scholarly journals Activity-dependent regulation of prestin expression in mouse outer hair cells

2015 ◽  
Vol 113 (10) ◽  
pp. 3531-3542 ◽  
Author(s):  
Yohan Song ◽  
Anping Xia ◽  
Hee Yoon Lee ◽  
Rosalie Wang ◽  
Anthony J. Ricci ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Hair Cells ◽  
Information Transfer ◽  
Outer Hair Cell ◽  
Endocochlear Potential ◽  
Outer Hair Cells ◽  
Tectorial Membrane ◽  
Inner Hair Cell ◽  
Activity Dependent

Prestin is a membrane protein necessary for outer hair cell (OHC) electromotility and normal hearing. Its regulatory mechanisms are unknown. Several mouse models of hearing loss demonstrate increased prestin, inspiring us to investigate how hearing loss might feedback onto OHCs. To test whether centrally mediated feedback regulates prestin, we developed a novel model of inner hair cell loss. Injection of diphtheria toxin (DT) into adult CBA mice produced significant loss of inner hair cells without affecting OHCs. Thus, DT-injected mice were deaf because they had no afferent auditory input despite OHCs continuing to receive normal auditory mechanical stimulation and having normal function. Patch-clamp experiments demonstrated no change in OHC prestin, indicating that loss of information transfer centrally did not alter prestin expression. To test whether local mechanical feedback regulates prestin, we used TectaC1509G mice, where the tectorial membrane is malformed and only some OHCs are stimulated. OHCs connected to the tectorial membrane had normal prestin levels, whereas OHCs not connected to the tectorial membrane had elevated prestin levels, supporting an activity-dependent model. To test whether the endocochlear potential was necessary for prestin regulation, we studied TectaC1509G mice at different developmental ages. OHCs not connected to the tectorial membrane had lower than normal prestin levels before the onset of the endocochlear potential and higher than normal prestin levels after the onset of the endocochlear potential. Taken together, these data indicate that OHC prestin levels are regulated through local feedback that requires mechanoelectrical transduction currents. This adaptation may serve to compensate for variations in the local mechanical environment.

scholarly journals MANF supports the inner hair cell synapse and the outer hair cell stereocilia bundle in the cochlea

2021 ◽  
Vol 5 (2) ◽  
pp. e202101068
Author(s):  
Kuu Ikäheimo ◽  
Anni Herranen ◽  
Vilma Iivanainen ◽  
Tuuli Lankinen ◽  
Antti A Aarnisalo ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Er Stress ◽  
Hair Cell ◽  
Hair Cells ◽  
High Frequency ◽  
Outer Hair Cell ◽  
Outer Hair Cells ◽  
Inner Hair Cell ◽  
Age Related ◽  
Er Homeostasis

Failure in the structural maintenance of the hair cell stereocilia bundle and ribbon synapse causes hearing loss. Here, we have studied how ER stress elicits hair cell pathology, using mouse models with inactivation of Manf (mesencephalic astrocyte-derived neurotrophic factor), encoding an ER-homeostasis-promoting protein. From hearing onset, Manf deficiency caused disarray of the outer hair cell stereocilia bundle and reduced cochlear sound amplification capability throughout the tonotopic axis. In high-frequency outer hair cells, the pathology ended in molecular changes in the stereocilia taper region and in strong stereocilia fusion. In high-frequency inner hair cells, Manf deficiency degraded ribbon synapses. The altered phenotype strongly depended on the mouse genetic background. Altogether, the failure in the ER homeostasis maintenance induced early-onset stereociliopathy and synaptopathy and accelerated the effect of genetic causes driving age-related hearing loss. Correspondingly, MANF mutation in a human patient induced severe sensorineural hearing loss from a young age onward. Thus, we present MANF as a novel protein and ER stress as a mechanism that regulate auditory hair cell maintenance in both mice and humans.

scholarly journals Unmyelinated type II afferent neurons report cochlear damage

2015 ◽  
Vol 112 (47) ◽  
pp. 14723-14727 ◽  
Author(s):  
Chang Liu ◽  
Elisabeth Glowatzki ◽  
Paul Albert Fuchs
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Outer Hair Cell ◽  
Cell Damage ◽  
Large Diameter ◽  
Outer Hair Cells ◽  
Type I ◽  
Type Ii ◽  
Inner Hair Cell ◽  
Hair Cell Damage

