The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
Integration of Long-Term-Memory-Related Synaptic Plasticity Involves Bidirectional Regulation of Gene Expression and Chromatin Structure
Open accessAbstract
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]
Citations
Cites
The Integrative Action of the Nervous System.
Sherrington, C. (1907) · The Journal of Nervous and Mental Disease · doi:10.1097/00005053-190734120-00021 · Cited by 4,136
The molecular biology of memory storage: a dialogue between genes and synapses
Kandel, E. R. (2001) · Science · doi:10.1126/science.1067020 · Cited by 3,917
Self-citationPhosphorylated CREB binds specifically to the nuclear protein CBP
Chrivia, J. C., Kwok, R. P. S., Lamb, N., Hagiwara, M., Montminy, M. R., & Goodman, R. H. (1993) · Nature · doi:10.1038/365855a0 · Cited by 2,052
CBP/p300 in cell growth, transformation, and development
Goodman, R. H., & Smolik, S. (2000) · Genes & Development · doi:10.1101/gad.14.13.1553 · Cited by 1,778
Protein synthesis and memory: A review.
Davis, H. P., & Squire, L. R. (1984) · Psychological Bulletin · doi:10.1037/0033-2909.96.3.518 · Cited by 1,505
The Integrative Action of the Nervous System.
Freeman, F. N., & SHERRINGTON, S. C. (1907) · The Journal of Philosophy Psychology and Scientific Methods · doi:10.2307/2010953 · Cited by 906
A Critical Period for Macromolecular Synthesis in Long-Term Heterosynaptic Facilitation in Aplysia
Montarolo, P. G., Goelet, P., Castellucci, V. F., Morgan, J., Kandel, E. R., & Schacher, S. (1986) · Science · doi:10.1126/science.3775383 · Cited by 769
Self-citationMartin, K. C., Casadio, A., Zhu, H., Yaping, E., Rose, J. C., Chen, M., Bailey, C. H., & Kandel, E. R. (1997) · Cell · doi:10.1016/s0092-8674(00)80484-5 · Cited by 740
Self-citationKuo, M., & Allis, C. D. (1999) · Methods · doi:10.1006/meth.1999.0879 · Cited by 601
Bartsch, D., Ghirardi, M., Skehel, P. A., Karl, K. A., Herder, S. P., Chen, M., Bailey, C. H., & Kandel, E. R. (1995) · Cell · doi:10.1016/0092-8674(95)90213-9 · Cited by 572
Self-citationMartin, K. C., Michael, D., Rose, J. C., Barad, M., Casadio, A., Zhu, H., & Kandel, E. R. (1997) · Neuron · doi:10.1016/s0896-6273(00)80330-x · Cited by 545
Self-citationC/EBP is an immediate-early gene required for the consolidation of long-term facilitation in Aplysia
Alberini, C. M., Ghirardl, M., Metz, R., & Kandel, E. R. (1994) · Cell · doi:10.1016/0092-8674(94)90386-7 · Cited by 523
Self-citationMapping chromosomal proteins in vivo by formaldehyde-crosslinked-chromatin immunoprecipitation
Orlando, V. (2000) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(99)01535-2 · Cited by 506
Casadio, A., Martin, K. C., Giustetto, M., Zhu, H., Chen, M., Bartsch, D., Bailey, C. H., & Kandel, E. R. (1999) · Cell · doi:10.1016/s0092-8674(00)81653-0 · Cited by 503
Self-citationFurumai, R., Komatsu, Y., Nishino, N., Khochbin, S., Yoshida, M., & Horinouchi, S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.1.87 · Cited by 412
Conjunction dysfunction: CBP/p300 in human disease
Giles, R. H., Peters, D. J. M., & Breuning, M. H. (1998) · Trends in Genetics · doi:10.1016/s0168-9525(98)01438-3 · Cited by 401
Bartsch, D., Casadio, A., Karl, K. A., Serodio, P., & Kandel, E. R. (1998) · Cell · doi:10.1016/s0092-8674(00)81752-3 · Cited by 373
Self-citationSchacher, S., & Proshansky, E. (1983) · Journal of Neuroscience · doi:10.1523/jneurosci.03-12-02403.1983 · Cited by 279
Phosphorylation by p44 MAP Kinase/ERK1 Stimulates CBP Histone Acetyl Transferase Activity in Vitro
Ait‐Si‐Ali, S., Carlisi, D., Ramírez-Clavijo, S. R., Upegui-Gonzalez, L.-C., Duquet, A., Robin, P., Rudkin, B. B., Harel‐Bellan, A., & Trouche, D. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.1132 · Cited by 126
Long-term heterosynaptic inhibition in Aplysia
Montarolo, P. G., Kandel, E. R., & Schacher, S. (1988) · Nature · doi:10.1038/333171a0 · Cited by 118
Self-citationSherff, C. M., & Carew, T. J. (1999) · Science · doi:10.1126/science.285.5435.1911 · Cited by 85
Lee, J. A., Kim, H. K., Kim, K., Han, J., Lee, Y., Lim, C., Chang, D., Kubo, T., & Kaang, B. (2001) · Learning & Memory · doi:10.1101/lm.40201 · Cited by 78
Yamamoto, N., Hegde, A. N., Chain, D. G., & Schwartz, J. H. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0732415.x · Cited by 64
Self-citationWagner, B. L., Bauer, A., Schütz, G., & Montminy, M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.12.8263 · Cited by 26
Cited by
Sorted by citations
Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action
Tsankova, N. M., Berton, O., Renthal, W., Kumar, A., Neve, R. L., & Nestler, E. J. (2006) · Nature Neuroscience · doi:10.1038/nn1659 · Cited by 1,780
HDAC2 negatively regulates memory formation and synaptic plasticity
Guan, J.-S., Haggarty, S. J., Giacometti, E., Dannenberg, J.-H., Joseph, N., Gao, J., Nieland, T. J. F., Zhou, Y., Wang, X., Mazitschek, R., et al. (2009) · Nature · doi:10.1038/nature07925 · Cited by 1,644
Epigenetic regulation in psychiatric disorders
Tsankova, N., Renthal, W., Kumar, A., & Nestler, E. J. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2132 · Cited by 1,400
Covalent Modification of DNA Regulates Memory Formation
Miller, C. A., & Sweatt, J. D. (2007) · Neuron · doi:10.1016/j.neuron.2007.02.022 · Cited by 1,220
The Molecular and Systems Biology of Memory
Kandel, E. R., Dudai, Y., & Mayford, M. R. (2014) · Cell · doi:10.1016/j.cell.2014.03.001 · Cited by 1,134
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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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