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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Detalles Bibliográficos
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
Descripción
Sumario: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.

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