In the mammalian cochlea, acoustic information is carried to the brain by the predominant (95%) large-diameter, myelinated type I afferents, each of which is postsynaptic to a single inner hair cell. The remaining thin, unmyelinated type II afferents extend hundreds of microns along the cochlear duct to contact many outer hair cells. Despite this extensive arbor, type II afferents are weakly activated by outer hair cell transmitter release and are insensitive to sound. Intriguingly, type II afferents remain intact in damaged regions of the cochlea. Here, we show that type II afferents are activated when outer hair cells are damaged. This response depends on both ionotropic (P2X) and metabotropic (P2Y) purinergic receptors, binding ATP released from nearby supporting cells in response to hair cell damage. Selective activation of P2Y receptors increased type II afferent excitability by the closure of KCNQ-type potassium channels, a potential mechanism for the painful hypersensitivity (that we term “noxacusis” to distinguish from hyperacusis without pain) that can accompany hearing loss. Exposure to the KCNQ channel activator retigabine suppressed the type II fiber’s response to hair cell damage. Type II afferents may be the cochlea’s nociceptors, prompting avoidance of further damage to the irreparable inner ear.

scholarly journals Inner Hair Cell and Neuron Degeneration Contribute to Hearing Loss in a Dfna2-Like Mouse Model

2018 ◽  
Author(s):  
Camila Carignano ◽  
Esteban Pablo Barila ◽  
Ezequiel Ignacio Rías ◽  
Leonardo Dionisio ◽  
Eugenio Aztiria ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Hair Cells ◽  
Spiral Ganglion ◽  
Outer Hair Cells ◽  
Ganglion Neuron ◽  
Spiral Ganglion Neuron ◽  
Inner Hair Cell ◽  
Neuron Degeneration ◽  
Knock Out

HIGHLIGHTSKCNQ4 knock-out mouse shows hair cells and spiral ganglion neuron degeneration.Inner hair cells and spiral ganglion neuron loss begin 30 weeks later than outer hair cells in Kcnq4-/- mice.Inner hair cell loss kinetic is faster than that of outer hair cells in cochlear basal turn in Kcnq4-/-.Outer hair cells from Kcnq4-/- mice degenerate slower in apical than in basal turn.Kcnq4 knock-out allele expressed in C3H/HeJ strain reproduces the two phases of DFNA2 hearing loss.GRAPHICAL ABSTRACT

Psychophysical Tuning Curves in Subjects with Tinnitus Suggest Outer Hair Cell Lesions

1995 ◽  
Vol 113 (3) ◽  
pp. 223-233 ◽  
Author(s):  
Curtin R. Mitchell ◽  
Thomas A. Creedon
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Hair Cells ◽  
Outer Hair Cell ◽  
Tuning Curve ◽  
Control Design ◽  
Nerve Fibers ◽  
Outer Hair Cells ◽  
Tuning Curves ◽  
Hearing Thresholds

A study by Penner (J Speech Hear Res 1980;23:779–86) found evidence for Impaired lateral suppression in subjects with tinnitus and sensorineural hearing loss. If lateral suppression is related to tuning curve sharpness and lateral suppression is impaired, the shape of the tuning curve should be affected. The purpose of this study was to determine whether subjects with tinnitus have psychophysical tuning curves that are different from those of subjects without tinnitus. Psychophysical tuning curves and hearing thresholds were obtained from 18 subjects, 7 with tinnitus and 11 without tinnitus. Only subjects with normal audiograms (through 8 kHz) were selected for this study. In subjects with tinnitus psychophysical tuning curves were obtained in the region pitch-matched to their tinnitus. In nontinnitus subjects psychophysical tuning curves were determined at the same frequencies as for the tinnitus subjects in a yoked-control design. The slopes of the tails and tips and the Q10 and other measures were calculated for each tuning curve. The psychophysical tuning curves in subjects with tinnitus were significantly different (0.01 level) from those of control subjects and often had hypersensitive tails and some elevated tips. These shapes of tuning curves are consistent with cochlear lesions involving the loss of outer hair cells without damage to the Inner hair cells or nerve fibers.

scholarly journals Inner hair cell stereocilia are embedded in the tectorial membrane

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pierre Hakizimana ◽  
Anders Fridberger
Keyword(s):  
Electron Microscopy ◽  
Hair Cell ◽  
Mechanical Stimulation ◽  
Hair Cells ◽  
Viscous Drag ◽  
Tectorial Membrane ◽  
Inner Hair Cell ◽  
Inner Hair Cells ◽  
Inward Currents

AbstractMammalian 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.

