Unravelling the molecular players at the cholinergic efferent synapse of the zebrafish lateral line

Autores
Carpaneto Freixas, Agustín Eduardo; Moglie, Marcelo Javier; Castagnola, Tais; Salatino, Lucía; Domene, Sabina; Marcovich, Irina; Gallino, Sofia Ludmila; Wedemeyer, Carolina; Goutman, Juan Diego; Plazas, Paola Viviana; Elgoyhen, Ana Belen
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The lateral line (LL) is a sensory system that allows fish and amphibians to detect water currents. LL responsiveness is modulated by efferent neurons which aid to distinguish between external and self-generated stimuli, maintaining sensitivity to relevant cues. One component of the efferent system is cholinergic, the activation of which inhibits afferent activity. LL hair cells (HC) share structural, functional and molecular similarities with those of the cochlea, making them a popular model for studying human hearing and balance disorders. Due to these commonalities, one could propose that the receptor at the LL efferent synapse is a α9α10 nicotinic cholinergic one (nAChR). However, the identities of the molecular players underlying acetylcholine (ACh)-mediated inhibition in the LL remain unknown. Surprisingly, through the analysis of single-cell expression studies and in situ hybridization, we describe that α9, but not α10 subunits, are enriched in zebrafish HC. Moreover, the heterologous expression of zebrafish α9 subunits indicates that homomeric receptors are functional and exhibit robust ACh-gated currents blocked by α-Bungarotoxin and strychnine. In addition, in vivo Ca2+ imaging on mechanically-stimulated zebrafish LL HC show that ACh elicits a decrease in evoked Ca2+ signals, irrespective of HC polarity. This effect is blocked by both α-Bungarotoxin and apamin, indicating coupling of ACh-mediated effects to SK potassium channels. Our results indicate that an α9-containing (α9*) nAChR operates at the zebrafish LL efferent synapse. Moreover, the activation of α9* nAChRs most likely leads to LL HC hyperpolarization served by the activation of Ca2+-dependent SK potassium channels.
Fil: Carpaneto Freixas, Agustín Eduardo. 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: Castagnola, Tais. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Salatino, Lucía. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacologia; Argentina
Fil: Domene, Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Marcovich, Irina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Gallino, Sofia Ludmila. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
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: 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: Plazas, Paola Viviana. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; 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
Materia
efferent
nicotinic receptor
zebrafish
lateral line
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:11336/137761
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/137761
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Unravelling the molecular players at the cholinergic efferent synapse of the zebrafish lateral lineCarpaneto Freixas, Agustín EduardoMoglie, Marcelo JavierCastagnola, TaisSalatino, LucíaDomene, SabinaMarcovich, IrinaGallino, Sofia LudmilaWedemeyer, CarolinaGoutman, Juan DiegoPlazas, Paola VivianaElgoyhen, Ana Belenefferentnicotinic receptorzebrafishlateral linehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The lateral line (LL) is a sensory system that allows fish and amphibians to detect water currents. LL responsiveness is modulated by efferent neurons which aid to distinguish between external and self-generated stimuli, maintaining sensitivity to relevant cues. One component of the efferent system is cholinergic, the activation of which inhibits afferent activity. LL hair cells (HC) share structural, functional and molecular similarities with those of the cochlea, making them a popular model for studying human hearing and balance disorders. Due to these commonalities, one could propose that the receptor at the LL efferent synapse is a α9α10 nicotinic cholinergic one (nAChR). However, the identities of the molecular players underlying acetylcholine (ACh)-mediated inhibition in the LL remain unknown. Surprisingly, through the analysis of single-cell expression studies and in situ hybridization, we describe that α9, but not α10 subunits, are enriched in zebrafish HC. Moreover, the heterologous expression of zebrafish α9 subunits indicates that homomeric receptors are functional and exhibit robust ACh-gated currents blocked by α-Bungarotoxin and strychnine. In addition, in vivo Ca2+ imaging on mechanically-stimulated zebrafish LL HC show that ACh elicits a decrease in evoked Ca2+ signals, irrespective of HC polarity. This effect is blocked by both α-Bungarotoxin and apamin, indicating coupling of ACh-mediated effects to SK potassium channels. Our results indicate that an α9-containing (α9*) nAChR operates at the zebrafish LL efferent synapse. Moreover, the activation of α9* nAChRs most likely leads to LL HC hyperpolarization served by the activation of Ca2+-dependent SK potassium channels.Fil: Carpaneto Freixas, Agustín Eduardo. 