Disruption of lateral olivocochlear neurons with a dopaminergic neurotoxin depresses spontaneous auditory nerve activity

Prell, Colleen G. Le; Dolan, David F.; Hughes, Larry F.; Altschuler, Richard A.; Shore, Susan E.; Bledsoe, Sanford C.

doi:10.1016/j.neulet.2014.08.040

Cited by 10 publications

(8 citation statements)

References 48 publications

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“…When the LSO is lesioned in the guinea pig brainstem using melittin ( Le Prell et al, 2003b ) or the LOC system is lesioned in the guinea pig cochlea using MPTP ( Le Prell et al, 2005 ), sound-driven AN activity is decreased. When the guinea pig LOC system is lesioned using MPTP, spontaneous AN firing is also decreased ( Le Prell et al, 2014a ). We have long speculated that the decreases in spontaneous and sound driven AN firing after OCB transection, LSO lesion, or LOC lesion could be the result of compromised CGRP release when the LOC system is disrupted ( Le Prell et al, 2003b ; Le Prell et al, 2005 ; Le Prell, 2007 ; Le Prell et al, 2014a ).…”

Section: Discussionmentioning

confidence: 99%

Effects of Calcitonin-Gene-Related-Peptide on Auditory Nerve Activity

Prell

Hughes

Dolan

et al. 2021

Front. Cell Dev. Biol.

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Calcitonin-gene-related peptide (CGRP) is a lateral olivocochlear (LOC) efferent neurotransmitter. Depression of sound-driven auditory brainstem response amplitude in CGRP-null mice suggests the potential for endogenous CGRP release to upregulate spontaneous and/or sound-driven auditory nerve (AN) activity. We chronically infused CGRP into the guinea pig cochlea and evaluated changes in AN activity as well as outer hair cell (OHC) function. The amplitude of both round window noise (a measure of ensemble spontaneous activity) and the synchronous whole-nerve response to sound (compound action potential, CAP) were enhanced. Lack of change in both onset adaptation and steady state amplitude of sound-evoked distortion product otoacoustic emission (DPOAE) responses indicated CGRP had no effect on OHCs, suggesting the origin of the observed changes was neural. Combined with results from the CGRP-null mice, these results appear to confirm that endogenous CGRP enhances auditory nerve activity when released by the LOC neurons. However, infusion of the CGRP receptor antagonist CGRP (8–37) did not reliably influence spontaneous or sound-driven AN activity, or OHC function, results that contrast with the decreased ABR amplitude measured in CGRP-null mice.

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Section: Discussionmentioning

confidence: 99%

Effects of Calcitonin-Gene-Related-Peptide on Auditory Nerve Activity

Prell

Hughes

Dolan

et al. 2021

Front. Cell Dev. Biol.

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“…Because the MOC projection is myelinated and the LOC projection is not, stimulation of the IVth floor of the ventricle also predominately activates the MOC pathway. However, it is possible to selectively disrupt the LOC pathway using a neurotoxin and Le Prell et al ( 2014a ) found that disruption of LOC neurons depressed spontaneous cochlear nerve activity. When the CGRP component of the LOC system was eliminated, the loss of CGRP caused reduced cochlear nerve activity and resulted in increased 50% PPI thresholds in quiet and in background noise.…”

Section: Discussionmentioning

confidence: 99%

“…Loss of either the MOC or LOC system after cochlear development does not affect auditory thresholds, yet both systems are activated by sound. Sound suppresses MOC responses (as assessed by otoacoustic emissions and cochlear action potentials and nerve activity) and CGRP transmission through the LOC system has been shown to enhance suprathreshold cochlear nerve activity suggesting that both systems may work in tandem to enhance behavioral responses to sound (Maison et al, 2002 , 2003a ; Guinan et al, 2005 ; Guinan, 2006 , 2010 , 2013 , 2014 ; Le Prell et al, 2014a , b ; Dickerson et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

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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“…In other words, the effect of damaging LOC parent neurons on auditory nerve responses seems to be species specific. Disruption of LOC efferents with a dopaminergic neurotoxin depresses the spontaneous activity of auditory nerve fibers in guinea pig ( 73 ).…”

Section: Anatomy and Physiology Of Olivocochlear Efferents In Animalsmentioning

confidence: 99%

Olivocochlear Efferents in Animals and Humans: From Anatomy to Clinical Relevance

Lopez‐Poveda

2018

Front. Neurol.

104

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Olivocochlear efferents allow the central auditory system to adjust the functioning of the inner ear during active and passive listening. While many aspects of efferent anatomy, physiology and function are well established, others remain controversial. This article reviews the current knowledge on olivocochlear efferents, with emphasis on human medial efferents. The review covers (1) the anatomy and physiology of olivocochlear efferents in animals; (2) the methods used for investigating this auditory feedback system in humans, their limitations and best practices; (3) the characteristics of medial-olivocochlear efferents in humans, with a critical analysis of some discrepancies across human studies and between animal and human studies; (4) the possible roles of olivocochlear efferents in hearing, discussing the evidence in favor and against their role in facilitating the detection of signals in noise and in protecting the auditory system from excessive acoustic stimulation; and (5) the emerging association between abnormal olivocochlear efferent function and several health conditions. Finally, we summarize some open issues and introduce promising approaches for investigating the roles of efferents in human hearing using cochlear implants.

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Disruption of lateral olivocochlear neurons with a dopaminergic neurotoxin depresses spontaneous auditory nerve activity

Cited by 10 publications

References 48 publications

Effects of Calcitonin-Gene-Related-Peptide on Auditory Nerve Activity

Effects of Calcitonin-Gene-Related-Peptide on Auditory Nerve Activity

Reflex Modification Audiometry Reveals Dual Roles for Olivocochlear Neurotransmission

Olivocochlear Efferents in Animals and Humans: From Anatomy to Clinical Relevance

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