Integrin-driven actin polymerization consolidates long-term potentiation
Abstract
Long-term potentiation (LTP), like memory, becomes progressively more resistant to disruption with time after its formation. Here we show that threshold conditions for inducing LTP cause a rapid, long-lasting increase in polymerized filamentous actin in dendritic spines of adult hippocampus. Two independent manipulations that reverse LTP disrupted this effect when applied shortly after induction but not 30 min later. Function-blocking antibodies to β1 family integrins selectively eliminated both actin polymerization and stabilization of LTP. We propose that the initial stages of consolidation involve integrin-driven events common to cells engaged in activities that require rapid morphological changes.
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Actin polymerization is an essential step of LTP-stabilizing processes.
“Actin polymerization is an essential step of this kind (9, 15–17)”
From Synaptic evidence for the efficacy of spaced learning (2012) · cites this paper as [16]
Cites
Cell Migration: Integrating Signals from Front to Back
Ridley, A. J., Schwartz, M. A., Burridge, K., Firtel, R., Ginsberg, M. H., Borisy, G. G., Parsons, J. T., & Horwitz, A. R. (2003) · Science · doi:10.1126/science.1092053 · Cited by 4,929 · see citing works
Memory - A century of consolidation
McGaugh, J. L. (2000) · Science · doi:10.1126/science.287.5451.248 · Cited by 4,250 · see citing works
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
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 · see citing works
Morphological Changes in Dendritic Spines Associated with Long-Term Synaptic Plasticity
Yuste, R., & Bonhoeffer, T. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1071 · Cited by 1,269 · see citing works
The Biochemistry of Memory: A New and Specific Hypothesis
LYNCH, G. S., & Baudry, M. (1984) · Science · doi:10.1126/science.6144182 · Cited by 1,045 · see citing works
Self-citationRapid Actin-Based Plasticity in Dendritic Spines
Fischer, M., Kaech, S., Knutti, D., & Matus, A. (1998) · Neuron · doi:10.1016/s0896-6273(00)80467-5 · Cited by 905 · see citing works
Okamoto, K.-I., Nagai, T., Miyawaki, A., & Hayashi, Y. (2004) · Nature Neuroscience · doi:10.1038/nn1311 · Cited by 854 · see citing works
Fukazawa, Y., Saitoh, Y., Ozawa, F., Ohta, Y., Mizuno, K., & Inokuchi, K. (2003) · Neuron · doi:10.1016/s0896-6273(03)00206-x · Cited by 695 · see citing works
Toward a molecular definition of long-term memory storage
Bailey, C. H., Bartsch, D., & Kandel, E. R. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.13445 · Cited by 691 · see citing works
Integrin signaling to the actin cytoskeleton
DeMali, K. A., Wennerberg, K., & Burridge, K. (2003) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(03)00109-1 · Cited by 504 · see citing works
Lee, K. S., Schottler, F., Oliver, M. E., & LYNCH, G. S. (1980) · Journal of Neurophysiology · doi:10.1152/jn.1980.44.2.247 · Cited by 473 · see citing works
Self-citationThe retroactive effect of electroshock on learning.
Duncan, C. P. (1949) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0058173 · Cited by 428 · see citing works
Mechanisms of actin rearrangements mediating platelet activation.
Hartwig, J. H. (1992) · The Journal of Cell Biology · doi:10.1083/jcb.118.6.1421 · Cited by 408 · see citing works
Krucker, T., Siggins, G. R., & Halpain, S. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.100139797 · Cited by 374 · see citing works
Stable hippocampal long-term potentiation elicited by ‘theta’ pattern stimulation
Staubli, U. V., & LYNCH, G. S. (1987) · Brain Research · doi:10.1016/0006-8993(87)91605-2 · Cited by 345 · see citing works
Self-citationAbraham, W. C., Logan, B. J., Greenwood, J. M., & Dragunow, M. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-21-09626.2002 · Cited by 338 · see citing works
Barrionuevo, G., Schottler, F., & Lynch, G. (1980) · Life Sciences · doi:10.1016/0024-3205(80)90509-3 · Cited by 321 · see citing works
Self-citationStable depression of potentiated synaptic responses in the hippocampus with 1–5 Hz stimulation
Staubli, U. V., & LYNCH, G. S. (1990) · Brain Research · doi:10.1016/0006-8993(90)91096-y · Cited by 301 · see citing works
Self-citationActivity-induced targeting of profilin and stabilization of dendritic spine morphology
Ackermann, M., & Matus, A. I. (2003) · Nature Neuroscience · doi:10.1038/nn1135 · Cited by 274 · see citing works
CAKβ/Pyk2 Kinase Is a Signaling Link for Induction of Long-Term Potentiation in CA1 Hippocampus
Huang, Y.-Q., Lu, W.-Y., Ali, D. W., Pelkey, K. A., Pitcher, G. M., Lu, Y. M., Aoto, H., Roder, J. C., Sasaki, T., Salter, M. W., et al. (2001) · Neuron · doi:10.1016/s0896-6273(01)00220-3 · Cited by 274 · see citing works
Integrin Subunit Gene Expression Is Regionally Differentiated in Adult Brain
Pinkstaff, J. K., Detterich, J., Lynch, G., & Gall, C. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-05-01541.1999 · Cited by 250 · see citing works
Self-citationMatsuoka, Y., Li, X., & Bennett, V. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.142.2.485 · Cited by 226 · see citing works
