scholarly journals Loss of Cochlear Ribbon Synapse Is a Critical Contributor to Chronic Salicylate Sodium Treatment-Induced Tinnitus without Change Hearing Threshold

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Wei Zhang ◽  
Zhe Peng ◽  
ShuKui Yu ◽  
Qing-Ling Song ◽  
Teng-Fei Qu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Acoustic Startle ◽  
Acoustic Startle Response ◽  
Hearing Threshold ◽  
Significant Loss ◽  
Acoustic Startle Reflex ◽  
Ribbon Synapse ◽  
Inner Hair Cell ◽  
Adult Rats ◽  
Ribbon Synapses

Tinnitus is a common auditory disease worldwide; it is estimated that more than 10% of all individuals experience this hearing disorder during their lifetime. Tinnitus is sometimes accompanied by hearing loss. However, hearing loss is not acquired in some other tinnitus generations. In this study, we injected adult rats with salicylate sodium (SS) (200 mg/kg/day for 10 days) and found no significant hearing threshold changes at 2, 4, 8, 12, 14, 16, 20, or 24 kHz (all p>0.05). Tinnitus was confirmed in the treated rats via Behaviour Testing of Acoustic Startle Response (ASR) and Gap Prepulse Inhibition Test of Acoustic Startle Reflex (GPIAS). A immunostaining study showed that there is significant loss of anti-CtBP2 puncta (a marker of cochlear inner hair cell (HC) ribbon synapses) in treated animals in apical, middle, and basal turns (all p<0.05). The ABR wave I amplitudes were significantly reduced at 4, 8, 12, 14, 16, and 20 kHz (all p<0.05). No significant losses of outer HCs, inner HCs, or HC cilia were observed (all p>0.05). Thus, our study suggests that loss of cochlear inner HC ribbon synapse after SS exposure is a contributor to the development of tinnitus without changing hearing threshold.

scholarly journals Synaptic Release Potentiation at Aging Auditory Ribbon Synapses

2021 ◽  
Vol 13 ◽  
Author(s):  
Thibault Peineau ◽  
Séverin Belleudy ◽  
Susanna Pietropaolo ◽  
Yohan Bouleau ◽  
Didier Dulon
Keyword(s):  
Hearing Loss ◽  
Acoustic Startle ◽  
Auditory Brainstem ◽  
Bk Channels ◽  
Acoustic Startle Reflex ◽  
Inner Hair Cell ◽  
Functional Changes ◽  
Ribbon Synapses ◽  
Age Related ◽  
Cadherin 23

Age-related hidden hearing loss is often described as a cochlear synaptopathy that results from a progressive degeneration of the inner hair cell (IHC) ribbon synapses. The functional changes occurring at these synapses during aging are not fully understood. Here, we characterized this aging process in IHCs of C57BL/6J mice, a strain which is known to carry a cadherin-23 mutation and experiences early hearing loss with age. These mice, while displaying a large increase in auditory brainstem thresholds due to 50% loss of IHC synaptic ribbons at middle age (postnatal day 365), paradoxically showed enhanced acoustic startle reflex suggesting a hyperacusis-like response. The auditory defect was associated with a large shrinkage of the IHCs' cell body and a drastic enlargement of their remaining presynaptic ribbons which were facing enlarged postsynaptic AMPAR clusters. Presynaptic Ca2+ microdomains and the capacity of IHCs to sustain high rates of exocytosis were largely increased, while on the contrary the expression of the fast-repolarizing BK channels, known to negatively control transmitter release, was decreased. This age-related synaptic plasticity in IHCs suggested a functional potentiation of synaptic transmission at the surviving synapses, a process that could partially compensate the decrease in synapse number and underlie hyperacusis.

scholarly journals N-Methyl-D-Aspartate Receptors Involvement in the Gentamicin-Induced Hearing Loss and Pathological Changes of Ribbon Synapse in the Mouse Cochlear Inner Hair Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Juan Hong ◽  
Yan Chen ◽  
Yanping Zhang ◽  
Jieying Li ◽  
Liujie Ren ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Auditory Brainstem ◽  
Ribbon Synapse ◽  
Synaptic Ribbons ◽  
Pathological Changes ◽  
Inner Hair Cell ◽  
Ribbon Synapses ◽  
Brainstem Response ◽  
Mature Mouse ◽  
Response Thresholds

Cochlear inner hair cell (IHC) ribbon synapses play an important role in sound encoding and neurotransmitter release. Previous reports show that both noise and aminoglycoside exposures lead to reduced numbers and morphologic changes of synaptic ribbons. In this work, we determined the distribution of N-methyl-D-aspartate receptors (NMDARs) and their role in the gentamicin-induced pathological changes of cochlear IHC ribbon synaptic elements. In normal mature mouse cochleae, the majority of NMDARs were distributed on the modiolar side of IHCs and close to the IHC nuclei region, while most of synaptic ribbons and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) were located on neural terminals closer to the IHC basal poles. After gentamicin exposure, the NMDARs increased and moved towards the IHC basal poles. At the same time, synaptic ribbons and AMPARs moved toward the IHC bundle poles on the afferent dendrites. The number of ribbon synapse decreased, and this was accompanied by increased auditory brainstem response thresholds and reduced wave I amplitudes. NMDAR antagonist MK801 treatment reduced the gentamicin-induced hearing loss and the pathological changes of IHC ribbon synapse, suggesting that NMDARs were involved in gentamicin-induced ototoxicity by regulating the number and distribution of IHC ribbon synapses.

Caudal Pontine Reticular Formation of C57BL/6J Mice: Responses to Startle Stimuli, Inhibition by Tones, and Plasticity

1998 ◽  
Vol 79 (5) ◽  
pp. 2603-2614 ◽  
Author(s):  
Stephanie Carlson ◽  
James F. Willott
Keyword(s):  
Hearing Loss ◽  
Reticular Formation ◽  
Auditory System ◽  
Neural Plasticity ◽  
High Frequency ◽  
Acoustic Startle ◽  
Acoustic Startle Response ◽  
Pontine Reticular Formation ◽  
High Frequency Hearing Loss ◽  
Old Mice

Carlson, Stephanie and James F. Willott. Caudal pontine reticular formation of C57BL/6J mice: responses to startle stimuli, inhibition by tones, and plasticity. J. Neurophysiol. 79: 2603–2614, 1998. C57BL/6J (C57) mice were used to examine relationships between the behavioral acoustic startle response (ASR) and the responses of neurons in the caudal pontine reticular formation (PnC) in three contexts: 1) responses evoked by basic startle stimuli; 2) the prepulse inhibition (PPI) paradigm; and 3) the effects of high-frequency hearing loss and concomitant neural plasticity that occurs in middle-aged C57 mice. 1) Responses (evoked action potentials) of PnC neurons closely paralleled the ASR with respect to latency, threshold, and responses to rapidly presented stimuli. 2) “Neural PPI” (inhibition of responses evoked by a startle stimulus when preceded by a tone prepulse) was observed in all PnC neurons studied. 3) In PnC neurons of 6-mo-old mice with high-frequency (>20 kHz) hearing loss, neural PPI was enhanced with 12- and 4-kHz prepulses, as it is behaviorally. These are frequencies that have become “overrepresented” in the central auditory system of 6-mo-old C57 mice. Thus neural plasticity in the auditory system, induced by high-frequency hearing loss, is correlated with increased salience of the inhibiting tones in both behavioral and neural PPI paradigms.

Iron deficiency affects acoustic startle response and latency, but not prepulse inhibition in young adult rats

2006 ◽  
Vol 87 (5) ◽  
pp. 917-924 ◽  
Author(s):  
Maggie S. Burhans ◽  
Catherine Dailey ◽  
Jason Wiesinger ◽  
Laura E. Murray-Kolb ◽  
Byron C. Jones ◽  
...  
Keyword(s):  
Young Adult ◽  
Iron Deficiency ◽  
Prepulse Inhibition ◽  
Startle Response ◽  
Acoustic Startle ◽  
Acoustic Startle Response ◽  
Adult Rats

The effects of perinatal AZT exposure on the acoustic startle response in adult rats

2002 ◽  
Vol 24 (6) ◽  
pp. 773-781 ◽  
Author(s):  
Susan M Melnick ◽  
Jeremy Weedon ◽  
Diana L Dow-Edwards
Keyword(s):  
Startle Response ◽  
Acoustic Startle ◽  
Acoustic Startle Response ◽  
Adult Rats

scholarly journals Acoustically Enriched Environment during the Critical Period of Postnatal Development Positively Modulates Gap Detection and Frequency Discrimination Abilities in Adult Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Kateryna Pysanenko ◽  
Natalia Rybalko ◽  
Zbyněk Bureš ◽  
Daniel Šuta ◽  
Jiří Lindovský ◽  
...  
Keyword(s):  
Critical Period ◽  
Acoustic Startle ◽  
Acoustic Startle Response ◽  
Frequency Discrimination ◽  
Enriched Environment ◽  
Frequency Resolution ◽  
Gap Detection ◽  
Behavioral Tests ◽  
Adult Rats ◽  
Acoustic Environment

Throughout life, sensory systems adapt to the sensory environment to provide optimal responses to relevant tasks. In the case of a developing system, sensory inputs induce changes that are permanent and detectable up to adulthood. Previously, we have shown that rearing rat pups in a complex acoustic environment (spectrally and temporally modulated sound) from postnatal day 14 (P14) to P28 permanently improves the response characteristics of neurons in the inferior colliculus and auditory cortex, influencing tonotopical arrangement, response thresholds and strength, and frequency selectivity, along with stochasticity and the reproducibility of neuronal spiking patterns. In this study, we used a set of behavioral tests based on a recording of the acoustic startle response (ASR) and its prepulse inhibition (PPI), with the aim to extend the evidence of the persistent beneficial effects of the developmental acoustical enrichment. The enriched animals were generally not more sensitive to startling sounds, and also, their PPI of ASR, induced by noise or pure tone pulses, was comparable to the controls. They did, however, exhibit a more pronounced PPI when the prepulse stimulus was represented either by a change in the frequency of a background tone or by a silent gap in background noise. The differences in the PPI of ASR between the enriched and control animals were significant at lower (55 dB SPL), but not at higher (65-75 dB SPL), intensities of background sound. Thus, rearing pups in the acoustically enriched environment led to an improvement of the frequency resolution and gap detection ability under more difficult testing conditions, i.e., with a worsened stimulus clarity. We confirmed, using behavioral tests, that an acoustically enriched environment during the critical period of development influences the frequency and temporal processing in the auditory system, and these changes persist until adulthood.

