Efferent neurons control hearing sensitivity and protect hearing from noise through the regulation of gap junctions between cochlear supporting cells

2021 ◽  
Author(s):  
Hong-Bo Zhao ◽  
Li-Man Liu ◽  
Ning Yu ◽  
Yan Zhu ◽  
Ling Mei ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Hair Cells ◽  
Nerve Fibers ◽  
Supporting Cells ◽  
Hearing Sensitivity ◽  
Efferent System ◽  
Efferent Pathway ◽  
Cochlear Amplification ◽  
Efferent Neurons ◽  
Cochlear Supporting Cells

It is critical for hearing that the descending cochlear efferent system provide a negative feedback to hair cells to regulate hearing sensitivity and provide the protection of hearing from noise. Here, we report that the medial olivocochlear (MOC) efferent nerves, which project to outer hair cells (OHCs), also could innervate OHC surrounding supporting cells (SCs) to regulate hearing sensitivity. MOC nerve fibers are cholinergic and acetylcholine (ACh) is a primary neurotransmitter. MOC nerve endings, presynaptic vesicular acetylcholine transporters (VAChT), and postsynaptic ACh receptors were visible in SCs and the SC area. Application of ACh in the SC could evoke a typical inward current, which reduced gap junctions (GJs) between SCs and consequently declined OHC electromotility, which is an active cochlear amplification and can increase hearing sensitivity. This indirect, GJ-mediated inhibition enhanced the direct inhibition of ACh on OHC electromotility but had long-lasting influence. In vivo experiments further demonstrated that deficiency of this GJ-mediated efferent pathway declined the regulation of active cochlear amplification and compromised the protection against noise. In particular, distortion production otoacoustic emission (DPOAE) showed a delayed reduction after noise exposure. Our findings reveal a new pathway for the MOC efferent system via innervating SCs to control active cochlear amplification and hearing sensitivity. These data also suggest that this GJ-mediated efferent pathway may play a critical role in the long-term efferent inhibition and is required for protecting hearing from noise trauma.

scholarly journals Efferent control of hearing sensitivity and protection via inner ear supporting cells

2020 ◽  
Author(s):  
Hong-Bo Zhao ◽  
Li-Man Liu ◽  
Ling Mei ◽  
Ning Yu ◽  
Jin Chen ◽  
...  
Keyword(s):  
Hair Cells ◽  
Nerve Fibers ◽  
Dependent Manner ◽  
Supporting Cells ◽  
Noise Trauma ◽  
Hearing Sensitivity ◽  
Efferent System ◽  
Efferent Control ◽  
Cochlear Amplification ◽  
Cochlear Supporting Cells

It is critical for hearing that the descending cochlear efferent system provide negative feedback to hair cells to regulate hearing sensitivity and provide protection from noise. The medial olivocochlear (MOC) efferent nerves project to outer hair cells (OHCs) and inhibit OHC electromotility, which is an active cochlear amplification and can increase hearing sensitivity. Here, we report that the MOC efferent nerves also have functional innervation with the cochlear supporting cells to regulate hearing sensitivity. The MOC efferent nerve fibers and the corresponding MOC neurotransmitter acetylcholine (ACh) receptors were visible in the cochlear supporting cells. Application of ACh in the cochlear supporting cells could also evoke inward currents in a dose-dependent manner and reduced gap junctional (GJ) coupling between the cochlear supporting cells, which consequently declined electromotility in OHCs. This indirect inhibitory effect through the mediated GJs between the cochlear supporting cells on OHC electromotility was consistent and enhanced the direct inhibition of ACh on OHC electromotility but had long-lasting influence. In vivo experiments further demonstrated that deficiency of this GJ-mediated efferent control pathway declined the regulation of active cochlear amplification and impaired the protection from noise trauma. Our findings reveal a new pathway for the cochlear efferent system to control hearing sensitivity, and also demonstrate that this supporting cell GJ-mediated efferent pathway is critical for control of hearing sensitivity and the protection of hearing from noise trauma.

