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Persistent Accumulation of Calcium/Calmodulin-Dependent Protein Kinase II in Dendritic Spines after Induction of NMDA Receptor-Dependent Chemical Long-Term Potentiation
Open accessAbstract
Calcium/calmodulin-dependent protein kinase II (CaMKII) is a leading candidate for a synaptic memory molecule because it is persistently activated after long-term potentiation (LTP) induction and because mutations that block this persistent activity prevent LTP and learning. Previous work showed that synaptic stimulation causes a rapidly reversible translocation of CaMKII to the synaptic region. We have now measured green fluorescent protein (GFP)-CaMKIIα translocation into synaptic spines during NMDA receptor-dependent chemical LTP (cLTP) and find that under these conditions, translocation is persistent. Using red fluorescent protein as a cell morphology marker, we found that there are two components of the persistent accumulation. cLTP produces a persistent increase in spine volume, and some of the increase in GFP-CaMKIIα is secondary to this volume change. In addition, cLTP results in a dramatic increase in the bound fraction of GFP-CaMKIIα in spines. To further study the bound pool, immunogold electron microscopy was used to measure CaMKIIα in the postsynaptic density (PSD), an important regulator of synaptic function. cLTP produced a persistent increase in the PSD-associated pool of CaMKIIα. These results are consistent with the hypothesis that CaMKIIα accumulation at synapses is a memory trace of past synaptic activity.
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“Calcium ions play a crucial role in initiating downstream signaling during long-term potentiation (LTP) and depression (LTD) and influx of calcium is both necessary and sufficient for structural synaptic plasticity (Pettit et al., 1994; Lledo et al., 1995; Otmakhov et al., 2004).”
From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Otmakhov et al., 2004
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“A–C: chemical long-term potentiation (chemLTP) induction results in persistent accumulation of CaMKIIα at the PSD.”
From Synaptic memory and CaMKII (2023) · cites this paper as [217]
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“The persistent accumulation of CaMKII at the PSD following an LTP-inducing stimulus is shown in FIGURE 6, A–C (217).”
From Synaptic memory and CaMKII (2023) · cites this paper as [217]
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“In addition, LTP-inducing stimuli result in the persistent accumulation of CaMKII in the PSD (FIGURE 6, A–C) (217).”
From Synaptic memory and CaMKII (2023) · cites this paper as [217]
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Citations
Cites
A synaptic model of memory: long-term potentiation in the hippocampus
Bliss, T. V. P., & Collingridge, G. L. (1993) · Nature · doi:10.1038/361031a0 · Cited by 11,566
Glutamate neurotoxicity and diseases of the nervous system
Choi, D. W. (1988) · Neuron · doi:10.1016/0896-6273(88)90162-6 · Cited by 8,188
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
A monomeric red fluorescent protein
Campbell, R. E., Tour, O., Palmer, A. E., Steinbach, P. A., Baird, G. S., Zacharias, D. A., & Tsien, R. Y. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.082243699 · Cited by 2,346
The molecular basis of CaMKII function in synaptic and behavioural memory
Lisman, J., Schulman, H., & Cline, H. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn753 · Cited by 1,860
Self-citationHayashi, Y., Shi, S.-H., Esteban, J. A., Piccini, A., Poncer, J.-C., & Malinow, R. (2000) · Science · doi:10.1126/science.287.5461.2262 · Cited by 1,524
Deficient Hippocampal Long-Term Potentiation in α-Calcium-Calmodulin Kinase II Mutant Mice
Silva, A. J., Stevens, C. F., Tonegawa, S., & Wang, Y. (1992) · Science · doi:10.1126/science.1378648 · Cited by 1,472
Inhibition of Postsynaptic PKC or CaMKII Blocks Induction But Not Expression of LTP
Malinow, R., Schulman, H., & Tsien, R. W. (1989) · Science · doi:10.1126/science.2549638 · Cited by 1,325
Shi, S.-H., Hayashi, Y., Esteban, J. A., & Malinow, R. (2001) · Cell · doi:10.1016/s0092-8674(01)00321-x · Cited by 1,094
Autophosphorylation at Thr 286 of the α Calcium-Calmodulin Kinase II in LTP and Learning
Giese, K. P., Fedorov, N. B., Filipkowski, R. K., & Silva, A. J. (1998) · Science · doi:10.1126/science.279.5352.870 · Cited by 1,055
Regulatory phosphorylation of AMPA-type glutamate receptors by CaM-KII during long-term potentiation
Barria, A., Muller, D., Derkach, V., Griffith, L. C., & Soderling, T. R. (1997) · Science · doi:10.1126/science.276.5321.2042 · Cited by 1,049
Derkach, V., Barria, A., & Soderling, T. R. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.6.3269 · Cited by 842
Cell Type and Pathway Dependence of Synaptic AMPA Receptor Number and Variability in the Hippocampus
Nusser, Z., Lujan, R., Laube, G., Roberts, J. D. B., Molnar, E., & Somogyi, P. (1998) · Neuron · doi:10.1016/s0896-6273(00)80565-6 · Cited by 804
Lee, H.-K., Takamiya, K., Han, J.-S., Man, H., Kim, C.-H., Rumbaugh, G., Yu, S., Ding, L., He, C., Petralia, R. S., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00122-3 · Cited by 802
Interaction with the NMDA receptor locks CaMKII in an active conformation
Bayer, K.-U., De Koninck, P., Leonard, A. S., Hell, J. W., & Schulman, H. (2001) · Nature · doi:10.1038/35081080 · Cited by 732
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
Shen, K., & Meyer, T. (1999) · Science · doi:10.1126/science.284.5411.162 · Cited by 673
Synaptic plasticity and dynamic modulation of the postsynaptic membrane
Lüscher, C., Nicoll, R. A., Malenka, R. C., & Müller, D. (2000) · Nature Neuroscience · doi:10.1038/75714 · Cited by 662
Structure–function of the multifunctional Ca2+/calmodulin-dependent protein kinase II
HUDMON, A., & SCHULMAN, H. (2002) · Biochemical Journal · doi:10.1042/bj20020228 · Cited by 615
Lisman (2001) · doi:10.1016/s0896-6273(01)00364-6 · Cited by 480
Self-citationDirect measurement of coupling between dendritic spines and shafts
Svoboda, K., Tank, D. W., & Denk, W. (1996) · Science · doi:10.1126/science.272.5262.716 · Cited by 472
Strack, S., & Colbran, R. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.33.20689 · Cited by 466
Fukunaga, K., Stoppini, L., Miyamoto, E., & Muller, D. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53037-4 · Cited by 398
Leonard, A. S., Lim, I. A., Hemsworth, D. E., Horne, M. C., & Hell, J. W. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.6.3239 · Cited by 385
From form to function: calcium compartmentalization in dendritic spines
Yuste, R., Majewska, A. K., & Holthoff, K. (2000) · Nature Neuroscience · doi:10.1038/76609 · Cited by 378
Strack, S., McNeill, R. B., & Colbran, R. J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001471200 · Cited by 356
Shen, K., Teruel, M. N., Subramanian, K., & Meyer, T. (1998) · Neuron · doi:10.1016/s0896-6273(00)80569-3 · Cited by 350
Ouyang, Y., Rosenstein, A. J., Kreiman, G., Schuman, E., & Kennedy, M. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-18-07823.1999 · Cited by 310
Strack, S., Choi, S., Lovinger, D. M., & Colbran, R. J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.21.13467 · Cited by 293
Inhibitory Autophosphorylation of CaMKII Controls PSD Association, Plasticity, and Learning
Elgersma, Y., Fedorov, N. B., Ikonen, S., Choi, E. S., Elgersma, M., Carvalho, O. M., Giese, K. P., & Silva, A. J. (2002) · Neuron · doi:10.1016/s0896-6273(02)01007-3 · Cited by 290
Krapivinsky, G., Medina, I., Krapivinsky, L., Gapon, S., & Clapham, D. E. (2004) · Neuron · doi:10.1016/j.neuron.2004.08.003 · Cited by 287
Forskolin-Induced LTP in the CA1 Hippocampal Region Is NMDA Receptor Dependent
Otmakhov, N., Khibnik, L. A., Otmakhova, N. A., Carpenter, S. M., Riahi, S., Asrican, B., & Lisman, J. E. (2004) · Journal of Neurophysiology · doi:10.1152/jn.00941.2003 · Cited by 253
Self-citationNeuronal transfection in brain slices using particle-mediated gene transfer
Lo, D. C., McAllister, A. K., & Katz, L. C. (1994) · Neuron · doi:10.1016/0896-6273(94)90412-x · Cited by 230
Otmakhov, N., Griffith, L. C., & Lisman, J. E. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-14-05357.1997 · Cited by 207
Self-citationMolecular memory by reversible translocation of calcium/calmodulin-dependent protein kinase II
Shen, K., Teruel, M. N., Connor, J. H., Shenolikar, S., & Meyer, T. (2000) · Nature Neuroscience · doi:10.1038/78783 · Cited by 206
Direct measurement of quantal changes underlying long-term potentiation in CA1 hippocampus.
Liao, D., Jones, A., & Malinow, R. (1992) · Neuron · doi:10.1016/0896-6273(92)90068-o · Cited by 193
Molecular mechanisms of CaMKII activation in neuronal plasticity
Fink, C. (2002) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(02)00327-6 · Cited by 191
Glutamate-induced transient modification of the postsynaptic density
Dosemeci, A., Tao-Cheng, J.-H., Vinade, L., Winters, C. A., Pozzo-Miller, L., & Reese, T. S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.181336998 · Cited by 184 · cited 2×
“There thus appear to be two forms of translocation, a transient form (Shen and Meyer, 1999; Shen et al., 2000; Dosemeci et al., 2001; Gleason et al., 2003) that may occur under some experimental conditions and a persistent form that occurs under conditions that induce LTP.”
