scholarly journals Activity of CaMKIIa+ dorsal cochlear nucleus neurons are crucial for tinnitus perception but not for tinnitus induction

2021 ◽  
Author(s):  
Thawann Malfatti ◽  
Barbara Ciralli ◽  
Markus M Hilscher ◽  
Richardson N Leao ◽  
Katarina E Leao
Keyword(s):  
Cochlear Nucleus ◽  
Noise Exposure ◽  
Acoustic Startle ◽  
Auditory Brainstem ◽  
Dorsal Cochlear Nucleus ◽  
Homeostatic Plasticity ◽  
Designer Drugs ◽  
Auditory Brainstem Responses ◽  
Control Group ◽  
Sound Perception

The dorsal cochlear nucleus (DCN) is a region known to integrate somatosensory and auditory inputs and is identified as a potential key structure in the generation of phantom sound perception, especially noise-induced tinnitus. Yet, how altered homeostatic plasticity of the DCN induces and maintains the sensation of tinnitus is not clear. Here, we chemogenetically decrease activity of a subgroup of DCN neurons, Ca2+/Calmodulin kinase 2α (CaMKIIα) positive DCN neurons, using Gi-coupled human M4 Designer Receptors Exclusively Activated by Designer Drugs (hM4Di DREADDs), to investigate their role in noise-induced tinnitus. Mice were over-exposed to loud noise (9-11kHz, 90dBSPL, 1h, followed by 2h of silence) and auditory brainstem responses (ABRs) and gap prepulse inhibition of acoustic startle (GPIAS) were recorded two days before and two weeks after noise exposure to identify animals with a significantly decreased inhibition of startle, indicating tinnitus but without permanent hearing loss. Neuronal activity of CaMKIIα+ neurons expressing hM4Di in the DCN was lowered by administration of clozapine-N-oxide (CNO). We found that acutely decreasing firing rate of CaMKIIα+ DCN units decrease tinnitus-like responses (p = 0.038, n = 11 mice), compared to the control group that showed no improvement in GPIAS (control virus; CaMKIIα-YFP + CNO, p = 0.696, n = 7 mice). Extracellular recordings confirmed CNO to decrease unit firing frequency of CaMKIIα-hM4Di+ mice and alter best frequency and tuning width of response to sound. However, these effects were not seen if CNO had been previously administered during the noise overexposure (n = 6 experimental and 6 control mice). Our results suggest that CaMKIIα-hM4Di positive cells in the DCN are not crucial for tinnitus induction but play a significant role in maintaining tinnitus perception in mice.

scholarly journals Noise-induced hyperactivity in the inferior colliculus: its relationship with hyperactivity in the dorsal cochlear nucleus

2012 ◽  
Vol 108 (4) ◽  
pp. 976-988 ◽  
Author(s):  
N. F. Manzoor ◽  
F. G. Licari ◽  
M. Klapchar ◽  
R. L. Elkin ◽  
Y. Gao ◽  
...  
Keyword(s):  
Spontaneous Activity ◽  
Inferior Colliculus ◽  
Cochlear Nucleus ◽  
Time Course ◽  
Noise Exposure ◽  
Dorsal Cochlear Nucleus ◽  
Control Group ◽  
Before And After ◽  
Intense Noise ◽  
And Control

