2733
-
Tidskriftsartikel (refereegranskat)abstract
- Otoacoustic emissions, sounds generated by the inner ear, are widely used for diagnosing hearing disorders and studying cochlear mechanics. However, it remains unclear how emissions travel from their generation sites to the cochlear base. The prevailing view is that emissions reach the cochlear base via a backward-traveling wave, a slow-propagating transverse wave, along the cochlear partition. A different view is that emissions propagate to the cochlear base via the cochlear fluids as a compressional wave, a fast longitudinal wave. These theories were experimentally tested in this study by measuring basilar membrane (BM) vibrations at the cubic distortion product (DP) frequency from two longitudinal locations with a laser interferometer. Generation sites of DPs were varied by changing frequencies of primary tones while keeping the frequency ratio constant. Here, we show that BM vibration amplitude and phase at the DP frequency are very similar to responses evoked by external tones. Importantly, the BM vibration phase at a basal location leads that at a more apical location, indicating a traveling wave that propagates in the forward direction. These data are in conflict with the backward- traveling-wave theory but are consistent with the idea that the emission comes out of the cochlea predominantly through compressional waves in the cochlear fluids.
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| 39. |
- He, Wenxuan, et al.
(författare)
-
The reticular lamina and basilar membrane vibrations in the transverse direction in the basal turn of the living gerbil cochlea
- 2022
-
Ingår i: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- The prevailing theory of cochlear function states that outer hair cells amplify sound-induced vibration to improve hearing sensitivity and frequency specificity. Recent micromechanical measurements in the basal turn of gerbil cochleae through the round window have demonstrated that the reticular lamina vibration lags the basilar membrane vibration, and it is physiologically vulnerable not only at the best frequency but also at the low frequencies. These results suggest that outer hair cells from a broad cochlear region enhance hearing sensitivity through a global hydromechanical mechanism. However, the time difference between the reticular lamina and basilar membrane vibration has been thought to result from a systematic measurement error caused by the optical axis non-perpendicular to the cochlear partition. To address this concern, we measured the reticular lamina and basilar membrane vibrations in the transverse direction through an opening in the cochlear lateral wall in this study. Present results show that the phase difference between the reticular lamina and basilar membrane vibration decreases with frequency by similar to 180 degrees from low frequencies to the best frequency, consistent with those measured through the round window. Together with the round-window measurement, the low-coherence interferometry through the cochlear lateral wall demonstrates that the time difference between the reticular lamina and basilar membrane vibration results from the cochlear active processing rather than a measurement error.
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| 40. |
- Jacob, Stefan, et al.
(författare)
-
A digital heterodyne laser interferometer for studying cochlear mechanics
- 2009
-
Ingår i: Journal of Neuroscience Methods. - : Elsevier BV. - 0165-0270 .- 1872-678X. ; 179:2, s. 271-277
-
Tidskriftsartikel (refereegranskat)abstract
- Laser interferometry is the technique of choice for studying the smallest displacements of the hearing organ. For low intensity sound stimulation, these displacements may be below 1 nm. This cannot be reliably measured with other presently available techniques in an intact organ of Corti. In a heterodyne interferometer, light is projected against an object of study and motion of the target along the optical axis causes phase and frequency modulations of the back-reflected light. To recover object motion, the reflected light is made to interfere with a reference beam of artificially altered frequency, producing a beating signal. In conventional interferometers, this carrier signal is demodulated with analog electronics. In this paper, we describe a digital implementation of the technique, using direct carrier sampling. In order to obtain the necessary reference signal for demodulation we introduce an additional third light path. Together, this results in lower noise and reduces the cost of the system.Within the hearing organ, different structures may move in different directions. It is therefore necessary to precisely measure the angle of incidence of the laser light, and to precisely localize the anatomical structure where the measurement is performed. Therefore, the interferometer is integrated with a laser scanning confocal microscope that permits us to map crucial morphometric parameters in each experiment. We provide key construction parameters and a detailed performance characterization. We also show that the system accurately measures the diminutive vibrations present in the apical turn of the cochlea during low-level sound stimulation.
