scholarly journals Characterizing the Access of Cholinergic Antagonists to Efferent Synapses in the Inner Ear

2021 ◽  
Vol 15 ◽  
Author(s):  
Choongheon Lee ◽  
Anjali K. Sinha ◽  
Kenneth Henry ◽  
Anqi W. Walbaum ◽  
Peter A. Crooks ◽  
...  
Keyword(s):  
Inner Ear ◽  
Middle Ear ◽  
Otoacoustic Emissions ◽  
Cholinergic Antagonists ◽  
Cholinergic Drugs ◽  
Administration Routes ◽  
Distortion Product ◽  
Vestibular Afferents ◽  
Auditory Physiology ◽  
Efferent Neurons

Stimulation of cholinergic efferent neurons innervating the inner ear has profound, well-characterized effects on vestibular and auditory physiology, after activating distinct ACh receptors (AChRs) on afferents and hair cells in peripheral endorgans. Efferent-mediated fast and slow excitation of vestibular afferents are mediated by α4β2*-containing nicotinic AChRs (nAChRs) and muscarinic AChRs (mAChRs), respectively. On the auditory side, efferent-mediated suppression of distortion product otoacoustic emissions (DPOAEs) is mediated by α9α10nAChRs. Previous characterization of these synaptic mechanisms utilized cholinergic drugs, that when systemically administered, also reach the CNS, which may limit their utility in probing efferent function without also considering central effects. Use of peripherally-acting cholinergic drugs with local application strategies may be useful, but this approach has remained relatively unexplored. Using multiple administration routes, we performed a combination of vestibular afferent and DPOAE recordings during efferent stimulation in mouse and turtle to determine whether charged mAChR or α9α10nAChR antagonists, with little CNS entry, can still engage efferent synaptic targets in the inner ear. The charged mAChR antagonists glycopyrrolate and methscopolamine blocked efferent-mediated slow excitation of mouse vestibular afferents following intraperitoneal, middle ear, or direct perilymphatic administration. Both mAChR antagonists were effective when delivered to the middle ear, contralateral to the side of afferent recordings, suggesting they gain vascular access after first entering the perilymphatic compartment. In contrast, charged α9α10nAChR antagonists blocked efferent-mediated suppression of DPOAEs only upon direct perilymphatic application, but failed to reach efferent synapses when systemically administered. These data show that efferent mechanisms are viable targets for further characterizing drug access in the inner ear.

scholarly journals Frequency matching of vocalizations to inner-ear sensitivity along an altitudinal gradient in the coqui frog

2009 ◽  
Vol 6 (2) ◽  
pp. 278-281 ◽  
Author(s):  
Sebastiaan W. F. Meenderink ◽  
Mirja Kits ◽  
Peter M. Narins
Keyword(s):  
Body Size ◽  
Inner Ear ◽  
Sea Level ◽  
Otoacoustic Emissions ◽  
Altitudinal Gradient ◽  
Distortion Product Otoacoustic Emissions ◽  
Frequency Range ◽  
Frequency Matching ◽  
Distortion Product ◽  
Sensitivity Change

Acoustic communication involves both the generation and the detection of a signal. In the coqui frog ( Eleutherodactylus coqui ), it is known that the spectral contents of its calls systematically change with altitude above sea level. Here, distortion product otoacoustic emissions are used to assess the frequency range over which the inner ear is sensitive. It is found that both the spectral contents of the calls and the inner-ear sensitivity change in a similar fashion along an altitudinal gradient. As a result, the call frequencies and the auditory tuning are closely matched at all altitudes. We suggest that the animal's body size determines the frequency particulars of the call apparatus and the inner ear.

scholarly journals Subclinical Auditory Dysfunction: Relationship Between Distortion Product Otoacoustic Emissions and the Audiogram

2021 ◽  
pp. 1-16
Author(s):  
Naomi F. Bramhall ◽  
Garnett P. McMillan ◽  
Amy N. Mashburn
Keyword(s):  
Otoacoustic Emissions ◽  
Pure Tone ◽  
Noise Exposure ◽  
Outer Hair Cell ◽  
Self Report ◽  
Distortion Product Otoacoustic Emissions ◽  
Sample Mean ◽  
Distortion Product ◽  
Clinically Normal ◽  
Auditory Physiology