Intense noise exposure causes hyperactivity to develop in the mammalian dorsal cochlear nucleus (DCN) and inferior colliculus (IC). It has not yet been established whether the IC hyperactivity is driven by hyperactivity from extrinsic sources that include the DCN or instead is maintained independently of this input. We have investigated the extent to which IC hyperactivity is dependent on input from the contralateral DCN by comparing recordings of spontaneous activity in the IC of noise-exposed and control hamsters before and after ablation of the contralateral DCN. One group of animals was binaurally exposed to intense sound (10 kHz, 115 dB SPL, 4 h), whereas the control group was not. Both groups were studied electrophysiologically 2–3 wk later by first mapping spontaneous activity along the tonotopic axis of the IC to confirm induction of hyperactivity. Spontaneous activity was then recorded at a hyperactive IC locus over two 30-min periods, one with DCNs intact and the other after ablation of the contralateral DCN. In a subset of animals, activity was again mapped along the tonotopic axis after the time course of the activity was recorded before and after DCN ablation. Following recordings, the brains were fixed, and histological evaluations were performed to assess the extent of DCN ablation. Ablation of the DCN resulted in major reductions of IC hyperactivity. Levels of postablation activity in exposed animals were similar to the levels of activity in the IC of control animals, indicating an almost complete loss of hyperactivity in exposed animals. The results suggest that hyperactivity in the IC is dependent on support from extrinsic sources that include and may even begin with the DCN. This finding does not rule out longer term compensatory or homeostatic adjustments that might restore hyperactivity in the IC over time.

scholarly journals Effect of Electroacupuncture on Noise-Induced Hearing Loss in Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Chia-Hao Chang ◽  
Chia-Der Lin ◽  
Ching-Liang Hsieh
Keyword(s):  
Hearing Loss ◽  
Noise Exposure ◽  
Histopathological Examination ◽  
Spiral Ganglion ◽  
Auditory Brainstem ◽  
Auditory Threshold ◽  
Auditory Brainstem Responses ◽  
Control Group ◽  
Noise Induced Hearing Loss ◽  
Ganglion Neurons

Acupuncture has long been used to relieve some inner ear diseases such as deafness and tinnitus. The present study examined the effect of electroacupuncture (EA) on noise-induced hearing loss (NIHL) in animals. A NIHL rat model was established. Electroacupuncture pretreatment at 2 Hz or posttreatment at the right Zhongzhu (TE3) acupoint was applied for 1 hour. Auditory thresholds were measured using auditory brainstem responses (ABRs), and histopathology of the cochlea was examined. The results indicated that the baseline auditory threshold of ABR was not significantly different between the control (no noise), EA-only (only EA without noise), noise (noise exposure only), pre-EA (pretreating EA then noise), and post-EA (noise exposure then posttreating with EA) groups. Significant auditory threshold shifts were found in the noise, pre-EA, and post-EA groups in the immediate period after noise exposure, whereas auditory recovery was better in the pre-EA and post-EA groups than that in the noise group at the three days, one week (W1), two weeks (W2), three weeks (W3), and four weeks(W4) after noise stimulation. Histopathological examination revealed greater loss of the density of spiral ganglion neurons in the noise group than in the control group at W1 and W2. Although significant loss of spiral ganglion loss happened in pre-EA and post-EA groups, such loss was less than the loss of the noise group, especially W1. These results indicate that either pretreatment or posttreatment with EA may facilitate auditory recovery after NIHL. The detailed mechanism through which EA alleviates NIHL requires further study.

scholarly journals Efficacy of 2 Different Intratympanic Steroid Regimen on Prevention of Cisplatin Ototoxicity: An Experimental Study

