A gain-of-function mutation in the α9 nicotinic acetylcholine receptor alters medial olivocochlear efferent short-term synaptic plasticity

Autores
Wedemeyer, Carolina; Vattino, Lucas Gabriel; Moglie, Marcelo Javier; Ballestero, Jimena Andrea; Maison, Stéphane F.; Di Guilmi, Mariano Nicolás; Taranda, Julian; Liberman, M. Charles; Fuchs, Paul A.; Katz, Eleonora; Elgoyhen, Ana Belen
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Gain control of the auditory system operates at multiple levels. Cholinergic medial olivocochlear (MOC) fibers originate in the brainstem and make synaptic contacts at the base of the outer hair cells (OHCs), the final targets of several feedback loops from the periphery and higher-processing centers. Efferent activation inhibitsOHCactive amplification within the mammalian cochlea, through the activation of a calcium-permeable α 9 α 10 ionotropic cholinergic nicotinic receptor (nAChR), functionally coupled to calcium activated SK2 potassium channels. Correct operation of this feedback requires careful matching of acoustic input with the strength of cochlear inhibition (Galambos, 1956; Wiederhold and Kiang, 1970; Gifford and Guinan, 1987), which is driven by the rate of MOCactivity and short-term facilitation at theMOC-OHCsynapse (Ballestero et al., 2011; Katz and Elgoyhen, 2014). The present work shows (in mice of either sex) that a mutation in the α 9α 10 nAChR with increased duration of channel gating (Taranda et al., 2009) greatly elongates hair cell-evoked IPSCs and Ca2+signals. Interestingly, MOC–OHC synapses of L9’T mice presented reduced quantum content and increased presynaptic facilitation. These phenotypic changes lead to enhanced and sustained synaptic responses and OHC hyperpolarization upon high-frequency stimulation of MOC terminals. At the cochlear physiology level these changes were matched by a longer time course of efferent MOC suppression. This indicates that the properties of theMOC-OHCsynapse directly determine the efficacy of the MOCfeedback to the cochlea being a main player in the “gain control” of the auditory periphery.
Fil: Wedemeyer, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Vattino, Lucas Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Moglie, Marcelo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Ballestero, Jimena Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Maison, Stéphane F.. Harvard Medical School; Estados Unidos
Fil: Di Guilmi, Mariano Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Taranda, Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Liberman, M. Charles. Harvard Medical School; Estados Unidos
Fil: Fuchs, Paul A.. The Johns Hopkins University School of Medicine; Estados Unidos
Fil: Katz, Eleonora. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina
Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Materia
COCHLEA
EFFERENT INHIBITION
HAIR CELLS
SYNAPTIC PLASTICITY
α9α10 nAChR
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/79826
Acceder
id CONICETDig_900343b1ed7113e5ef62e0db8c4fa6e1
oai_identifier_str oai:ri.conicet.gov.ar:11336/79826
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A gain-of-function mutation in the α9 nicotinic acetylcholine receptor alters medial olivocochlear efferent short-term synaptic plasticityWedemeyer, CarolinaVattino, Lucas GabrielMoglie, Marcelo JavierBallestero, Jimena AndreaMaison, Stéphane F.Di Guilmi, Mariano NicolásTaranda, JulianLiberman, M. CharlesFuchs, Paul A.Katz, EleonoraElgoyhen, Ana BelenCOCHLEAEFFERENT INHIBITIONHAIR CELLSSYNAPTIC PLASTICITYα9α10 nAChRhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Gain control of the auditory system operates at multiple levels. Cholinergic medial olivocochlear (MOC) fibers originate in the brainstem and make synaptic contacts at the base of the outer hair cells (OHCs), the final targets of several feedback loops from the periphery and higher-processing centers. Efferent activation inhibitsOHCactive amplification within the mammalian cochlea, through the activation of a calcium-permeable α 9 α 10 ionotropic cholinergic nicotinic receptor (nAChR), functionally coupled to calcium activated SK2 potassium channels. Correct operation of this feedback requires careful matching of acoustic input with the strength of cochlear inhibition (Galambos, 1956; Wiederhold and Kiang, 1970; Gifford and Guinan, 1987), which is driven by the rate of MOCactivity and short-term facilitation at theMOC-OHCsynapse (Ballestero et al., 2011; Katz and Elgoyhen, 2014). The present work shows (in mice of either sex) that a mutation in the α 9α 10 nAChR with increased duration of channel gating (Taranda et al., 2009) greatly elongates hair cell-evoked IPSCs and Ca2+signals. Interestingly, MOC–OHC synapses of L9’T mice presented reduced quantum content and increased presynaptic facilitation. These phenotypic changes lead to enhanced and sustained synaptic responses and OHC hyperpolarization upon high-frequency stimulation of MOC terminals. At the cochlear physiology level these changes were matched by a longer time course of efferent MOC suppression. This indicates that the properties of theMOC-OHCsynapse directly determine the efficacy of the MOCfeedback to the cochlea being a main player in the “gain control” of the auditory periphery.Fil: Wedemeyer, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Vattino, Lucas Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Moglie, Marcelo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Ballestero, Jimena Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Maison, Stéphane F.. Harvard Medical School; Estados UnidosFil: Di Guilmi, Mariano Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Taranda, Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Liberman, M. Charles. Harvard Medical School; Estados UnidosFil: Fuchs, Paul A.. The Johns Hopkins University School of Medicine; Estados UnidosFil: Katz, Eleonora. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; ArgentinaFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaSociety for Neuroscience2018-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/79826Wedemeyer, Carolina; Vattino, Lucas Gabriel; Moglie, Marcelo Javier; Ballestero, Jimena Andrea; Maison, Stéphane F.; et al.; A gain-of-function mutation in the α9 nicotinic acetylcholine receptor alters medial olivocochlear efferent short-term synaptic plasticity; Society for Neuroscience; Journal of Neuroscience; 38; 16; 4-2018; 3939-39540270-6474CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29572431/info:eu-repo/semantics/altIdentifier/doi/10.1523/JNEUROSCI.2528-17.2018info:eu-repo/semantics/altIdentifier/url/https://www.jneurosci.org/content/38/16/3939info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:14:06Zoai:ri.conicet.gov.ar:11336/79826instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:14:06.264CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A gain-of-function mutation in the α9 nicotinic acetylcholine receptor alters medial olivocochlear efferent short-term synaptic plasticity
title A gain-of-function mutation in the α9 nicotinic acetylcholine receptor alters medial olivocochlear efferent short-term synaptic plasticity
spellingShingle A gain-of-function mutation in the α9 nicotinic acetylcholine receptor alters medial olivocochlear efferent short-term synaptic plasticity
Wedemeyer, Carolina
COCHLEA
EFFERENT INHIBITION
HAIR CELLS
SYNAPTIC PLASTICITY
α9α10 nAChR
title_short A gain-of-function mutation in the α9 nicotinic acetylcholine receptor alters medial olivocochlear efferent short-term synaptic plasticity
title_full A gain-of-function mutation in the α9 nicotinic acetylcholine receptor alters medial olivocochlear efferent short-term synaptic plasticity
title_fullStr A gain-of-function mutation in the α9 nicotinic acetylcholine receptor alters medial olivocochlear efferent short-term synaptic plasticity
title_full_unstemmed A gain-of-function mutation in the α9 nicotinic acetylcholine receptor alters medial olivocochlear efferent short-term synaptic plasticity
title_sort A gain-of-function mutation in the α9 nicotinic acetylcholine receptor alters medial olivocochlear efferent short-term synaptic plasticity
dc.creator.none.fl_str_mv Wedemeyer, Carolina
Vattino, Lucas Gabriel
Moglie, Marcelo Javier
Ballestero, Jimena Andrea
Maison, Stéphane F.
Di Guilmi, Mariano Nicolás
Taranda, Julian
Liberman, M. Charles
Fuchs, Paul A.
Katz, Eleonora
Elgoyhen, Ana Belen
author Wedemeyer, Carolina
author_facet Wedemeyer, Carolina
Vattino, Lucas Gabriel
Moglie, Marcelo Javier
Ballestero, Jimena Andrea
Maison, Stéphane F.
Di Guilmi, Mariano Nicolás
Taranda, Julian
Liberman, M. Charles
Fuchs, Paul A.
Katz, Eleonora
Elgoyhen, Ana Belen
author_role author
author2 Vattino, Lucas Gabriel
Moglie, Marcelo Javier
Ballestero, Jimena Andrea
Maison, Stéphane F.
Di Guilmi, Mariano Nicolás
Taranda, Julian
Liberman, M. Charles
Fuchs, Paul A.