Carboplatin-Induced Oxidative Injury in Rat Inferior Colliculus

2003 ◽  
Vol 22 (5) ◽  
pp. 335-342 ◽  
Author(s):  
Kazim Husain ◽  
Craig Whitworth ◽  
Stephen Hazelrigg ◽  
Leonard Rybak
Keyword(s):  
Superoxide Dismutase ◽  
Hearing Loss ◽  
Inferior Colliculus ◽  
Auditory System ◽  
Hearing Threshold ◽  
Oxidative Injury ◽  
High Dose ◽  
Antioxidant Enzyme Activities ◽  
Central Auditory System ◽  
Inner Hair Cell

Carboplatin is currently being used as an anticancer drug against human cancers. However, high dose of carboplatin chemotherapy resulted in ototoxicity in cancer patients. Carboplatin-induced ototoxicity was related to oxidative stress to the cochlea and inner hair cell loss in animals. It is likely that initial oxidative injury spreads throughout the neuroaxis of the auditory system later. The study aim was to evaluate carboplatin-induced hearing loss and oxidative injury to the central auditory system (inferior colliculus) of the rat. Male Wistar rats were divided into two groups of seven animals each and treated as follows: (1) control (normal saline, intraperitoneal [IP]) and (2) carboplatin (256 mg/kg, IP). Auditory brain-evoked responses (ABRs) were recorded before and 4 days after treatments. The animals were sacrificed on the 4th day and inferior colliculus from brain stem and cerebellum were isolated and analyzed. Carboplatin significantly elevated the hearing threshold shifts at clicks, 2-, 4-, 8-, 16-, and 32-k Hz tone burst stimuli. Carboplatin significantly increased nitric oxide and lipid peroxidation, xanthine oxidase, and manganese superoxide dismutase activities in the inferior colliculus, but not in the cerebellum, indicating an enhanced flux of free radicals in the central auditory system. Carboplatin significantly depressed the reduced to oxidized glutathione ratio, antioxidant enzyme activities, such as copper-zinc superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase, and enzyme protein expressions in the inferior colliculus, but not in the cerebellum, 4 days after treatment. The data suggest that carboplatin induced oxidative injury specifically in the inferior colliculus of the rat leading to hearing loss.

scholarly journals Electrophysiological assessment and pharmacological treatment of blast-induced tinnitus

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0243903
Author(s):  
Jianzhong Lu ◽  
Matthew B. West ◽  
Xiaoping Du ◽  
Qunfeng Cai ◽  
Donald L. Ewert ◽  
...  
Keyword(s):  
Amplitude Ratio ◽  
Expression Patterns ◽  
Acoustic Startle ◽  
Acoustic Startle Response ◽  
Auditory Pathway ◽  
Auditory Brainstem ◽  
Auditory Brainstem Responses ◽  
Significant Treatment ◽  
Ribbon Synapses ◽  
Behavioral Evidence

Tinnitus, the phantom perception of sound, often occurs as a clinical sequela of auditory traumas. In an effort to develop an objective test and therapeutic approach for tinnitus, the present study was performed in blast-exposed rats and focused on measurements of auditory brainstem responses (ABRs), prepulse inhibition of the acoustic startle response, and presynaptic ribbon densities on cochlear inner hair cells (IHCs). Although the exact mechanism is unknown, the “central gain theory” posits that tinnitus is a perceptual indicator of abnormal increases in the gain (or neural amplification) of the central auditory system to compensate for peripheral loss of sensory input from the cochlea. Our data from vehicle-treated rats supports this rationale; namely, blast-induced cochlear synaptopathy correlated with imbalanced elevations in the ratio of centrally-derived ABR wave V amplitudes to peripherally-derived wave I amplitudes, resulting in behavioral evidence of tinnitus. Logistic regression modeling demonstrated that the ABR wave V/I amplitude ratio served as a reliable metric for objectively identifying tinnitus. Furthermore, histopathological examinations in blast-exposed rats revealed tinnitus-related changes in the expression patterns of key plasticity factors in the central auditory pathway, including chronic loss of Arc/Arg3.1 mobilization. Using a formulation of N-acetylcysteine (NAC) and disodium 2,4-disulfophenyl-N-tert-butylnitrone (HPN-07) as a therapeutic for addressing blast-induced neurodegeneration, we measured a significant treatment effect on preservation or restoration of IHC ribbon synapses, normalization of ABR wave V/I amplitude ratios, and reduced behavioral evidence of tinnitus in blast-exposed rats, all of which accorded with mitigated histopathological evidence of tinnitus-related neuropathy and maladaptive neuroplasticity.

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