Activation of presynaptic GABA b(1a,2) receptors inhibits synaptic transmission at mammalian inhibitory cholinergic olivocochlear-hair cell synapses

Autores
Wedemeyer, Carolina; Zorrilla de San Martín, Javier; Ballestero, Jimena Andrea; Gomez Casati, Maria Eugenia; Torbidoni, Ana Vanesa; Fuchs, Paul A.; Bettler, Bernhard; Elgoyhen, Ana Belen; Katz, Eleonora
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The synapse between olivocochlear (OC) neurons and cochlear mechanosensory hair cells is cholinergic, fast, and inhibitory. The inhibitory sign of this cholinergic synapse is accounted for by the activation of Ca 2+ -permeable postsynaptic α9α10 nicotinic receptors coupled to the opening of hyperpolarizing Ca 2+ -activated small-conductance type 2 (SK2)K + channels. Acetylcholine (ACh) release at this synapse is supported by both P/Q- and N-type voltage-gated calcium channels (VGCCs). Although the OC synapse is cholinergic, an abundantOCGABAinnervation is present along themammaliancochlea. The role of this neurotransmitter at theOCefferent innervation, however, is for the most part unknown.Weshow thatGABAfails to evoke fast postsynaptic inhibitory currents in apical developing inner and outer hair cells. However, electrical stimulation ofOCefferent fibers activates presynapticGABA B(1a,2) receptors [GABAB (1a,2) Rs] that downregulate the amount of ACh released at the OC-hair cell synapse, by inhibiting P/Q-type VGCCs. We confirmed the expression of GABA B Rs at OC terminals contacting the hair cells by coimmunostaining for GFP and synaptophysin in transgenic mice expressing GABA B1 -GFP fusion proteins. Moreover, coimmunostaining with antibodies against the GABA synthetic enzyme glutamic acid decarboxylase and synaptophysin support the idea that GABA is directly synthesized at OC terminals contacting the hair cells during development. Thus, we demonstrate for the first time a physiological role for GABA in cochlear synaptic function. In addition, our data suggest that the GABA B1a isoform selectively inhibits release at efferent cholinergic synapses.
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: Zorrilla de San Martín, 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: Gomez Casati, Maria Eugenia. 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
Fil: Torbidoni, Ana Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Fuchs, Paul A.. Johns Hopkins University; Estados Unidos
Fil: Bettler, Bernhard. Universidad de Basilea; Suiza
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
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
Materia
Hair cells
Cholinergic
GABAB receptors
Synaptic transmission
Efferent innervation
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:11336/79619
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/79619
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Activation of presynaptic GABA b(1a,2) receptors inhibits synaptic transmission at mammalian inhibitory cholinergic olivocochlear-hair cell synapsesWedemeyer, CarolinaZorrilla de San Martín, JavierBallestero, Jimena AndreaGomez Casati, Maria EugeniaTorbidoni, Ana VanesaFuchs, Paul A.Bettler, BernhardElgoyhen, Ana BelenKatz, EleonoraHair cellsCholinergicGABAB receptorsSynaptic transmissionEfferent innervationhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The synapse between olivocochlear (OC) neurons and cochlear mechanosensory hair cells is cholinergic, fast, and inhibitory. The inhibitory sign of this cholinergic synapse is accounted for by the activation of Ca 2+ -permeable postsynaptic α9α10 nicotinic receptors coupled to the opening of hyperpolarizing Ca 2+ -activated small-conductance type 2 (SK2)K + channels. Acetylcholine (ACh) release at this synapse is supported by both P/Q- and N-type voltage-gated calcium channels (VGCCs). Although the OC synapse is cholinergic, an abundantOCGABAinnervation is present along themammaliancochlea. The role of this neurotransmitter at theOCefferent innervation, however, is for the most part unknown.Weshow thatGABAfails to evoke fast postsynaptic inhibitory currents in apical developing inner and outer hair cells. However, electrical stimulation ofOCefferent fibers activates presynapticGABA B(1a,2) receptors [GABAB (1a,2) Rs] that downregulate the amount of ACh released at the OC-hair cell synapse, by inhibiting P/Q-type VGCCs. We confirmed the expression of GABA B Rs at OC terminals contacting the hair cells by coimmunostaining for GFP and synaptophysin in transgenic mice expressing GABA B1 -GFP fusion proteins. Moreover, coimmunostaining with antibodies against the GABA synthetic enzyme glutamic acid decarboxylase and synaptophysin support the idea that GABA is directly synthesized at OC terminals contacting the hair cells during development. Thus, we demonstrate for the first time a physiological role for GABA in cochlear synaptic function. In addition, our data suggest that the GABA B1a isoform selectively inhibits release at efferent cholinergic synapses.Fil: Wedemeyer, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Zorrilla de San Martín, 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: Gomez Casati, Maria Eugenia. 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; ArgentinaFil: Torbidoni, Ana Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Fuchs, Paul A.. Johns Hopkins University; Estados UnidosFil: Bettler, Bernhard. Universidad de Basilea; SuizaFil: 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; ArgentinaFil: 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; ArgentinaSociety for Neuroscience2013-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/79619Wedemeyer, Carolina; Zorrilla de San Martín, Javier; Ballestero, Jimena Andrea; Gomez Casati, Maria Eugenia; Torbidoni, Ana Vanesa; et al.; Activation of presynaptic GABA b(1a,2) receptors inhibits synaptic transmission at mammalian inhibitory cholinergic olivocochlear-hair cell synapses; Society for Neuroscience; Journal of Neuroscience; 33; 39; 9-2013; 15477-154870270-6474CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24068816/info:eu-repo/semantics/altIdentifier/doi/10.1523/JNEUROSCI.2554-13.2013info:eu-repo/semantics/altIdentifier/url/https://www.jneurosci.org/content/33/39/15477info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:02:26Zoai:ri.conicet.gov.ar:11336/79619instacron: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:34982025-10-15 15:02:27.282CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Activation of presynaptic GABA b(1a,2) receptors inhibits synaptic transmission at mammalian inhibitory cholinergic olivocochlear-hair cell synapses
title Activation of presynaptic GABA b(1a,2) receptors inhibits synaptic transmission at mammalian inhibitory cholinergic olivocochlear-hair cell synapses
spellingShingle Activation of presynaptic GABA b(1a,2) receptors inhibits synaptic transmission at mammalian inhibitory cholinergic olivocochlear-hair cell synapses
Wedemeyer, Carolina
Hair cells
Cholinergic
GABAB receptors
Synaptic transmission
Efferent innervation
title_short Activation of presynaptic GABA b(1a,2) receptors inhibits synaptic transmission at mammalian inhibitory cholinergic olivocochlear-hair cell synapses
title_full Activation of presynaptic GABA b(1a,2) receptors inhibits synaptic transmission at mammalian inhibitory cholinergic olivocochlear-hair cell synapses
title_fullStr Activation of presynaptic GABA b(1a,2) receptors inhibits synaptic transmission at mammalian inhibitory cholinergic olivocochlear-hair cell synapses
title_full_unstemmed Activation of presynaptic GABA b(1a,2) receptors inhibits synaptic transmission at mammalian inhibitory cholinergic olivocochlear-hair cell synapses
title_sort Activation of presynaptic GABA b(1a,2) receptors inhibits synaptic transmission at mammalian inhibitory cholinergic olivocochlear-hair cell synapses
dc.creator.none.fl_str_mv Wedemeyer, Carolina
Zorrilla de San Martín, Javier
Ballestero, Jimena Andrea
Gomez Casati, Maria Eugenia
Torbidoni, Ana Vanesa
Fuchs, Paul A.
Bettler, Bernhard
Elgoyhen, Ana Belen
Katz, Eleonora
author Wedemeyer, Carolina
author_facet Wedemeyer, Carolina
Zorrilla de San Martín, Javier
Ballestero, Jimena Andrea
Gomez Casati, Maria Eugenia
Torbidoni, Ana Vanesa
Fuchs, Paul A.
Bettler, Bernhard
Elgoyhen, Ana Belen
Katz, Eleonora
author_role author
author2 Zorrilla de San Martín, Javier
Ballestero, Jimena Andrea
Gomez Casati, Maria Eugenia
Torbidoni, Ana Vanesa
Fuchs, Paul A.