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| 41. |
- Jacob, Stefan, et al.
(författare)
-
Noise-induced alterations in cochlear mechanics, electromotility, and cochlear amplification
- 2013
-
Ingår i: Pflügers Archiv. - : Springer. - 0031-6768 .- 1432-2013. ; 465:6, s. 907-917
-
Tidskriftsartikel (refereegranskat)abstract
- Loud sounds are a common cause of hearing loss. Very intense sounds may result in permanent hearing loss, but lower levels typically cause a transient decrease in auditory sensitivity. Studies have arrived at different conclusions as regards the physiological mechanisms underlying such temporary threshold shifts. Here, we investigated the effect of acoustic overstimulation on the mechanics of the low-frequency areas of the guinea pig cochlea. We demonstrate that brief loud sound exposure results in an increased phase lag and a paradoxical frequency-specific increase of sound-evoked displacement. Despite the increased displacement, electrically evoked motion is reduced. Because electromotility is important for amplifying low-level sounds, this change was associated with a decrease in measures of cochlear amplification. These changes recovered over the course of 30-40 min. Overstimulation also caused an increase in cytoplasmic calcium levels of both hair cells and supporting cells. These data suggest that reduced organ of Corti stiffness contributes to temporary threshold shifts.
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| 42. |
- Jacob, Stefan, et al.
(författare)
-
Rapid confocal imaging for measuring sound-induced motion of the hearing organ in the apical region
- 2007
-
Ingår i: Journal of Biomedical Optics. - : SPIE - International Society for Optical Engineering. - 1083-3668 .- 1560-2281. ; 12:2, s. 021005-1-021005-6
-
Tidskriftsartikel (refereegranskat)abstract
- We describe a novel confocal image acquisition system capable of measuring the sound-evoked motion of the organ of Corti. The hearing organ is imaged with a standard laser scanning confocal microscope during sound stimulation. The exact temporal relation between each image pixel and the sound stimulus is quantified. The motion of the structures under study is obtained by fitting a Fourier series to the time dimension of a continuous sequence of acquired images. Previous versions of this acquisition system used a simple search to find pixels with similar phase values. The Fourier series approach permits substantially faster image acquisition with reduced noise levels and improved motion estimation. The system is validated by imaging various vibrating samples attached to a feedback-controlled piezoelectric translator. When using a rigid sample attached to the translator, the system is capable of measuring motion with peak-to-peak amplitudes smaller than 50 nm with an error below 20% at frequencies between 50 and 600 Hz. Examples of image sequences from the inner ear are given, along with detailed performance characteristics of the method.
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| 43. |
- Jacob, Stefan, et al.
(författare)
-
The endocochlear potential alters cochlear micromechanics
- 2011
-
Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 100:11, s. 2586-2594
-
Tidskriftsartikel (refereegranskat)abstract
- Acoustic stimulation gates mechanically sensitive ion channels in cochlear sensory hair cells. Even in the absence of sound, a fraction of these channels remains open, forming a conductance between hair cells and the adjacent fluid space, scala media. Restoring the lost endogenous polarization of scala media in an in vitro preparation of the whole cochlea depolarizes the hair cell soma. Using both digital laser interferometry and time-resolved confocal imaging, we show that this causes a structural refinement within the organ of Corti that is dependent on the somatic electromotility of the outer hair cells (OHCs). Specifically, the inner part of the reticular lamina up to the second row of OHCs is pulled toward the basilar membrane, whereas the outer part (third row of OHCs and the Hensen's cells) unexpectedly moves in the opposite direction. A similar differentiated response pattern is observed for sound-evoked vibrations: restoration of the endogenous polarization decreases vibrations of the inner part of the reticular lamina and results in up to a 10-fold increase of vibrations of the outer part. We conclude that the endogenous polarization of scala media affects the function of the hearing organ by altering its geometry, mechanical and electrical properties.