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: Castagnola, Tais. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Salatino, Lucía. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacologia; ArgentinaFil: Domene, Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Marcovich, Irina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Gallino, Sofia Ludmila. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Wedemeyer, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Goutman, Juan Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Plazas, Paola Viviana. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaSociety for Neuroscience2020-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/137761Carpaneto Freixas, Agustín Eduardo; Moglie, Marcelo Javier; Castagnola, Tais; Salatino, Lucía; Domene, Sabina; et al.; Unravelling the molecular players at the cholinergic efferent synapse of the zebrafish lateral line; Society for Neuroscience; Journal of Neuroscience; 11-2020; 1-140270-6474CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.jneurosci.org/lookup/doi/10.1523/JNEUROSCI.1772-20.2020info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:22:07Zoai:ri.conicet.gov.ar:11336/137761instacron: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:34982025-10-22 11:22:07.967CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Unravelling the molecular players at the cholinergic efferent synapse of the zebrafish lateral line
title Unravelling the molecular players at the cholinergic efferent synapse of the zebrafish lateral line
spellingShingle Unravelling the molecular players at the cholinergic efferent synapse of the zebrafish lateral line
Carpaneto Freixas, Agustín Eduardo
efferent
nicotinic receptor
zebrafish
lateral line
title_short Unravelling the molecular players at the cholinergic efferent synapse of the zebrafish lateral line
title_full Unravelling the molecular players at the cholinergic efferent synapse of the zebrafish lateral line
title_fullStr Unravelling the molecular players at the cholinergic efferent synapse of the zebrafish lateral line
title_full_unstemmed Unravelling the molecular players at the cholinergic efferent synapse of the zebrafish lateral line
title_sort Unravelling the molecular players at the cholinergic efferent synapse of the zebrafish lateral line
dc.creator.none.fl_str_mv Carpaneto Freixas, Agustín Eduardo
Moglie, Marcelo Javier
Castagnola, Tais
Salatino, Lucía
Domene, Sabina
Marcovich, Irina
Gallino, Sofia Ludmila
Wedemeyer, Carolina
Goutman, Juan Diego
Plazas, Paola Viviana
Elgoyhen, Ana Belen
author Carpaneto Freixas, Agustín Eduardo
author_facet Carpaneto Freixas, Agustín Eduardo
Moglie, Marcelo Javier
Castagnola, Tais
Salatino, Lucía
Domene, Sabina
Marcovich, Irina
Gallino, Sofia Ludmila
Wedemeyer, Carolina
Goutman, Juan Diego
Plazas, Paola Viviana
Elgoyhen, Ana Belen
author_role author
author2 Moglie, Marcelo Javier
Castagnola, Tais
Salatino, Lucía
Domene, Sabina
Marcovich, Irina
Gallino, Sofia Ludmila
Wedemeyer, Carolina
Goutman, Juan Diego
Plazas, Paola Viviana
Elgoyhen, Ana Belen
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv efferent
nicotinic receptor
zebrafish
lateral line
topic efferent
nicotinic receptor
zebrafish
lateral line
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The lateral line (LL) is a sensory system that allows fish and amphibians to detect water currents. LL responsiveness is modulated by efferent neurons which aid to distinguish between external and self-generated stimuli, maintaining sensitivity to relevant cues. One component of the efferent system is cholinergic, the activation of which inhibits afferent activity. LL hair cells (HC) share structural, functional and molecular similarities with those of the cochlea, making them a popular model for studying human hearing and balance disorders. Due to these commonalities, one could propose that the receptor at the LL efferent synapse is a α9α10 nicotinic cholinergic one (nAChR). However, the identities of the molecular players underlying acetylcholine (ACh)-mediated inhibition in the LL remain unknown. Surprisingly, through the analysis of single-cell expression studies and in situ hybridization, we describe that α9, but not α10 subunits, are enriched in zebrafish HC. Moreover, the heterologous expression of zebrafish α9 subunits indicates that homomeric receptors are functional and exhibit robust ACh-gated currents blocked by α-Bungarotoxin and strychnine. In addition, in vivo Ca2+ imaging on mechanically-stimulated zebrafish LL HC show that ACh elicits a decrease in evoked Ca2+ signals, irrespective of HC polarity. This effect is blocked by both α-Bungarotoxin and apamin, indicating coupling of ACh-mediated effects to SK potassium channels. Our results indicate that an α9-containing (α9*) nAChR operates at the zebrafish LL efferent synapse. Moreover, the activation of α9* nAChRs most likely leads to LL HC hyperpolarization served by the activation of Ca2+-dependent SK potassium channels.
