scholarly journals Hair cells use active zones with different voltage dependence of Ca2+ influx to decompose sounds into complementary neural codes

2016 ◽  
Vol 113 (32) ◽  
pp. E4716-E4725 ◽  
Author(s):  
Tzu-Lun Ohn ◽  
Mark A. Rutherford ◽  
Zhizi Jing ◽  
Sangyong Jung ◽  
Carlos J. Duque-Afonso ◽  
...  
Keyword(s):  
Hair Cells ◽  
Dynamic Range ◽  
Spiral Ganglion ◽  
Spatial Gradient ◽  
Auditory Information ◽  
Neural Codes ◽  
Deafness Gene ◽  
Wide Range ◽  
Ganglion Neurons ◽  
Channel Properties

For sounds of a given frequency, spiral ganglion neurons (SGNs) with different thresholds and dynamic ranges collectively encode the wide range of audible sound pressures. Heterogeneity of synapses between inner hair cells (IHCs) and SGNs is an attractive candidate mechanism for generating complementary neural codes covering the entire dynamic range. Here, we quantified active zone (AZ) properties as a function of AZ position within mouse IHCs by combining patch clamp and imaging of presynaptic Ca2+ influx and by immunohistochemistry. We report substantial AZ heterogeneity whereby the voltage of half-maximal activation of Ca2+ influx ranged over ∼20 mV. Ca2+ influx at AZs facing away from the ganglion activated at weaker depolarizations. Estimates of AZ size and Ca2+ channel number were correlated and larger when AZs faced the ganglion. Disruption of the deafness gene GIPC3 in mice shifted the activation of presynaptic Ca2+ influx to more hyperpolarized potentials and increased the spontaneous SGN discharge. Moreover, Gipc3 disruption enhanced Ca2+ influx and exocytosis in IHCs, reversed the spatial gradient of maximal Ca2+ influx in IHCs, and increased the maximal firing rate of SGNs at sound onset. We propose that IHCs diversify Ca2+ channel properties among AZs and thereby contribute to decomposing auditory information into complementary representations in SGNs.

scholarly journals Anti-inflammatory compounds improve spiral ganglion neuron survival after aminoglycoside-induced hair cell loss in rats

2021 ◽  
Author(s):  
Muhammad T. Rahman ◽  
Erin M. Bailey ◽  
Benjamin M. Gansemer ◽  
Andrew Pieper ◽  
J. Robert Manak ◽  
...  
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Spiral Ganglion ◽  
Cell Loss ◽  
Spiral Ganglion Neuron ◽  
Auditory Information ◽  
Activated Macrophages ◽  
Hair Cell Loss ◽  
Cochlear Hair Cells ◽  
Ganglion Neurons

AbstractSpiral ganglion neurons (SGNs) relay auditory information from cochlear hair cells to the central nervous system. After hair cells are destroyed by aminoglycoside antibiotics, SGNs gradually die. However, the reasons for this cochlear neurodegeneration are unclear. We used microarray gene expression profiling to assess transcriptomic changes in the spiral ganglia of kanamycin-deafened and age-matched control rats and found that many of the genes upregulated after deafening are associated with immune/inflammatory responses. In support of this, we observed increased numbers of macrophages in the spiral ganglion of deafened rats. We also found, via CD68 immunoreactivity, an increase in activated macrophages after deafening. An increase in CD68-associated nuclei was observed by postnatal day 23, a time before significant SGN degeneration is observed. Finally, we show that the immunosuppressive drugs dexamethasone and ibuprofen, as well as the NAD salvage pathway activator P7C3, provide at least some neuroprotection post-deafening. Ibuprofen and dexamethasone also decreased the degree of macrophage activation. These results suggest that activated macrophages specifically, and perhaps a more general neuroinflammatory response, are actively contributing to SGN degeneration after hair cell loss.

New insights into glutamate ototoxicity in cochlear hair cells and spiral ganglion neurons

2010 ◽  
Vol 130 (12) ◽  
pp. 1316-1323 ◽  
Author(s):  
Haitao Lu ◽  
Xiang Wang ◽  
Wenyan Sun ◽  
Yao Hu ◽  
Shusheng Gong
Keyword(s):  
Hair Cells ◽  
Spiral Ganglion ◽  
Spiral Ganglion Neurons ◽  
Cochlear Hair Cells ◽  
Ganglion Neurons

scholarly journals Exocyst Complex Member EXOC5 Is Required for Survival of Hair Cells and Spiral Ganglion Neurons and Maintenance of Hearing

2018 ◽  
Vol 55 (8) ◽  
pp. 6518-6532 ◽  
Author(s):  
Byeonghyeon Lee ◽  
Jeong-In Baek ◽  
Hyehyun Min ◽  
Seung-Hyun Bae ◽  
Kyeonghye Moon ◽  
...  
Keyword(s):  
Hair Cells ◽  
Spiral Ganglion ◽  
Spiral Ganglion Neurons ◽  
Exocyst Complex ◽  
Ganglion Neurons

scholarly journals Correction to: Exocyst Complex Member EXOC5 Is Required for Survival of Hair Cells and Spiral Ganglion Neurons and Maintenance of Hearing