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| 44. |
- Neng, Lingling, et al.
(författare)
-
Isolation and culture of endothelial cells, pericytes and perivascular resident macrophage-like melanocytes from the young mouse ear
- 2013
-
Ingår i: Nature Protocols. - : Nature Publishing Group. - 1754-2189 .- 1750-2799. ; 8:4, s. 709-720
-
Tidskriftsartikel (refereegranskat)abstract
- This protocol describes a growth medium-based approach for obtaining cochlear endothelial cells (ECs), pericytes (PCs) and perivascular resident macrophage-like melanocytes (PVM/Ms) from the stria vascularis of mice aged between P10 and P15 (P, postnatal day). The procedure does not involve mechanical or enzymatic digestion of the sample tissue. Explants of stria vascularis, 'mini-chips', are selectively cultured in growth medium, and primary cell lines are obtained in 7-10 d. The method is simple and reliable, and it provides high-quality ECs, PVM/Ms and PCs with a purity >90% after two passages. This protocol is suitable for producing primary culture cells from organs and tissues of small volume and high anatomical complexity, such as the inner ear capillaries. The highly purified primary cell lines enable cell culture-based in vitro modeling of cell-cell interactions, barrier control function and drug action.
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| 45. |
- Nuttall, Alfred L., et al.
(författare)
-
A mechanoelectrical mechanism for detection of sound envelopes in the hearing organ
- 2018
-
Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- To understand speech, the slowly varying outline, or envelope, of the acoustic stimulus is used to distinguish words. A small amount of information about the envelope is sufficient for speech recognition, but the mechanism used by the auditory system to extract the envelope is not known. Several different theories have been proposed, including envelope detection by auditory nerve dendrites as well as various mechanisms involving the sensory hair cells. We used recordings from human and animal inner ears to show that the dominant mechanism for envelope detection is distortion introduced by mechanoelectrical transduction channels. This electrical distortion, which is not apparent in the sound-evoked vibrations of the basilar membrane, tracks the envelope, excites the auditory nerve, and transmits information about the shape of the envelope to the brain.
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| 46. |
- Nuttall, Alfred L, et al.
(författare)
-
Instrumentation for studies of cochlear mechanics : from von Békésy forward
- 2012
-
Ingår i: Hearing Research. - : Elsevier BV. - 0378-5955 .- 1878-5891. ; 293:1-2, s. 3-11
-
Tidskriftsartikel (refereegranskat)abstract
- Georg von Békésy designed the instruments needed for his research. He also created physical models of the cochlea allowing him to manipulate the parameters (such as volume elasticity) that could be involved in controlling traveling waves. This review is about the specific devices that he used to study the motion of the basilar membrane thus allowing the analysis that lead to his Nobel Prize Award. The review moves forward in time mentioning the subsequent use of von Békésy's methods and later technologies important for motion studies of the organ of Corti. Some of the seminal findings and the controversies of cochlear mechanics are mentioned in relation to the technical developments.
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| 47. |
- Pierre, Pernilla Videhult, et al.