Purpose Distortion product otoacoustic emissions (DPOAEs) and audiometric thresholds have been used to account for the impacts of subclinical outer hair cell (OHC) dysfunction on auditory perception and measures of auditory physiology. However, the relationship between DPOAEs and the audiogram is unclear. This study investigated this relationship by determining how well DPOAE levels can predict the audiogram among individuals with clinically normal hearing. Additionally, the impacts of age, noise exposure, and the perception of tinnitus on the ability of DPOAE levels to predict the audiogram were evaluated. Method Suprathreshold DPOAE levels from 1 to 10 kHz and pure-tone thresholds from 0.25 to 16 kHz were measured in 366 ears from 194 young adults (19–35 years old) with clinically normal audiograms and middle ear function. The measured DPOAE levels at all frequencies were used to predict pure-tone thresholds at each frequency. Participants were grouped by age, self-reported noise exposure/Veteran status, and self-report of tinnitus. Results Including DPOAE levels in the pure-tone threshold prediction model improved threshold predictions at all frequencies from 0.25 to 16 kHz compared with a model based only on sample mean pure-tone thresholds, but these improvements were modest. DPOAE levels for f 2 frequencies of 4 and 5 kHz were particularly influential in predicting pure-tone thresholds above 4 kHz. However, prediction accuracy varied based on participant characteristics. On average, predicted pure-tone thresholds were better than measured thresholds among Veterans, individuals with tinnitus, and the oldest age group. Conclusions These results indicate a complex relationship between DPOAE levels and the audiogram. Underestimation of pure-tone thresholds for some groups suggests that additional factors other than OHC damage may impact thresholds among individuals within these categories. These findings suggest that DPOAE levels and pure-tone thresholds may differ in terms of how well they reflect subclinical OHC dysfunction. Supplemental Material https://doi.org/10.23641/asha.13564745

Relationships among Standard and Wideband Measures of Middle Ear Function and Distortion Product Otoacoustic Emissions

2011 ◽  
Vol 22 (05) ◽  
pp. 253-264 ◽  
Author(s):  
Kim S. Schairer ◽  
Brooke Morrison ◽  
Ellyn Szewczyk ◽  
Cynthia G. Fowler
Keyword(s):  
Middle Ear ◽  
Repeated Measures ◽  
Otoacoustic Emissions ◽  
Transfer Functions ◽  
Ambient Pressure ◽  
Normal Hearing ◽  
Distortion Product Otoacoustic Emissions ◽  
Distortion Product ◽  
Two Systems ◽  
The Relationship

Background: The overall goal of the current study was to examine the relationships among uncompensated admittance (Ya) at ambient pressure extracted from tympanograms, energy reflectance (ER) measures at ambient pressure from wideband acoustic transfer functions (WATF), and distortion product otoacoustic emissions (DPOAEs). If WATF measures of Ya are comparable to tympanometric measures of Ya at ambient pressure, it would be further evidence that the two systems provide comparable information at ambient pressure. Such a relationship could be used as a cross-check or validation for WATF measures and support the use of WATFs in lieu of tympanograms in some applications. Finally, if WATF measures of Ya and/or ER at DPOAE stimulus frequencies can account for some of the variability observed in DPOAE levels and/or signal-to-noise ratios (SNRs) in ears with normal hearing, the relationships could be used to improve hearing screening procedures. Purpose: The hypotheses were as follows: (1) measures of Ya at ambient pressure are significantly correlated as measured with tympanometric and WATF procedures and (2) measures of Ya and ER at DPOAE stimulus frequencies are significantly correlated with DPOAE level and SNR. Research Design: Repeated measures in human adults. Study Sample: Forty ears of 20 adults with normal hearing and middle ear function were included in the final sample. Data Collection and Analysis: Tympanograms were obtained using probe frequencies of 226, 678, and 1000 Hz; WATFs were obtained using a click probe, and DPOAEs were elicited with f2's of 1000, 2000, and 4000 Hz. A repeated measures analysis of variance (RM-ANOVA) was completed to identify significant differences between ears and among probe frequencies for Ya measured at ambient pressure from the Tympstar and for Ya measured at the three closest frequencies on the WATFs. Lines were fit to the comparison of Ya from the Tympstar and WATF, and percent variance accounted for (r2) was calculated. Ya and ER were extracted at all stimulus frequencies that were used to elicit DPOAEs and were compared to DPOAE levels and SNRs. RM-ANOVAs were completed to identify any significant differences in DPOAE level and SNR between ears and among f2 conditions. Lines were fit to the comparison of Ya and ER measures at f1 and f2 with the DPOAE levels and SNRs. The relationship between behavioral air conduction threshold at each f2 and DPOAE level (and SNR) was examined with regression analysis. Results: Ya was significantly correlated between the tympanometric and WATF measures at all three probe-tone frequencies. Ya and ER at f1 and f2 were significantly correlated with DPOAE level for f2 = 4000 Hz. Conclusions: The implications are as follows: (1) WATFs, which can be obtained with the same probe microphone system as DPOAEs, could be used as a supplement to tympanometry in a diagnostic test battery, and the relationship between Ya measured on the two systems could be used for verification, and (2) Ya and ER measures from WATFs at both DPOAE stimulus frequencies account for some of the variability observed in DPOAE levels at f2 = 4000 Hz in normal ears.

