Molecular mechanisms underlying neuronal synaptic plasticity: systems biology meets computational neuroscience in the wilds of synaptic plasticity
Open accessAbstract
Interactions among signaling pathways that are activated by transmembrane receptors produce complex networks and emergent dynamical behaviors that are implicated in synaptic plasticity. Temporal dynamics and spatial aspects are critical determinants of cell responses such as synaptic plasticity, although the mapping between spatiotemporal activity pattern and direction of synaptic plasticity is not completely understood. Computational modeling of neuronal signaling pathways has significantly contributed to understanding signaling pathways underlying synaptic plasticity. Spatial models of signaling pathways in hippocampal neurons have revealed mechanisms underlying the spatial distribution of extracellular signal-related kinase (ERK) activation in hippocampal neurons. Other spatial models have demonstrated that the major role of anchoring proteins in striatal and hippocampal synaptic plasticity is to place molecules near their activators. Simulations of yet other models have revealed that the spatial distribution of synaptic plasticity may differ for potentiation versus depression. In general, the most significant advances have been made by interactive modeling and experiments; thus, an interdisciplinary approach should be applied to investigate critical issues in neuronal signaling pathways. These issues include identifying which transmembrane receptors are key for activating ERK in neurons, and the crucial targets of kinases that produce long-lasting synaptic plasticity. Although the number of computer programs for computationally efficient simulation of large reaction-diffusion networks is increasing, parameter estimation and sensitivity analysis in these spatial models remain more difficult than in single compartment models. Advances in live cell imaging coupled with further software development will continue to accelerate the development of spatial models of synaptic plasticity.
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
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?
Local translation of messenger RNAs at or near synapses is a critical mechanism for maintaining persistent changes in synaptic strength and for memory consolidation.
“This local translation of messenger RNAs (mRNAs) at or near synapses is a critical mechanism for maintaining persistent changes in synaptic strength and for memory consolidation (Figure 5).”
From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [71]
In “What are critical targets of kinases for LTP and memory” (page unavailable), the review describes local dendritic translation and a model in which locally synthesized CaMKII may help sustain long-lasting synaptic plasticity. It also states that long-term memories require protein synthesis, but does not establish that translation specifically at or near synapses is critical for memory consolidation. The claim presents an open mechanistic question as a settled conclusion. (LLM, conf=0.85)
Experimental — accuracy not yet measuredEarly phases of LTP (E-LTP) are mediated by post-translational modifications in existing proteins and occur independently of protein synthesis.
“While early phases of LTP (E-LTP) are mediated by post-translational modifications in existing proteins and occur independently of protein synthesis, the long-lasting forms of synaptic plasticity, including late-phase LTP (L-LTP) and LTD, require new local protein synthesis within dendrites, a process where specificity is determined by RNA-binding proteins and activity-dependent capture [71,72].”
From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [71]
In “What are critical targets of kinases for LTP and memory” (page unavailable), the paper describes phosphorylation associated with LTP and says long-lasting LTP requires protein synthesis. Its discussion of synaptic tagging says stimulation may produce only early-phase LTP, but it does not establish that E-LTP is mediated by modifications of existing proteins or occurs independently of protein synthesis. (LLM, conf=0.78)
Experimental — accuracy not yet measuredLong-lasting forms of synaptic plasticity, including late-phase LTP (L-LTP) and LTD, require new local protein synthesis within dendrites, with specificity determined by RNA-binding proteins and activity-dependent capture.
“While early phases of LTP (E-LTP) are mediated by post-translational modifications in existing proteins and occur independently of protein synthesis, the long-lasting forms of synaptic plasticity, including late-phase LTP (L-LTP) and LTD, require new local protein synthesis within dendrites, a process where specificity is determined by RNA-binding proteins and activity-dependent capture [71,72].”
