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Noise-Induced Hearing Loss Alters Potassium-Chloride CoTransporter KCC2 and GABA Inhibition in the auditory centers

Homeostatic plasticity, the ability of neurons to maintain their averaged activity constant around a set point value, is thought to account for the central hyperactivity after hearing loss. Here, we investigated the putative role of GABAergic neurotransmission in this mechanism after a noise-induced...

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Autores principales: Parameshwarappa, Vinay, Siponen, Marina, Watabe, Isabelle, Karkaba, Alaa, Galazyuk, Alex, Noreña, Arnaud
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Journal Experts 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602088/
https://www.ncbi.nlm.nih.gov/pubmed/37886592
http://dx.doi.org/10.21203/rs.3.rs-3389804/v1
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author Parameshwarappa, Vinay
Siponen, Marina
Watabe, Isabelle
Karkaba, Alaa
Galazyuk, Alex
Noreña, Arnaud
author_facet Parameshwarappa, Vinay
Siponen, Marina
Watabe, Isabelle
Karkaba, Alaa
Galazyuk, Alex
Noreña, Arnaud
author_sort Parameshwarappa, Vinay
collection PubMed
description Homeostatic plasticity, the ability of neurons to maintain their averaged activity constant around a set point value, is thought to account for the central hyperactivity after hearing loss. Here, we investigated the putative role of GABAergic neurotransmission in this mechanism after a noise-induced hearing loss larger than 50 dB in high frequencies in guinea pigs. The effect of GABAergic inhibition is linked to the normal functioning of K+–Cl− co-transporter isoform 2 (KCC2) which maintains a low intracellular concentration of chloride. The expression of membrane KCC2 were investigated before after noise trauma in the ventral and dorsal cochlear nucleus (VCN and DCN, respectively) and in the inferior colliculus (IC). Moreover, the effect of gabazine (GBZ), a GABA antagonist, was also studied on the neural activity in IC. We show that KCC2 is downregulated in VCN, DCN and IC 3 days after noise trauma, and in DCN and IC 30 days after the trauma. As expected, GBZ application in the IC of control animals resulted in an increase of spontaneous and stimulus-evoked activity. In the noise exposed animals, on the other hand, GBZ application decreased the stimulus-evoked activity in IC neurons. The functional implications of these central changes are discussed.
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spelling pubmed-106020882023-10-27 Noise-Induced Hearing Loss Alters Potassium-Chloride CoTransporter KCC2 and GABA Inhibition in the auditory centers Parameshwarappa, Vinay Siponen, Marina Watabe, Isabelle Karkaba, Alaa Galazyuk, Alex Noreña, Arnaud Res Sq Article Homeostatic plasticity, the ability of neurons to maintain their averaged activity constant around a set point value, is thought to account for the central hyperactivity after hearing loss. Here, we investigated the putative role of GABAergic neurotransmission in this mechanism after a noise-induced hearing loss larger than 50 dB in high frequencies in guinea pigs. The effect of GABAergic inhibition is linked to the normal functioning of K+–Cl− co-transporter isoform 2 (KCC2) which maintains a low intracellular concentration of chloride. The expression of membrane KCC2 were investigated before after noise trauma in the ventral and dorsal cochlear nucleus (VCN and DCN, respectively) and in the inferior colliculus (IC). Moreover, the effect of gabazine (GBZ), a GABA antagonist, was also studied on the neural activity in IC. We show that KCC2 is downregulated in VCN, DCN and IC 3 days after noise trauma, and in DCN and IC 30 days after the trauma. As expected, GBZ application in the IC of control animals resulted in an increase of spontaneous and stimulus-evoked activity. In the noise exposed animals, on the other hand, GBZ application decreased the stimulus-evoked activity in IC neurons. The functional implications of these central changes are discussed. American Journal Experts 2023-10-09 /pmc/articles/PMC10602088/ /pubmed/37886592 http://dx.doi.org/10.21203/rs.3.rs-3389804/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Parameshwarappa, Vinay
Siponen, Marina
Watabe, Isabelle
Karkaba, Alaa
Galazyuk, Alex
Noreña, Arnaud
Noise-Induced Hearing Loss Alters Potassium-Chloride CoTransporter KCC2 and GABA Inhibition in the auditory centers
title Noise-Induced Hearing Loss Alters Potassium-Chloride CoTransporter KCC2 and GABA Inhibition in the auditory centers
title_full Noise-Induced Hearing Loss Alters Potassium-Chloride CoTransporter KCC2 and GABA Inhibition in the auditory centers
title_fullStr Noise-Induced Hearing Loss Alters Potassium-Chloride CoTransporter KCC2 and GABA Inhibition in the auditory centers
title_full_unstemmed Noise-Induced Hearing Loss Alters Potassium-Chloride CoTransporter KCC2 and GABA Inhibition in the auditory centers
title_short Noise-Induced Hearing Loss Alters Potassium-Chloride CoTransporter KCC2 and GABA Inhibition in the auditory centers
title_sort noise-induced hearing loss alters potassium-chloride cotransporter kcc2 and gaba inhibition in the auditory centers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602088/
https://www.ncbi.nlm.nih.gov/pubmed/37886592
http://dx.doi.org/10.21203/rs.3.rs-3389804/v1
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