High-Voltage Electron Microscopic Study of the Inner Ear: Technique and Preliminary Results

1983 ◽  
Vol 92 (1_suppl) ◽  
pp. 3-12 ◽  
Author(s):  
Tomonori Takasaka ◽  
Hideich Shinkawa ◽  
Kozo Watanuki ◽  
Sho Hashimoto ◽  
Kazutomo Kawamoto
Keyword(s):  
Electron Microscopy ◽  
Hair Cell ◽  
Inner Ear ◽  
High Voltage ◽  
Hair Cells ◽  
Outer Hair Cells ◽  
Tectorial Membrane ◽  
Preliminary Results ◽  
Voltage Electron ◽  
Cuticular Plate

The technique and some preliminary results of the application of high-voltage electron microscopy (HVEM) to the study of inner ear morphology in the guinea pig are reported in this paper. The main advantage of HVEM is that sharp images of thicker specimens can be obtained because of the greater penetrating power of high energy electrons. The optimum thickness of the sections examined with an accelerating voltage of 1,000 kV was found to be between 500 to 800 nm. The sections below 500 nm in thickness often had insufficient contrast, while those above 800 nm were rather difficult to interpret due to overlap of images of the organelles. The whole structure of the sensory hairs from the tip to the rootlet was more frequently observed in the 800-nm thick sections. Thus the fine details of the hair attachment to the tectorial membrane as well as the hair rootlet extension into the cuticular plate could be thoroughly studied in the HVEM. In specimens fixed in aldehyde containing 2% tannic acid, the attachment of the tips of the outer hair cell stereocilia to the tectorial membrane was observed. For the inner hair cells, however, the tips of the hairs were separated from the undersurface of the tectorial membrane. The majority of the rootlets of the outer hair cells terminated at the midportion of the cuticular plate, while most of the inner hair cell rootlets traversed the entire width of the cuticular plate and extended into the apical cytoplasm. These differences in ultrastructural appearance may indicate that the two kinds of hair cells play different roles in the acoustic transduction process. The three-dimensional arrangement of the nerve endings on the hair cells was also studied by the serial thick-sectioning technique in the HVEM. In general, an entire arrangement of the nerve endings was almost completely cut in less than ten 800-nm thick sections instead of the 50- to 100-ultrathin (ie, less than 100 nm) conventional sections for transmission electron microscopy. The present study confirms an earlier report that the first row outer hair cells in the third cochlear turn are innervated by nearly equal numbers of efferent and afferent endings, the average number being nine.

Early Evidence of Cochlear Damage in a Large Sample of Percussionists

2005 ◽  
Vol 20 (3) ◽  
pp. 135-139
Author(s):  
Jodee A Pride ◽  
David R Cunningham
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Otoacoustic Emissions ◽  
Outer Hair Cell ◽  
Cell Damage ◽  
Normal Hearing ◽  
Outer Hair Cells ◽  
Sensory Loss ◽  
Distortion Product ◽  
Hair Cell Damage

Percussionists can be exposed to intermittent sound stimuli that exceed 145 dB SPL, although damage may occur to the outer hair cells at levels of 120 dB SPL. The present study measured distortion-product otoacoustic emissions (DPOAEs) in a group of 86 normal-hearing percussionists and 39 normal-hearing nonpercussionists. Results indicate that normal-hearing percussionists have lower DPOAE amplitudes than normal-hearing nonpercussionists. DPOAE amplitudes were significantly lower at 6000 Hz in both the left and right ears for percussionists. Percussionists also more frequently had absent DPOAEs, with the greatest differences occurring at 6000 Hz (absent DPOAEs in 25% of percussionists vs 10% of nonpercussionists). When all frequencies are considered as a group, 33% of the percussionists had an absent DPOAE in either ear at some frequency, compared to only 23% of the nonpercussionists. Otoacoustic emissions are more sensitive to outer hair cell damage than pure-tone threshold measurements and can serve as an important measurement of sensory loss (i.e., outer hair cell damage) in musicians before the person perceives the hearing loss. DPOAE monitoring for musicians, along with appropriate education and intervention, might help prevent or minimize music-induced hearing loss.

scholarly journals Disruption of Hars2 in Cochlear Hair Cells Causes Progressive Mitochondrial Dysfunction and Hearing Loss in Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Pengcheng Xu ◽  
Longhao Wang ◽  
Hu Peng ◽  
Huihui Liu ◽  
Hongchao Liu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Mitochondrial Dysfunction ◽  
Hair Cells ◽  
Cell Loss ◽  
Outer Hair Cells ◽  
Hair Cell Loss ◽  
Progressive Hearing Loss ◽  
Cochlear Hair Cells ◽  
Inner Hair Cells

