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.
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MMP-9 activity is primarily associated with the growth and strengthening of synapses.
“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
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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 · 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
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 · 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
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 · see citing works
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 · see citing works
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 · see citing works
Shi, S.-H., Hayashi, Y., Esteban, J. A., & Malinow, R. (2001) · Cell · doi:10.1016/s0092-8674(01)00321-x · Cited by 1,094 · see citing works
Larson, J., Wong, D., & Lynch, G. (1986) · Brain Research · doi:10.1016/0006-8993(86)90579-2 · Cited by 1,037 · 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
Self-citationS-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death
Gu, Z., Kaul, M., Yan, B., Kridel, S. J., Cui, J., Strongin, A., Smith, J. W., Liddington, R. C., & Lipton, S. A. (2002) · Science · doi:10.1126/science.1073634 · Cited by 950 · 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
Recycling Endosomes Supply AMPA Receptors for LTP
Park, M., Penick, E. C., Edwards, J. G., Kauer, J. A., & Ehlers, M. D. (2004) · Science · doi:10.1126/science.1102026 · Cited by 730 · 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
Protein synthesis and neurotrophin-dependent structural plasticity of single dendritic spines
Tanaka, J.-I., Horiike, Y., Matsuzaki, M., Miyazaki, T., Ellis-Davies, G. C. R., & Kasai, H. (2008) · Science · doi:10.1126/science.1152864 · Cited by 615 · cited 2× · see citing works
“We then tested the requirement for protein synthesis in MMP-9 structural and functional plasticity, because previous studies have indicated that in the presence of protein synthesis inhibitors, LTP is largely blocked and spine expansion becomes unstable (5, 29).”
MethodResultExtracellular matrix molecules and synaptic plasticity
Dityatev, A., & Schachner, M. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1115 · Cited by 564 · see citing works
Matrix metalloproteinase-9 is required for hippocampal late-phase long-term potentiation and memory
Nagy, V., Bozdagi, O., Matynia, A., Balcerzyk, M., Okulski, P., Dzwonek, J., Costa, R. M., Silva, A. J., Kaczmarek, L., & Huntley, G. W. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.4359-05.2006 · Cited by 499 · see citing works
Self-citationThe Subspine Organization of Actin Fibers Regulates the Structure and Plasticity of Dendritic Spines
Honkura, N., Matsuzaki, M., Noguchi, J., Ellis-Davies, G. C. R., & Kasai, H. (2008) · Neuron · doi:10.1016/j.neuron.2008.01.013 · Cited by 490 · see citing works
Glutamate Receptor Exocytosis and Spine Enlargement during Chemically Induced Long-Term Potentiation
Kopec, C. D., Li, B., Wei, W., Boehm, J., & Malinow, R. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.3918-05.2006 · Cited by 486 · see citing works
Postsynaptic Membrane Fusion and Long-Term Potentiation
Lledo, P.-M., Zhang, X., Südhof, T. C., Malenka, R. C., & Nicoll, R. A. (1998) · Science · doi:10.1126/science.279.5349.399 · Cited by 413 · see citing works
High actin concentrations in brain dendritic spines and postsynaptic densities.
