mGluR1 enhances efferent inhibition of inner hair cells in the developing rat cochlea
- Autores
- Ye, Zhanlei; Goutman, Juan Diego; Pyott, Sonja J.; Glowatzki, Elisabeth
- Año de publicación
- 2017
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Key points: Spontaneous activity of the sensory inner hair cells shapes maturation of the developing ascending (afferent) auditory system before hearing begins. Just before the onset of hearing, descending (efferent) input from cholinergic neurons originating in the brainstem inhibit inner hair cell spontaneous activity and may further refine maturation. We show that agonist activation of the group I metabotropic glutamate receptor mGluR1 increases the strength of this efferent inhibition by enhancing the presynaptic release of acetylcholine. We further show that the endogenous release of glutamate from the inner hair cells may increase the strength of efferent inhibition via the activation of group I metabotropic glutamate receptors. Thus, before the onset of hearing, metabotropic glutamate signalling establishes a local negative feedback loop that is positioned to regulate inner hair cell excitability and refine maturation of the auditory system. Abstract: Just before the onset of hearing, the inner hair cells (IHCs) receive inhibitory efferent input from cholinergic medial olivocochlear (MOC) neurons originating in the brainstem. This input may serve a role in the maturation of the ascending (afferent) auditory system by inhibiting spontaneous activity of the IHCs. To investigate the molecular mechanisms regulating these IHC efferent synapses, we combined electrical stimulation of the efferent fibres with patch clamp recordings from the IHCs to measure efferent synaptic strength. By examining evoked responses, we show that activation of metabotropic glutamate receptors (mGluRs) by general and group I-specific mGluR agonists enhances IHC efferent inhibition. This enhancement is blocked by application of a group I mGluR1-specific antagonist, indicating that enhancement of IHC efferent inhibition is mediated by group I mGluRs and specifically by mGluR1s. By comparing spontaneous and evoked responses, we show that group I mGluR agonists act presynaptically to increase neurotransmitter release without affecting postsynaptic responsiveness. Moreover, endogenous glutamate released from the IHCs also enhances IHC efferent inhibition via the activation of group I mGluRs. Finally, immunofluorescence analysis indicates that the efferent terminals are sufficiently close to IHC glutamate release sites to allow activation of mGluRs on the efferent terminals by glutamate spillover. Together, these results suggest that glutamate released from the IHCs activates group I mGluRs (mGluR1s), probably present on the efferent terminals, which, in turn, enhances release of acetylcholine and inhibition of the IHCs. Thus, mGluRs establish a local negative feedback loop positioned to regulate IHC activity and maturation of the ascending auditory system in the developing cochlea.
Fil: Ye, Zhanlei. Harvard University; Estados Unidos
Fil: Goutman, Juan Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Pyott, Sonja J.. University Medical Center Groningen; Países Bajos
Fil: Glowatzki, Elisabeth. University Johns Hopkins; Estados Unidos - Materia
-
Glutamate
Medial Olivocochlear Nucleus
Metabotropic Glutamate Receptors
Quantal Analysis
Synapse - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/65228
Ver los metadatos del registro completo
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oai:ri.conicet.gov.ar:11336/65228 |
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mGluR1 enhances efferent inhibition of inner hair cells in the developing rat cochleaYe, ZhanleiGoutman, Juan DiegoPyott, Sonja J.Glowatzki, ElisabethGlutamateMedial Olivocochlear NucleusMetabotropic Glutamate ReceptorsQuantal AnalysisSynapsehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Key points: Spontaneous activity of the sensory inner hair cells shapes maturation of the developing ascending (afferent) auditory system before hearing begins. Just before the onset of hearing, descending (efferent) input from cholinergic neurons originating in the brainstem inhibit inner hair cell spontaneous activity and may further refine maturation. We show that agonist activation of the group I metabotropic glutamate receptor mGluR1 increases the strength of this efferent inhibition by enhancing the presynaptic release of acetylcholine. We further show that the endogenous release of glutamate from the inner hair cells may increase the strength of efferent inhibition via the activation of group I metabotropic glutamate receptors. Thus, before the onset of hearing, metabotropic glutamate signalling establishes a local negative feedback loop that is positioned to regulate inner hair cell excitability and refine maturation of the auditory system. Abstract: Just before the onset of hearing, the inner hair cells (IHCs) receive inhibitory efferent input from cholinergic medial olivocochlear (MOC) neurons originating in the brainstem. This input may serve a role in the maturation of the ascending (afferent) auditory system by inhibiting spontaneous activity of the IHCs. To investigate the molecular mechanisms regulating these IHC efferent synapses, we combined electrical stimulation of the efferent fibres with patch clamp recordings from the IHCs to measure efferent synaptic strength. By examining evoked responses, we show that activation of metabotropic