Cited by 497Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsGenomics and Chromatin Dynamics

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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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Guan, Zhonghui, Giustetto, Maurizio, Lomvardas, Stavros, Kim, Joung-Hun, Miniaci, Maria Concetta, Schwartz, James H., Thanos, Dimitris, Kandel, Eric R.·2002·Cell

DOI 10.1016/s0092-8674(02)01074-7

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Abstract

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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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: Guan, Zhonghui
Giustetto, Maurizio
Lomvardas, Stavros
Kim, Joung-Hun
Miniaci, Maria Concetta
Thanos, Dimitris
Kandel, Eric R.
Venue: Cell
Publisher: Elsevier BV
Published: 2002-11
Volume: 111
Issue: 4
Pages: 483-493
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/s0092-8674(02)01074-7
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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Integration of Long-Term-Memory-Related Synaptic Plasticity Involves Bidirectional Regulation of Gene Expression and Chromatin Structure

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