Safety and Efficacy of Topical Mitomycin C in Myringotomy Patency

2001 ◽  
Vol 124 (4) ◽  
pp. 368-373 ◽  
Author(s):  
David Jassir ◽  
Craig A. Buchman ◽  
Orlando Gomez-Marin
Keyword(s):  
Guinea Pig ◽  
Mitomycin C ◽  
Middle Ear ◽  
Otoacoustic Emissions ◽  
Saline Solution ◽  
Argon Laser ◽  
Distortion Product Otoacoustic Emissions ◽  
Safety And Efficacy ◽  
Distortion Product ◽  
Middle Ear Ventilation

OBJECTIVE: To develop an alternative method for prolonged middle ear ventilation using topical mitomycin C. STUDY DESIGN AND SETTING: Twenty guinea pigs with normal ears had bilateral myringotomies performed using the argon laser. After myringotomy, either mitomycin C (0.4 mg/mL) or saline pledgets were applied topically. Monitoring consisted of otomicroscopy and distortion-product otoacoustic emissions. RESULTS: Before myringotomy, all tympanic membranes were intact, and distortion-product otoacoustic emissions were measurable. After myringotomy, none (0%) of the saline-treated myringotomies were patent at day 7 as compared with 100% of the mitomycin C-treated myringotomies. At day 42, 10 (52.6%) of 19 mitomycin-treated myringotomies remained patent and 4 (28.6%) of 14 were patent at 131 days. Five (13.1%) ears developed purulent otorrhea; 3 were mitomycin C-treated and 2 were treated with saline solution. Distortion-product otoacoustic emissions testing did not document any evidence of ototoxicity. CONCLUSION: Topical mitomycin C appears to be safe and effective at prolonging the duration of myringotomy patency in the guinea pig. SIGNIFICANCE: Mitomycin C may be useful as an adjunct for preventing myringotomy closure.

Injectable Form of Cross-Linked Hyaluronan is Effective for Middle Ear Wound Healing

2007 ◽  
Vol 116 (9) ◽  
pp. 667-673 ◽  
Author(s):  
Simon Angeli ◽  
Sarah Connell ◽  
Brian Gibson ◽  
Ali Ozdek ◽  
John T. McElveen ◽  
...  
Keyword(s):  
Wound Healing ◽  
Middle Ear ◽  
Otoacoustic Emissions ◽  
Inflammatory Cells ◽  
Control Group ◽  
Term Study ◽  
Distortion Product ◽  
Long Term Study ◽  
Group 2 ◽  
Group 1

Objectives: Two studies were designed to investigate a hyaluronan (HA) gel for middle ear (ME) wound healing. Methods: We used a guinea pig model of ME wound healing. In a long-term study, we performed a comparison of hearing and ME inflammation in 3 groups. Group 1 (n = 8) underwent bilateral wounding of ME mucosa and unilateral packing of the ME with HA gel (Sepragel). Group 2 (n = 6) was the same as group 1 except that the packing was absorbable bovine collagen sponges (Gelfoam). Group 3, the control group (n = 14), had operated, unpacked ears. In a short-term study, we investigated ME retention of HA gel at 1 and 2 weeks (n = 16). Results: At 1 week, all ears showed decreased distortion product otoacoustic emissions (DPOAEs) and auditory brain stem responses (ABRs) secondary to ME packing and postsurgical inflammation. The controls recovered preoperative DPOAEs and ABRs by week 2. Group 1 had decreased low-frequency DPOAEs at weeks 2 and 6, but their high-frequency DPOAEs and ABRs recovered to preoperative values by week 6. Group 2 had hearing losses that persisted throughout the study. Group 1 showed normal ME and inner ear histologic characteristics. Group 2 showed inflammatory cells within the ME and cochleas. Group 1 showed less packing retention than did group 2 at week 6 (p = 016). Eighty-five percent of the HA packing remained at 1 week, and 73% at 2 weeks. Conclusions: Hyaluronan gel was a relatively safe and effective ME packing material in our animal model.