Electron Microscopic Findings in Presbycusic Degeneration of the Basal Turn of the Human Cochlea

1979 ◽  
Vol 87 (6) ◽  
pp. 818-836 ◽  
Author(s):  
Joseph B. Nadol
Keyword(s):  
Light Microscopy ◽  
Hair Cells ◽  
Basilar Membrane ◽  
Ganglion Cells ◽  
Nerve Fibers ◽  
Degenerative Changes ◽  
Supporting Cells ◽  
Neural Degeneration ◽  
Basal Turn ◽  
Temporal Bones

Three human temporal bones with presbycusis affecting the basal turn of the cochlea were studied by light and electron microscopy. Conditions in two ears examined by light microscopy were typical of primary neural degeneration, with a descending audiometric pattern, loss of cochlear neurons in the basal turn, and preservation of the organ of Corti. Ultrastructural analysis revealed normal hair cells and marked degenerative changes of the remaining neural fibers, especially in the basal turn. These changes included a decrease in the number of synapses at the base of hair cells, accumulation of cellular debris in the spiral bundles, abnormalities of the dendritic fibers and their sheaths in the osseous spiral lamina, and degenerative changes in the spiral ganglion cells and axons. These changes were interpreted as an intermediate stage of degeneration prior to total loss of nerve fibers and ganglion cells as visualized by light microscopy. In the third ear the changes observed were typical of primary degeneration of hair and supporting cells in the basal turn with secondary neural degeneration. Additional observations at an ultrastructural level included maintenance of the tight junctions of the scala media despite loss of both hair and supporting cells, suggesting a capacity for cellular “healing” in the inner ear. Degenerative changes were found in the remaining neural fibers in the osseous spiral lamina. In addition, there was marked thickening of the basilar membrane in the basal turn, which consisted of an increased number of fibrils and an accumulation of amorphous osmiophilic material in the basilar membrane. This finding supports the concept that mechanical alterations may occur in presbycusis of the basal turn.

scholarly journals Purinergic signaling in cochlear supporting cells reduces hair cell excitability by increasing the extracellular space

2019 ◽  
Author(s):  
Travis A. Babola ◽  
Calvin J. Kersbergen ◽  
Han Chin Wang ◽  
Dwight E. Bergles
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Extracellular Space ◽  
Molecular Mechanisms ◽  
Purinergic Signaling ◽  
Burst Firing ◽  
Supporting Cells ◽  
Cell Excitability ◽  
Sensory Pathways ◽  
Cochlear Supporting Cells

AbstractNeurons in developing sensory pathways exhibit spontaneous bursts of electrical activity that are critical for survival, maturation and circuit refinement. In the auditory system, intrinsically generated activity arises within the cochlea, but the molecular mechanisms that initiate this activity remain poorly understood. We show that burst firing of mouse inner hair cells prior to hearing onset requires P2RY1 autoreceptors expressed by inner supporting cells. P2RY1 activation triggers K+ efflux and depolarization of hair cells, as well as osmotic shrinkage of supporting cells that dramatically increased the extracellular space and speed of K+ redistribution. Pharmacological inhibition or genetic disruption of P2RY1 suppressed neuronal burst firing by reducing K+ release, but unexpectedly enhanced their tonic firing, as water resorption by supporting cells reduced the extracellular space, slowing K+ clearance. These studies indicate that purinergic signaling in supporting cells regulates hair cell excitability by controlling the volume of the extracellular space.

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.

Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells

Nature ◽  
2006 ◽  
Vol 441 (7096) ◽  
pp. 984-987 ◽  
Author(s):  
Patricia M. White ◽  
Angelika Doetzlhofer ◽  
Yun Shain Lee ◽  
Andrew K. Groves ◽  
Neil Segil
Keyword(s):  
Hair Cells ◽  
Supporting Cells ◽  
Cochlear Supporting Cells

scholarly journals Cochlear supporting cells function as macrophage-like cells and protect audiosensory receptor hair cells from pathogens

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yushi Hayashi ◽  
Hidenori Suzuki ◽  
Wataru Nakajima ◽  
Ikuno Uehara ◽  
Atsuko Tanimura ◽  
...  
Keyword(s):  
Hair Cells ◽  
Supporting Cells ◽  
Cochlear Supporting Cells

scholarly journals Virus-infection in cochlear supporting cells induces audiosensory receptor hair cell death by TRAIL-induced necroptosis

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260443
Author(s):  
Yushi Hayashi ◽  
Hidenori Suzuki ◽  
Wataru Nakajima ◽  
Ikuno Uehara ◽  
Atsuko Tanimura ◽  
...  
Keyword(s):  
Hair Cells ◽  
Neutralizing Antibodies ◽  
Viral Infections ◽  
Sensory Epithelium ◽  
Supporting Cells ◽  
Cochlear Hair Cells ◽  
Receptor Cells ◽  
Macrophage Depletion ◽  
Cochlear Supporting Cells ◽  
Necrosis Factor

Although sensorineural hearing loss (SHL) is relatively common, its cause has not been identified in most cases. Previous studies have suggested that viral infection is a major cause of SHL, especially sudden SHL, but the system that protects against pathogens in the inner ear, which is isolated by the blood-labyrinthine barrier, remains poorly understood. We recently showed that, as audiosensory receptor cells, cochlear hair cells (HCs) are protected by surrounding accessory supporting cells (SCs) and greater epithelial ridge (GER or Kölliker’s organ) cells (GERCs) against viral infections. Here, we found that virus-infected SCs and GERCs induce HC death via production of the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). Notably, the HCs expressed the TRAIL death receptors (DR) DR4 and DR5, and virus-induced HC death was suppressed by TRAIL-neutralizing antibodies. TRAIL-induced HC death was not caused by apoptosis, and was inhibited by necroptosis inhibitors. Moreover, corticosteroids, the only effective drug for SHL, inhibited the virus-induced transformation of SCs and GERCs into macrophage-like cells and HC death, while macrophage depletion also inhibited virus-induced HC death. These results reveal a novel mechanism underlying virus-induced HC death in the cochlear sensory epithelium and suggest a possible target for preventing virus-induced SHL.

scholarly journals Dual expression of Atoh1 and Ikzf2 promotes transformation of adult cochlear supporting cells into outer hair cells

2021 ◽  
Author(s):  
Suhong Sun ◽  
Shuting Li ◽  
Zhengnan Luo ◽  
Minhui Ren ◽  
Shunji He ◽  
...  
Keyword(s):  
Single Cell ◽  
Hearing Impairment ◽  
Hair Cells ◽  
Outer Hair Cells ◽  
Supporting Cells ◽  
Differentiation Status ◽  
Cochlear Supporting Cells ◽  
Simultaneous Expression ◽  
Dual Expression

ABSTRACTMammalian cochlear outer hair cells (OHCs) are essential for hearing. OHC degeneration causes severe hearing impairment. Previous attempts of regenerating new OHCs from cochlear supporting cells (SCs) had yielded cells lacking Prestin, a key motor protein for OHC function. Thus, regeneration of Prestin+ OHCs remains a challenge for repairing OHC damage in vivo. Here, we reported that successful in vivo conversion of adult cochlear SCs into Prestin+ OHC-like cells could be achieved by simultaneous expression of Atoh1 and Ikzf2, two key transcriptional factors necessary for OHC development. New OHC-like cells exhibited upregulation of hundreds of OHC genes and downregulation of SC genes. Single cell transcriptomic analysis demonstrated that the differentiation status of these OHC-like cells was much more advanced than previously achieved. Thus, we have established an efficient approach to promote regeneration of Prestin+ OHCs and paved the way for repairing damaged cochlea in vivo via transdifferentiation of SCs.

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