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Integration of Long-Term-Memory-Related Synaptic Plasticity Involves Bidirectional Regulation of Gene Expression and Chromatin Structure
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Excitatory and inhibitory inputs converge on single neurons and are integrated into a coherent output. Although much is known about short-term integration, little is known about how neurons sum opposing signals for long-term synaptic plasticity and memory storage. In Aplysia, we find that when a sensory neuron simultaneously receives inputs from the facilitatory transmitter 5-HT at one set of synapses and the inhibitory transmitter FMRFamide at another, long-term facilitation is blocked and synapse-specific long-term depression dominates. Chromatin immunoprecipitation assays show that 5-HT induces the downstream gene C/EBP by activating CREB1, which recruits CBP for histone acetylation, whereas FMRFa leads to CREB1 displacement by CREB2 and recruitment of HDAC5 to deacetylate histones. When the two transmitters are applied together, facilitation is blocked because CREB2 and HDAC5 displace CREB1-CBP, thereby deacetylating histones.
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“Epigenetics can regulate neuronal plasticity and memory consolidation.38–41”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [41]
In the citing paper
“Chromatin remodeling plays a role in multiple physiological and pathological processes in the brain, including circadian rhythms, 32 learning and memory, 33 drug addiction, 34 and depression.”
From Epigenetic mechanisms of major depression: Targeting neuronal plasticity (2018) · cites this paper as [33]
In the citing paper
“HDAC-mediated epigenetic regulation of transcription impacts neuronal plasticity and behavior.”
From Epigenetic mechanisms of major depression: Targeting neuronal plasticity (2018) · cites this paper as [33]
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Metadata
- Authors
- Guan, Z., Giustetto, M., Lomvardas, S., Kim, J.-H., Miniaci, M. C., Schwartz, J. H., Thanos, D., & Kandel, E. R.
- Affiliations
- New York State Psychiatric Institute (US)
- Howard Hughes Medical Institute (US)
- Columbia University (US)
- Corresponding author
- Kandel, Eric R.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2002-11
- Volume
- 111
- Issue
- 4
- Pages
- 483-493
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2074489888
- Cited by
- 497
- References
- 24
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 13 · 2023: 11 · 2022: 15 · 2021: 21 · 2020: 16 · 2019: 17 · 2018: 14 · 2017: 21 · 2016: 25 · 2015: 19 · 2014: 41 · 2013: 38 · 2012: 29
- FWCI
- 6.18
- 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, 3911 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
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Open Access System for Information Sharing (Pohang University of Science and Technology) (submittedVersion)
- Funders
- National Institute of Mental Health (MH-48850, R01MH048850)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- long-term synaptic plasticity, memory storage, Aplysia, FMRFamide, inhibitory synaptic input, CREB1, ATF4, C/EBP, CBP, histone acetylation, HDAC5, histone deacetylation, chromatin structure, gene expression regulation, long-term depression, sensory neurons
- MeSH terms
- Acetylation, Animals, Aplysia, Chromatin, Gene Expression Regulation, Histone Deacetylases, Histones, Motor Neurons, Nerve Tissue Proteins, Neurons, Afferent, Nuclear Proteins, Repressor Proteins, Serotonin, Synapses, Transcription Factors, Transcription, Genetic, Trans-Activators, Cyclic AMP Response Element-Binding Protein, Long-Term Potentiation, FMRFamide, CCAAT-Enhancer-Binding Proteins, TATA-Box Binding Protein, Long-Term Synaptic Depression, CREB-Binding Protein
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