Matus, A., Ackermann, M., Pehling, G., Byers, H. R., & Fujiwara, K. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.23.7590 · Cited by 401 · see citing works
Szklarczyk, A., Lapinska, J., Rylski, M., McKay, R. D. G., & Kaczmarek, L. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-03-00920.2002 · Cited by 392 · see citing works
Reactivation of Phosphorylated Actin Depolymerizing Factor and Identification of the Regulatory Site
Agnew, B. J., Minamide, L. S., & Bamburg, J. R. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.29.17582 · Cited by 378 · see citing works
Matrix metalloproteinases in brain development and remodeling: Synaptic functions and targets
Ethell, I. M., & Ethell, D. W. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21273 · Cited by 378 · 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
Control of actin dynamics in cell motility
Carlier, M.-F., & Pantaloni, D. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1997.1062 · Cited by 351 · 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
Synaptic calcium transients in single spines indicate that NMDA receptors are not saturated
Mainen, Z. F., Malinow, R., & Svoboda, K. (1999) · Nature · doi:10.1038/20187 · Cited by 314 · see citing works
Changes in Synaptic Morphology Accompany Actin Signaling during LTP
Chen, L. Y., Rex, C. S., Casale, M. S., Gall, C. M., & Lynch, G. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.0164-07.2007 · Cited by 296 · see citing works
Meighan, S. E., Meighan, P. C., Choudhury, P., Davis, C. J., Olson, M. L., Zornes, P. A., Wright, J. W., & Harding, J. W. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03565.x · Cited by 281 · 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
Activity-Dependent Regulation of Synaptic AMPA Receptor Composition and Abundance by β3 Integrins
Cingolani, L. A., Thalhammer, A., Yu, L. M. Y., Catalano, M., Ramos, T., Colicos, M. A., & Goda, Y. (2008) · Neuron · doi:10.1016/j.neuron.2008.04.011 · Cited by 223 · see citing works
Spine Expansion and Stabilization Associated with Long-Term Potentiation
Yang, Y., Wang, X.-B., Frerking, M., & Zhou, Q. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.3998-07.2008 · Cited by 222 · see citing works
Self-citationIntegrin-driven actin polymerization consolidates long-term potentiation
Kramár, E. A., Lin, B., Rex, C. S., Gall, C. M., & Lynch, G. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601354103 · Cited by 221 · see citing works
GluR1 Links Structural and Functional Plasticity at Excitatory Synapses
Kopec, C. D., Réal, É., Kessels, H. W. H. G., & Malinow, R. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.3503-07.2007 · Cited by 220 · 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
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
Wiesner, S., Legate, K. R., & Fässler, R. (2005) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-005-4522-8 · Cited by 190 · see citing works
Bozdagi, O., Nagy, V., Kwei, K. T., & Huntley, G. W. (2007) · Journal of Neurophysiology · doi:10.1152/jn.00202.2007 · Cited by 182 · see citing works
Self-citationTheta 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
Factors regulating the reversibility of long-term potentiation
Staubli, U., & Chun, D. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-02-00853.1996 · Cited by 169 · see citing works
Chan, C.-S., Weeber, E. J., Zong, L., Fuchs, E., Sweatt, J. D., & Davis, R. L. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.4110-05.2006 · Cited by 165 · see citing works
TIMP-1 Abolishes MMP-9-Dependent Long-lasting Long-term Potentiation in the Prefrontal Cortex
Okulski, P., Jay, T. M., Jaworski, J., Duniec, K., Dzwonek, J., Konopacki, F. A., Wilczynski, G. M., Sánchez‐Capelo, A., Mallet, J. J., & Kaczmarek, L. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.09.012 · Cited by 154 · see citing works
Evidence That Long-Term Potentiation Occurs within Individual Hippocampal Synapses during Learning
Fedulov, V., Rex, C. S., Simmons, D. A., Palmer, L. C., Gall, C. M., & LYNCH, G. S. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2003-07.2007 · Cited by 150 · see citing works
Spatial organization of cofilin in dendritic spines
Rácz, B., & Weinberg, R. J. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2005.11.025 · Cited by 121 · see citing works
Nagy, V., Bozdagi, O., & Huntley, G. W. (2007) · Learning & Memory · doi:10.1101/lm.678307 · Cited by 107 · see citing works
