Activity-dependent Nr4a2 induction modulates synaptic expression of AMPA receptors and plasticity via a Ca 2+/ CRTC1/CREB pathway
Català-Solsona, Judit (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Lituma, Pablo (Albert Einstein College of Medicine (Nova York, Estats Units d'Amèrica))
Lutzu, Stefano (Albert Einstein College of Medicine (Nova York, Estats Units d'Amèrica))
Siedlecki-Wullich, Dolores (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Fábregas Ordóñez, Cristina (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Miñano Molina, Alfredo Jesús (Universitat Autònoma de Barcelona. Institut de Neurociències)
Saura Antolín, Carlos (Universitat Autònoma de Barcelona. Institut de Neurociències)
Castillo, Pablo (Albert Einstein College of Medicine (Nova York, Estats Units d'Amèrica))
Rodríguez Álvarez, José (Universitat Autònoma de Barcelona. Institut de Neurociències)
Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular

Date:	2023
Description:	14 pàg.
Abstract:	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.
Rights:	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.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	LTD ; Nr4a2 ; Glutamate receptors ; Hippocampus ; Neuronal activity ; Synaptic plasticity
Published in:	The journal of neuroscience, Vol. 43, Núm. 17 (April 2023) , p. 3028-3041, ISSN 1529-2401

DOI: 10.1523/JNEUROSCI.1341-22.2023
PMID: 36931707

14 p, 3.2 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles