Minimal Effects of Age and Exposure to a Noisy Environment on Hearing in Alpha9 Nicotinic Receptor Knockout Mice

Lauer, Amanda M.

doi:10.3389/fnins.2017.00304

Cited by 14 publications

(16 citation statements)

References 73 publications

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“…These 50% PPI response changes with the MOC pathway silenced or over-activated, are similar to what is predicted by the rate-level functions of auditory unit recordings with and without MOC stimulation (Winslow and Sachs, 1987 , 1988 ; Sachs et al, 1989 ). We had expected to observe a PPI threshold shift in background noise but did not observe any significant differences, yet this lack of significance could be due to the higher variance observed in the α9 nAChR (–/–) animals, as has been observed in other studies using this mouse line (Lauer, 2017 ). We are not sure if higher order pathways could have compensated for genetically altered MOC feedback (Salvi et al, 2000 , 2016 ; Auerbach et al, 2014 ), yet if there was higher-order compensation, this compensation did not fully negate changes observed in the CGRP (–/–) animals.…”

Section: Discussionmentioning

confidence: 70%

Reflex Modification Audiometry Reveals Dual Roles for Olivocochlear Neurotransmission

Allen

Luebke

2017

Front. Cell. Neurosci.

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Approximately 15% of American adults report some degree of difficulty hearing in a noisy environment or have auditory filtering difficulties. There are objective clinical tests of auditory filtering, yet few tests exist for mouse models that do not rely on extensive training. We have used reflex modification audiometry (RMA) and developed exclusion criteria for the mouse model. This RMA based test makes use of the acoustic startle response (ASR) and the ability of prepulses to inhibit the ASR [i.e., prepulse inhibition (PPI)] to assess the mouse's ability to detect prepulse signals presented in quiet or embedded in masking noise. We have studied PPI behavior across four inbred mouse strains with normal cochlear function and developed pre-testing exclusion criteria and test/retest reliability measures. Moreover, because both the medial (MOC) and the lateral (LOC) olivocochlear efferent feedback systems have been proposed to improve auditory behavior performance, especially in noisy backgrounds, we have examined PPI abilities in mice (with their littermate controls) either lacking the MOC receptor subunit α9 nicotinic acetylcholine receptor [α9 nAChR (–/–)] or expressing an overactive receptor [Ld'T mutation in α9 nAChR KI], or lacking an LOC efferent neuropeptide, alpha calcitonin gene-related peptide [αCGRP (–/–)] only in the CNS. Because CGRP receptor formation has been shown to mature from juvenile to adult ages, we also studied if this maturation would be reflected in PPI behavioral responses in juvenile and adult (+/+) controls and in adult αCGRP (–/–) animals. We show that 50% PPI response thresholds (sound level with 50% correct responses) in quiet are decreased in the (–/–) α9 nAChR animals, and 50% PPI responses are increased for mice with an overactive receptor (α9 nAChR KI) and are increased in adult mice lacking αCGRP (–/–). However, in background noise, only mice lacking αCGRP exhibited increased 50% PPI response thresholds, as there were no significant differences between α9 nAChR adult mouse lines and their littermate controls. These findings suggest that MOC and LOC olivocochlear neurotransmission work in tandem to improve behavioral responses to sound. These experiments further pave the way for rapid behavioral hearing assessments in other mouse models.

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Section: Discussionmentioning

confidence: 70%

Reflex Modification Audiometry Reveals Dual Roles for Olivocochlear Neurotransmission

Allen

Luebke

2017

Front. Cell. Neurosci.

