Knockout of ERK1 MAP Kinase Enhances Synaptic Plasticity in the Striatum and Facilitates Striatal-Mediated Learning and Memory
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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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During development, ERK1 and ERK2 have divergent functions since ERK1 null mice are grossly viable and fertile while ERK2 null mice are embryonic lethal.
“During development, ERK1 and ERK2 have divergent functions since ERK1 null mice are grossly viable and fertile while ERK2 null mice are embryonic lethal7–9.”
From Conditional loss of ERK1 and ERK2 results in abnormal placentation and delayed parturition in the mouse (2019) · cites this paper as [7]
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Self-citation
- 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
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2002-05
- Volume
- 34
- Issue
- 5
- Pages
- 807-820
- ISSN
- 0896-6273 (ISSN-L)
- 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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