2019 ◽  
pp. 014556131987431
Author(s):  
Burak Mustafa Taş ◽  
Gökçe Şimşek ◽  
Musa Azman ◽  
Rahmi Kılıç
Keyword(s):  
Otoacoustic Emission ◽  
Auditory Brainstem ◽  
Organ Injury ◽  
Auditory Brainstem Responses ◽  
Control Group ◽  
Protective Effects ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Ototoxicity is the general name of cochlear and vestibular organ injury resulting from encountering various therapeutic agents and chemical substances. Cisplatin is commonly used in the treatment of many cancers. In this study, the efficacy of intratympanic steroids was compared for preventing cisplatin ototoxicity. In this study, 32 (64 ears) rats were used by separating into 4 groups. Cisplatin was administered intraperitoneally to the first group (n = 8). Methylprednisolone and then cisplatin were administered intratympanically to the second group (n = 8). On the third group (n = 8), dexamethasone and then cisplatin were administered intratympanically. To the fourth group (n = 8), 0.9% NaCl and then cisplatin were given intratympanically. Otoacoustic emission (OAE) measurements and auditory brainstem responses (ABRs) tests were performed on all groups before and 72 hours after the procedure. Pretreatment of ABR-IV values were 4.29 ± 0.19 milliseconds in group 2 and 4.27 ± 0.16 milliseconds in group 3, whereas posttreatment ABR-IV values were 4.95 ± 0.35 milliseconds in group 2 and 4.65 ± 0.26 milliseconds in group 3. The ABR-IV values were measured significantly shorter in the rats given dexamethasone and methylprednisolone, according to control and cisplatin groups ( P < .001). Pretreatment of ABR I-IV interval values were 2.98 ± 0.34 milliseconds and 3.03 ± 0.42 milliseconds in group 1 and group 4, respectively, and ABR I-IV interval values in group 1 and group 4 posttreatment were 3.49 ± 0.39 milliseconds and 3.5 ± 0.39 milliseconds in group 1 and group 4, respectively. Auditory brainstem responses I-IV interval was significantly longer in the cisplatin and control group than in the rats given dexamethasone and methylprednisolone ( P < .001). After cisplatin treatment, OAE amplitudes decreased significantly in group 1 and group 4 for all frequencies, while OAE values were protected in methylprednisolone and dexamethasone group ( P < .001). In conclusion, it has been shown that both agents have protective effects on cisplatin ototoxicity, with dexamethasone slightly more than methylprednisolone.

scholarly journals Attention-related modulation of auditory brainstem responses during contralateral noise exposure

Neuroreport ◽  
2008 ◽  
Vol 19 (16) ◽  
pp. 1593-1599 ◽  
Author(s):  
Kazunari Ikeda ◽  
Takahiro Sekiguchi ◽  
Akiko Hayashi
Keyword(s):  
Noise Exposure ◽  
Auditory Brainstem ◽  
Auditory Brainstem Responses ◽  
Contralateral Noise

scholarly journals Effects of Age and Noise Exposure on Proxy Measures of Cochlear Synaptopathy

2019 ◽  
Vol 23 ◽  
pp. 233121651987730 ◽  
Author(s):  
Garreth Prendergast ◽  
Samuel Couth ◽  
Rebecca E. Millman ◽  
Hannah Guest ◽  
Karolina Kluk ◽  
...  
Keyword(s):  
Speech Perception ◽  
Noise Exposure ◽  
Auditory Brainstem ◽  
Auditory Brainstem Responses ◽  
Behavioral Measures ◽  
Speech Perception In Noise ◽  
Phase Discrimination ◽  
Age Related ◽  
Interaural Phase ◽  
Age Range

Although there is strong histological evidence for age-related synaptopathy in humans, evidence for the existence of noise-induced cochlear synaptopathy in humans is inconclusive. Here, we sought to evaluate the relative contributions of age and noise exposure to cochlear synaptopathy using a series of electrophysiological and behavioral measures. We extended an existing cohort by including 33 adults in the age range 37 to 60, resulting in a total of 156 participants, with the additional older participants resulting in a weakening of the correlation between lifetime noise exposure and age. We used six independent regression models (corrected for multiple comparisons), in which age, lifetime noise exposure, and high-frequency audiometric thresholds were used to predict measures of synaptopathy, with a focus on differential measures. The models for auditory brainstem responses, envelope-following responses, interaural phase discrimination, and the co-ordinate response measure of speech perception were not statistically significant. However, both age and noise exposure were significant predictors of performance on the digit triplet test of speech perception in noise, with greater noise exposure (unexpectedly) predicting better performance in the 80 dB sound pressure level (SPL) condition and greater age predicting better performance in the 40 dB SPL condition. Amplitude modulation detection thresholds were also significantly predicted by age, with older listeners performing better than younger listeners at 80 dB SPL. Overall, the results are inconsistent with the predicted effects of synaptopathy.

