scholarly journals Immunohistochemistry localises myosin-7a to cochlear efferent boutons

2022 ◽  
Vol 7 ◽  
pp. 1
Author(s):  
Piotr Sirko ◽  
Andrei S. Kozlov
Keyword(s):  
Hearing Loss ◽  
Vestibular System ◽  
Hair Cells ◽  
Usher Syndrome ◽  
Organ Of Corti ◽  
Outer Hair Cells ◽  
Actin Binding ◽  
Adult Rat ◽  
Cochlear Gain ◽  
Medial Olivocochlear

Background: Myosin 7a is an actin-binding motor protein involved in the formation of hair-cell stereocilia both in the cochlea and in the vestibular system. Mutations in myosin 7a are linked to congenital hearing loss and are present in 50% of Type-1 Usher syndrome patients who suffer from progressive hearing loss and vestibular system dysfunction. Methods: Myosin 7a is often used to visualise sensory hair cells due to its well characterised and localised expression profile. We thus conducted myosin-7a immunostaining across all three turns of the adult rat organ of Corti to visualise hair cells. Results: As expected, we observed myosin 7a staining in both inner and outer hair cells. Unexpectedly, we also observed strong myosin 7a staining in the medial olivocochlear efferent synaptic boutons contacting the outer hair cells. Efferent bouton myosin-7a staining was present across all three turns of the cochlea. We verified this localisation by co-staining with a known efferent bouton marker, the vesicular acetylcholine transporter. Conclusions: In addition to its role in stereocilia formation and maintenance, myosin 7a or certain myosin-7a expression variants might play a role in efferent synaptic transmission in the cochlea and thus ultimately influence cochlear gain regulation. Our immunohistochemistry results should be validated with other methods to confirm these serendipitous findings.

scholarly journals Single-unit labeling of medial olivocochlear neurons: the cochlear frequency map for efferent axons

2014 ◽  
Vol 111 (11) ◽  
pp. 2177-2186 ◽  
Author(s):  
M. Christian Brown
Keyword(s):  
Hair Cells ◽  
Single Unit ◽  
Dynamic Range ◽  
Organ Of Corti ◽  
Nerve Fibers ◽  
Outer Hair Cells ◽  
Cochlear Amplifier ◽  
Noise Masking ◽  
Efferent Neurons ◽  
Medial Olivocochlear

Medial olivocochlear (MOC) neurons are efferent neurons that project axons from the brain to the cochlea. Their action on outer hair cells reduces the gain of the “cochlear amplifier,” which shifts the dynamic range of hearing and reduces the effects of noise masking. The MOC effects in one ear can be elicited by sound in that ipsilateral ear or by sound in the contralateral ear. To study how MOC neurons project onto the cochlea to mediate these effects, single-unit labeling in guinea pigs was used to study the mapping of MOC neurons for neurons responsive to ipsilateral sound vs. those responsive to contralateral sound. MOC neurons were sharply tuned to sound frequency with a well-defined characteristic frequency (CF). However, their labeled termination spans in the organ of Corti ranged from narrow to broad, innervating between 14 and 69 outer hair cells per axon in a “patchy” pattern. For units responsive to ipsilateral sound, the midpoint of innervation was mapped according to CF in a relationship generally similar to, but with more variability than, that of auditory-nerve fibers. Thus, based on CF mappings, most of the MOC terminations miss outer hair cells involved in the cochlear amplifier for their CF, which are located more basally. Compared with ipsilaterally responsive neurons, contralaterally responsive neurons had an apical offset in termination and a larger span of innervation (an average of 10.41% cochlear distance), suggesting that when contralateral sound activates the MOC reflex, the actions are different than those for ipsilateral sound.

scholarly journals A Natural Occurring Mouse Model with Adgrv1 Mutation of Usher Syndrome 2C and Characterization of its Recombinant Inbred Strains

2018 ◽  
Vol 47 (5) ◽  
pp. 1883-1897 ◽  
Author(s):  
Weiming Yan ◽  
Pan Long ◽  
Tao Chen ◽  
Wei Liu ◽  
Lu Yao ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Retinal Degeneration ◽  
Western Blotting ◽  
Hair Cells ◽  
Recombinant Inbred ◽  
Usher Syndrome ◽  
Inbred Strains ◽  
Outer Hair Cells ◽  
Recombinant Inbred Strains

