Activity-dependent Nr4a2 induction modulates synaptic expression of AMPA receptors and plasticity via a Ca 2+/ CRTC1/CREB pathway

Transcription factors have a pivotal role in synaptic plasticity and the associated modification of neuronal networks required for memory formation and consolidation. The nuclear receptors subfamily 4 group A (Nr4a) have emerged as possible modulators of hippocampal synaptic plasticity and cognitive...

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Autores: Català-Solsona, Judit|||0000-0002-2927-9135, Lituma, Pablo|||0000-0001-8442-3622, Lutzu, Stefano|||0000-0002-6497-2381, Siedlecki-Wullich, Dolores|||0000-0002-9099-9406, Fábregas Ordóñez, Cristina|||0009-0001-8549-6599, Miñano Molina, Alfredo Jesús|||0000-0002-7761-5682, Saura Antolín, Carlos|||0000-0003-3692-5657, Castillo, Pablo, Rodríguez Álvarez, José|||0000-0001-8582-8082
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:307991
Acceso en línea:https://ddd.uab.cat/record/307991
https://dx.doi.org/urn:doi:10.1523/JNEUROSCI.1341-22.2023
Access Level:acceso abierto
Palabra clave:LTD
Nr4a2
Glutamate receptors
Hippocampus
Neuronal activity
Synaptic plasticity
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spelling Activity-dependent Nr4a2 induction modulates synaptic expression of AMPA receptors and plasticity via a Ca 2+/ CRTC1/CREB pathwayCatalà-Solsona, Judit|||0000-0002-2927-9135Lituma, Pablo|||0000-0001-8442-3622Lutzu, Stefano|||0000-0002-6497-2381Siedlecki-Wullich, Dolores|||0000-0002-9099-9406Fábregas Ordóñez, Cristina|||0009-0001-8549-6599Miñano Molina, Alfredo Jesús|||0000-0002-7761-5682Saura Antolín, Carlos|||0000-0003-3692-5657Castillo, PabloRodríguez Álvarez, José|||0000-0001-8582-8082LTDNr4a2Glutamate receptorsHippocampusNeuronal activitySynaptic plasticityTranscription factors have a pivotal role in synaptic plasticity and the associated modification of neuronal networks required for memory formation and consolidation. The nuclear receptors subfamily 4 group A (Nr4a) have emerged as possible modulators of hippocampal synaptic plasticity and cognitive functions. However, the molecular and cellular mechanisms underlying Nr4a2-mediated hippocampal synaptic plasticity are not completely known. Here, we report that neuronal activity enhances Nr4a2 expression and function in cultured mouse hippocampal neurons (both sexes) by an ionotropic glutamate receptor/Ca2+/cAMP response element-binding protein/CREB-regulated transcription factor 1 (iGluR/Ca2+/CREB/CRTC1) pathway. Nr4a2 activation mediates Brain-derived neurotrophic factor (BDNF) production and increases expression of iGluRs, thereby affecting long-term depression (LTD) at CA3-CA1 synapses in acute mouse hippocampal slices (both sexes). Altogether, our results indicate that the iGluR/Ca2+/CREB/CRTC1 pathway mediates activity-dependent expression of Nr4a2 which is involved in glutamatergic synaptic plasticity by increasing BDNF and synaptic GluA1-AMPARs. Therefore, Nr4a2 activation could be a therapeutical approach for brain disorders associated with dysregulated synaptic plasticity.Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular 22023-01-0120232023-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/307991https://dx.doi.org/urn:doi:10.1523/JNEUROSCI.1341-22.2023reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3079912026-06-06T12:50:31Z
dc.title.none.fl_str_mv Activity-dependent Nr4a2 induction modulates synaptic expression of AMPA receptors and plasticity via a Ca 2+/ CRTC1/CREB pathway
title Activity-dependent Nr4a2 induction modulates synaptic expression of AMPA receptors and plasticity via a Ca 2+/ CRTC1/CREB pathway
spellingShingle Activity-dependent Nr4a2 induction modulates synaptic expression of AMPA receptors and plasticity via a Ca 2+/ CRTC1/CREB pathway
Català-Solsona, Judit|||0000-0002-2927-9135
LTD
Nr4a2
Glutamate receptors
Hippocampus
Neuronal activity
Synaptic plasticity