2019 ◽  
Vol 56 (3) ◽  
pp. 2300-2300
Author(s):  
Byeonghyeon Lee ◽  
Jeong-In Baek ◽  
Hyehyun Min ◽  
Seung-Hyun Bae ◽  
Kyeonghye Moon ◽  
...  
Keyword(s):  
Hair Cells ◽  
Spiral Ganglion ◽  
Spiral Ganglion Neurons ◽  
Exocyst Complex ◽  
Ganglion Neurons

scholarly journals Pyroptosis Accelerates Spiral Ganglion Neuronal Degeneration Induced by Aminoglycosides in the Cochlea

2021 ◽  
Author(s):  
Yazhi Xing ◽  
Jia Fang ◽  
Zhuangzhuang Li ◽  
Mingxian Li ◽  
Chengqi Liu ◽  
...  
Keyword(s):  
Cell Death ◽  
Rna Sequencing ◽  
Hair Cells ◽  
Nlrp3 Inflammasome ◽  
Auditory Brainstem Response ◽  
Spiral Ganglion ◽  
Auditory Brainstem ◽  
Response Threshold ◽  
Brainstem Response ◽  
Ganglion Neurons

Abstract Background In aminoglycoside-induced hearing loss, damage to spiral ganglion neurons (SGNs) accelerates gradually after the acute outer hair cell death, accompanied by macrophage infiltration and cytokine release. Pyroptosis plays a critical role in neurodegenerative diseases. Here, we explored the potential role of pyroptosis in SGN degeneration. Methods C57BL/6J mice were randomly divided into a kanamycin plus furosemide group and saline control group. Auditory functions were evaluated by auditory brainstem response tests conducted before treatment and at 1, 5, 15, and 30 days after treatment. HCs and SGNs were assessed for morphological alterations. SGNs were subjected to RNA sequencing and mRNA and protein analyses of NLRP3 inflammasome-related molecules. Macrophage activation was evaluated based on morphological and mRNA alterations. The effect of NLRP3 inhibition on SGN survival after kanamycin treatment was evaluated in organ explant cultures treated with Mcc950, a specific inhibitor of the NLRP3 inflammasome. Results Kanamycin and furosemide administration led to irreversible deterioration of the auditory brainstem response threshold, accompanied by acute loss of outer hair cells and gradually progressive loss of inner hair cells. SGNs showed a progressive decrease in quantity, as well as swelling and membrane rupture, at 15 and 30 days. RNA sequencing of SGNs showed that inflammation and immune-related responses were significantly upregulated, as was the expression of the inflammasome-related gene NLRP3. During 30 days of kanamycin exposure, the canonical pyroptosis pathway was constantly activated in SGNs. Activation and infiltration of microglia-like cells/macrophages, and increased production of cytokines, hallmarks of neuroinflammation, were also observed. Mcc950 significantly ameliorated SGN degeneration by inhibiting NLRP3 expression and promoting release of interleukins 1β and 18. Conclusions Pyroptosis causes cell death during aminoglycoside-induced SGN degeneration. Activation of the NLRP3 inflammasome leads to a cascade of inflammatory events in SGNs. Inhibition of the NLRP3 inflammasome significantly alleviates SGN damage, suggesting that it could serve as a new molecular target for the treatment of aminoglycoside-induced SGN degeneration.

scholarly journals Spatiotemporal Developmental Upregulation of Prestin Correlates With the Severity and Location of Cyclodextrin-Induced Outer Hair Cell Loss and Hearing Loss

2021 ◽  
Vol 9 ◽  
Author(s):  
Dalian Ding ◽  
Haiyan Jiang ◽  
Senthilvelan Manohar ◽  
Xiaopeng Liu ◽  
Li Li ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Auditory Nerve ◽  
High Frequency ◽  
Spiral Ganglion ◽  
Low Frequency ◽  
Nerve Fibers ◽  
Spiral Ganglion Neurons ◽  
Auditory Nerve Fibers ◽  
Ganglion Neurons

2-Hyroxypropyl-beta-cyclodextrin (HPβCD) is being used to treat Niemann-Pick C1, a fatal neurodegenerative disease caused by abnormal cholesterol metabolism. HPβCD slows disease progression, but unfortunately causes severe, rapid onset hearing loss by destroying the outer hair cells (OHC). HPβCD-induced damage is believed to be related to the expression of prestin in OHCs. Because prestin is postnatally upregulated from the cochlear base toward the apex, we hypothesized that HPβCD ototoxicity would spread from the high-frequency base toward the low-frequency apex of the cochlea. Consistent with this hypothesis, cochlear hearing impairments and OHC loss rapidly spread from the high-frequency base toward the low-frequency apex of the cochlea when HPβCD administration shifted from postnatal day 3 (P3) to P28. HPβCD-induced histopathologies were initially confined to the OHCs, but between 4- and 6-weeks post-treatment, there was an unexpected, rapid and massive expansion of the lesion to include most inner hair cells (IHC), pillar cells (PC), peripheral auditory nerve fibers, and spiral ganglion neurons at location where OHCs were missing. The magnitude and spatial extent of HPβCD-induced OHC death was tightly correlated with the postnatal day when HPβCD was administered which coincided with the spatiotemporal upregulation of prestin in OHCs. A second, massive wave of degeneration involving IHCs, PC, auditory nerve fibers and spiral ganglion neurons abruptly emerged 4–6 weeks post-HPβCD treatment. This secondary wave of degeneration combined with the initial OHC loss results in a profound, irreversible hearing loss.

Sign in / Sign up

Export Citation Format

Share Document