GluN2A-mediated currents and calcium signal in human iPSC-derived neurons

Gene expression data indicate that during human brain development, neurons change the NMDA receptor (NMDAR) subunit composition to modulate their function, favouring the GluN2A subunit over GluN2B-a hallmark of neuronal maturation. However, evidence supporting this phenomenon in human iPSC-derived n...

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Autores: Escamilla, S, Avilés-Granados, C, Peralta, FA, Paternain, AV, Cortés-Gómez, MA, Zetterberg, H, de la Peña, E, Salas-Lucia, F, Sáez-Valero, J, Cuchillo-Ibáñez, I
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2026
País:España
Institución:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repositorio:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:dnet:r-fisabio___::b4b3250effb3650f92844515dd6de7a8
Acceso en línea:https://fisabio.portalinvestigacion.com/publicaciones/21169
Access Level:acceso abierto
Palabra clave:Cerebral cortex development
Neurodifferentiation
NMDAR
GluN2B
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spelling GluN2A-mediated currents and calcium signal in human iPSC-derived neuronsEscamilla, SAvilés-Granados, CPeralta, FAPaternain, AVCortés-Gómez, MAZetterberg, Hde la Peña, ESalas-Lucia, FSáez-Valero, JCuchillo-Ibáñez, ICerebral cortex developmentNeurodifferentiationNMDARGluN2BGene expression data indicate that during human brain development, neurons change the NMDA receptor (NMDAR) subunit composition to modulate their function, favouring the GluN2A subunit over GluN2B-a hallmark of neuronal maturation. However, evidence supporting this phenomenon in human iPSC-derived neurons remains elusive. Here, using two differentiation methods in parallel (BrainPhys Neuronal Medium, BPM, and Neural Maintenance Medium, NMM), we provide evidence of increased synaptic localization of NMDARs during neuronal maturation and that GluN2A subunit is crucial for the NMDA physiological function-inducing inward currents and calcium entrance at 60 days of differentiation. Calcium responses to specific agonists, particularly NMDA, were elevated in cells cultured under BPM conditions. This is likely attributable to their more mature neuronal phenotype and the RNA-seq identified upregulation of genes involved in intracellular calcium signaling proteins. Our results offer insight into how glutamate receptor subunits mature during brain development, delineating approaches to study NMDAR activity in health and disease.NATURE PORTFOLIO2026info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fisabio.portalinvestigacion.com/publicaciones/21169Scientific ReportsISSN: 20452322reponame:r-FISABIO. Repositorio Institucional de Producción Científicainstname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)Inglésinfo:eu-repo/semantics/openAccessoai:dnet:r-fisabio___::b4b3250effb3650f92844515dd6de7a82026-06-11T12:45:17Z
dc.title.none.fl_str_mv GluN2A-mediated currents and calcium signal in human iPSC-derived neurons
title GluN2A-mediated currents and calcium signal in human iPSC-derived neurons
spellingShingle GluN2A-mediated currents and calcium signal in human iPSC-derived neurons
Escamilla, S
Cerebral cortex development
Neurodifferentiation
NMDAR
GluN2B
title_short GluN2A-mediated currents and calcium signal in human iPSC-derived neurons
title_full GluN2A-mediated currents and calcium signal in human iPSC-derived neurons
title_fullStr GluN2A-mediated currents and calcium signal in human iPSC-derived neurons
title_full_unstemmed GluN2A-mediated currents and calcium signal in human iPSC-derived neurons
title_sort GluN2A-mediated currents and calcium signal in human iPSC-derived neurons
dc.creator.none.fl_str_mv Escamilla, S
Avilés-Granados, C
Peralta, FA
Paternain, AV
Cortés-Gómez, MA
Zetterberg, H
de la Peña, E
Salas-Lucia, F
Sáez-Valero, J
Cuchillo-Ibáñez, I
author Escamilla, S
author_facet Escamilla, S
Avilés-Granados, C
Peralta, FA
Paternain, AV
Cortés-Gómez, MA
Zetterberg, H
de la Peña, E
Salas-Lucia, F
Sáez-Valero, J
Cuchillo-Ibáñez, I
author_role author
author2 Avilés-Granados, C
Peralta, FA
Paternain, AV
Cortés-Gómez, MA
Zetterberg, H
de la Peña, E
Salas-Lucia, F
Sáez-Valero, J
Cuchillo-Ibáñez, I
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cerebral cortex development
Neurodifferentiation
NMDAR
GluN2B
topic Cerebral cortex development
Neurodifferentiation
NMDAR
GluN2B
description Gene expression data indicate that during human brain development, neurons change the NMDA receptor (NMDAR) subunit composition to modulate their function, favouring the GluN2A subunit over GluN2B-a hallmark of neuronal maturation. However, evidence supporting this phenomenon in human iPSC-derived neurons remains elusive. Here, using two differentiation methods in parallel (BrainPhys Neuronal Medium, BPM, and Neural Maintenance Medium, NMM), we provide evidence of increased synaptic localization of NMDARs during neuronal maturation and that GluN2A subunit is crucial for the NMDA physiological function-inducing inward currents and calcium entrance at 60 days of differentiation. Calcium responses to specific agonists, particularly NMDA, were elevated in cells cultured under BPM conditions. This is likely attributable to their more mature neuronal phenotype and the RNA-seq identified upregulation of genes involved in intracellular calcium signaling proteins. Our results offer insight into how glutamate receptor subunits mature during brain development, delineating approaches to study NMDAR activity in health and disease.
publishDate 2026
dc.date.none.fl_str_mv 2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fisabio.portalinvestigacion.com/publicaciones/21169
url https://fisabio.portalinvestigacion.com/publicaciones/21169
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv NATURE PORTFOLIO
publisher.none.fl_str_mv NATURE PORTFOLIO
dc.source.none.fl_str_mv Scientific Reports
ISSN: 20452322
reponame:r-FISABIO. Repositorio Institucional de Producción Científica
instname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
instname_str Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
reponame_str r-FISABIO. Repositorio Institucional de Producción Científica
collection r-FISABIO. Repositorio Institucional de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
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