scholarly journals Clinical Investigation and Mechanism of Air-Bone Gaps in Large Vestibular Aqueduct Syndrome

2007 ◽  
Vol 116 (7) ◽  
pp. 532-541 ◽  
Author(s):  
Saumil N. Merchant ◽  
Hideko H. Nakajima ◽  
Christopher Halpin ◽  
Joseph B. Nadol ◽  
Daniel J. Lee ◽  
...  
Keyword(s):  
Inner Ear ◽  
Middle Ear ◽  
Bone Conduction ◽  
Distortion Product Otoacoustic Emission ◽  
Low Frequencies ◽  
Distortion Product ◽  
Vestibular Aqueduct ◽  
Acoustic Reflexes ◽  
Large Vestibular Aqueduct Syndrome ◽  
Large Vestibular Aqueduct

Objectives: Patients with large vestibular aqueduct syndrome (LVAS) often demonstrate an air-bone gap at the low frequencies on audiometric testing. The mechanism causing such a gap has not been well elucidated. We investigated middle ear sound transmission in patients with LVAS, and present a hypothesis to explain the air-bone gap. Methods: Observations were made on 8 ears from 5 individuals with LVAS. The diagnosis of LVAS was made by computed tomography in all cases. Investigations included standard audiometry and measurements of umbo velocity by laser Doppler vibrometry (LDV) in all cases, as well as tympanometry, acoustic reflex testing, vestibular evoked myogenic potential (VEMP) testing, distortion product otoacoustic emission (DPOAE) testing, and middle ear exploration in some ears. Results: One ear with LVAS had anacusis. The other 7 ears demonstrated air-bone gaps at the low frequencies, with mean gaps of 51 dB at 250 Hz, 31 dB at 500 Hz, and 12 dB at 1,000 Hz. In these 7 ears with air-bone gaps, LDV showed the umbo velocity to be normal or high normal in all 7; tympanometry was normal in all 6 ears tested; acoustic reflexes were present in 3 of the 4 ears tested; VEMP responses were present in all 3 ears tested; DPOAEs were present in 1 of the 2 ears tested, and exploratory tympanotomy in 1 case showed a normal middle ear. The above data suggest that an air-bone gap in LVAS is not due to disease in the middle ear. The data are consistent with the hypothesis that a large vestibular aqueduct introduces a third mobile window into the inner ear, which can produce an air-bone gap by 1) shunting air-conducted sound away from the cochlea, thus elevating air conduction thresholds, and 2) increasing the difference in impedance between the scala vestibuli side and the scala tympani side of the cochlear partition during bone conduction testing, thus improving thresholds for bone-conducted sound. Conclusions: We conclude that LVAS can present with an air-bone gap that can mimic middle ear disease. Diagnostic testing using acoustic reflexes, VEMPs, DPOAEs, and LDV can help to identify a non?middle ear source for such a gap, thereby avoiding negative middle ear exploration. A large vestibular aqueduct may act as a third mobile window in the inner ear, resulting in an air-bone gap at low frequencies.

scholarly journals Beyond the limits: identifying the high-frequency detectors in the anuran ear

2020 ◽  
Vol 16 (7) ◽  
pp. 20200343
Author(s):  
Ariadna Cobo-Cuan ◽  
T. Ulmar Grafe ◽  
Peter M. Narins
Keyword(s):  
Inner Ear ◽  
High Frequency ◽  
Otoacoustic Emissions ◽  
Sensory System ◽  
Low Frequency ◽  
Basilar Papilla ◽  
High Frequency Ultrasound ◽  
Ultrasonic Signals ◽  
Distortion Product ◽  
Frog Species

Despite the predominance of low-frequency hearing in anuran amphibians, a few frog species have evolved high-frequency communication within certain environmental contexts. Huia cavitympanum is the most remarkable anuran with regard to upper frequency limits; it is the first frog species known to emit exclusively ultrasonic signals. Characteristics of the Distortion Product Otoacoustic Emissions from the amphibian papilla and the basilar papilla were analysed to gain insight into the structures responsible for high-frequency/ultrasound sensitivity. Our results confirm the matching of vocalization spectra and inner ear tuning in this species. Compared to most anurans, H. cavitympanum has a hyperextended hearing range spanning from audible to ultrasonic frequencies, far above the previously established ‘spectral limits’ for the amphibian ear. The exceptional high-frequency sensitivity in the inner ear of H. cavitympanum illustrates the remarkable plasticity of the auditory system and the extent to which evolution can modify a sensory system to adapt it to its environment.

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