Background/Aims: Our laboratory discovered a Kunming mouse with enormous electroretinogram (ERG) defects. Its auditory brainstem response (ABR) threshold was significantly elevated and closely resembled the features of Usher syndrome (USH). This study sought to cross these USH-like mice (named KMush/ush mice) with CBA/CaJ mice to establish recombinant inbred strains and identify their phenotypes and genotypes. Methods: KMush/ush mice were crossed with CBA/CaJ mice to establish inbred strains by sibling mating. ERG, ABR, ocular fundus morphology, histological examinations of the retina and inner ear, quantitative real-time polymerase chain reaction, western blotting, and exon sequencing were performed to assess the phenotypes and genotypes of the offspring strains. Results: The F1 hybrids from crossing KMush/ush and CBA/CaJ mice had normal ERG and ABR responses. The F2 offspring from intercrossing the F1 mice showed a segregation of the retinitis pigmentosa (RP) and hearing loss phenotypes. The CBA-1ush/ush mice had an RP phenotype that was characterized by a vanished ERG waveform and loss of the outer nuclear layer. Their Pde6b gene had a nonsense mutation that resulted in the failure of protein production in western blotting. However, the ABR threshold of this strain of mice was normal. The CBA-2ush/ush mice had normal retinal function and architecture. Their ABR threshold was increased, with a dramatic degeneration of the stereocilia bundles in the outer hair cells of the inner ear. Whole exome sequencing and exon sequencing revealed a deletion of one base pair in exon 31 of the Adgrv1 gene, which would result in the premature termination of protein encoding. The level of Adgrv1 mRNA was reduced in the CBA-2ush/ush mice. The CBA-3ush/ush mice had phenotypes of RP, elevated ABR threshold, and degeneration of the stereocilia bundles in the outer hair cells. They were closely associated with the nonsense mutations of Pde6b and Adgrv1, respectively. Conclusion: We isolated a mouse strain with hearing loss from inbred mice with retinal degeneration and established it as a recombinant inbred strain with a spontaneous mutation in Adgrv1, the human Usher syndrome 2C gene. The retinal degeneration was cause by a mutation in Pde6b, while the hearing loss was caused by a mutation in Adgrv1.

scholarly journals Elmod3 knockout leads to progressive hearing loss and abnormalities in cochlear hair cell stereocilia

2019 ◽  
Vol 28 (24) ◽  
pp. 4103-4112 ◽  
Author(s):  
Wu Li ◽  
Yong Feng ◽  
Anhai Chen ◽  
Taoxi Li ◽  
Sida Huang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Actin Cytoskeleton ◽  
Hearing Impairment ◽  
Hair Cells ◽  
Organ Of Corti ◽  
Vestibular Function ◽  
Outer Hair Cells ◽  
Auditory Function ◽  
Cochlear Hair Cells

Abstract ELMOD3, an ARL2 GTPase-activating protein, is implicated in causing hearing impairment in humans. However, the specific role of ELMOD3 in auditory function is still far from being elucidated. In the present study, we used the CRISPR/Cas9 technology to establish an Elmod3 knockout mice line in the C57BL/6 background (hereinafter referred to as Elmod3−/− mice) and investigated the role of Elmod3 in the cochlea and auditory function. Elmod3−/− mice started to exhibit hearing loss from 2 months of age, and the deafness progressed with aging, while the vestibular function of Elmod3−/− mice was normal. We also observed that Elmod3−/− mice showed thinning and receding hair cells in the organ of Corti and much lower expression of F-actin cytoskeleton in the cochlea compared with wild-type mice. The deafness associated with the mutation may be caused by cochlear hair cells dysfunction, which manifests with shortening and fusion of inner hair cells stereocilia and progressive degeneration of outer hair cells stereocilia. Our finding associates Elmod3 deficiencies with stereocilia dysmorphologies and reveals that they might play roles in the actin cytoskeleton dynamics in cochlear hair cells, and thus relate to hearing impairment.

scholarly journals Preventing presbycusis in mice with enhanced medial olivocochlear feedback

2020 ◽  
Vol 117 (21) ◽  
pp. 11811-11819 ◽  
Author(s):  
Luis E. Boero ◽  
Valeria C. Castagna ◽  
Gonzalo Terreros ◽  
Marcelo J. Moglie ◽  
Sebastián Silva ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Outer Hair Cells ◽  
Auditory Brainstem Responses ◽  
Cochlear Function ◽  
Gain Of Function ◽  
Distortion Product ◽  
Age Related ◽  
Medial Olivocochlear ◽  
Age Related Hearing Loss