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“…We recorded ABRs 1 month after exposure to measure auditory sensitivity and determine if the auditory brainstem exhibited hyperactivity. Procedures were similar to those described by McGuire et al (2015) and Lauer (2017) . Mice were anesthetized with 100 mg/kg ketamine and 20 mg/kg xylazine and placed on a heating pad inside a small sound-attenuating chamber (IAC) lined with Sonex acoustic foam to reduce acoustic reflections.…”

Section: Methodsmentioning

confidence: 99%

Central Compensation in Auditory Brainstem after Damaging Noise Exposure

Schrode

Muniak

Kim

et al. 2018

eNeuro

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Noise exposure is one of the most common causes of hearing loss and peripheral damage to the auditory system. A growing literature suggests that the auditory system can compensate for peripheral loss through increased central neural activity. The current study sought to investigate the link between noise exposure, increases in central gain, synaptic reorganization, and auditory function. All axons of the auditory nerve project to the cochlear nucleus, making it a requisite nucleus for sound detection. As the first synapse in the central auditory system, the cochlear nucleus is well positioned to respond plastically to loss of peripheral input. To investigate noise-induced compensation in the central auditory system, we measured auditory brainstem responses (ABRs) and auditory perception and collected tissue from mice exposed to broadband noise. Noise-exposed mice showed elevated ABR thresholds, reduced ABR wave 1 amplitudes, and spiral ganglion neuron loss. Despite peripheral damage, noise-exposed mice were hyperreactive to loud sounds and showed nearly normal behavioral sound detection thresholds. Ratios of late ABR peaks (2–4) relative to the first ABR peak indicated that brainstem pathways were hyperactive in noise-exposed mice, while anatomical analysis indicated there was an imbalance between expression of excitatory and inhibitory proteins in the ventral cochlear nucleus. The results of the current study suggest that a reorganization of excitation and inhibition in the ventral cochlear nucleus may drive hyperactivity in the central auditory system. This increase in central gain can compensate for peripheral loss to restore some aspects of auditory function.

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“…The ABR threshold was calculated automatically, using a custom MATLAB script. The threshold was defined as the sound intensity level at which the peak-totrough amplitude of the ABR wave was at least two standard deviations above the mean baseline amplitude estimated from the last 5 ms in the recording when no sound stimulus was present (Lina and Lauer, 2013;McGuire et al, 2015;Lauer, 2017;Schrode et al, 2018). A value of 95 dB SPL was used as a threshold for cases where one could not be found.…”

Section: Auditory Brainstem Response (Abr)mentioning

confidence: 99%

Olivocochlear Changes Associated With Aging Predominantly Affect the Medial Olivocochlear System

et al. 2021

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Age-related hearing loss (ARHL) is a public health problem that has been associated with negative health outcomes ranging from increased frailty to an elevated risk of developing dementia. Significant gaps remain in our knowledge of the underlying central neural mechanisms, especially those related to the efferent auditory pathways. Thus, the aim of this study was to quantify and compare age-related alterations in the cholinergic olivocochlear efferent auditory neurons. We assessed, in young-adult and aged CBA mice, the number of cholinergic olivocochlear neurons, auditory brainstem response (ABR) thresholds in silence and in presence of background noise, and the expression of excitatory and inhibitory proteins in the ventral nucleus of the trapezoid body (VNTB) and in the lateral superior olive (LSO). In association with aging, we found a significant decrease in the number of medial olivocochlear (MOC) cholinergic neurons together with changes in the ratio of excitatory and inhibitory proteins in the VNTB. Furthermore, in old mice we identified a correlation between the number of MOC neurons and ABR thresholds in the presence of background noise. In contrast, the alterations observed in the lateral olivocochlear (LOC) system were less significant. The decrease in the number of LOC cells associated with aging was 2.7-fold lower than in MOC and in the absence of changes in the expression of excitatory and inhibitory proteins in the LSO. These differences suggest that aging alters the medial and lateral olivocochlear efferent pathways in a differential manner and that the changes observed may account for some of the symptoms seen in ARHL.

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Minimal Effects of Age and Exposure to a Noisy Environment on Hearing in Alpha9 Nicotinic Receptor Knockout Mice

Cited by 14 publications

References 73 publications

Reflex Modification Audiometry Reveals Dual Roles for Olivocochlear Neurotransmission

Reflex Modification Audiometry Reveals Dual Roles for Olivocochlear Neurotransmission

Central Compensation in Auditory Brainstem after Damaging Noise Exposure

Olivocochlear Changes Associated With Aging Predominantly Affect the Medial Olivocochlear System

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