Meighan, P. C., Meighan, S. E., Davis, C. J., Wright, J. W., & Harding, J. W. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04682.x · Cited by 95 · see citing works
Dagnell, C., Kemi, C., Klominek, J., Eriksson, P. O., Sköld, C. M., Eklund, A., Grünewald, J., & Höglund, C. O. (2007) · Translational research · doi:10.1016/j.trsl.2007.05.001 · Cited by 45 · see citing works
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Vandooren, J., den Steen, P. E. V., & Opdenakker, G. (2013) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2013.770819 · Cited by 767 · see citing works
Scofield, M. D., Heinsbroek, J. A., Gipson, C. D., Kupchik, Y. M., Spencer, S., Smith, A. C. W., Roberts-Wolfe, D., & Kalivas, P. W. (2016) · Pharmacological Reviews · doi:10.1124/pr.116.012484 · Cited by 598 · see citing works
Unraveling mechanisms of homeostatic synaptic plasticity
Pozo, K., & Goda, Y. (2010) · Neuron · doi:10.1016/j.neuron.2010.04.028 · Cited by 565 · see citing works
The dual role of the extracellular matrix in synaptic plasticity and homeostasis
Dityatev, A., Schachner, M., & Sonderegger, P. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2898 · Cited by 559 · see citing works
MMP ‐9 in translation: from molecule to brain physiology, pathology, and therapy
Vafadari, B., Salamian, A., & Kaczmarek, L. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13415 · Cited by 381 · see citing works
MicroRNA Loss Enhances Learning and Memory in Mice
Konopka, W., Kiryk, A., Novak, M., Herwerth, M., Parkitna, J. R., Wawrzyniak, M., Kowarsch, A., Michaluk, P., Dzwonek, J., Arnsperger, T., et al. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.3030-10.2010 · Cited by 268 · see citing works
Dendritic spine formation and stabilization
Yoshihara, Y., De Roo, M., & Muller, D. (2009) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2009.05.013 · Cited by 292 · see citing works
Synaptic circuit remodelling by matrix metalloproteinases in health and disease
Huntley, G. W. (2012) · Nature reviews. Neuroscience · doi:10.1038/nrn3320 · Cited by 282 · see citing works
Self-citationDeconstruction for Reconstruction: The Role of Proteolysis in Neural Plasticity and Disease
Bingol, B., & Sheng, M. (2011) · Neuron · doi:10.1016/j.neuron.2010.11.006 · Cited by 275 · see citing works
Very long-term memories may be stored in the pattern of holes in the perineuronal net
Tsien, R. Y. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1310158110 · Cited by 244 · see citing works
Metzincin Proteases and Their Inhibitors: Foes or Friends in Nervous System Physiology?
Rivera, S., Khrestchatisky, M., Kaczmarek, L., Rosenberg, G. A., & Jaworski, D. M. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.3467-10.2010 · Cited by 237 · see citing works
Reinhard, S. M., Razak, K., & Ethell, I. M. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00280 · Cited by 219 · see citing works
Transsynaptic Signaling by Activity-Dependent Cleavage of Neuroligin-1
Peixoto, R. T., Kunz, P. A., Kwon, H., Mabb, A. M., Sabatini, B. L., Philpot, B. D., & Ehlers, M. (2012) · Neuron · doi:10.1016/j.neuron.2012.07.006 · Cited by 224 · see citing works
Influence of matrix metalloproteinase MMP-9 on dendritic spine morphology
Michaluk, P., Wawrzyniak, M., Alot, P., Szczot, M., Wyrembek, P., Mercik, K., Medvedev, N., Wilczek, E., De Roo, M., Zuschratter, W., et al. (2011) · Journal of Cell Science · doi:10.1242/jcs.090852 · Cited by 214 · see citing works
Copper signaling in the mammalian nervous system: Synaptic effects
Gaier, E. D., Eipper, B. A., & Mains, R. E. (2012) · Journal of Neuroscience Research · doi:10.1002/jnr.23143 · Cited by 210 · see citing works
Plasticity of Spine Structure: Local Signaling, Translation and Cytoskeletal Reorganization
Nakahata, Y., & Yasuda, R. (2018) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2018.00029 · Cited by 209 · see citing works
MMPs in learning and memory and neuropsychiatric disorders
Beroun, A., Mitra, S., Michaluk, P., Pijet, B., Stefaniuk, M., & Kaczmarek, L. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03180-8 · Cited by 207 · see citing works
Matrix Metalloproteinase-9 Controls NMDA Receptor Surface Diffusion through Integrin β1 Signaling
Michaluk, P., Mikasová, L., Groc, L., Frischknecht, R., Choquet, D., & Kaczmarek, L. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.5346-08.2009 · Cited by 204 · see citing works
Verslegers, M., Lemmens, K., Hove, I. V., & Moons, L. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.03.004 · Cited by 196 · see citing works
A role for microglia in synaptic plasticity?
