ERK/MAPK regulates hippocampal histone phosphorylation following contextual fear conditioning
Open accessAbstract
Long-term memory formation is regulated by many distinct molecular mechanisms that control gene expression. An emerging model for effecting a stable, coordinated pattern of gene transcription involves epigenetic tagging through modifications of histones or DNA. In this study, we investigated the regulation of histone phosphorylation in the hippocampus by the ERK/MAPK (extracellular signal-regulated kinase/mitogen-activated protein kinase) pathway. We found that activation of ERK/MAPK in vitro significantly increased histone H3 phosphorylation in hippocampal area CA1. Furthermore, we found that contextual fear conditioning in vivo leads to a rapid time-dependent increase in histone H3 phosphorylation in area CA1. This increase paralleled the time course of contextual fear-dependent activation of ERK, and was inhibited in vivo by a latent inhibition paradigm as well as by injection of an N -methyl-d-aspartic acid receptor (NMDA-R) antagonist. Finally, injection of an inhibitor of MEK (MAP kinase/ERK kinase), the unique dual-specificity kinase upstream of ERK, blocked the increase in histone H3 phosphorylation seen after contextual fear conditioning. These results demonstrate that changes in histone phosphorylation in the hippocampus are regulated by ERK/MAPK following a behavioral fear conditioning paradigm.
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Expression of H3S10 phosphorylation was increased in the hippocampus in mice exposed to fear conditioning.
“the expression of H3S10 phosphorylation (H3S10p) was increased in the hippocampus in mice exposed to fear conditioning.185”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [185]
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- Authors
- Chwang, W. B., O’Riordan, K. J., Levenson, J. M., & Sweatt, J. D.
- Affiliations
- Baylor College of Medicine (US)
- Venue
- Learning & Memory
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2006-05
- Volume
- 13
- Issue
- 3
- Pages
- 322-328
- ISSN
- 1072-0502 (ISSN-L)
- 1549-5485
- PMC
- PMC1475813
- OpenAlex
- W2143524000
- Cited by
- 341
- References
- 4
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 9 · 2023: 8 · 2022: 11 · 2021: 10 · 2020: 10 · 2019: 9 · 2018: 17 · 2017: 16 · 2016: 18 · 2015: 12 · 2014: 34 · 2013: 47 · 2012: 22
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Learning & Memory (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Health Assistance Foundation
- National Institutes of Health (NS37444)
- National Institute of Mental Health (MH 57014, R01MH057014)
- National Institute of Neurological Disorders and Stroke (NS 37444, NS-13546, R01NS013546, P01NS037444)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- ERK signaling, histone H3 phosphorylation, hippocampus, CA1, contextual fear conditioning, long-term memory, epigenetic regulation, MEK inhibition, NMDA receptor, latent inhibition, fear memory
- MeSH terms
- Animals, Association Learning, Conditioning, Classical, Fear, Gene Expression Regulation, Hippocampus, Histones, Male, Memory, Neurons, Phosphorylation, Signal Transduction, Rats, Wistar, Extracellular Signal-Regulated MAP Kinases, Rats, In Vitro Techniques
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