Safety and Efficacy of Chitosan-Dextran Hydrogel in the Middle Ear in an Animal Model

2016 ◽  
Vol 21 (4) ◽  
pp. 254-260
Author(s):  
Selin Ünsaler ◽  
Bora Başaran ◽  
Şule Öztürk Sarı ◽  
Eyüp Kara ◽  
Kemal Değer ◽  
...  
Keyword(s):  
Middle Ear ◽  
Auditory Brainstem ◽  
Contralateral Side ◽  
Auditory Brainstem Responses ◽  
Control Group ◽  
Ear Surgery ◽  
Significant Difference ◽  
Intratympanic Injection ◽  
Temporal Bones ◽  
Histopathologic Findings

Objectives: To investigate the efficacy of chitosan-dextran hydrogel (CDH) in preventing postoperative adhesions between the tympanic membrane (TM) and intratympanic structures, and to evaluate its ototoxicity in an animal study. Methods: In the first step, ototoxicity was evaluated with 7 male albino guinea pigs (GPs) via auditory brainstem responses (ABR) before and 4 weeks after unilateral intratympanic injection of CDH and saline solution contralaterally. In the second step, 12 GPs underwent bilateral ear surgery. The middle ear (ME) mucosa was abraded, and the cavity was filled with CDH on one side and packed with Gelfoam on the contralateral side. A control group of 6 GPs underwent the same procedure except that no material was applied in the ME. The animals were euthanized at the end of the 7th week, and otomicroscopic findings were noted and the temporal bones harvested for the histologic examination. The findings were scored and compared. Results: There was no statistically significant difference between the pre- and postoperative ABR thresholds. In the otomicroscopic findings, the most prominent difference between the two groups was the presence of retraction of the TM in the Gelfoam group. The histopathologic findings revealed a higher degree of inflammation in the Gelfoam group compared with the CDH group. Conclusion: This study demonstrated that CDH has no ototoxic effects in GPs. Its use as an ME packing material revealed significantly less TM retraction and inflammatory reaction compared with Gelfoam.

scholarly journals miR-153/KCNQ4 axis contributes to noise-induced hearing loss in a mouse model

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Qin Wang ◽  
Wei Li ◽  
Cuiyun Cai ◽  
Peng Hu ◽  
Ruosha Lai
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Noise Exposure ◽  
Auditory Brainstem ◽  
Sensory Epithelium ◽  
Outer Hair Cells ◽  
Broadband Noise ◽  
Hek293 Cells ◽  
Auditory Brainstem Responses ◽  
Luciferase Reporter

AbstractDamage to the cochlear sensory epithelium is a key contributor to noise-induced sensorineural hearing loss (SNHL). KCNQ4 plays an important role in the cochlear potassium circulation and outer hair cells survival. As miR-153 can target and regulate KCNQ4, we sought to study the role of miR-153 in SNHL. 12-week-old male CBA/J mice were exposed to 2–20 kHz broadband noise at 96 dB SPL to induce temporary threshold shifts and 101 dB SPL to induce permanent threshold shifts. Hearing loss was determined by auditory brainstem responses (ABR). Relative expression of miR-153 and KCNQ4 in mice cochlea were determined by Real-Time quantitative PCR. miR-153 mimics were co-transfected with wild type or mutated KCNQ4 into HEK293 cells. Luciferase reporter assay was used to validate the binding between miR-153 and KCNQ4. AAV-sp-153 was constructed and administrated intra-peritoneally 24- and 2-h prior and immediately after noise exposure to knockdown miR-153. The KCNQ4 is mainly expressed in outer hair cells (OHCs). We showed that the expression of KCNQ4 in mice cochlea was reduced and miR-153 expression was significantly increased after noise exposure compared to control. miR-153 bound to 3′UTR of KNCQ4, and the knockdown of miR-153 with the AAV-sp-153 administration restored KCNQ4 mRNA and protein expression. In addition, the knockdown of miR-153 reduced ABR threshold shifts at 8, 16, and 32 kHz after permanent threshold shifts (PTS) noise exposure. Correspondingly, OHC losses were attenuated with inhibition of miR-153. This study demonstrates that miR-153 inhibition significantly restores KNCQ4 in cochlea after noise exposure, which attenuates SNHL. Our study provides a new potential therapeutic target in the prevention and treatment of SNHL.