Tremblay, M.-È., & Majewska, A. K. (2011) · Communicative & Integrative Biology · doi:10.4161/cib.4.2.14506 · Cited by 176 · see citing works
Activity-dependent exocytosis of lysosomes regulates the structural plasticity of dendritic spines
Padamsey, Z., McGuinness, L., Bardo, S. J., Reinhart, M., Tong, R., Hedegaard, A., Hart, M. L., & Emptage, N. J. (2017) · Neuron · doi:10.1016/j.neuron.2016.11.013 · Cited by 186 · see citing works
Miyata, S., & Kitagawa, H. (2017) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2017.06.010 · Cited by 171 · see citing works
Zinc transporter 3 (ZnT3) and vesicular zinc in central nervous system function
McAllister, B. B., & Dyck, R. H. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.06.006 · Cited by 170 · see citing works
Integrins in synapse regulation
Park, Y. K., & Goda, Y. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2016.138 · Cited by 167 · see citing works
Shaping Synapses by the Neural Extracellular Matrix
Ferrer-Ferrer, M., & Dityatev, A. (2018) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2018.00040 · Cited by 169 · see citing works
High MMP-9 activity levels in fragile X syndrome are lowered by minocycline
Dziembowska, M., Pretto, D. I., Janusz, A., Kaczmarek, L., Leigh, M. J., Gabriel, N., Durbin‐Johnson, B., Hagerman, R. J., & Tassone, F. (2013) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.36023 · Cited by 161 · see citing works
Sidhu, H., Dansie, L. E., Hickmott, P. W., Ethell, D. W., & Ethell, I. M. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1162-14.2014 · Cited by 155 · see citing works
The Brain’s Extracellular Matrix and Its Role in Synaptic Plasticity
Frischknecht, R., & Gundelfinger, E. D. (2012) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-7091-0932-8_7 · Cited by 156 · see citing works
Orlando, C., Ster, J., Gerber, U., Fawcett, J. W., & Raineteau, O. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.2406-12.2012 · Cited by 153 · see citing works
de Vivo, L., Landi, S., Panniello, M., Baroncelli, L., Chierzi, S., Mariotti, L., Spolidoro, M., Pizzorusso, T., Maffei, L., & Ratto, G. M. (2013) · Nature Communications · doi:10.1038/ncomms2491 · Cited by 148 · see citing works
Converting juvenile into adult plasticity: a role for the brain's extracellular matrix
Gundelfinger, E. D., Frischknecht, R., Choquet, D., & Heine, M. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07253.x · Cited by 136 · see citing works
Rotschafer, S. E., Trujillo, M. S., Dansie, L. E., Ethell, I. M., & Razak, K. A. (2012) · Brain Research · doi:10.1016/j.brainres.2011.12.041 · Cited by 130 · see citing works
Regulation of spine and synapse formation by activity-dependent intracellular signaling pathways
Saneyoshi, T., Fortin, D. A., & Soderling, T. R. (2010) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2009.09.013 · Cited by 133 · see citing works
Activity-Dependent Local Translation of Matrix Metalloproteinase-9
Dziembowska, M., Miłek, J., Janusz, A., Rejmak, E., Romanowska, E., Górkiewicz, T., Tiron, A., Bramham, C. R., & Kaczmarek, L. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.6028-11.2012 · Cited by 127 · see citing works
MMP9: A novel function in synaptic plasticity
Dziembowska, M., & Włodarczyk, J. (2012) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2012.01.023 · Cited by 125 · see citing works
Extracellular matrix molecules, their receptors, and secreted proteases in synaptic plasticity
Włodarczyk, J., Mukhina, I. V., Kaczmarek, L., & Dityatev, A. E. (2011) · Developmental Neurobiology · doi:10.1002/dneu.20958 · Cited by 123 · see citing works
Saldarriaga, W., Tassone, F., González-Teshima, L. Y., Forero-Forero, J. V., Ayala‐Zapata, S., & Hagerman, R. J. (2014) · Colombia medica · doi:10.25100/cm.v45i4.1810 · Cited by 122 · see citing works
Learning rules and persistence of dendritic spines