glutamate receptors (mGluRs) by general and group I-specific mGluR agonists enhances IHC efferent inhibition. This enhancement is blocked by application of a group I mGluR1-specific antagonist, indicating that enhancement of IHC efferent inhibition is mediated by group I mGluRs and specifically by mGluR1s. By comparing spontaneous and evoked responses, we show that group I mGluR agonists act presynaptically to increase neurotransmitter release without affecting postsynaptic responsiveness. Moreover, endogenous glutamate released from the IHCs also enhances IHC efferent inhibition via the activation of group I mGluRs. Finally, immunofluorescence analysis indicates that the efferent terminals are sufficiently close to IHC glutamate release sites to allow activation of mGluRs on the efferent terminals by glutamate spillover. Together, these results suggest that glutamate released from the IHCs activates group I mGluRs (mGluR1s), probably present on the efferent terminals, which, in turn, enhances release of acetylcholine and inhibition of the IHCs. Thus, mGluRs establish a local negative feedback loop positioned to regulate IHC activity and maturation of the ascending auditory system in the developing cochlea.Fil: Ye, Zhanlei. Harvard University; Estados UnidosFil: Goutman, Juan Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Pyott, Sonja J.. University Medical Center Groningen; Países BajosFil: Glowatzki, Elisabeth. University Johns Hopkins; Estados UnidosWiley Blackwell Publishing, Inc2017-06-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/65228Ye, Zhanlei; Goutman, Juan Diego; Pyott, Sonja J.; Glowatzki, Elisabeth; mGluR1 enhances efferent inhibition of inner hair cells in the developing rat cochlea; Wiley Blackwell Publishing, Inc; The Journal Of Physiology; 595; 11; 1-6-2017; 3483-34950022-3751CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1113/JP272604info:eu-repo/semantics/altIdentifier/url/https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP272604info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451706/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:47:05Zoai:ri.conicet.gov.ar:11336/65228instacron: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:34982025-09-29 09:47:05.578CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
mGluR1 enhances efferent inhibition of inner hair cells in the developing rat cochlea |
title |
mGluR1 enhances efferent inhibition of inner hair cells in the developing rat cochlea |
spellingShingle |
mGluR1 enhances efferent inhibition of inner hair cells in the developing rat cochlea Ye, Zhanlei Glutamate Medial Olivocochlear Nucleus Metabotropic Glutamate Receptors Quantal Analysis Synapse |
title_short |
mGluR1 enhances efferent inhibition of inner hair cells in the developing rat cochlea |
title_full |
mGluR1 enhances efferent inhibition of inner hair cells in the developing rat cochlea |
title_fullStr |
mGluR1 enhances efferent inhibition of inner hair cells in the developing rat cochlea |
title_full_unstemmed |
mGluR1 enhances efferent inhibition of inner hair cells in the developing rat cochlea |
title_sort |
mGluR1 enhances efferent inhibition of inner hair cells in the developing rat cochlea |
dc.creator.none.fl_str_mv |
Ye, Zhanlei Goutman, Juan Diego Pyott, Sonja J. Glowatzki, Elisabeth |
author |
Ye, Zhanlei |
author_facet |
Ye, Zhanlei Goutman, Juan Diego Pyott, Sonja J. Glowatzki, Elisabeth |
author_role |
author |
author2 |
Goutman, Juan Diego Pyott, Sonja J. Glowatzki, Elisabeth |
author2_role |
author author author |
dc.subject.none.fl_str_mv |
Glutamate Medial Olivocochlear Nucleus Metabotropic Glutamate Receptors Quantal Analysis Synapse |
topic |
Glutamate Medial Olivocochlear Nucleus Metabotropic Glutamate Receptors Quantal Analysis Synapse |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
Key points: Spontaneous activity of the sensory inner hair cells shapes maturation of the developing ascending (afferent) auditory system before hearing begins. Just before the onset of hearing, descending (efferent) input from cholinergic neurons originating in the brainstem inhibit inner hair cell spontaneous activity and may further refine maturation. We show that agonist activation of the group I metabotropic glutamate receptor mGluR1 increases the strength of this efferent inhibition by enhancing the presynaptic release of acetylcholine. We further show that the endogenous release of glutamate from the inner hair cells may increase the strength of efferent inhibition via the activation of group I metabotropic glutamate receptors. Thus, before the onset of hearing, metabotropic glutamate signalling establishes a local negative feedback loop that is positioned to regulate inner hair cell excitability and refine maturation of the auditory system. Abstract: Just before the onset of hearing, the inner hair cells (IHCs) receive inhibitory efferent input from cholinergic medial olivocochlear (MOC) neurons originating in the brainstem. This input may serve a role in the maturation of the ascending (afferent) auditory system by inhibiting spontaneous activity of the IHCs. To investigate the molecular mechanisms regulating these IHC efferent synapses, we combined electrical stimulation of the efferent fibres with patch clamp recordings from the IHCs to measure efferent synaptic strength. By examining evoked responses, we show that activation of metabotropic glutamate receptors (mGluRs) by general and group I-specific mGluR agonists enhances IHC efferent inhibition. This