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Knockout of ERK1 MAP Kinase Enhances Synaptic Plasticity in the Striatum and Facilitates Striatal-Mediated Learning and Memory

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Mazzucchelli, Cristina, Vantaggiato, Chiara, Ciamei, Alessandro, Fasano, Stefania, Pakhotin, Pavel, Krezel, Wojciech, Welzl, Hans, Wolfer, David P, Pagès, Gilles, Valverde, Olga, Marowsky, Anne, Porrazzo, Annamaria, Orban, Paul C, Maldonado, Rafael, Ehrengruber, Markus U, Cestari, Vincenzo, Lipp, Hans-Peter, Chapman, Paul F, Pouysségur, Jacques, Brambilla, Riccardo·2002·Neuron

DOI 10.1016/s0896-6273(02)00716-x

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Abstract

Extracellular signal-regulated kinases (ERK1 and 2) are synaptic signaling components necessary for several forms of learning. In mice lacking ERK1, we observe a dramatic enhancement of striatum-dependent long-term memory, which correlates with a facilitation of long-term potentiation in the nucleus accumbens. At the cellular level, we find that ablation of ERK1 results in a stimulus-dependent increase of ERK2 signaling, likely due to its enhanced interaction with the upstream kinase MEK. Consistently, such activity change is responsible for the hypersensitivity of ERK1 mutant mice to the rewarding properties of morphine. Our results reveal an unexpected complexity of ERK-dependent signaling in the brain and a critical regulatory role for ERK1 in the long-term adaptive changes underlying striatum-dependent behavioral plasticity and drug addiction.

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Authors: Mazzucchelli, C., Vantaggiato, C., Ciamei, A., Fasano, S., Pakhotin, P., Krezel, W., Welzl, H., Wolfer, D. P., Pagès, G., Valverde, O., Marowsky, A., Porrazzo, A., Orban, P. C., Maldonado, R., Ehrengruber, M. U., Cestari, V., Lipp, H.-P., Chapman, P. F., Pouysségur, J., & Brambilla, R.
Affiliations: National Research Council (IT)
Cardiff University (GB)
University of Zurich (CH)
Centre National de la Recherche Scientifique (FR)
Universitat Pompeu Fabra (ES)
Corresponding author: Brambilla, Riccardo
ORCID: Vantaggiato, Chiara
Fasano, Stefania
Wolfer, David P
Pagès, Gilles
Valverde, Olga
Marowsky, Anne
Orban, Paul C
Maldonado, Rafael
Cestari, Vincenzo
Pouysségur, Jacques
Brambilla, Riccardo
Venue: Neuron
Publisher: Elsevier BV
Published: 2002-05
Volume: 34
Issue: 5
Pages: 807-820
ISSN: 0896-6273 (ISSN-L)
DOI: 10.1016/s0896-6273(02)00716-x
OpenAlex: W1967318257
Cited by: 456
References: 41
Citations by year: 2026: 2 · 2025: 6 · 2024: 4 · 2023: 3 · 2022: 8 · 2021: 8 · 2020: 11 · 2019: 14 · 2018: 17 · 2017: 15 · 2016: 22 · 2015: 18 · 2014: 23 · 2013: 20 · 2012: 31
FWCI: 9.18
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 4095 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Neuron (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords: ERK1, ERK2, MEK, MAPK signaling, striatum, synaptic plasticity, long-term potentiation, nucleus accumbens, learning and memory, morphine reward, drug addiction, behavioral plasticity, knockout mice
MeSH terms: Amygdala, Animals, Avoidance Learning, Behavior, Animal, Cognition Disorders, Corpus Striatum, Female, Hippocampus, Male, Memory, Morphine, Motor Activity, Mutation, Nerve Net, Nervous System Malformations, Synaptic Transmission, Nucleus Accumbens, Up-Regulation, Presynaptic Terminals, Long-Term Potentiation, Mice, Knockout, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinases, MAP Kinase Kinase Kinases, Mitogen-Activated Protein Kinase 3, Mice

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Knockout of ERK1 MAP Kinase Enhances Synaptic Plasticity in the Striatum and Facilitates Striatal-Mediated Learning and Memory

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