Increased spontaneous firing rates in auditory midbrain following noise exposure are specifically abolished by a Kv3 channel modulator

Lucy A. Anderson, Lara L. Hesse, Nadia Pilati, Warren M. H. Bakay, Giuseppe Alvaro, Charles H. Large, David McAlpine, Roland Schaette, Jennifer F. Linden

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Noise exposure has been shown to produce long-lasting increases in spontaneous activity in central auditory structures in animal models, and similar pathologies are thought to contribute to clinical phenomena such as hyperacusis or tinnitus in humans. Here we demonstrate that multi-unit spontaneous neuronal activity in the inferior colliculus (IC) of mice is significantly elevated four weeks following noise exposure at recording sites with frequency tuning within or near the noise exposure band, and this selective central auditory pathology can be normalised through administration of a novel compound that modulates activity of Kv3 voltage-gated ion channels. The compound had no statistically significant effect on IC spontaneous activity without noise exposure, nor on thresholds or frequency tuning of tone-evoked responses either with or without noise exposure. Administration of the compound produced some reduction in the magnitude of evoked responses to a broadband noise, but unlike effects on spontaneous rates, these effects on evoked responses were not specific to recording sites with frequency tuning within the noise exposure band. Thus, the results suggest that modulators of Kv3 channels can selectively counteract increases in spontaneous activity in the auditory midbrain associated with noise exposure.

LanguageEnglish
Pages77-89
Number of pages13
JournalHearing Research
Volume365
DOIs
Publication statusPublished - Aug 2018
Externally publishedYes

Fingerprint

Mesencephalon
Noise
Inferior Colliculi
Hyperacusis
Pathology
Tinnitus
Ion Channels
Animal Models

Cite this

Anderson, Lucy A. ; Hesse, Lara L. ; Pilati, Nadia ; Bakay, Warren M. H. ; Alvaro, Giuseppe ; Large, Charles H. ; McAlpine, David ; Schaette, Roland ; Linden, Jennifer F. / Increased spontaneous firing rates in auditory midbrain following noise exposure are specifically abolished by a Kv3 channel modulator. In: Hearing Research. 2018 ; Vol. 365. pp. 77-89.
@article{924d9de015ff4ab38bd6bd124103ba1f,
title = "Increased spontaneous firing rates in auditory midbrain following noise exposure are specifically abolished by a Kv3 channel modulator",
abstract = "Noise exposure has been shown to produce long-lasting increases in spontaneous activity in central auditory structures in animal models, and similar pathologies are thought to contribute to clinical phenomena such as hyperacusis or tinnitus in humans. Here we demonstrate that multi-unit spontaneous neuronal activity in the inferior colliculus (IC) of mice is significantly elevated four weeks following noise exposure at recording sites with frequency tuning within or near the noise exposure band, and this selective central auditory pathology can be normalised through administration of a novel compound that modulates activity of Kv3 voltage-gated ion channels. The compound had no statistically significant effect on IC spontaneous activity without noise exposure, nor on thresholds or frequency tuning of tone-evoked responses either with or without noise exposure. Administration of the compound produced some reduction in the magnitude of evoked responses to a broadband noise, but unlike effects on spontaneous rates, these effects on evoked responses were not specific to recording sites with frequency tuning within the noise exposure band. Thus, the results suggest that modulators of Kv3 channels can selectively counteract increases in spontaneous activity in the auditory midbrain associated with noise exposure.",
keywords = "inferior colliculus, noise exposure, acoustic trauma, potassium channels, spontaneous activity, AUT00063",
author = "Anderson, {Lucy A.} and Hesse, {Lara L.} and Nadia Pilati and Bakay, {Warren M. H.} and Giuseppe Alvaro and Large, {Charles H.} and David McAlpine and Roland Schaette and Linden, {Jennifer F.}",
year = "2018",
month = "8",
doi = "10.1016/j.heares.2018.04.012",
language = "English",
volume = "365",
pages = "77--89",
journal = "Hearing Research",
issn = "0378-5955",
publisher = "Elsevier",

}

Increased spontaneous firing rates in auditory midbrain following noise exposure are specifically abolished by a Kv3 channel modulator. / Anderson, Lucy A.; Hesse, Lara L.; Pilati, Nadia; Bakay, Warren M. H.; Alvaro, Giuseppe; Large, Charles H.; McAlpine, David; Schaette, Roland; Linden, Jennifer F.

In: Hearing Research, Vol. 365, 08.2018, p. 77-89.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Increased spontaneous firing rates in auditory midbrain following noise exposure are specifically abolished by a Kv3 channel modulator

AU - Anderson,Lucy A.

AU - Hesse,Lara L.

AU - Pilati,Nadia

AU - Bakay,Warren M. H.

AU - Alvaro,Giuseppe

AU - Large,Charles H.

AU - McAlpine,David

AU - Schaette,Roland

AU - Linden,Jennifer F.

PY - 2018/8

Y1 - 2018/8

N2 - Noise exposure has been shown to produce long-lasting increases in spontaneous activity in central auditory structures in animal models, and similar pathologies are thought to contribute to clinical phenomena such as hyperacusis or tinnitus in humans. Here we demonstrate that multi-unit spontaneous neuronal activity in the inferior colliculus (IC) of mice is significantly elevated four weeks following noise exposure at recording sites with frequency tuning within or near the noise exposure band, and this selective central auditory pathology can be normalised through administration of a novel compound that modulates activity of Kv3 voltage-gated ion channels. The compound had no statistically significant effect on IC spontaneous activity without noise exposure, nor on thresholds or frequency tuning of tone-evoked responses either with or without noise exposure. Administration of the compound produced some reduction in the magnitude of evoked responses to a broadband noise, but unlike effects on spontaneous rates, these effects on evoked responses were not specific to recording sites with frequency tuning within the noise exposure band. Thus, the results suggest that modulators of Kv3 channels can selectively counteract increases in spontaneous activity in the auditory midbrain associated with noise exposure.

AB - Noise exposure has been shown to produce long-lasting increases in spontaneous activity in central auditory structures in animal models, and similar pathologies are thought to contribute to clinical phenomena such as hyperacusis or tinnitus in humans. Here we demonstrate that multi-unit spontaneous neuronal activity in the inferior colliculus (IC) of mice is significantly elevated four weeks following noise exposure at recording sites with frequency tuning within or near the noise exposure band, and this selective central auditory pathology can be normalised through administration of a novel compound that modulates activity of Kv3 voltage-gated ion channels. The compound had no statistically significant effect on IC spontaneous activity without noise exposure, nor on thresholds or frequency tuning of tone-evoked responses either with or without noise exposure. Administration of the compound produced some reduction in the magnitude of evoked responses to a broadband noise, but unlike effects on spontaneous rates, these effects on evoked responses were not specific to recording sites with frequency tuning within the noise exposure band. Thus, the results suggest that modulators of Kv3 channels can selectively counteract increases in spontaneous activity in the auditory midbrain associated with noise exposure.

KW - inferior colliculus

KW - noise exposure

KW - acoustic trauma

KW - potassium channels

KW - spontaneous activity

KW - AUT00063

UR - http://www.scopus.com/inward/record.url?scp=85047226342&partnerID=8YFLogxK

U2 - 10.1016/j.heares.2018.04.012

DO - 10.1016/j.heares.2018.04.012

M3 - Article

VL - 365

SP - 77

EP - 89

JO - Hearing Research

T2 - Hearing Research

JF - Hearing Research

SN - 0378-5955

ER -