From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [71]
In “What are critical targets of kinases for LTP and memory” (page unavailable), the paper says long-lasting LTP requires protein synthesis, describes local dendritic translation, and presents synaptic tagging and capture as a hypothesis for spatial specificity. It discusses CPEB1 as a regulator of translation, but does not say RNA-binding proteins determine that specificity or establish that long-lasting LTD generally requires local dendritic synthesis. (LLM, conf=0.86)
Experimental — accuracy not yet measuredParameter estimation and sensitivity analysis in spatial models (reaction-diffusion networks) remain significantly more difficult than in single-compartment models.
“However, parameter estimation and sensitivity analysis in spatial models (reaction-diffusion networks) remain significantly more difficult than in single-compartment models [71].”
From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [71]
Glycine receptors are ligand-gated chloride channels that mediate fast inhibitory neurotransmission, predominantly in the spinal cord and brainstem, but also play roles in embryonic brain development, learning, memory, and pain sensitization.
“Glycine receptors (GlyRs) are ligand-gated chloride channels that mediate fast inhibitory neurotransmission, predominantly in the spinal cord and brainstem, but also play roles in embryonic brain development, learning, memory, and pain sensitization. 71”
From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [71]
Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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 · see citing works
da Luz, A. C. D. D. S., Dias, G. P., Bevilaqua, M. C. D. N., Cocks, G. D., Gardino, P. F., Thuret, S., & Nardi, A. E. (2013) · Neuropsychobiology · doi:10.1159/000353269 · Cited by 4,012 · see citing works
Malenka, R. C., & Bear, M. F. (2004) · Neuron · doi:10.1016/j.neuron.2004.09.012 · Cited by 3,968 · 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
Emergent Properties of Networks of Biological Signaling Pathways
Bhalla, U. S., & Iyengar, R. (1999) · Science · doi:10.1126/science.283.5400.381 · Cited by 1,686 · see citing works
Long-Lasting Neurotrophin-Induced Enhancement of Synaptic Transmission in the Adult Hippocampus
Kang, H., & Schuman, E. M. (1995) · Science · doi:10.1126/science.7886457 · Cited by 1,354 · see citing works
Cell-signalling dynamics in time and space
Kholodenko, B. N. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1838 · Cited by 1,347 · see citing works
Abel, T., Nguyen, P. V., Barad, M., Deuel, T. A. S., Kandel, E. R., & Bourtchouladze, R. (1997) · Cell · doi:10.1016/s0092-8674(00)81904-2 · Cited by 1,217 · see citing works
BDNF function in adult synaptic plasticity: The synaptic consolidation hypothesis
Bramham, C. R., & Messaoudi, E. (2005) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2005.06.003 · Cited by 1,193 · see citing works
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 · see citing works
Ferrell, J. E. (2002) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(02)00314-9 · Cited by 1,121 · see citing works
Involvement of a calcineurin/ inhibitor-1 phosphatase cascade in hippocampal long-term depression
Mulkey, R. M., Endo, S., Shenolikar, S., & Malenka, R. C. (1994) · Nature · doi:10.1038/369486a0 · Cited by 1,083 · see citing works
AKAP signalling complexes: focal points in space and time
Wong, W., & Scott, J. D. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1527 · Cited by 1,073 · see citing works
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 · see citing works