Kasai, H., Hayama, T., Ishikawa, M., Watanabe, S., Yagishita, S., & Noguchi, J. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07344.x · Cited by 118 · see citing works
Memory-Related Synaptic Plasticity Is Sexually Dimorphic in Rodent Hippocampus
Wang, W., Le, A. A., Hou, B., Lauterborn, J. C., Cox, C. D., Levin, E. R., LYNCH, G. S., & Gall, C. M. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.0801-18.2018 · Cited by 121 · see citing works
Wiera, G., & Mozrzymas, J. W. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00427 · Cited by 117 · see citing works
In Sickness and in Health: Perineuronal Nets and Synaptic Plasticity in Psychiatric Disorders
Pantazopoulos, H., & Berretta, S. (2015) · Neural Plasticity · doi:10.1155/2016/9847696 · Cited by 118 · see citing works
Synaptic Remodeling Depends on Signaling between Serotonin Receptors and the Extracellular Matrix
Bijata, M., Labus, J., Guseva, D., Stawarski, M., Butzlaff, M., Dzwonek, J., Schneeberg, J., Böhm, K., Michaluk, P., Rusakov, D. A., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.05.023 · Cited by 119 · see citing works
Bozdagi, O., Wang, X.-B., Nikitczuk, J. S., Anderson, T. R., Bloss, E. B., Radice, G. L., Zhou, Q., Benson, D. L., & Huntley, G. W. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.1223-10.2010 · Cited by 116 · see citing works
Self-citationExtracellular matrix in plasticity and epileptogenesis
Dityatev, A. E., & Fellin, T. (2008) · Neuron Glia Biology · doi:10.1017/s1740925x09000118 · Cited by 116 · see citing works
Structural Modulation of Dendritic Spines during Synaptic Plasticity
Fortin, D. A., Srivastava, T., & Soderling, T. R. (2011) · The Neuroscientist · doi:10.1177/1073858411407206 · Cited by 116 · see citing works
Matrix metalloproteinase‐3 in the central nervous system: a look on the bright side
Hove, I. V., Lemmens, K., de Velde, S. V., Verslegers, M., & Moons, L. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2012.07900.x · Cited by 112 · see citing works
Structural plasticity: mechanisms and contribution to developmental psychiatric disorders
Bernardinelli, Y., Nikonenko, I., & Müller, D. (2014) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2014.00123 · Cited by 108 · see citing works
Conant, K. E., Wang, Y., Szklarczyk, A., Dudak, A., Mattson, M. P., & Lim, S. T. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2009.12.061 · Cited by 110 · see citing works
Saldarriaga, W., Tassone, F., González-Teshima, L. Y., Forero-Forero, J. V., Ayala‐Zapata, S., & Hagerman, R. J. (2014) · PubMed Central · Cited by 109 · see citing works
ADF/cofilin: a crucial regulator of synapse physiology and behavior
Rust, M. B. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-1941-z · Cited by 104 · see citing works
Matrix Metalloproteinase 9 in Epilepsy: The Role of Neuroinflammation in Seizure Development
Bronisz, E., & Kurkowska‐Jastrzębska, I. (2016) · Mediators of Inflammation · doi:10.1155/2016/7369020 · Cited by 105 · see citing works
Matrix Metalloproteinase (MMP) 9 Transcription in Mouse Brain Induced by Fear Learning
Ganguly, K., Rejmak, E., Mikosz, M., Nikolaev, E., Knapska, E., & Kaczmarek, L. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.457903 · Cited by 100 · see citing works
RetractedLynch, G., Kramár, E. A., Babayan, A. H., Rumbaugh, G., & Gall, C. M. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.07.006 · Cited by 97 · see citing works
Extracellular matrix control of dendritic spine and synapse structure and plasticity in adulthood
Levy, A. D., Omar, M. H., & Koleske, A. J. (2014) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2014.00116 · Cited by 96 · see citing works
ECM receptors in neuronal structure, synaptic plasticity, and behavior
Kerrisk, M. E., Cingolani, L. A., & Koleske, A. J. (2014) · Progress in brain research · doi:10.1016/b978-0-444-63486-3.00005-0 · Cited by 90 · see citing works
Long-lasting effects of minocycline on behavior in young but not adult Fragile X mice.