“Growing old” is the most common cause of hearing loss. Age-related hearing loss (ARHL) (presbycusis) first affects the ability to understand speech in background noise, even when auditory thresholds in quiet are normal. It has been suggested that cochlear denervation (“synaptopathy”) is an early contributor to age-related auditory decline. In the present work, we characterized age-related cochlear synaptic degeneration and hair cell loss in mice with enhanced α9α10 cholinergic nicotinic receptors gating kinetics (“gain of function” nAChRs). These mediate inhibitory olivocochlear feedback through the activation of associated calcium-gated potassium channels. Cochlear function was assessed via distortion product otoacoustic emissions and auditory brainstem responses. Cochlear structure was characterized in immunolabeled organ of Corti whole mounts using confocal microscopy to quantify hair cells, auditory neurons, presynaptic ribbons, and postsynaptic glutamate receptors. Aged wild-type mice had elevated acoustic thresholds and synaptic loss. Afferent synapses were lost from inner hair cells throughout the aged cochlea, together with some loss of outer hair cells. In contrast, cochlear structure and function were preserved in aged mice with gain-of-function nAChRs that provide enhanced olivocochlear inhibition, suggesting that efferent feedback is important for long-term maintenance of inner ear function. Our work provides evidence that olivocochlear-mediated resistance to presbycusis-ARHL occurs via the α9α10 nAChR complexes on outer hair cells. Thus, enhancement of the medial olivocochlear system could be a viable strategy to prevent age-related hearing loss.

Efferent Components of the Auditory System

1980 ◽  
Vol 89 (5_suppl) ◽  
pp. 114-120 ◽  
Author(s):  
W. Bruce Warr
Keyword(s):  
Axonal Transport ◽  
Hair Cells ◽  
Organ Of Corti ◽  
Outer Hair Cells ◽  
Superior Olivary Complex ◽  
Cell Group ◽  
Efferent Innervation ◽  
Tissue Sections ◽  
Cells Of Origin ◽  
Medial Olivocochlear

The origins and terminations of the olivocochlear bundle, which provides an efferent innervation to the organ of Corti, are described on the basis of experiments using axonal transport of tracer substances and light microscopy in the cat. The cells of origin were labeled by the retrograde tracer horseradish peroxidase which was injected unilaterally into the cochlea. Labeled cells in the superior olivary complex could be dichotomized according to their location (lateral or medial), their size (small or large), and their preferred side of projection (uncrossed or crossed). All labeled olivocochlear neurons exhibited a positive reaction for acetylcholinesterase. To determine the cochlear projections of the neurons, injections of a radioactive amino acid were made into either the lateral or medial olivocochlear cell group. After allowing time for synthesis and axonal transport of radio-labeled protein to reach synaptic endings in the cochleas, the tissue sections of these specimens were processed for autoradiography. The results indicate that lateral olivocochlear neurons project to the region beneath the inner hair cells of both sides, whereas medial olivocochlear neurons project to the region beneath the outer hair cells of both sides. These findings are in substantial accord with previous experimental work but suggest that the organ of Corti receives a dual efferent innervation which is organized according to the location and morphology of its cells of origin. Accordingly, it is proposed that the two efferent components of the cochlear innervation described here be referred to as the lateral and medial olivocochlear systems, replacing the current designations of crossed and uncrossed olivocochlear bundles, the latter which are demonstrably heterogeneous in their origins and terminations and, probably, also in their functions.

Association of Conductive Hearing Loss with the Structural Changes in the Organ of Corti

ORL ◽  
2021 ◽  
pp. 1-8
Author(s):  
Sinan Eroglu ◽  
Rasit Cevizci ◽  
Handan Turan Dizdar ◽  
Hasan Deniz Tansuker ◽  
Erdogan Bulut ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Cell Morphology ◽  
Hair Cells ◽  
Structural Changes ◽  
Organ Of Corti ◽  
Outer Hair Cells ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