Bisogno, T., Howell, F., Williams, G., Minassi, A., Cascio, M. G., Ligresti, A., Matias, I., Schiano-Moriello, A., Paul, P., Williams, E.-J., et al. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200305129 · Cited by 1,039 · see citing works
A Requirement for Local Protein Synthesis in Neurotrophin-Induced Hippocampal Synaptic Plasticity
Kang, H., & Schuman, E. M. (1996) · Science · doi:10.1126/science.273.5280.1402 · Cited by 985 · see citing works
PKA phosphorylation of AMPA receptor subunits controls synaptic trafficking underlying plasticity
Esteban, J. A., Shi, S.-H., Wilson, C., Nuriya, M., Huganir, R. L., & Malinow, R. (2003) · Nature Neuroscience · doi:10.1038/nn997 · Cited by 894 · see citing works
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 · see citing works
Cerebellar Long-Term Depression: Characterization, Signal Transduction, and Functional Roles
Ito, M. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.3.1143 · Cited by 832 · see citing works
Dynamic reorganization of striatal circuits during the acquisition and consolidation of a skill
Yin, H. H., Mulcare, S. P., Hilário, M. R. F., Clouse, E., Holloway, T., Davis, M. I., Hansson, A. C., Lovinger, D. M., & Costa, R. M. (2009) · Nature Neuroscience · doi:10.1038/nn.2261 · Cited by 818 · see citing works
Characterization of multiple phosphorylation sites on the AMPA receptor GluR1 subunit
Roche, K. W., O'Brien, R. J., Mammen, A. L., Bernhardt, J., & Huganir, R. L. (1996) · Neuron · doi:10.1016/s0896-6273(00)80144-0 · Cited by 812 · see citing works
Making memories last: the synaptic tagging and capture hypothesis
Redondo, R. L., & Morris, R. G. M. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn2963 · Cited by 792 · see citing works
ENDOCANNABINOID-MEDIATED SYNAPTIC PLASTICITY IN THE CNS
Chevaleyre, V., Takahashi, K. A., & Castillo, P. E. (2006) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.29.051605.112834 · Cited by 779 · see citing works
Postsynaptic endocannabinoid release is critical to long-term depression in the striatum
Gerdeman, G. L., Ronesi, J. A., & Lovinger, D. M. (2002) · Nature Neuroscience · doi:10.1038/nn832 · Cited by 767 · see citing works
Houslay, M. D., & Adams, D. R. (2003) · Biochemical Journal · doi:10.1042/bj20021698 · Cited by 764 · see citing works
Long-term synaptic depression in the striatum: physiological and pharmacological characterization
Calabresi, P., Maj, R., Pisani, A., Mercuri, N. B., & Bernardi, G. (1992) · Journal of Neuroscience · doi:10.1523/jneurosci.12-11-04224.1992 · Cited by 673 · see citing works
Lee, H.-K., Kameyama, K., Huganir, R. L., & Bear, M. F. (1998) · Neuron · doi:10.1016/s0896-6273(00)80632-7 · Cited by 668 · see citing works
Protein Kinase C as a Molecular Machine for Decoding Calcium and Diacylglycerol Signals
Oancea, E., & Meyer, T. (1998) · Cell · doi:10.1016/s0092-8674(00)81763-8 · Cited by 640 · see citing works
Locally dynamic synaptic learning rules in pyramidal neuron dendrites
Harvey, C. D., & Svoboda, K. (2007) · Nature · doi:10.1038/nature06416 · Cited by 625 · see citing works
Impey, S., Mark, M., Villacres, E. C., Poser, S., Chavkin, C., & Storm, D. R. (1996) · Neuron · doi:10.1016/s0896-6273(00)80120-8 · Cited by 593 · see citing works
Dendritic mRNA: transport, translation and function
Bramham, C. R., & Wells, D. G. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2150 · Cited by 574 · see citing works
Luttrell, L. M., Hawes, B. E., van Biesen, T., Luttrell, D. K., Lansing, T. J., & Lefkowitz, R. J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.32.19443 · Cited by 525 · see citing works
Bower, J. M., & Beeman, D. (1998) · Springer eBooks · doi:10.1007/978-1-4612-1634-6 · Cited by 518 · see citing works
Ahn, S., Shenoy, S. K., Wei, H., & Lefkowitz, R. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m405878200 · Cited by 508 · see citing works