Dansie, L. E., Phommahaxay, K., Okusanya, A. G., Uwadia, J., Huang, M., Rotschafer, S. E., Razak, K. A., Ethell, D. W., & Ethell, I. M. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.04.058 · Cited by 95 · see citing works
Krishnaswamy, V. R., Benbenishty, A., Blinder, P., & Sagi, I. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03182-6 · Cited by 92 · see citing works
Charrier, C., Machado, P., Tweedie‐Cullen, R. Y., Rutishauser, D., Mansuy, I. M., & Triller, A. (2010) · Nature Neuroscience · doi:10.1038/nn.2645 · Cited by 94 · see citing works
Integrin Dynamics Produce a Delayed Stage of Long-Term Potentiation and Memory Consolidation
Babayan, A. H., Kramár, E. A., Barrett, R. M., Jafari, M., Häettig, J., Chen, L. Y., Rex, C. S., Lauterborn, J. C., Wood, M. A., Gall, C. M., et al. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.2024-12.2012 · Cited by 93 · see citing works
Gdalyahu, A., Lázaro, M. T., Peñagarikano, O., Golshani, P., Trachtenberg, J. T., & Gescwind, D. H. (2015) · PLoS ONE · doi:10.1371/journal.pone.0125633 · Cited by 92 · see citing works
Hampson, R. E., Song, D. B., Chan, R. H. M., Sweatt, A. J., Riley, M. R., Gerhardt, G. A., Shin, D. C., Marmarelis, V. Z., Berger, T. W., & Deadwyler, S. A. (2012) · IEEE Transactions on Neural Systems and Rehabilitation Engineering · doi:10.1109/tnsre.2012.2189163 · Cited by 89 · see citing works
Murase, S., Lantz, C. L., & Quinlan, E. M. (2017) · eLife · doi:10.7554/elife.27345 · Cited by 87 · see citing works
Reward Learning Requires Activity of Matrix Metalloproteinase-9 in the Central Amygdala
Knapska, E., Lioudyno, V. I., Kiryk, A., Mikosz, M., Górkiewicz, T., Michaluk, P., Gawlak, M., Chaturvedi, M., Mochol, G., Balcerzyk, M., et al. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.5239-12.2013 · Cited by 87 · see citing works
Alaiyed, S., McCann, M., Mahajan, G., Rajkowska, G., Stockmeier, C. A., Kellar, K. J., Wu, J. Y., & Conant, K. (2020) · The Journal of Neuroscience · doi:10.1523/jneurosci.2387-19.2020 · Cited by 84 · see citing works
Molecular signature of extracellular matrix pathology in schizophrenia
Pantazopoulos, H., Katsel, P., Haroutunian, V. H., Chelini, G., Klengel, T., & Berretta, S. (2020) · European Journal of Neuroscience · doi:10.1111/ejn.15009 · Cited by 79 · see citing works
Matrix metalloproteinase-9 involvement in the structural plasticity of dendritic spines
Stawarski, M., Stefaniuk, M., & Włodarczyk, J. (2014) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2014.00068 · Cited by 83 · see citing works
Szepesi, Z., Hosy, E., Ruszczycki, B., Bijata, M., Pyskaty, M., Bikbaev, A., Heine, M., Choquet, D., Kaczmarek, L., & Wlodarczyk, J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0098274 · Cited by 83 · see citing works
Kuzniewska, B., Rejmak, E., Malik, A. R., Jaworski, J., Kaczmarek, L., & Kalita, K. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00008-13 · Cited by 82 · see citing works
Li, Y.-J., Wang, Z.-H., Zhang, B., Xiao, Z., Wang, M.-J., Shi, S., Bai, J., Lin, T., Guo, C., Zhang, S.-J., et al. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-80 · Cited by 82 · see citing works
Roszkowska, M., Skupien, A., Wójtowicz, T., Konopka, A., Gorlewicz, A., Kisiel, M., Bekisz, M., Ruszczycki, B., Doleżyczek, H., Rejmak, E., et al. (2016) · Molecular Biology of the Cell · doi:10.1091/mbc.e16-06-0423 · Cited by 78 · see citing works