title_short Activity-dependent Nr4a2 induction modulates synaptic expression of AMPA receptors and plasticity via a Ca 2+/ CRTC1/CREB pathway
title_full Activity-dependent Nr4a2 induction modulates synaptic expression of AMPA receptors and plasticity via a Ca 2+/ CRTC1/CREB pathway
title_fullStr Activity-dependent Nr4a2 induction modulates synaptic expression of AMPA receptors and plasticity via a Ca 2+/ CRTC1/CREB pathway
title_full_unstemmed Activity-dependent Nr4a2 induction modulates synaptic expression of AMPA receptors and plasticity via a Ca 2+/ CRTC1/CREB pathway
title_sort Activity-dependent Nr4a2 induction modulates synaptic expression of AMPA receptors and plasticity via a Ca 2+/ CRTC1/CREB pathway
dc.creator.none.fl_str_mv Català-Solsona, Judit|||0000-0002-2927-9135
Lituma, Pablo|||0000-0001-8442-3622
Lutzu, Stefano|||0000-0002-6497-2381
Siedlecki-Wullich, Dolores|||0000-0002-9099-9406
Fábregas Ordóñez, Cristina|||0009-0001-8549-6599
Miñano Molina, Alfredo Jesús|||0000-0002-7761-5682
Saura Antolín, Carlos|||0000-0003-3692-5657
Castillo, Pablo
Rodríguez Álvarez, José|||0000-0001-8582-8082
author Català-Solsona, Judit|||0000-0002-2927-9135
author_facet Català-Solsona, Judit|||0000-0002-2927-9135
Lituma, Pablo|||0000-0001-8442-3622
Lutzu, Stefano|||0000-0002-6497-2381
Siedlecki-Wullich, Dolores|||0000-0002-9099-9406
Fábregas Ordóñez, Cristina|||0009-0001-8549-6599
Miñano Molina, Alfredo Jesús|||0000-0002-7761-5682
Saura Antolín, Carlos|||0000-0003-3692-5657
Castillo, Pablo
Rodríguez Álvarez, José|||0000-0001-8582-8082
author_role author
author2 Lituma, Pablo|||0000-0001-8442-3622
Lutzu, Stefano|||0000-0002-6497-2381
Siedlecki-Wullich, Dolores|||0000-0002-9099-9406
Fábregas Ordóñez, Cristina|||0009-0001-8549-6599
Miñano Molina, Alfredo Jesús|||0000-0002-7761-5682
Saura Antolín, Carlos|||0000-0003-3692-5657
Castillo, Pablo
Rodríguez Álvarez, José|||0000-0001-8582-8082
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular
dc.subject.none.fl_str_mv LTD
Nr4a2
Glutamate receptors
Hippocampus
Neuronal activity
Synaptic plasticity
topic LTD
Nr4a2
Glutamate receptors
Hippocampus
Neuronal activity
Synaptic plasticity
description Transcription factors have a pivotal role in synaptic plasticity and the associated modification of neuronal networks required for memory formation and consolidation. The nuclear receptors subfamily 4 group A (Nr4a) have emerged as possible modulators of hippocampal synaptic plasticity and cognitive functions. However, the molecular and cellular mechanisms underlying Nr4a2-mediated hippocampal synaptic plasticity are not completely known. Here, we report that neuronal activity enhances Nr4a2 expression and function in cultured mouse hippocampal neurons (both sexes) by an ionotropic glutamate receptor/Ca2+/cAMP response element-binding protein/CREB-regulated transcription factor 1 (iGluR/Ca2+/CREB/CRTC1) pathway. Nr4a2 activation mediates Brain-derived neurotrophic factor (BDNF) production and increases expression of iGluRs, thereby affecting long-term depression (LTD) at CA3-CA1 synapses in acute mouse hippocampal slices (both sexes). Altogether, our results indicate that the iGluR/Ca2+/CREB/CRTC1 pathway mediates activity-dependent expression of Nr4a2 which is involved in glutamatergic synaptic plasticity by increasing BDNF and synaptic GluA1-AMPARs. Therefore, Nr4a2 activation could be a therapeutical approach for brain disorders associated with dysregulated synaptic plasticity.
publishDate 2023
dc.date.none.fl_str_mv 2
2023-01-01
2023
2023-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/307991
https://dx.doi.org/urn:doi:10.1523/JNEUROSCI.1341-22.2023
url https://ddd.uab.cat/record/307991
https://dx.doi.org/urn:doi:10.1523/JNEUROSCI.1341-22.2023
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
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repository.mail.fl_str_mv
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