Heterotrimeric G‐proteins: a short history
Milligan, G., & Kostenis, E. (2006) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706405 · Cited by 494 · see citing works
Pittenger, C., Huang, Y. Y., Paletzki, R. F., Bourtchouladze, R., Scanlin, H., Vronskaya, S., & Kandel, E. R. (2002) · Neuron · doi:10.1016/s0896-6273(02)00684-0 · Cited by 464 · see citing works
Sleep deprivation impairs cAMP signalling in the hippocampus
Vecsey, C. G., Baillie, G. S., Jaganath, D., Havekes, R., Daniels, A., Wimmer, M., Huang, T., Brown, K. M., Li, X.-Y., Descalzi, G., et al. (2009) · Nature · doi:10.1038/nature08488 · Cited by 454 · see citing works
Ras-dependent Mitogen-activated Protein Kinase Activation by G Protein-coupled Receptors
Rocca, G. J. D., van Biesen, T., Daaka, Y., Luttrell, D. K., Luttrell, L. M., & Lefkowitz, R. J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.31.19125 · Cited by 451 · see citing works
Prediction and validation of the distinct dynamics of transient and sustained ERK activation
Sasagawa, S., Ozaki, Y.-I., Fujita, K. A., & Kuroda, S. (2005) · Nature Cell Biology · doi:10.1038/ncb1233 · Cited by 451 · see citing works
Kao, S.-C., Jaiswal, R. K., Kölch, W., & Landreth, G. E. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008870200 · Cited by 381 · see citing works
Late-associativity, synaptic tagging, and the role of dopamine during LTP and LTD
Sajikumar, S. (2004) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2004.03.003 · Cited by 341 · see citing works
Wood, M. A., Kaplan, M. P., Park, A., Blanchard, E. J., Oliveira, A. M. M., Lombardi, T. L., & Abel, T. G. (2005) · Learning & Memory · doi:10.1101/lm.86605 · Cited by 333 · see citing works
Detailed Simulations of Cell Biology with Smoldyn 2.1
Andrews, S. S., Addy, N. J., Brent, R., & Arkin, A. P. (2010) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000705 · Cited by 317 · see citing works
Wickens, J. R., Begg, A., & Arbuthnott, G. W. (1996) · Neuroscience · doi:10.1016/0306-4522(95)00436-m · Cited by 294 · see citing works
Neves, S. R., Tsokas, P., Sarkar, A., Grace, E. A., Rangamani, P., Taubenfeld, S. M., Alberini, C. M., Schaff, J. C., Blitzer, R. D., Moraru, I. I., et al. (2008) · Cell · doi:10.1016/j.cell.2008.04.025 · Cited by 280 · see citing works
Orphan G-protein-coupled receptors and natural ligand discovery
Howard, A. D., McAllister, G., Feighner, S. D., Liu, Q., Nargund, R. P., der Ploeg, L. H. T. V., & Patchett, A. A. (2001) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(00)01636-9 · Cited by 271 · see citing works
Hervé, D., Lévi‐Strauss, M., Marey‐Semper, I., Verney, C., Tassin, J., Glowinski, J., & Girault, J. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-05-02237.1993 · Cited by 264 · see citing works
Yasuda, R., Harvey, C. D., Zhong, H., Sobczyk, A., Aelst, L. V., & Svoboda, K. (2006) · Nature Neuroscience · doi:10.1038/nn1635 · Cited by 261 · see citing works
Lee, H.-K., Takamiya, K., He, K., Song, L., & Huganir, R. L. (2010) · Journal of Neurophysiology · doi:10.1152/jn.00835.2009 · Cited by 261 · see citing works
Virtual Cell modelling and simulation software environment
Moraru, I. I., Schaff, J. C., Slepchenko, B. M., Blinov, M. L., Morgan, F., Lakshminarayana, A., Gao, F., Li, Y., & Loew, L. M. (2008) · IET Systems Biology · doi:10.1049/iet-syb:20080102 · Cited by 236 · see citing works
Calmodulin as a direct detector of Ca2+ signals
Faas, G. C., Raghavachari, S., Lisman, J. E., & Módy, I. (2011) · Nature Neuroscience · doi:10.1038/nn.2746 · Cited by 200 · see citing works
Ca2+-Stimulated Adenylyl Cyclases Regulate ERK-Dependent Activation of MSK1 during Fear Conditioning