(författare)
-
Subjective and Clinically Assessed Hearing Loss; A Cross-Sectional Register-Based Study on a Swedish Population Aged 18 through 50 Years
- 2015
-
Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Questionnaire studies suggest that hearing is declining among young adults. However, few studies have examined the reliability of hearing questionnaires among young adult subjects. This study examined the associations between pure tone audiometrically assessed (PTA) hearing loss and questionnaire responses in young to middle aged adults. Materials and Methods A cross-sectional study using questionnaire and screening PTA (500 through 6000 Hz) data from 15322 Swedish subjects (62% women) aged 18 through 50 years. PTA hearing loss was defined as a hearing threshold above 20 dB in both ears at one or more frequencies. Data were analysed with chi-square tests, nonlinear regression, binary logistic regression, and the generalized estimating equation (GEE) approach. Results The prevalence of PTA hearing loss was 6.0% in men and 2.9% in women (p less than 0.001). Slight hearing impairment was reported by 18.5% of the men and 14.8% of the women (p less than 0.001), whereas 0.5% of men and women reported very impaired hearing. Using multivariate GEE modelling, the odds ratio of PTA hearing loss was 30.4 (95% CI, 12.7-72.9) in men and 36.5 (17.2-77.3) in women reporting very impaired hearing. The corresponding figures in those reporting slightly impaired hearing were 7.06 (5.25-9.49) in men and 8.99 (6.38-12.7) in women. These values depended on the sound stimulus frequency (p = 0.001). The area under the ROC curve was 0.904 (0.892-0.915) in men and 0.886 (0.872-0.900) in women. Conclusions Subjective hearing impairment predicted clinically assessed hearing loss, suggesting that there is cause for concern as regards the future development of hearing in young to middle-aged people.
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| 48. |
- Prasad, Sonal, et al.
(författare)
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Investigating the Role of Radixin in Modulation of Stereocilia Length and Stiffness
- 2018
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Ingår i: TO THE EAR AND BACK AGAIN - ADVANCES IN AUDITORY BIOPHYSICS. - : AMER INST PHYSICS. - 9780735416703
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Konferensbidrag (refereegranskat)abstract
- Mammalian hearing depends on deflection of stereocilia on the sensory outer hair cells of the inner ear. Previous data indicate that the stiffness of outer hair cell stereocilia are actively regulated. The molecular mechanism that regulate the deflection of stereocilia are presently less known. The aim of the study is to investigate the mechanistic pathway that underlie the stiffness modulation of outer hair cell stereocilia. Our hypothesis is that the membrane-cytoskeleton linker protein radixin, which is present at high concentration in stereocilia, could contribute to stiffness regulation. To test this hypothesis, we use the radixin blocker DX-52-1 which binds strongly and specifically to radixin. Time-resolved confocal imaging was used to visualize the sound-evoked motion of stereocilia in a semi-intact preparation of the guinea pig temporal bone. Cochlear microphonic potentials were also measured, using electrodes positioned in scala media. We found that the DX-52-1 inhibitor leads to an increase in stereocilia movements and decline in the amplitude of the cochlear microphonic potential. However, DX-52-1 caused a paradoxical increase in electromotility. These results suggest that radixin has a functionally important regulatory role in the mature inner ear.
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| 49. |
- Prasad, Sonal, 1988-, et al.
(författare)
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Radixin modulates the function of outer hair cell stereocilia
- 2020
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Ingår i: Communications Biology. - : Nature Research. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- The stereocilia of the inner ear sensory cells contain the actin-binding protein radixin, encoded by RDX. Radixin is important for hearing but remains functionally obscure. To determine how radixin influences hearing sensitivity, we used a custom rapid imaging technique to visualize stereocilia motion while measuring electrical potential amplitudes during acoustic stimulation. Radixin inhibition decreased sound-evoked electrical potentials. Other functional measures, including electrically induced sensory cell motility and sound-evoked stereocilia deflections, showed a minor amplitude increase. These unique functional alterations demonstrate radixin as necessary for conversion of sound into electrical signals at acoustic rates. We identified patients with RDX variants with normal hearing at birth who showed rapidly deteriorating hearing during the first months of life. This may be overlooked by newborn hearing screening and explained by multiple disturbances in postnatal sensory cells. We conclude radixin is necessary for ensuring normal conversion of sound to electrical signals in the inner ear.
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| 50. |
- Ramamoorthy, Sripriya, et al.
(författare)
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Filtering of Acoustic Signals within the Hearing Organ
- 2014
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Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 34:27, s. 9051-9058
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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