Bettler, Bernhard
Elgoyhen, Ana Belen
Katz, Eleonora
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Hair cells
Cholinergic
GABAB receptors
Synaptic transmission
Efferent innervation
topic Hair cells
Cholinergic
GABAB receptors
Synaptic transmission
Efferent innervation
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The synapse between olivocochlear (OC) neurons and cochlear mechanosensory hair cells is cholinergic, fast, and inhibitory. The inhibitory sign of this cholinergic synapse is accounted for by the activation of Ca 2+ -permeable postsynaptic α9α10 nicotinic receptors coupled to the opening of hyperpolarizing Ca 2+ -activated small-conductance type 2 (SK2)K + channels. Acetylcholine (ACh) release at this synapse is supported by both P/Q- and N-type voltage-gated calcium channels (VGCCs). Although the OC synapse is cholinergic, an abundantOCGABAinnervation is present along themammaliancochlea. The role of this neurotransmitter at theOCefferent innervation, however, is for the most part unknown.Weshow thatGABAfails to evoke fast postsynaptic inhibitory currents in apical developing inner and outer hair cells. However, electrical stimulation ofOCefferent fibers activates presynapticGABA B(1a,2) receptors [GABAB (1a,2) Rs] that downregulate the amount of ACh released at the OC-hair cell synapse, by inhibiting P/Q-type VGCCs. We confirmed the expression of GABA B Rs at OC terminals contacting the hair cells by coimmunostaining for GFP and synaptophysin in transgenic mice expressing GABA B1 -GFP fusion proteins. Moreover, coimmunostaining with antibodies against the GABA synthetic enzyme glutamic acid decarboxylase and synaptophysin support the idea that GABA is directly synthesized at OC terminals contacting the hair cells during development. Thus, we demonstrate for the first time a physiological role for GABA in cochlear synaptic function. In addition, our data suggest that the GABA B1a isoform selectively inhibits release at efferent cholinergic synapses.
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: Zorrilla de San Martín, 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: Gomez Casati, Maria Eugenia. 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
Fil: Torbidoni, Ana Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Fuchs, Paul A.. Johns Hopkins University; Estados Unidos
Fil: Bettler, Bernhard. Universidad de Basilea; Suiza
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
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
description The synapse between olivocochlear (OC) neurons and cochlear mechanosensory hair cells is cholinergic, fast, and inhibitory. The inhibitory sign of this cholinergic synapse is accounted for by the activation of Ca 2+ -permeable postsynaptic α9α10 nicotinic receptors coupled to the opening of hyperpolarizing Ca 2+ -activated small-conductance type 2 (SK2)K + channels. Acetylcholine (ACh) release at this synapse is supported by both P/Q- and N-type voltage-gated calcium channels (VGCCs). Although the OC synapse is cholinergic, an abundantOCGABAinnervation is present along themammaliancochlea. The role of this neurotransmitter at theOCefferent innervation, however, is for the most part unknown.Weshow thatGABAfails to evoke fast postsynaptic inhibitory currents in apical developing inner and outer hair cells. However, electrical stimulation ofOCefferent fibers activates presynapticGABA B(1a,2) receptors [GABAB (1a,2) Rs] that downregulate the amount of ACh released at the OC-hair cell synapse, by inhibiting P/Q-type VGCCs. We confirmed the expression of GABA B Rs at OC terminals contacting the hair cells by coimmunostaining for GFP and synaptophysin in transgenic mice expressing GABA B1 -GFP fusion proteins. Moreover, coimmunostaining with antibodies against the GABA synthetic enzyme glutamic acid decarboxylase and synaptophysin support the idea that GABA is directly synthesized at OC terminals contacting the hair cells during development. Thus, we demonstrate for the first time a physiological role for GABA in cochlear synaptic function. In addition, our data suggest that the GABA B1a isoform selectively inhibits release at efferent cholinergic synapses.
publishDate 2013
dc.date.none.fl_str_mv 2013-09
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/11336/79619
Wedemeyer, Carolina; Zorrilla de San Martín, Javier; Ballestero, Jimena Andrea; Gomez Casati, Maria Eugenia; Torbidoni, Ana Vanesa; et al.; Activation of presynaptic GABA b(1a,2) receptors inhibits synaptic transmission at mammalian inhibitory cholinergic olivocochlear-hair cell synapses; Society for Neuroscience; Journal of Neuroscience; 33; 39; 9-2013; 15477-15487
0270-6474
CONICET Digital
CONICET
url http://hdl.handle.net/11336/79619
identifier_str_mv Wedemeyer, Carolina; Zorrilla de San Martín, Javier; Ballestero, Jimena Andrea; Gomez Casati, Maria Eugenia; Torbidoni, Ana Vanesa; et al.; Activation of presynaptic GABA b(1a,2) receptors inhibits synaptic transmission at mammalian inhibitory cholinergic olivocochlear-hair cell synapses; Society for Neuroscience; Journal of Neuroscience; 33; 39; 9-2013; 15477-15487
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/24068816/
info:eu-repo/semantics/altIdentifier/doi/10.1523/JNEUROSCI.2554-13.2013
info:eu-repo/semantics/altIdentifier/url/https://www.jneurosci.org/content/33/39/15477
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
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application/pdf
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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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