Co-release of GABA and ACh from medial olivocochlear neurons fine tunes cochlear efferent inhibition

Autores
Castagnola, Tais; Castagna, Valeria Carolina; Kitcher, Sian R.; Torres Cadenas, Lester; Di Guilmi, Mariano Nicolás; Gomez Casati, Maria Eugenia; Buonfiglio, Paula Inés; Dalamon, Viviana Karina; Katz, Eleonora; Elgoyhen, Ana Belen; Weisz, Catherin; Goutman, Juan Diego; Wedemeyer, Carolina
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
During development, inner hair cells (IHCs) in the mammalian cochlea are unresponsive to acoustic stimuli but instead exhibit spontaneous activity. During this same period, neurons originating from the medial olivocochlear complex (MOC) transiently innervate IHCs, regulating their firing pattern which is crucial for the correct development of the auditory pathway. Although the MOC-IHC is a cholinergic synapse, previous evidence indicates the widespread presence of gamma-aminobutyric acid (GABA) signaling markers, including presynaptic GABAB receptors (GABABR). In this study, we explore the source of GABA by optogenetically activating either cholinergic or GABAergic fibers. The optogenetic stimulation of MOC terminals from GAD;ChR2-eYFP and ChAT;ChR2-eYFP mice evoked synaptic currents in IHCs that were blocked by α-bungarotoxin. This suggests that GABAergic fibers release ACh and activate α9α10 nicotinic acetylcholine receptors (nAChRs). Additionally, MOC cholinergic fibers release not only ACh but also GABA, as the effect of GABA on ACh response amplitude was prevented by applying the GABAB-R blocker (CGP 36216). Using optical neurotransmitter detection and calcium imaging techniques, we examined the extent of GABAergic modulation at the single synapse level. Our findings suggest heterogeneity in GABA modulation, as only 15 out of 31 recorded synaptic sites were modulated by applying the GABABR specific antagonist, CGP (100-200 μM). In conclusion, we provide compelling evidence that GABA and ACh are co-released from at least a subset of MOC terminals. In this circuit, GABA functions as a negative feedback mechanism, locally regulating the extent of cholinergic inhibition at certain efferent-IHC synapses during an immature stage.
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: Castagna, Valeria Carolina. 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. Cátedra de Farmacología; Argentina
Fil: Kitcher, Sian R.. National Institutes of Health; Estados Unidos. National Institute On Deafness And Other Communication; Estados Unidos
Fil: Torres Cadenas, Lester. National Institutes of Health; Estados Unidos. National Institute On Deafness And Other Communication; 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: 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. Cátedra de Farmacología; Argentina
Fil: Buonfiglio, Paula Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Dalamon, Viviana Karina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; 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
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. Cátedra de Farmacología; Argentina
Fil: Weisz, Catherin. National Institutes of Health; Estados Unidos. National Institute On Deafness And Other Communication; 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: Wedemeyer, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Materia
GAMMA-AMINOBUTYRIC ACID (GABA)
DEVELOPEMENT
MEDIAL OLIVOCOCHLEAR (MOC)
SYNAPSE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/262722
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/262722
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Co-release of GABA and ACh from medial olivocochlear neurons fine tunes cochlear efferent inhibitionCastagnola, TaisCastagna, Valeria CarolinaKitcher, Sian R.Torres Cadenas, LesterDi Guilmi, Mariano NicolásGomez Casati, Maria EugeniaBuonfiglio, Paula InésDalamon, Viviana KarinaKatz, EleonoraElgoyhen, Ana BelenWeisz, CatherinGoutman, Juan DiegoWedemeyer, CarolinaGAMMA-AMINOBUTYRIC ACID (GABA)DEVELOPEMENTMEDIAL OLIVOCOCHLEAR (MOC)SYNAPSEhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3During development, inner hair cells (IHCs) in the mammalian cochlea are unresponsive to acoustic stimuli but instead exhibit spontaneous activity. During this same period, neurons originating from the medial olivocochlear complex (MOC) transiently innervate IHCs, regulating their firing pattern which is crucial for the correct development of the auditory pathway. Although the MOC-IHC is a cholinergic synapse, previous evidence indicates the widespread presence of gamma-aminobutyric acid (GABA) signaling markers, including presynaptic GABAB receptors (GABABR). In this study, we explore the source of GABA by optogenetically activating either cholinergic or