2026-04-05T12:44:52Zhttps://recercat.cat/oai/request

oai:recercat.cat:2072/4821442025-05-08T16:36:34Zcom_2072_98col_2072_378192

Activity-dependent Nr4a2 induction modulates synaptic expression of AMPA receptors and plasticity via a Ca 2+/ CRTC1/CREB pathway Català-Solsona, Judit Lituma, Pablo Lutzu, Stefano Siedlecki-Wullich, Dolores Fábregas Ordóñez, Cristina Miñano Molina, Alfredo Jesús Saura Antolín, Carlos Castillo, Pablo Rodríguez Álvarez, José Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular LTD Nr4a2 Glutamate receptors Hippocampus Neuronal activity Synaptic plasticity 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. 2023 Article The journal of neuroscience ; Vol. 43, Núm. 17 (April 2023), p. 3028-3041 open access Aquest 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/