Arc regulates spine morphology and maintains network stability in vivo
Open accessAbstract
Long-term memory relies on modulation of synaptic connections in response to experience. This plasticity involves trafficking of AMPA receptors (AMPAR) and alteration of spine morphology. Arc, a gene induced by synaptic activity, mediates the endocytosis of AMPA receptors and is required for both long-term and homeostatic plasticity. We found that Arc increases spine density and regulates spine morphology by increasing the proportion of thin spines. Furthermore, Arc specifically reduces surface GluR1 internalization at thin spines, and Arc mutants that fail to facilitate AMPAR endocytosis do not increase the proportion of thin spines, suggesting that Arc-mediated AMPAR endocytosis facilitates alterations in spine morphology. Thus, by linking spine morphology with AMPAR endocytosis, Arc balances synaptic downscaling with increased structural plasticity. Supporting this, loss of Arc in vivo leads to a significant decrease in the proportion of thin spines and an epileptic-like network hyperexcitability.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Arc regulates spine size and the distribution of spine type.
“It has been demonstrated that Arc regulates spine size and the distribution of spine type14.”
Spine morphology correlates with synaptic strength and structural plasticity.
“Spine morphology correlates with synaptic strength and structural plasticity; for instance, thin spines are highly motile and likely to respond to activity-induced changes, whereas mushroom spines have larger post-synaptic densities (PSDs) and are more stable [13], [14].”
From Arf4 Determines Dentate Gyrus-Mediated Pattern Separation by Regulating Dendritic Spine Development (2012) · cites this paper as [13]
Cites
Structural basis of long-term potentiation in single dendritic spines
Matsuzaki, M., Honkura, N., Ellis-Davies, G. C. R., & Kasai, H. (2004) · Nature · doi:10.1038/nature02617 · Cited by 2,500 · see citing works
Shrinkage of dendritic spines associated with long-term depression of hippocampal synapses
Zhou, Q., Homma, K. J., & Poo, M.-M. (2004) · Neuron · doi:10.1016/j.neuron.2004.11.011 · Cited by 1,025 · see citing works
Waung, M. W., Pfeiffer, B. E., Nosyreva, E. D., Ronesi, J. A., & Huber, K. M. (2008) · Neuron · doi:10.1016/j.neuron.2008.05.014 · Cited by 474 · see citing works
Kirov, S. A., Petrak, L. J., Fiala, J. C., & Harris, K. M. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.04.053 · Cited by 172 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Guenthner, C. J., Miyamichi, K., Yang, H. H., Heller, H. C., & Luo, L. (2013) · Neuron · doi:10.1016/j.neuron.2013.03.025 · Cited by 705 · see citing works
Arc in synaptic plasticity: from gene to behavior
Korb, E., & Finkbeiner, S. (2011) · Trends in Neurosciences · doi:10.1016/j.tins.2011.08.007 · Cited by 388 · see citing works
Self-citationInverse synaptic tagging of inactive synapses via dynamic interaction of Arc/Arg3.1 with CaMKIIβ
Okuno, H., Akashi, K., Ishii, Y., Yagishita-Kyo, N., Suzuki, K., Nonaka, M., Kawashima, T., Fujii, H., Takemoto-Kimura, S., Abe, M., et al. (2012) · Cell · doi:10.1016/j.cell.2012.02.062 · Cited by 310 · see citing works
De Rubeis, S., Pasciuto, E., Li, K. W., Fernández, E., Di Marino, D., Buzzi, A., Ostroff, L. E., Klann, E., Zwartkruis, F. J. T., Komiyama, N. H., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.06.039 · Cited by 296 · see citing works
Role of p38/MAPKs in Alzheimer's Disease: Implications for Amyloid Beta Toxicity Targeted Therapy
Kheiri, G., Dolatshahi, M., Rahmani, F., & Rezaei, N. (2018) · Reviews in the Neurosciences · doi:10.1515/revneuro-2018-0008 · Cited by 211 · see citing works
Synapse development organized by neuronal activity-regulated immediate-early genes
Kim, S., Kim, H., & Um, J. W. (2018) · Experimental & Molecular Medicine · doi:10.1038/s12276-018-0025-1 · Cited by 77 · see citing works
Risks of cognitive detriments after low dose heavy ion and proton exposures
Cucinotta, F. A., & Cacao, E. (2019) · International Journal of Radiation Biology · doi:10.1080/09553002.2019.1623427 · Cited by 58 · see citing works
Liu, Z.-H., Ding, J.-J., Yang, Q.-Q., Song, H.-Z., Chen, X.-T., Xu, Y., Xiao, G.-R., & Wang, H.-L. (2016) · Scientific Reports · doi:10.1038/srep32492 · Cited by 53 · see citing works
de Bartolomeis, A., Buonaguro, E. F., Latte, G., Rossi, R., Marmo, F., Iasevoli, F., & Tomasetti, C. (2017) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2017.00240 · Cited by 44 · see citing works
Arf4 Determines Dentate Gyrus-Mediated Pattern Separation by Regulating Dendritic Spine Development
Jain, S., Yoon, S. Y., Zhu, L., Brodbeck, J., Dai, J., Walker, D., & Huang, Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046340 · Cited by 43 · see citing works
Xie, Y.-C., Yao, Z.-H., Yao, X.-L., Pan, J.-Z., Zhang, S.-F., Zhang, Y., & Hu, J.-C. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-180782 · Cited by 24 · see citing works
Adolescence alcohol exposure impairs fear extinction and alters medial prefrontal cortex plasticity
Lawson, K., Scarlata, M. J., Cho, W. C., Mangan, C., Petersen, D., Thompson, H. M., Ehnstrom, S., Mousley, A. L., Bezek, J. L., & Bergstrom, H. C. (2022) · Neuropharmacology · doi:10.1016/j.neuropharm.2022.109048 · Cited by 16 · see citing works
- Authors
- Peebles, C. L., Yoo, J., Thwin, M. T., Palop, J. J., Noebels, J. L., & Finkbeiner, S.
- Affiliations
- Gladstone Institutes (US)
- Baylor College of Medicine (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-10-04
- Volume
- 107
- Issue
- 42
- Pages
- 18173-18178
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2964216
- OpenAlex
- W2020469828
- Cited by
- 245
- References
- 4
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 12 · 2023: 13 · 2022: 20 · 2021: 17 · 2020: 15 · 2019: 12 · 2018: 25 · 2017: 28 · 2016: 18 · 2015: 13 · 2014: 12 · 2013: 20 · 2012: 17
- FWCI
- 6.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- W. M. Keck Foundation
- Epilepsy Foundation
- Massachusetts Institute of Technology
- University College London
- National Institutes of Health (1c06rr018928-01, AG‐022074)
- Intellectual and Developmental Disabilities Research Center (HD024064)
- University of California, Irvine
- National Institute on Aging (P01AG022074)
- National Institute of General Medical Sciences (HD024064)
- National Institute of Neurological Disorders and Stroke (2R01 NS0390746, R01NS045191, NS29709, R01NS029709)
- National Center for Research Resources (C06-RR-018928)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 024064, P30HD024064)
- 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, dendritic spine morphology, AMPA receptor endocytosis, GluR1, synaptic plasticity, homeostatic plasticity, synaptic downscaling, network stability, long-term memory, synaptic homeostasis
- MeSH terms
- Animals, Cytoskeletal Proteins, Memory, Nerve Tissue Proteins, Neuropeptide Y, Synapses, Receptors, AMPA, Mice, Knockout, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