Sindreu, C. B., Scheiner, Z. S., & Storm, D. R. (2007) · Neuron · doi:10.1016/j.neuron.2006.11.024 · Cited by 192 · see citing works
Lerner, T. N., & Kreitzer, A. C. (2012) · Neuron · doi:10.1016/j.neuron.2011.11.015 · Cited by 185 · see citing works
A biophysical model of bidirectional synaptic plasticity: Dependence on AMPA and NMDA receptors
Castellani, G., Quinlan, E., Cooper, L., & Shouval, H. (2001) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.201404598 · Cited by 175 · see citing works
Wang, Z., Dillon, T. J., Pokala, V., Mishra, S., Labudda, K., Hunter, B. N., & Stork, P. A. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.6.2130-2145.2006 · Cited by 170 · see citing works
Wells, D. G., Dong, X., Quinlan, E. M., Huang, Y., Bear, M. F., Richter, J. D., & Fallon, J. R. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-24-09541.2001 · Cited by 160 · see citing works
Tag-Trigger-Consolidation: A Model of Early and Late Long-Term-Potentiation and Depression
Claudia Clopath, A., Ziegler, L., Vasilaki, E., Buesing, L., & Gerstner, W. (2008) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000248 · Cited by 152 · see citing works
STDP in a Bistable Synapse Model Based on CaMKII and Associated Signaling Pathways
Graupner, M., & Brunel, N. (2007) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0030221 · Cited by 143 · see citing works
Distinct coincidence detectors govern the corticostriatal spike timing-dependent plasticity
Fino, É., Paillé, V., Cui, Y., Morera‐Herreras, T., Deniau, J., & Venance, L. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.188466 · Cited by 141 · see citing works
Ramachandran, B., & Frey, J. U. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.2045-09.2009 · Cited by 130 · see citing works
CBP, a transcriptional coactivator and acetyltransferase
McManus, K. J., & Hendzel, M. J. (2001) · Biochemistry and Cell Biology · doi:10.1139/o01-076 · Cited by 127 · see citing works
Oliveira, R. F., Terrin, A., Benedetto, G. D., Cannon, R. C., Koh, W., Kim, M., Zaccolo, M., & Blackwell, K. T. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011725 · Cited by 119 · see citing works
Self-citationNavakkode, S., Sajikumar, S., & Frey, J. U. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1796-04.2004 · Cited by 114 · see citing works
A positive feedback signal transduction loop determines timing of cerebellar long-term depression
Tanaka, K., & Augustine, G. (2008) · Neuron · doi:10.1016/j.neuron.2008.06.026 · Cited by 112 · see citing works
A Kinetic Model of Dopamine- and Calcium-Dependent Striatal Synaptic Plasticity
Nakano, T., Doi, T., Yoshimoto, J., & Doya, K. (2010) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000670 · Cited by 111 · see citing works
Luttrell, L. M. (2005) · Journal of Molecular Neuroscience · doi:10.1385/jmn:26:2-3:253 · Cited by 111 · see citing works
Fasano, S., D'Antoni, A., Orban, P. C., Valjent, E., Putignano, E., Vara, H., Pizzorusso, T., Giustetto, M., Yoon, B.-J., Soloway, P. D., et al. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.03.014 · Cited by 107 · see citing works
PKA-mediated phosphorylation of the β1-adrenergic receptor promotes Gs/Gi switching
Martin, N. P., Whalen, E. J., Zamah, A. M., Pierce, K. L., & Lefkowitz, R. J. (2004) · Cellular Signalling · doi:10.1016/j.cellsig.2004.05.002 · Cited by 105 · see citing works
Pittenger, C., Fasano, S., Mazzocchi‐Jones, D., Dunnett, S. B., Kandel, E. R., & Brambilla, R. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.5406-05.2006 · Cited by 103 · see citing works
PyMOOSE: Interoperable scripting in Python for MOOSE
Bhalla, U. S. (2008) · Frontiers in Neuroinformatics · doi:10.3389/neuro.11.006.2008 · Cited by 102 · see citing works