scholarly journals Ephrin-A3 Is Required for Tonotopic Map Precision and Auditory Function in the Mouse Auditory Brainstem

2021 ◽  
Author(s):  
Natalia Hoshino ◽  
Yazan Altarshan ◽  
Ahmad Alzein ◽  
Amali Fernando ◽  
Hieu Nguyen ◽  
...  
Keyword(s):  
Axon Guidance ◽  
Cochlear Nucleus ◽  
Auditory Brainstem ◽  
Nerve Fibers ◽  
Auditory Brainstem Responses ◽  
Dependent Manner ◽  
Anteroventral Cochlear Nucleus ◽  
Sound Discrimination ◽  
Frequency Changes ◽  
Second Wave

Abstract Tonotopy is a prominent feature of the vertebrate auditory system and forms the basis for sound discrimination, but the molecular mechanism underlying its formation remain largely elusive. Ephrin/Eph signaling is known to play important roles in axon guidance during topographic mapping in other sensory systems. Here, we determined that ephrin-A3 molecules are expressed in a ventral to dorsal descending gradient along the tonotopic axis in developing mouse cochlear nucleus. During cochlear nucleus innervation by auditory nerve fibers, ephrin-A3 forward signaling can repel these fibers in a stage-dependent manner. In ephrin-A3 mutant animals, the tonotopic map is degraded and isofrequency bands of neuronal activation become imprecise in the anteroventral cochlear nucleus. Ephrin-A3 mutants also exhibit a delayed second wave in auditory brainstem responses and impaired detection sound frequency changes. Our findings establish an essential role for ephrin-A3 in forming precise tonotopy in the auditory brainstem to ensure accurate sound discrimination.

Auditory Brainstem Response, Middle Latency Response, and Late Cortical Evoked Potentials in Children with Learning Disabilities

2002 ◽  
Vol 13 (07) ◽  
pp. 367-382 ◽  
Author(s):  
Suzanne C. Purdy ◽  
Andrea S. Kelly ◽  
Merren G. Davies
Keyword(s):  
Evoked Potentials ◽  
Auditory Processing ◽  
Auditory Evoked Potentials ◽  
Auditory Brainstem ◽  
Auditory Memory ◽  
Auditory Brainstem Responses ◽  
Control Group ◽  
Cortical Responses ◽  
Brainstem Response ◽  
Middle Latency

Auditory evoked potentials (AEPs) and behavioral tests were used to evaluate auditory processing in 10 children aged 7 to 11 years who were diagnosed as learning disabled (LD). AEPs included auditory brainstem responses (ABRs), middle latency responses (MLRs), and late cortical responses (P1, N1, P2, P3). Late cortical responses were recorded using an active listening oddball procedure. Auditory processing disorders were suspected in the LD children after a psychologist found phonologic processing and auditory memory problems. A control group of 10 age- and gender-matched children with no hearing or reported learning difficulties was also tested. Teacher ratings of classroom listening and SCAN Competing Words and Staggered Spondaic Word scores were poorer in the LD children. There were minor ABR latency differences between the two groups. Wave Na of the MLR was later and Nb was smaller in the LD group. The main differences in cortical responses were that P1 was earlier and P3 was later and smaller in the LD group.

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