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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/79619
Ver los metadatos del registro completo
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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 Técnicas2025-09-29T10:05:42Zoai: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:34982025-09-29 10:05:42.377CONICET 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 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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1844613896217821184 |
score |
13.070432 |