Time-Dependent Reversal of Long-Term Potentiation by an Integrin Antagonist
Stäubli, U., Chun, D., & Lynch, G. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-09-03460.1998 · Cited by 205 · see citing works
Self-citationThe Arp2/3 complex mediates actin polymerization induced by the small GTP-binding protein Cdc42
Ma, L., Rohatgi, R., & Kirschner, M. W. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.26.15362 · Cited by 205 · see citing works
Integrin Requirement for Hippocampal Synaptic Plasticity and Spatial Memory
Chan, C.-S., Weeber, E. J., Kurup, S., Sweatt, J. D., & Davis, R. L. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-18-07107.2003 · Cited by 202 · see citing works
Theta Stimulation Polymerizes Actin in Dendritic Spines of Hippocampus
Lin, B., Kramár, E. A., Bi, X., Brücher, F., Gall, C. M., & LYNCH, G. S. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4283-04.2005 · Cited by 180 · see citing works
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Staubli, U., & Chun, D. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-02-00853.1996 · Cited by 169 · see citing works
Vanderklish, P. W., Krushel, L. A., Holst, B. H., Gally, J. A., Crossin, K. L., & Edelman, G. M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.040565597 · Cited by 163 · see citing works
Fonseca, R., Nägerl, U. V., Morris, R., & Bonhoeffer, T. (2004) · Neuron · doi:10.1016/j.neuron.2004.10.033 · Cited by 160 · see citing works
Huang, C., Liang, Y., & Hsu, K. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106388200 · Cited by 152 · see citing works
Reversal of LTP by theta frequency stimulation
Larson, J., Xiao, P., & LYNCH, G. S. (1993) · Brain Research · doi:10.1016/0006-8993(93)90406-d · Cited by 145 · see citing works
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Arai, A., Kessler, M., & LYNCH, G. S. (1990) · Neuroscience Letters · doi:10.1016/0304-3940(90)90750-4 · Cited by 139 · see citing works
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Staubli, U. V., Vanderklish, P. W., & LYNCH, G. S. (1990) · Behavioral and Neural Biology · doi:10.1016/0163-1047(90)90712-f · Cited by 129 · see citing works
Self-citationBernard‐Trifilo, J. A., Kramár, E. A., Torp, R., Lin, C., Pineda, E. A., LYNCH, G. S., & Gall, C. M. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03062.x · Cited by 120 · see citing works
Self-citationVanderklish, P. W., Saido, T. C., Gal, C., et al. (1995) · Molecular Brain Research · doi:10.1016/0169-328x(95)00057-y · Cited by 112 · see citing works
Chun, D. E., Gall, C. M., Bi, X., & LYNCH, G. S. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00173-7 · Cited by 111 · see citing works
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del Cerro, S., Larson, J., Oliver, M. W., & LYNCH, G. S. (1990) · Brain Research · doi:10.1016/0006-8993(90)90660-4 · Cited by 104 · see citing works
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Burette, F., Jay, T. M., & Laroche, S. (1997) · Journal of Neurophysiology · doi:10.1152/jn.1997.78.2.1155 · Cited by 71 · see citing works
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Yang, Y. C., Ma, Y., Chen, S., Wang, C. W., & Lee, E. H. Y. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-10-04072.2003 · Cited by 43 · see citing works
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Stanton, P. K., Bramham, C. R., & Scharfman, H. E. (2005) · Springer eBooks · doi:10.1007/b107409 · Cited by 32 · see citing works
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Gall, C. M., & LYNCH, G. S. (2006) · Springer eBooks · doi:10.1007/0-387-25443-9_27 · Cited by 7 · see citing works
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Wang, X.-B., Bozdagi, O., Nikitczuk, J. S., Zhai, Z. W., Zhou, Q., & Huntley, G. W. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0807248105 · Cited by 316 · see citing works
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Self-citation
- Authors
- Kramár, E. A., Lin, B., Rex, C. S., Gall, C. M., & Lynch, G.
- Affiliations
- University of California, Irvine (US)
- Departments of *Psychiatry and Human Behavior,
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2006-04-04
- Volume
- 103
- Issue
- 14
- Pages
- 5579-5584
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2023371114
- Cited by
- 221
- References
- 50
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 9 · 2023: 6 · 2022: 10 · 2021: 8 · 2020: 2 · 2019: 9 · 2018: 6 · 2017: 7 · 2016: 12 · 2015: 7 · 2014: 13 · 2013: 16 · 2012: 17
- FWCI
- 7.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Funders
- National Institute of Mental Health (MH61007, R01MH061007)
- National Institute of Neurological Disorders and Stroke (NS 37799, R01NS037799)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- long-term potentiation, integrins, beta1 integrin, actin polymerization, dendritic spines, hippocampus, memory consolidation, actin cytoskeleton
- MeSH terms
- Actins, Animals, Biopolymers, Hippocampus, Male, Phalloidine, Rhodamines, Integrins, Rats, Sprague-Dawley, Long-Term Potentiation, Rats, In Vitro Techniques
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