<b><i>Objective:</i></b> The aim of the study was to evaluate the association of conductive hearing loss (CHL) with the structural changes in the organ of Corti. <b><i>Methods:</i></b> Twenty ears of 10 healthy adult Wistar albino rats were included in the study. The right ears (<i>n</i> = 10) of the animals served as controls (group 1), and no surgical intervention was performed in these ears. A tympanic membrane perforation without annulus removal was performed under operative microscope on the left ears (<i>n</i> = 5) in 5 of 10 animals (group 2). A tympanic membrane perforation with annulus removal was performed under operative microscope on the left ears (<i>n</i> = 5) of the remaining 5 animals (group 3). Auditory brainstem response testing was performed in the animals before the interventions. After 3 months, the animals were sacrificed, their temporal bones were removed, and inner ears were investigated using scanning electron microscopy (SEM). The organ of Corti was evaluated from the cochlear base to apex in the modiolar axis, and the parameters were scored semiquantitatively. <b><i>Results:</i></b> In group 1, the pre- and post-intervention hearing thresholds were similar (<i>p</i> &#x3e; 0.05). In group 2, a hearing decrease of at least 5 dB was encountered in all test frequencies (<i>p</i> &#x3e; 0.05). In group 3, at the frequency range of 2–32 kHz, there was a significant hearing loss after 3 months (<i>p</i> &#x3c; 0.01). After 3 months, the hearing thresholds in group 2 and 3 were higher than group 1 (<i>p</i> &#x3c; 0.01). The hearing threshold in group 3 was higher than group 2 (<i>p</i> &#x3c; 0.01). On SEM evaluation, the general cell morphology and stereocilia of the outer hair cells were preserved in all segments of the cochlea in group 1 with a mean SEM score of 0.2. There was segmental degeneration in the general cell morphology and outer hair cells in group 2 with a mean SEM score of 2.2. There was widespread degeneration in the general cell morphology and outer hair cells in group 3 with a mean SEM score of 3.2. The SEM scores of group 2 and 3 were significantly higher than group 1 (<i>p</i> &#x3c; 0.05). The SEM scores of group 3 were significantly higher than group 2 (<i>p</i> &#x3c; 0.05). <b><i>Conclusion:</i></b> CHL may be associated with an inner ear damage. The severity of damage appears to be associated with severity and duration of CHL. Early correction of CHL is advocated in order to reverse or prevent progression of the inner ear damage, which will enhance the success rates of hearing restoration surgeries. Subjective differences and compliance of the hearing aid users may be due to the impact of CHL on inner ear structures.

Melatonin and other antioxidants prolong the postmortem activity of the outer hair cells of the organ of Corti: Its relation to the type of death

1999 ◽  
Vol 27 (2) ◽  
pp. 73-77 ◽  
Author(s):  
Miguel A. Lopez-Gonzalez ◽  
Juan M. Guerrero ◽  
Francisco Rojas ◽  
Carmen Osuna ◽  
Francisco Delgado
Keyword(s):  
Hair Cells ◽  
Organ Of Corti ◽  
Outer Hair Cells

Innervation Densities of Inner and Outer Hair Cells of the Human Organ of Corti

ORL ◽  
1988 ◽  
Vol 50 (6) ◽  
pp. 363-370 ◽  
Author(s):  
Joseph B. Nadol, Jr.
Keyword(s):  
Hair Cells ◽  
Organ Of Corti ◽  
Outer Hair Cells ◽  
Human Organ

Outer hair cells in the mammalian cochlea and noise-induced hearing loss

Nature ◽  
1985 ◽  
Vol 315 (6021) ◽  
pp. 662-665 ◽  
Author(s):  
A. R. Cody ◽  
I. J. Russell
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Outer Hair Cells ◽  
Noise Induced Hearing Loss

scholarly journals A detection method for lactic dehydrogenase activity in the inner ear.

1978 ◽  
Vol 26 (4) ◽  
pp. 313-317 ◽  
Author(s):  
T Omata ◽  
I Ohtani ◽  
K Ohtsuki ◽  
J Ouchi
Keyword(s):  
Hair Cells ◽  
Osmium Tetroxide ◽  
Light And Electron Microscopy ◽  
Organ Of Corti ◽  
Lactic Dehydrogenase ◽  
Outer Hair Cells ◽  
Water Soluble ◽  
Reaction Products ◽  
Frozen Sections ◽  
Membranous Labyrinth

A method for the detection of lactic dehydrogenase enzymatic activity in outer hair cells of the rabbit is described. The membranous labyrinth with temporal bone was prefixed in glutaraldehyde. After being placed into the incubation medium, it was postfixed in osmium tetroxide. Specimens of the organ of Corti were removed. Then the specimens were embedded in water-soluble glycol and cut with a cryostat for light microscopy, and also they were embedded in Epon and cut for light and electron microscopy. Sectioning of the membranous labyrinth was very easily made when the specimens were embedded in both the water-soluble glycol and the Epon. The structures of the frozen sections as well as the Epon-embedded ones were well preserved. In the frozen sections the preservation and localization of reaction products were thoroughly kept, but monoformazan of the Epon-embedded sections was soluble.

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