Calmodulin Activation by Calcium Transients in the Postsynaptic Density of Dendritic Spines
Keller, D. X., Franks, K. M., Bartol, T. M., & B, T. J. S. A. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002045 · Cited by 98 · see citing works
Role of the Neurogranin Concentrated in Spines in the Induction of Long-Term Potentiation
Zhabotinsky, A. M., Camp, R. N., Epstein, I. R., & Lisman, J. E. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.0729-06.2006 · Cited by 95 · see citing works
Adermark, L., & Lovinger, D. M. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.0280-07.2007 · Cited by 93 · see citing works
Khodakhah, K., & Armstrong, C. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.25.14009 · Cited by 93 · see citing works
Shalin, S. C., Hernandez, C. M., Dougherty, M. K., Morrison, D. K., & Sweatt, J. D. (2006) · Neuron · doi:10.1016/j.neuron.2006.04.029 · Cited by 90 · see citing works
Phosphodiesterases and compartmentalized cAMP signalling in the heart
Zaccolo, M. (2006) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2006.01.002 · Cited by 88 · see citing works
Cirit, M., Wang, C., & Haugh, J. M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.148759 · Cited by 84 · see citing works
CaMKII regulates diacylglycerol lipase-α and striatal endocannabinoid signaling
Shonesy, B. C., Wang, X., Rose, K. L., Ramikie, T. S., Cavener, V. S., Rentz, T. J., Baucum, A. J., Jalan‐Sakrikar, N., Mackie, K., Winder, D. G., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3353 · Cited by 77 · see citing works
Competing G protein‐coupled receptor kinases balance G protein and β‐arrestin signaling
Heitzler, D., Durand, G., Gallay, N., Rizk, A., Ahn, S., Kim, J., Violin, J. D., Dupuy, L., Gauthier, C., Piketty, V., et al. (2012) · Molecular Systems Biology · doi:10.1038/msb.2012.22 · Cited by 77 · see citing works
Timing in synaptic plasticity: from detection to integration
Bi, G., & Rubin, J. E. (2005) · Trends in Neurosciences · doi:10.1016/j.tins.2005.02.002 · Cited by 74 · see citing works
A model of bidirectional synaptic plasticity: From signaling network to channel conductancePreprint
Castellani, G., Quinlan, E. M., Bersani, F., Cooper, L. N., & Shouval, H. Z. (2005) · Learning & Memory · doi:10.1101/lm.80705 · Cited by 74 · see citing works
Woo, N. H., Duffy, S. N., Abel, T., & Nguyen, P. V. (2003) · Hippocampus · doi:10.1002/hipo.10086 · Cited by 73 · see citing works
Search for new cyclic AMP‐binding proteins
Dremier, S., Kopperud, R., Døskeland, S. O., Dumont, J. E., & Maenhaut, C. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00561-1 · Cited by 73 · see citing works
Temporal Sensitivity of Protein Kinase A Activation in Late-Phase Long Term Potentiation
Kim, M., Huang, T., Abel, T., & Blackwell, K. T. (2010) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000691 · Cited by 72 · see citing works
Self-citationO’Dell, T. J., Connor, S. A., Gelinas, J. N., & Nguyen, P. (2010) · Cellular Signalling · doi:10.1016/j.cellsig.2009.12.004 · Cited by 69 · see citing works
Havekes, R., Canton, D. A., Park, A. J., Huang, T., Nie, T., Day, J. P., Guercio, L. A., Grimes, Q., Luczak, V., Gelman, I. H., et al. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.3612-12.2012 · Cited by 67 · see citing works
Cantrell, A. R., Tibbs, V. C., Westenbroek, R. E., Scheuer, T., & Catterall, W. A. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-17-j0003.1999 · Cited by 67 · see citing works
Regulation of excitability and plasticity by endocannabinoids and PKA in developing hippocampus
Yasuda, H., Huang, Y. Y., & Tsumoto, T. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708349105 · Cited by 65 · see citing works
Antunes, G., & Schutter, E. D. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.5976-11.2012 · Cited by 64 · see citing works