Neural Functions of Matrix Metalloproteinases: Plasticity, Neurogenesis, and Disease
Fujioka, H., Dairyo, Y., Yasunaga, K.-I., & Emoto, K. (2012) · Biochemistry Research International · doi:10.1155/2012/789083 · Cited by 81 · see citing works
Corticostriatal plasticity, neuronal ensembles, and regulation of drug-seeking behavior
Bobadilla, A., Heinsbroek, J. A., Gipson, C. D., Griffin, W. C., Fowler, C. D., Kenny, P. J., & Kalivas, P. W. (2017) · Progress in brain research · doi:10.1016/bs.pbr.2017.07.013 · Cited by 75 · see citing works
Wright, J. W., & Harding, J. W. (2009) · Neural Plasticity · doi:10.1155/2009/579382 · Cited by 79 · see citing works
A Hypothesized Role for Dendritic Remodeling in the Etiology of Mood and Anxiety Disorders
Gorman, J. M., & Docherty, J. P. (2010) · Journal of Neuropsychiatry · doi:10.1176/jnp.2010.22.3.256 · Cited by 79 · see citing works
Neural ECM proteases in learning and synaptic plasticity
Tsilibary, E. C., Tzinia, A. K., Radenović, L., Stamenković, V., Lebitko, T., Mucha, M. W., Pawlak, R., Frischknecht, R., & Kaczmarek, L. (2014) · Progress in brain research · doi:10.1016/b978-0-444-63486-3.00006-2 · Cited by 74 · see citing works
Sebastião, A., & Ribeiro, J. (2015) · Brain Research · doi:10.1016/j.brainres.2014.11.008 · Cited by 76 · see citing works
Smith, A. C. W., Scofield, M. D., & Kalivas, P. W. (2015) · Brain Research · doi:10.1016/j.brainres.2015.03.027 · Cited by 71 · see citing works
Matrix Metalloproteinase-9 as a Novel Player in Synaptic Plasticity and Schizophrenia: Table 1.
Łepeta, K., & Kaczmarek, L. (2015) · Schizophrenia Bulletin · doi:10.1093/schbul/sbv036 · Cited by 75 · see citing works
Transient ECM protease activity promotes synaptic plasticity
Magnowska, M., Górkiewicz, T., Beroun, A., Wawrzyniak, M., Rutkowska-Włodarczyk, I., Kaczmarek, L., & Włodarczyk, J. (2016) · Scientific Reports · doi:10.1038/srep27757 · Cited by 73 · see citing works
The tetrapartite synapse: a key concept in the pathophysiology of schizophrenia
Chelini, G., Pantazopoulos, H., Durning, P. T., & Berretta, S. (2018) · European Psychiatry · doi:10.1016/j.eurpsy.2018.02.003 · Cited by 73 · see citing works
Szepesi, Z., Bijata, M., Ruszczycki, B., Kaczmarek, L., & Włodarczyk, J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0063314 · Cited by 68 · see citing works
Stefaniuk, M., Beroun, A., Lebitko, T., Markina, O. A., Łęski, S., Meyza, K. Z., Grzywacz, A., Samochowiec, J., Samochowiec, A., Radwańska, K., et al. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.12.026 · Cited by 70 · see citing works
Yasunaga, K.-I., Kanamori, T., Morikawa, R., Suzuki, E., & Emoto, K. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.02.010 · Cited by 68 · see citing works
Howell, M. D., & Gottschall, P. E. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.05.034 · Cited by 66 · see citing works
Interactions between ICAM-5 and β1 integrins regulate neuronal synapse formation
Ning, L., Tian, L., Smirnov, S., Vihinen, H., Llano, O., Vick, K. A., Davis, R. L., Rivera, C., & Gahmberg, C. G. (2012) · Journal of Cell Science · doi:10.1242/jcs.106674 · Cited by 67 · see citing works
Reactive Astrocytes: Critical Players in the Development of Chronic Pain