enhancement is blocked by application of a group I mGluR1-specific antagonist, indicating that enhancement of IHC efferent inhibition is mediated by group I mGluRs and specifically by mGluR1s. By comparing spontaneous and evoked responses, we show that group I mGluR agonists act presynaptically to increase neurotransmitter release without affecting postsynaptic responsiveness. Moreover, endogenous glutamate released from the IHCs also enhances IHC efferent inhibition via the activation of group I mGluRs. Finally, immunofluorescence analysis indicates that the efferent terminals are sufficiently close to IHC glutamate release sites to allow activation of mGluRs on the efferent terminals by glutamate spillover. Together, these results suggest that glutamate released from the IHCs activates group I mGluRs (mGluR1s), probably present on the efferent terminals, which, in turn, enhances release of acetylcholine and inhibition of the IHCs. Thus, mGluRs establish a local negative feedback loop positioned to regulate IHC activity and maturation of the ascending auditory system in the developing cochlea. Fil: Ye, Zhanlei. Harvard University; Estados Unidos Fil: Goutman, Juan Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Pyott, Sonja J.. University Medical Center Groningen; Países Bajos Fil: Glowatzki, Elisabeth. University Johns Hopkins; Estados Unidos |
description |
Key points: Spontaneous activity of the sensory inner hair cells shapes maturation of the developing ascending (afferent) auditory system before hearing begins. Just before the onset of hearing, descending (efferent) input from cholinergic neurons originating in the brainstem inhibit inner hair cell spontaneous activity and may further refine maturation. We show that agonist activation of the group I metabotropic glutamate receptor mGluR1 increases the strength of this efferent inhibition by enhancing the presynaptic release of acetylcholine. We further show that the endogenous release of glutamate from the inner hair cells may increase the strength of efferent inhibition via the activation of group I metabotropic glutamate receptors. Thus, before the onset of hearing, metabotropic glutamate signalling establishes a local negative feedback loop that is positioned to regulate inner hair cell excitability and refine maturation of the auditory system. Abstract: Just before the onset of hearing, the inner hair cells (IHCs) receive inhibitory efferent input from cholinergic medial olivocochlear (MOC) neurons originating in the brainstem. This input may serve a role in the maturation of the ascending (afferent) auditory system by inhibiting spontaneous activity of the IHCs. To investigate the molecular mechanisms regulating these IHC efferent synapses, we combined electrical stimulation of the efferent fibres with patch clamp recordings from the IHCs to measure efferent synaptic strength. By examining evoked responses, we show that activation of metabotropic glutamate receptors (mGluRs) by general and group I-specific mGluR agonists enhances IHC efferent inhibition. This enhancement is blocked by application of a group I mGluR1-specific antagonist, indicating that enhancement of IHC efferent inhibition is mediated by group I mGluRs and specifically by mGluR1s. By comparing spontaneous and evoked responses, we show that group I mGluR agonists act presynaptically to increase neurotransmitter release without affecting postsynaptic responsiveness. Moreover, endogenous glutamate released from the IHCs also enhances IHC efferent inhibition via the activation of group I mGluRs. Finally, immunofluorescence analysis indicates that the efferent terminals are sufficiently close to IHC glutamate release sites to allow activation of mGluRs on the efferent terminals by glutamate spillover. Together, these results suggest that glutamate released from the IHCs activates group I mGluRs (mGluR1s), probably present on the efferent terminals, which, in turn, enhances release of acetylcholine and inhibition of the IHCs. Thus, mGluRs establish a local negative feedback loop positioned to regulate IHC activity and maturation of the ascending auditory system in the developing cochlea. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-06-01 |
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/11336/65228 Ye, Zhanlei; Goutman, Juan Diego; Pyott, Sonja J.; Glowatzki, Elisabeth; mGluR1 enhances efferent inhibition of inner hair cells in the developing rat cochlea; Wiley Blackwell Publishing, Inc; The Journal Of Physiology; 595; 11; 1-6-2017; 3483-3495 0022-3751 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/65228 |
identifier_str_mv |
Ye, Zhanlei; Goutman, Juan Diego; Pyott, Sonja J.; Glowatzki, Elisabeth; mGluR1 enhances efferent inhibition of inner hair cells in the developing rat cochlea; Wiley Blackwell Publishing, Inc; The Journal Of Physiology; 595; 11; 1-6-2017; 3483-3495 0022-3751 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1113/JP272604 info:eu-repo/semantics/altIdentifier/url/https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP272604 info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451706/ |
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 |
dc.publisher.none.fl_str_mv |
Wiley Blackwell Publishing, Inc |
publisher.none.fl_str_mv |
Wiley Blackwell Publishing, Inc |
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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1844613468246769664 |
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13.070432 |