GABAergic fibers. The optogenetic stimulation of MOC terminals from GAD;ChR2-eYFP and ChAT;ChR2-eYFP mice evoked synaptic currents in IHCs that were blocked by α-bungarotoxin. This suggests that GABAergic fibers release ACh and activate α9α10 nicotinic acetylcholine receptors (nAChRs). Additionally, MOC cholinergic fibers release not only ACh but also GABA, as the effect of GABA on ACh response amplitude was prevented by applying the GABAB-R blocker (CGP 36216). Using optical neurotransmitter detection and calcium imaging techniques, we examined the extent of GABAergic modulation at the single synapse level. Our findings suggest heterogeneity in GABA modulation, as only 15 out of 31 recorded synaptic sites were modulated by applying the GABABR specific antagonist, CGP (100-200 μM). In conclusion, we provide compelling evidence that GABA and ACh are co-released from at least a subset of MOC terminals. In this circuit, GABA functions as a negative feedback mechanism, locally regulating the extent of cholinergic inhibition at certain efferent-IHC synapses during an immature stage.Fil: Castagnola, Tais. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Castagna, Valeria Carolina. 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. Cátedra de Farmacología; ArgentinaFil: Kitcher, Sian R.. National Institutes of Health; Estados Unidos. National Institute On Deafness And Other Communication; Estados UnidosFil: Torres Cadenas, Lester. National Institutes of Health; Estados Unidos. National Institute On Deafness And Other Communication; 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: 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. Cátedra de Farmacología; ArgentinaFil: Buonfiglio, Paula Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Dalamon, Viviana Karina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Katz, Eleonora. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; 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. Cátedra de Farmacología; ArgentinaFil: Weisz, Catherin. National Institutes of Health; Estados Unidos. National Institute On Deafness And Other Communication; 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: Wedemeyer, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaCold Spring Harbor Laboratory Press2024-08-16info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/262722Castagnola, Tais; Castagna, Valeria Carolina; Kitcher, Sian R.; Torres Cadenas, Lester; Di Guilmi, Mariano Nicolás; et al.; Co-release of GABA and ACh from medial olivocochlear neurons fine tunes cochlear efferent inhibition; Cold Spring Harbor Laboratory Press; bioRxiv; 16-8-2024; 1-382692-8205CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1101/2024.08.12.607644info:eu-repo/semantics/altIdentifier/url/https://www.biorxiv.org/content/10.1101/2024.08.12.607644v1info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:45:20Zoai:ri.conicet.gov.ar:11336/262722instacron: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:34982025-09-03 09:45:21.187CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Co-release of GABA and ACh from medial olivocochlear neurons fine tunes cochlear efferent inhibition
title Co-release of GABA and ACh from medial olivocochlear neurons fine tunes cochlear efferent inhibition
spellingShingle Co-release of GABA and ACh from medial olivocochlear neurons fine tunes cochlear efferent inhibition
Castagnola, Tais
GAMMA-AMINOBUTYRIC ACID (GABA)
DEVELOPEMENT
MEDIAL OLIVOCOCHLEAR (MOC)
SYNAPSE
title_short Co-release of GABA and ACh from medial olivocochlear neurons fine tunes cochlear efferent inhibition
title_full Co-release of GABA and ACh from medial olivocochlear neurons fine tunes cochlear efferent inhibition
title_fullStr Co-release of GABA and ACh from medial olivocochlear neurons fine tunes cochlear efferent inhibition
title_full_unstemmed Co-release of GABA and ACh from medial olivocochlear neurons fine tunes cochlear efferent inhibition
title_sort Co-release of GABA and ACh from medial olivocochlear neurons fine tunes cochlear efferent inhibition
dc.creator.none.fl_str_mv Castagnola, Tais
Castagna, Valeria Carolina
Kitcher, Sian R.
Torres Cadenas, Lester
Di Guilmi, Mariano Nicolás
Gomez Casati, Maria Eugenia
Buonfiglio, Paula Inés
Dalamon, Viviana Karina
Katz, Eleonora
Elgoyhen, Ana Belen
Weisz, Catherin
Goutman, Juan Diego
Wedemeyer, Carolina
author Castagnola, Tais
author_facet Castagnola, Tais
Castagna, Valeria Carolina
Kitcher, Sian R.
Torres Cadenas, Lester
Di Guilmi, Mariano Nicolás
Gomez Casati, Maria Eugenia
Buonfiglio, Paula Inés
Dalamon, Viviana Karina
Katz, Eleonora
Elgoyhen, Ana Belen
Weisz, Catherin
Goutman, Juan Diego
Wedemeyer, Carolina
author_role author
author2 Castagna, Valeria Carolina
Kitcher, Sian R.