Katz, Eleonora
Elgoyhen, Ana Belen
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv COCHLEA
EFFERENT INHIBITION
HAIR CELLS
SYNAPTIC PLASTICITY
α9α10 nAChR
topic COCHLEA
EFFERENT INHIBITION
HAIR CELLS
SYNAPTIC PLASTICITY
α9α10 nAChR
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Gain control of the auditory system operates at multiple levels. Cholinergic medial olivocochlear (MOC) fibers originate in the brainstem and make synaptic contacts at the base of the outer hair cells (OHCs), the final targets of several feedback loops from the periphery and higher-processing centers. Efferent activation inhibitsOHCactive amplification within the mammalian cochlea, through the activation of a calcium-permeable α 9 α 10 ionotropic cholinergic nicotinic receptor (nAChR), functionally coupled to calcium activated SK2 potassium channels. Correct operation of this feedback requires careful matching of acoustic input with the strength of cochlear inhibition (Galambos, 1956; Wiederhold and Kiang, 1970; Gifford and Guinan, 1987), which is driven by the rate of MOCactivity and short-term facilitation at theMOC-OHCsynapse (Ballestero et al., 2011; Katz and Elgoyhen, 2014). The present work shows (in mice of either sex) that a mutation in the α 9α 10 nAChR with increased duration of channel gating (Taranda et al., 2009) greatly elongates hair cell-evoked IPSCs and Ca2+signals. Interestingly, MOC–OHC synapses of L9’T mice presented reduced quantum content and increased presynaptic facilitation. These phenotypic changes lead to enhanced and sustained synaptic responses and OHC hyperpolarization upon high-frequency stimulation of MOC terminals. At the cochlear physiology level these changes were matched by a longer time course of efferent MOC suppression. This indicates that the properties of theMOC-OHCsynapse directly determine the efficacy of the MOCfeedback to the cochlea being a main player in the “gain control” of the auditory periphery.
Fil: Wedemeyer, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Vattino, Lucas Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Moglie, Marcelo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Ballestero, Jimena Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Maison, Stéphane F.. Harvard Medical School; Estados Unidos
Fil: Di Guilmi, Mariano Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Taranda, Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Liberman, M. Charles. Harvard Medical School; Estados Unidos
Fil: Fuchs, Paul A.. The Johns Hopkins University School of Medicine; Estados Unidos
Fil: Katz, Eleonora. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina
Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
description Gain control of the auditory system operates at multiple levels. Cholinergic medial olivocochlear (MOC) fibers originate in the brainstem and make synaptic contacts at the base of the outer hair cells (OHCs), the final targets of several feedback loops from the periphery and higher-processing centers. Efferent activation inhibitsOHCactive amplification within the mammalian cochlea, through the activation of a calcium-permeable α 9 α 10 ionotropic cholinergic nicotinic receptor (nAChR), functionally coupled to calcium activated SK2 potassium channels. Correct operation of this feedback requires careful matching of acoustic input with the strength of cochlear inhibition (Galambos, 1956; Wiederhold and Kiang, 1970; Gifford and Guinan, 1987), which is driven by the rate of MOCactivity and short-term facilitation at theMOC-OHCsynapse (Ballestero et al., 2011; Katz and Elgoyhen, 2014). The present work shows (in mice of either sex) that a mutation in the α 9α 10 nAChR with increased duration of channel gating (Taranda et al., 2009) greatly elongates hair cell-evoked IPSCs and Ca2+signals. Interestingly, MOC–OHC synapses of L9’T mice presented reduced quantum content and increased presynaptic facilitation. These phenotypic changes lead to enhanced and sustained synaptic responses and OHC hyperpolarization upon high-frequency stimulation of MOC terminals. At the cochlear physiology level these changes were matched by a longer time course of efferent MOC suppression. This indicates that the properties of theMOC-OHCsynapse directly determine the efficacy of the MOCfeedback to the cochlea being a main player in the “gain control” of the auditory periphery.
publishDate 2018
dc.date.none.fl_str_mv 2018-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/79826
Wedemeyer, Carolina; Vattino, Lucas Gabriel; Moglie, Marcelo Javier; Ballestero, Jimena Andrea; Maison, Stéphane F.; et al.; A gain-of-function mutation in the α9 nicotinic acetylcholine receptor alters medial olivocochlear efferent short-term synaptic plasticity; Society for Neuroscience; Journal of Neuroscience; 38; 16; 4-2018; 3939-3954
0270-6474
CONICET Digital
CONICET
url http://hdl.handle.net/11336/79826
identifier_str_mv Wedemeyer, Carolina; Vattino, Lucas Gabriel; Moglie, Marcelo Javier; Ballestero, Jimena Andrea; Maison, Stéphane F.; et al.; A gain-of-function mutation in the α9 nicotinic acetylcholine receptor alters medial olivocochlear efferent short-term synaptic plasticity; Society for Neuroscience; Journal of Neuroscience; 38; 16; 4-2018; 3939-3954
0270-6474
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29572431/
info:eu-repo/semantics/altIdentifier/doi/10.1523/JNEUROSCI.2528-17.2018
info:eu-repo/semantics/altIdentifier/url/https://www.jneurosci.org/content/38/16/3939
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Society for Neuroscience
publisher.none.fl_str_mv Society for Neuroscience
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.993085

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