BackgroundSelf-citationKennedy, M. B. (1998) · Brain Research Reviews · doi:10.1016/s0165-0173(97)00043-x · Cited by 184
Walikonis, R. S., Oguni, A., Khorosheva, E. M., Jeng, C.-J., Asuncion, F. J., & Kennedy, M. B. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-02-00423.2001 · Cited by 181
Illario, M., Cavallo, A. L., Bayer, K. U., Matola, T. D., Fenzi, G., Rossi, G., & Vitale, M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305355200 · Cited by 171
Leonard, A. S., Bayer, K. U., Merrill, M. A., Lim, I. A., Shea, M. A., Schulman, H., & Hell, J. W. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205164200 · Cited by 139
Intracellular calmodulin availability accessed with two-photon cross-correlation
Kim, S. A., Heinze, K. G., Waxham, M. N., & Schwille, P. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2436461100 · Cited by 120
Strack, S., Robison, A. J., Bass, M. A., & Colbran, R. J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.c000319200 · Cited by 116
Dhavan, R., Greer, P. L., Morabito, M. A., Orlando, L. R., & Tsai, L. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-18-07879.2002 · Cited by 116
Makhinson, M., Chotiner, J. K., Watson, J. B., & O’Dell, T. J. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-07-02500.1999 · Cited by 113
Gardoni, F., Schrama, L. H., van Dalen, J. J. W., Gispen, W. H., Cattabeni, F., & Luca, M. D. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00985-0 · Cited by 111
Translocation of CaM kinase II to synaptic sites in vivo
Gleason, M. R., Higashijima, S., Dallman, J. E., Liu, K., Mandel, G., & Fetcho, J. R. (2003) · Nature Neuroscience · doi:10.1038/nn1011 · Cited by 90
Piccini, A., & Malinow, R. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-13-05387.2002 · Cited by 53
Inhibition of phosphatase activity prolongs NMDA-induced modification of the postsynaptic density
Döṣemeci, A., Vinadé, L., Winters, C. A., Reese, T. S., & Tao-Cheng, J.-H. (2002) · Journal of Neurocytology · doi:10.1023/a:1025735410738 · Cited by 44
Self-citationShen, K., & Meyer, T. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70010096.x · Cited by 43
Research works printed but not linked: 3
- 2003, Soc Neurosci Abstr, 29, 476.4
- 2001, Soc Neurosci Abstr, 27, 610.16
- 2003, Soc Neurosci Abstr, 29, 375.3
Cited by
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Mechanisms of CaMKII action in long-term potentiation
Lisman, J., Yasuda, R., & Raghavachari, S. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3192 · Cited by 1,134
Self-citationBalancing Structure and Function at Hippocampal Dendritic Spines
Bourne, J. N., & Harris, K. M. (2008) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.31.060407.125646 · Cited by 916
Structural dynamics of dendritic spines in memory and cognition
Kasai, H., Fukuda, M., Watanabe, S., Hayashi-Takagi, A., & Noguchi, J. (2010) · Trends in Neurosciences · doi:10.1016/j.tins.2010.01.001 · Cited by 804
Dendritic Excitability and Synaptic Plasticity
Sjöström, P. J., Rancz, E. A., Roth, A., & Häusser, M. (2008) · Physiological Reviews · doi:10.1152/physrev.00016.2007 · Cited by 740
NMDA Receptor Subunit Composition Controls Synaptic Plasticity by Regulating Binding to CaMKII
Barria, A., & Malinow, R. (2005) · Neuron · doi:10.1016/j.neuron.2005.08.034 · Cited by 709
Metadata
- Authors
- Otmakhov, N., Tao-Cheng, J.-H., Carpenter, S., Asrican, B., Dosemeci, A., Reese, T. S., & Lisman, J.
- Affiliations
- Brandeis University (US)
- National Institute of Neurological Disorders and Stroke (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2004-10-20
- Volume
- 24
- Issue
- 42
- Pages
- 9324-9331
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6730088
- OpenAlex
- W2071910925
- Cited by
- 258
- References
- 53
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 2 · 2023: 8 · 2022: 7 · 2021: 8 · 2020: 5 · 2019: 8 · 2018: 17 · 2017: 10 · 2016: 7 · 2015: 13 · 2014: 23 · 2013: 11 · 2012: 18
- FWCI
- 5.05
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Open Access Server of the Woods Hole Scientific Community (Woods Hole Scientific Community) (submittedVersion)
- Funders
- National Institutes of Health (R01 NS)
- National Institute of Neurological Disorders and Stroke (R01NS027337, R01 NS27337)
- 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 › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- CaMKII, calcium/calmodulin-dependent protein kinase II, dendritic spines, NMDA receptor, postsynaptic density, synaptic memory, long-term potentiation, learning
- MeSH terms
- Adenylyl Cyclases, Animals, Colforsin, Phosphodiesterase Inhibitors, Protein Binding, Recombinant Fusion Proteins, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Long-Term Potentiation, Calcium-Calmodulin-Dependent Protein Kinases, Rolipram, Protein Transport, Dendritic Spines, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2, In Vitro Techniques
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