Torres Cadenas, Lester
Di Guilmi, Mariano Nicolás
Gomez Casati, Maria Eugenia
Buonfiglio, Paula Inés
Dalamon, Viviana Karina
Katz, Eleonora
Elgoyhen, Ana Belen
Weisz, Catherin
Goutman, Juan Diego
Wedemeyer, Carolina
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv GAMMA-AMINOBUTYRIC ACID (GABA)
DEVELOPEMENT
MEDIAL OLIVOCOCHLEAR (MOC)
SYNAPSE
topic GAMMA-AMINOBUTYRIC ACID (GABA)
DEVELOPEMENT
MEDIAL OLIVOCOCHLEAR (MOC)
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 During development, inner hair cells (IHCs) in the mammalian cochlea are unresponsive to acoustic stimuli but instead exhibit spontaneous activity. During this same period, neurons originating from the medial olivocochlear complex (MOC) transiently innervate IHCs, regulating their firing pattern which is crucial for the correct development of the auditory pathway. Although the MOC-IHC is a cholinergic synapse, previous evidence indicates the widespread presence of gamma-aminobutyric acid (GABA) signaling markers, including presynaptic GABAB receptors (GABABR). In this study, we explore the source of GABA by optogenetically activating either cholinergic or GABAergic fibers. The optogenetic stimulation of MOC terminals from GAD;ChR2-eYFP and ChAT;ChR2-eYFP mice evoked synaptic currents in IHCs that were blocked by α-bungarotoxin. This suggests that GABAergic fibers release ACh and activate α9α10 nicotinic acetylcholine receptors (nAChRs). Additionally, MOC cholinergic fibers release not only ACh but also GABA, as the effect of GABA on ACh response amplitude was prevented by applying the GABAB-R blocker (CGP 36216). Using optical neurotransmitter detection and calcium imaging techniques, we examined the extent of GABAergic modulation at the single synapse level. Our findings suggest heterogeneity in GABA modulation, as only 15 out of 31 recorded synaptic sites were modulated by applying the GABABR specific antagonist, CGP (100-200 μM). In conclusion, we provide compelling evidence that GABA and ACh are co-released from at least a subset of MOC terminals. In this circuit, GABA functions as a negative feedback mechanism, locally regulating the extent of cholinergic inhibition at certain efferent-IHC synapses during an immature stage.
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: Castagna, Valeria Carolina. 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. Cátedra de Farmacología; Argentina
Fil: Kitcher, Sian R.. National Institutes of Health; Estados Unidos. National Institute On Deafness And Other Communication; Estados Unidos
Fil: Torres Cadenas, Lester. National Institutes of Health; Estados Unidos. National Institute On Deafness And Other Communication; 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: 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. Cátedra de Farmacología; Argentina
Fil: Buonfiglio, Paula Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Dalamon, Viviana Karina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; 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
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. Cátedra de Farmacología; Argentina
Fil: Weisz, Catherin. National Institutes of Health; Estados Unidos. National Institute On Deafness And Other Communication; 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: Wedemeyer, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
description During development, inner hair cells (IHCs) in the mammalian cochlea are unresponsive to acoustic stimuli but instead exhibit spontaneous activity. During this same period, neurons originating from the medial olivocochlear complex (MOC) transiently innervate IHCs, regulating their firing pattern which is crucial for the correct development of the auditory pathway. Although the MOC-IHC is a cholinergic synapse, previous evidence indicates the widespread presence of gamma-aminobutyric acid (GABA) signaling markers, including presynaptic GABAB receptors (GABABR). In this study, we explore the source of GABA by optogenetically activating either cholinergic or GABAergic fibers. The optogenetic stimulation of MOC terminals from GAD;ChR2-eYFP and ChAT;ChR2-eYFP mice evoked synaptic currents in IHCs that were blocked by α-bungarotoxin. This suggests that GABAergic fibers release ACh and activate α9α10 nicotinic acetylcholine receptors (nAChRs). Additionally, MOC cholinergic fibers release not only ACh but also GABA, as the effect of GABA on ACh response amplitude was prevented by applying the GABAB-R blocker (CGP 36216). Using optical neurotransmitter detection and calcium imaging techniques, we examined the extent of GABAergic modulation at the single synapse level. Our findings suggest heterogeneity in GABA modulation, as only 15 out of 31 recorded synaptic sites were modulated by applying the GABABR specific antagonist, CGP (100-200 μM). In conclusion, we provide compelling evidence that GABA and ACh are co-released from at least a subset of MOC terminals. In this circuit, GABA functions as a negative feedback mechanism, locally regulating the extent of cholinergic inhibition at certain efferent-IHC synapses during an immature stage.
publishDate 2024
dc.date.none.fl_str_mv 2024-08-16
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/11336/262722
Castagnola, Tais; Castagna, Valeria Carolina; Kitcher, Sian R.; Torres Cadenas, Lester; Di Guilmi, Mariano Nicolás; et al.; Co-release of GABA and ACh from medial olivocochlear neurons fine tunes cochlear efferent inhibition; Cold Spring Harbor Laboratory Press; bioRxiv; 16-8-2024; 1-38
2692-8205
CONICET Digital
CONICET
url http://hdl.handle.net/11336/262722
identifier_str_mv Castagnola, Tais; Castagna, Valeria Carolina; Kitcher, Sian R.; Torres Cadenas, Lester; Di Guilmi, Mariano Nicolás; et al.; Co-release of GABA and ACh from medial olivocochlear neurons fine tunes cochlear efferent inhibition; Cold Spring Harbor Laboratory Press; bioRxiv; 16-8-2024; 1-38
2692-8205
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1101/2024.08.12.607644
info:eu-repo/semantics/altIdentifier/url/https://www.biorxiv.org/content/10.1101/2024.08.12.607644v1
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
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 13.13397

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