The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Extracellular proteolysis by matrix metalloproteinase-9 drives dendritic spine enlargement and long-term potentiation coordinately
Open accessAbstract
Persistent dendritic spine enlargement is associated with stable long-term potentiation (LTP), and the latter is thought to underlie long-lasting memories. Extracellular proteolytic remodeling of the synaptic microenvironment could be important for such plasticity, but whether or how proteolytic remodeling contributes to persistent modifications in synapse structure and function is unknown. Matrix metalloproteinase-9 (MMP-9) is an extracellular protease that is activated perisynaptically after LTP induction and required for LTP maintenance. Here, by monitoring spine size and excitatory postsynaptic potentials (EPSPs) simultaneously with combined 2-photon time-lapse imaging and whole-cell recordings from hippocampal neurons, we find that MMP-9 is both necessary and sufficient to drive spine enlargement and synaptic potentiation concomitantly. Both structural and functional MMP-driven forms of plasticity are mediated through β1-containing integrin receptors, are associated with integrin-dependent cofilin inactivation within spines, and require actin polymerization. In contrast, postsynaptic exocytosis and protein synthesis are both required for MMP-9-induced potentiation, but not for initial MMP-9-induced spine expansion. However, spine expansion becomes unstable when postsynaptic exocytosis or protein synthesis is blocked, indicating that the 2 forms of plasticity are expressed independently but require interactions between them for persistence. When MMP activity is eliminated during theta-stimulation-induced LTP, both spine enlargement and synaptic potentiation are transient. Thus, MMP-mediated extracellular remodeling during LTP has an instructive role in establishing persistent modifications in both synapse structure and function of the kind critical for learning and memory.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
In the citing paper
“MMP-9 activity has been primarily associated with the growth and strengthening of synapses (Wang et al., 2008; Szepesi et al., 2014).”
From Light reintroduction after dark exposure reactivates plasticity in adults via perisynaptic activation of MMP-9 (2017) · cites this paper as Wang et al., 2008
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
How Matrix Metalloproteinases Regulate Cell Behavior
Sternlicht, M. D., & Werb, Z. (2001) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.17.1.463 · Cited by 3,959
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 2,483
Learning induces long-term potentiation in the hippocampus
Whitlock, J. R., Heynen, A. J., Shuler, M. G., & Bear, M. F. (2006) · Science · doi:10.1126/science.1128134 · Cited by 1,913
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
Induction of Cell Migration by Matrix Metalloprotease-2 Cleavage of Laminin-5
Giannelli, G., Falk-Marzillier, J., Schiraldi, O., Stetler-Stevenson, W. G., & Quaranta, V. (1997) · Science · doi:10.1126/science.277.5323.225 · Cited by 1,221
A Requirement for the Intercellular Messenger Nitric Oxide in Long-Term Potentiation
Schuman, E. M., & Madison, D. V. (1991) · Science · doi:10.1126/science.1720572 · Cited by 1,135
Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity
Lee, H.-K., Barbarosie, M., Kameyama, K., Bear, M. F., & Huganir, R. L. (2000) · Nature · doi:10.1038/35016089 · Cited by 1,116
Shi, S.-H., Hayashi, Y., Esteban, J. A., & Malinow, R. (2001) · Cell · doi:10.1016/s0092-8674(01)00321-x · Cited by 1,094
Larson, J., Wong, D., & Lynch, G. (1986) · Brain Research · doi:10.1016/0006-8993(86)90579-2 · Cited by 1,037
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
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Items 301–316 of 316
A transcriptional program remodels GABAergic synapses in C. elegans
Petersen, S. C. (2011)
Integrin Dynamics and Stages of Memory Formation
LYNCH, G. S., & Gall, C. M. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-809324-5.21109-7
Al‐Muhtasib, N. (2018) · DigitalGeorgetown (Georgetown University Library)
McAllister, B. B. (2018) · Libraries and Cultural Resources (University of Calgary) · doi:10.11575/prism/34901
Spindola, A. (2019) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.87.2019.tde-15052020-152022
Tronson, N. C. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.733945751.793560145
Activity-dependent turnover of the Perineural Extracellular Matrix
Petersen, G. C. (2024) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-10429
Spindola, A. (2019) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas)
Thejaswini, J., Negetha, V. K., & Rajan, K. E. (2026) · Developmental Neuroscience · doi:10.1159/000551210 · Cited by 1
Subramanian, D., Contreras, E. M., Dovek, L., Jaberi, R., Green, E., Lao, Y. K., Ethell, I. M., & Santhakumar, V. (2026) · Journal of Neuroinflammation · doi:10.1186/s12974-026-03890-4 · Cited by 2
Hodebourg, R., Duncan, L., Dereschewitz, E., & Kalivas, P. W. (2026) · Molecular Psychiatry · doi:10.1038/s41380-026-03687-0
The how and why for multiple forms of hippocampal LTP
Gall, C. M., Le, A. A., & LYNCH, G. S. (2026) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2026.1855059
Extracellular matrix and perineuronal nets in neural plasticity, memory, and epileptogenesis
Zhu, H., Li, Q., Li, Y., & Wang, W. (2026) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2026.1945520
Metadata
- Authors
- Wang, X.-B., Bozdagi, O., Nikitczuk, J. S., Zhai, Z. W., Zhou, Q., & Huntley, G. W.
- Affiliations
- Departments of aNeurology and
- Icahn School of Medicine at Mount Sinai (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-12-09
- Volume
- 105
- Issue
- 49
- Pages
- 19520-19525
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2614793
- OpenAlex
- W1977637789
- Cited by
- 316
- References
- 48
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 10 · 2023: 10 · 2022: 14 · 2021: 13 · 2020: 22 · 2019: 17 · 2018: 23 · 2017: 15 · 2016: 20 · 2015: 21 · 2014: 26 · 2013: 23 · 2012: 32
- FWCI
- 8.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ellison Medical Foundation
- Whitehall Foundation
- National Institute of Mental Health (R01MH075783, MH-075783)
- 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
- MMP-9, long-term potentiation, synaptic plasticity, extracellular proteolysis, beta1 integrin, cofilin, actin polymerization, protein synthesis, hippocampal neurons, memory formation
- MeSH terms
- Actins, Animals, Exocytosis, Extracellular Matrix, Neuronal Plasticity, Phosphorylation, Integrins, Rats, Sprague-Dawley, Long-Term Potentiation, Excitatory Postsynaptic Potentials, Matrix Metalloproteinase 9, Dendritic Spines, Actin Depolymerizing Factors, Rats
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