Tang, J. D., Bair, M., & Descalzi, G. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.682056 · Cited by 67 · see citing works
Casting a net on dendritic spines: The extracellular matrix and its receptors
Dansie, L. E., & Ethell, I. M. (2011) · Developmental Neurobiology · doi:10.1002/dneu.20963 · Cited by 66 · see citing works
Harrell, K. M., Reeves, T. M., & Phillips, L. L. (2012) · Journal of Neurotrauma · doi:10.1089/neu.2012.2383 · Cited by 65 · see citing works
Blocking human fear memory with the matrix metalloproteinase inhibitor doxycycline
Bach, D. R., Tzovara, A., & Vunder, J. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.65 · Cited by 64 · see citing works
Enhanced neuronal plasticity and elevated endogenous sAPPα levels in mice over‐expressing MMP9
Fragkouli, A., Papatheodoropoulos, C., Georgopoulos, S., Stamatakis, A., Stylianopoulou, F., Tsilibary, E. C., & Tzinia, A. K. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07637.x · Cited by 64 · see citing works
Takács, E., Nyilas, R., Szepesi, Z., Baracskay, P., Karlsen, B., Røsvold, T., Bjørkum, A. A., Czurkó, A., Kovács, Z., Kékesi, A. K., et al. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2010.03.003 · Cited by 63 · see citing works
Stamenković, V., Stamenković, S., Jaworski, T., Gawlak, M., Jovanović, M., Jakovčevski, I., Wilczynski, G. M., Kaczmarek, L., Schachner, M., Radenović, L., et al. (2016) · Brain Structure and Function · doi:10.1007/s00429-016-1224-y · Cited by 60 · see citing works
A Transcriptional Program Promotes Remodeling of GABAergic Synapses inCaenorhabditis elegans
Petersen, S. C., Watson, J. D., Richmond, J. E., Sarov, M., Walthall, W. W., & Miller, D. M. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.3181-11.2011 · Cited by 60 · see citing works
Abnormal intrinsic dynamics of dendritic spines in a fragile X syndrome mouse model in vivo
Nagaoka, A., Takehara, H., Hayashi‐Takagi, A., Noguchi, J., Ishii, K., Shirai, F., Yagishita, S., Akagi, T., Ichiki, T., & Kasai, H. (2016) · Scientific Reports · doi:10.1038/srep26651 · Cited by 60 · see citing works
Integrin adhesion in brain assembly: From molecular structure to neuropsychiatric disorders
Jaudon, F., Thalhammer, A., & Cingolani, L. A. (2020) · European Journal of Neuroscience · doi:10.1111/ejn.14859 · Cited by 57 · see citing works
Conant, K. E., Lonskaya, I., Szklarczyk, A., Krall, C., Steiner, J. P., Maguire‐Zeiss, K. A., & Seung Taik, L. I. M. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.07153.x · Cited by 58 · see citing works
Kaliszewska, A., Bijata, M., Kaczmarek, L., & Kossut, M. (2012) · Cerebral Cortex · doi:10.1093/cercor/bhr303 · Cited by 55 · see citing works
Wiera, G., Wozniak, G., Bajor, M., Kaczmarek, L., & Mozrzymas, J. W. (2013) · Hippocampus · doi:10.1002/hipo.22112 · Cited by 57 · see citing works
Perineuronal net degradation rescues CA2 plasticity in a mouse model of Rett syndrome
Carstens, K. E., Lustberg, D. J., Shaughnessy, E. K., McCann, K. E., Alexander, G. M., & Dudek, S. M. (2021) · Journal of Clinical Investigation · doi:10.1172/jci137221 · Cited by 57 · see citing works
Bjersing, J. L., Dehlin, M., Erlandsson, M. C., Bokarewa, M. I., & Mannerkorpi, K. (2012) · Arthritis Research & Therapy · doi:10.1186/ar3902 · Cited by 58 · see citing works
- 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
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