Fil: Carpaneto Freixas, Agustín Eduardo. 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: Castagnola, Tais. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Salatino, Lucía. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacologia; Argentina
Fil: Domene, Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Marcovich, Irina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Gallino, Sofia Ludmila. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
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: 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: Plazas, Paola Viviana. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; 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
description The lateral line (LL) is a sensory system that allows fish and amphibians to detect water currents. LL responsiveness is modulated by efferent neurons which aid to distinguish between external and self-generated stimuli, maintaining sensitivity to relevant cues. One component of the efferent system is cholinergic, the activation of which inhibits afferent activity. LL hair cells (HC) share structural, functional and molecular similarities with those of the cochlea, making them a popular model for studying human hearing and balance disorders. Due to these commonalities, one could propose that the receptor at the LL efferent synapse is a α9α10 nicotinic cholinergic one (nAChR). However, the identities of the molecular players underlying acetylcholine (ACh)-mediated inhibition in the LL remain unknown. Surprisingly, through the analysis of single-cell expression studies and in situ hybridization, we describe that α9, but not α10 subunits, are enriched in zebrafish HC. Moreover, the heterologous expression of zebrafish α9 subunits indicates that homomeric receptors are functional and exhibit robust ACh-gated currents blocked by α-Bungarotoxin and strychnine. In addition, in vivo Ca2+ imaging on mechanically-stimulated zebrafish LL HC show that ACh elicits a decrease in evoked Ca2+ signals, irrespective of HC polarity. This effect is blocked by both α-Bungarotoxin and apamin, indicating coupling of ACh-mediated effects to SK potassium channels. Our results indicate that an α9-containing (α9*) nAChR operates at the zebrafish LL efferent synapse. Moreover, the activation of α9* nAChRs most likely leads to LL HC hyperpolarization served by the activation of Ca2+-dependent SK potassium channels.
publishDate 2020
dc.date.none.fl_str_mv 2020-11
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/11336/137761
Carpaneto Freixas, Agustín Eduardo; Moglie, Marcelo Javier; Castagnola, Tais; Salatino, Lucía; Domene, Sabina; et al.; Unravelling the molecular players at the cholinergic efferent synapse of the zebrafish lateral line; Society for Neuroscience; Journal of Neuroscience; 11-2020; 1-14
0270-6474
CONICET Digital
CONICET
url http://hdl.handle.net/11336/137761
identifier_str_mv Carpaneto Freixas, Agustín Eduardo; Moglie, Marcelo Javier; Castagnola, Tais; Salatino, Lucía; Domene, Sabina; et al.; Unravelling the molecular players at the cholinergic efferent synapse of the zebrafish lateral line; Society for Neuroscience; Journal of Neuroscience; 11-2020; 1-14
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/http://www.jneurosci.org/lookup/doi/10.1523/JNEUROSCI.1772-20.2020
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
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 12.982451

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