The Arc of synaptic memory

Bramham, Clive R.; Alme, Maria N.; Bittins, Margarethe; Kuipers, Sjoukje D.; Nair, Rajeevkumar R.; Pai, Balagopal; Panja, Debabrata; Schubert, Manja; Soule, Jonathan; Tiron, Adrian; Wibrand, Karin

doi:10.1007/s00221-009-1959-2

Cited by 452Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsGenetics and Neurodevelopmental Disorders

The Arc of synaptic memory

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Bramham, Clive R., Alme, Maria N., Bittins, Margarethe, Kuipers, Sjoukje D., Nair, Rajeevkumar R., Pai, Balagopal, Panja, Debabrata, Schubert, Manja +3 more·2010·Experimental Brain Research

DOI 10.1007/s00221-009-1959-2PMC PMC2803749

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Abstract

The immediate early gene Arc is emerging as a versatile, finely tuned system capable of coupling changes in neuronal activity patterns to synaptic plasticity, thereby optimizing information storage in the nervous system. Here, we attempt to overview the Arc system spanning from transcriptional regulation of the Arc gene, to dendritic transport, metabolism, and translation of Arc mRNA, to post-translational modification, localization, and degradation of Arc protein. Within this framework we discuss the function of Arc in regulation of actin cytoskeletal dynamics underlying consolidation of long-term potentiation (LTP) and regulation of AMPA-type glutamate receptor endocytosis underlying long-term depression (LTD) and homeostatic plasticity. Behaviorally, Arc has a key role in consolidation of explicit and implicit forms of memory, with recent work implicating Arc in adaptation to stress as well as maladaptive plasticity connected to drug addiction. Arc holds considerable promise as a "master regulator" of protein synthesis-dependent forms of synaptic plasticity, but the mechanisms that modulate and switch Arc function are only beginning to be elucidated.

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Arc is an immediate early gene that may orchestrate the translation of dendritic mRNA required for actin polymerization and stable expansion of dendritic spines during LTP.
“Arc is one immediate early gene that may orchestrate the translation of dendritic mRNA required for actin polymerization and stable expansion of dendritic spines during LTP (Bramham et al. 2010).”
From NMDA receptor-dependent long-term potentiation and long-term depression (LTP/LTD). (2012) · cites this paper as Bramham et al. 2010
Local synthesis of ARC is central to synaptic remodelling and the long-term maintenance of synaptic changes.
“with local synthesis of ARC central to synaptic remodelling and the long-term maintenance of synaptic changes.47”
From De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia (2012) · cites this paper as [47]

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SUMO
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Antidepressant drug treatment induces Arc gene expression in the rat brain
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Robust stimulation of TrkB induces delayed increases in BDNF and Arc mRNA expressions in cultured rat cortical neurons via distinct mechanisms
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Identification of a cis‐acting element required for dendritic targeting of activity‐regulated cytoskeleton‐associated protein mRNA
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Interaction of Arc with CaM kinase II and stimulation of neurite extension by Arc in neuroblastoma cells expressing CaM kinase II
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Activity-regulated cytoskeleton-associated protein Arc/Arg3.1 binds to spectrin and associates with nuclear promyelocytic leukemia (PML) bodies
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The immediate early gene Arc is associated with behavioral resilience to stress exposure in an animal model of posttraumatic stress disorder
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Muscarinic acetylcholine receptor stimulation induces expression of the activity-regulated cytoskeleton-associated gene (ARC)
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Molecular Cloning and Characterization of Amida, a Novel Protein Which Interacts with a Neuron-specific Immediate Early Gene Product Arc, Contains Novel Nuclear Localization Signals, and Causes Cell Death in Cultured Cells
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Gene Expression in the Conversion of Early‐Phase to Late‐Phase Long‐Term Potentiation
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Chronic fluoxetine induces region‐specific changes in translation factor eIF4E and eEF2 activity in the rat brain
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Alternatively Spliced T-cell Receptor Transcripts Are Up-regulated in Response to Disruption of Either Splicing Elements or Reading Frame
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Single session of cocaine intravenous self-administration shapes goal-oriented behaviours and up-regulates Arc mRNA levels in rat medial prefrontal cortex
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Pondering the puzzle of PML (promyelocytic leukemia) nuclear bodies: Can we fit the pieces together using an RNA regulon?
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Sleep and the price of plasticity: from synaptic and cellular homeostasis to memory consolidation and integration
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“47 ARC mRNA is transported to sites of synaptic activity in complexes containing CYFIP1 , dissociation of which is required for ARC translation.”
Background
Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons
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Authors: Bramham, C. R., Alme, M. N., Bittins, M., Kuipers, S. D., Nair, R. R., Pai, B., Panja, D., Schubert, M., Soule, J., Tiron, A., & Wibrand, K.
Affiliations: University of Bergen (NO)
Corresponding author: Bramham, Clive R.
ORCID: Bramham, Clive R.
Alme, Maria N.
Bittins, Margarethe
Nair, Rajeevkumar R.
Pai, Balagopal
Panja, Debabrata
Schubert, Manja
Soule, Jonathan
Tiron, Adrian
Wibrand, Karin
Venue: Experimental Brain Research
Publisher: Springer Science and Business Media LLC
Published: 2009-08-19
Volume: 200
Issue: 2
Pages: 125-140
ISSN: 0014-4819 (ISSN-L)
1432-1106
DOI: 10.1007/s00221-009-1959-2
PMC: PMC2803749
OpenAlex: W2100126489
Cited by: 452
References: 160
Citations by year: 2026: 11 · 2025: 9 · 2024: 28 · 2023: 18 · 2022: 24 · 2021: 24 · 2020: 24 · 2019: 30 · 2018: 31 · 2017: 41 · 2016: 24 · 2015: 28 · 2014: 32 · 2013: 44 · 2012: 39
FWCI: 2.36
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc
Locations: Experimental Brain Research (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
NORA - Norwegian Open Research Archives (submittedVersion, cc-by-nc)
Funders: Universitetet i Bergen
Norges Forskningsråd
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 › Genetics › Genetics and Neurodevelopmental Disorders
Keywords: Arc, synaptic plasticity, immediate early genes, long-term potentiation, long-term depression, homeostatic plasticity, actin cytoskeleton dynamics, AMPA receptor endocytosis, memory consolidation, stress adaptation, drug addiction, protein synthesis, post-translational modification
MeSH terms: Animals, Cytoskeletal Proteins, Humans, Memory, Models, Neurological, Nerve Tissue Proteins, Neuronal Plasticity, Neurons, Synapses

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