Mutations in a number of genes encoding mitochondrial aminoacyl-tRNA synthetases lead to non-syndromic and/or syndromic sensorineural hearing loss in humans, while their cellular and physiological pathology in cochlea has rarely been investigated in vivo. In this study, we showed that histidyl-tRNA synthetase HARS2, whose deficiency is associated with Perrault syndrome 2 (PRLTS2), is robustly expressed in postnatal mouse cochlea including the outer and inner hair cells. Targeted knockout of Hars2 in mouse hair cells resulted in delayed onset (P30), rapidly progressive hearing loss similar to the PRLTS2 hearing phenotype. Significant hair cell loss was observed starting from P45 following elevated reactive oxygen species (ROS) level and activated mitochondrial apoptotic pathway. Despite of normal ribbon synapse formation, whole-cell patch clamp of the inner hair cells revealed reduced calcium influx and compromised sustained synaptic exocytosis prior to the hair cell loss at P30, consistent with the decreased supra-threshold wave I amplitudes of the auditory brainstem response. Starting from P14, increasing proportion of morphologically abnormal mitochondria was observed by transmission electron microscope, exhibiting swelling, deformation, loss of cristae and emergence of large intrinsic vacuoles that are associated with mitochondrial dysfunction. Though the mitochondrial abnormalities are more prominent in inner hair cells, it is the outer hair cells suffering more severe cell loss. Taken together, our results suggest that conditional knockout of Hars2 in mouse cochlear hair cells leads to accumulating mitochondrial dysfunction and ROS stress, triggers progressive hearing loss highlighted by hair cell synaptopathy and apoptosis, and is differentially perceived by inner and outer hair cells.

A study of active artificial hair cell models inspired by outer hair cell somatic motility

2016 ◽  
Vol 28 (6) ◽  
pp. 811-823 ◽  
Author(s):  
Bryan S Joyce ◽  
Pablo A Tarazaga
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Outer Hair Cell ◽  
Dynamic Range ◽  
Outer Hair Cells ◽  
Quality Factors ◽  
Control Laws ◽  
Sensor Performance ◽  
Nonlinear Amplification ◽  
Key Aspects

The cochlea displays an important, nonlinear amplification of sound-induced oscillations. In mammals, this amplification is largely powered by the somatic motility of the outer hair cells. The resulting cochlear amplifier has three important characteristics useful for hearing: an amplification of responses from low sound pressures, an improvement in frequency selectivity, and an ability to transduce a broad range of sound pressure levels. These useful features can be incorporated into designs for active artificial hair cells, bio-inspired sensors for use as microphones, accelerometers, or other dynamic sensors. The sensor consists of a cantilever beam with piezoelectric actuators. A feedback controller applies a voltage to the actuators to mimic the outer hair cells’ somatic motility. This article describes three control laws for an active artificial hair cell inspired by models of the outer hair cells’ somatic motility. The first control law is based on a phenomenological model of the cochlea while the second and third models incorporate physiological aspects of the biological cochlea to further improve sensor performance. Simulations show that these models qualitatively reproduce the key aspects of the mammalian cochlea, namely, amplification of oscillations from weak stimuli, higher quality factors, and a wider input dynamic range.

scholarly journals Direct Visualization of Organ of Corti Kinematics in a Hemicochlea

1999 ◽  
Vol 82 (5) ◽  
pp. 2798-2807 ◽  
Author(s):  
Xintian Hu ◽  
Burt N. Evans ◽  
Peter Dallos
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Basilar Membrane ◽  
Mechanical Vibration ◽  
Cell Receptor ◽  
Outer Hair Cells ◽  
Tectorial Membrane ◽  
Low Frequencies ◽  
Geometric Models ◽  
Membrane Vibration

The basilar membrane in the mammalian cochlea vibrates when the cochlea receives a sound stimulus. This mechanical vibration is transduced into hair cell receptor potentials and thereafter encoded by action potentials in the auditory nerve. Knowledge of the mechanical transformation that converts basilar membrane vibration into hair cell stimulation has been limited, until recently, to hypothetical geometric models. Experimental observations are largely lacking to prove or disprove the validity of these models. We have developed a hemicochlea preparation to visualize the kinematics of the cochlear micromechanism. Direct mechanical drive of 1–2 Hz sinusoidal command was applied to the basilar membrane. Vibration patterns of the basilar membrane, inner and outer hair cells, supporting cells, and tectorial membrane have been recorded concurrently by means of a video optical flow technique. Basilar membrane vibration was driven in a direction transversal to its plane. However, the direction of the resulting vibration was found to be essentially radial at the level of the reticular lamina and cuticular plates of inner and outer hair cells. The tectorial membrane vibration was mainly transversal. The transmission ratio between cilia displacement of inner and outer hair cells and basilar membrane vibration is in the range of 0.7–1.1. These observations support, in part, the classical geometric models at low frequencies. However, there appears to be less tectorial membrane motion than predicted, and it is largely in the transversal direction.

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