Hirono, M., Sugiyama, T., Kishimoto, Y., Sakai, I., Miyazawa, T., Kishio, M., Inoue, H., Nakao, K., Ikeda, M., Kawahara, S., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105413200 · Cited by 62 · see citing works
Izumi, Y., & Zorumski, C. F. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.243 · Cited by 61 · see citing works
Barriers to Diffusion in Dendrites and Estimation of Calcium Spread Following Synaptic Inputs
Biess, A., Korkotian, E., & Holcman, D. (2011) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002182 · Cited by 60 · see citing works
Smolen, P. D., Baxter, D. A., & Byrne, J. H. (2012) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002620 · Cited by 59 · see citing works
Subcellular Location of PKA Controls Striatal Plasticity: Stochastic Simulations in Spiny Dendrites
Oliveira, R. F., Kim, M., & Blackwell, K. T. (2012) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002383 · Cited by 58 · see citing works
Self-citationOptimal Learning Rules for Discrete Synapses
Barrett, A. B., & van Rossum, M. C. W. (2008) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000230 · Cited by 52 · see citing works
Hernjak, N., Slepchenko, B. M., Fernald, K., Fink, C. C., Fortin, D. A., Moraru, I. I., Watras, J. M., & Loew, L. M. (2005) · Biophysical Journal · doi:10.1529/biophysj.105.065771 · Cited by 52 · see citing works
Kim, M., Park, A. J., Havekes, R., Chay, A., Guercio, L. A., Oliveira, R. F., Abel, T. G., & Blackwell, K. T. (2011) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002084 · Cited by 50 · see citing works
Self-citationOstroveanu, A., van der Zee, E. A., Dolga, A. M., Luiten, P. G. M., Eisel, U. L. M., & Nijholt, I. M. (2007) · Brain Research · doi:10.1016/j.brainres.2007.01.117 · Cited by 49 · see citing works
Nie, T., McDonough, C. B., Huang, T. T., Nguyen, P., & Abel, T. G. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.1602-07.2007 · Cited by 46 · see citing works
Translational switch for long‐term maintenance of synaptic plasticity
Aslam, N., Kubota, Y., Wells, D. G., & Shouval, H. Z. (2009) · Molecular Systems Biology · doi:10.1038/msb.2009.38 · Cited by 46 · see citing works
A new strategy for assessing sensitivities in biochemical models
Sahle, S., Mendes, P., Hoops, S., & Kummer, U. (2008) · Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences · doi:10.1098/rsta.2008.0108 · Cited by 44 · see citing works
Kim, B., Hawes, S., Gillani, F., Wallace, L. J., & Blackwell, K. T. (2013) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002953 · Cited by 43 · see citing works
Self-citationJain, P., & Bhalla, U. S. (2009) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000287 · Cited by 40 · see citing works
Roles of phospholipase Cβ and NMDA receptor in activity‐dependent endocannabinoid release
Hashimotodani, Y., Ohno‐Shosaku, T., Watanabe, M., & Kano, M. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.137497 · Cited by 37 · see citing works
Spencer, J. P., & Murphy, K. (2002) · Neuroscience Letters · doi:10.1016/s0304-3940(02)00659-6 · Cited by 32 · see citing works
A propagating ERKII switch forms zones of elevated dendritic activation correlated with plasticity
Ajay, S. M., & Bhalla, U. S. (2007) · HFSP Journal · doi:10.2976/1.2721383/10.2976/1 · Cited by 30 · see citing works
Parvez, S., Ramachandran, B., & Frey, J. U. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.5808-09.2010 · Cited by 29 · see citing works
Sequestration of CaMKII in dendritic spines in silico
Khan, S., Zou, Y., Amjad, A., Gardezi, A., Smith, C. L., Winters, C., & Reese, T. S. (2011) · Journal of Computational Neuroscience · doi:10.1007/s10827-011-0323-2 · Cited by 29 · see citing works
Bhalla, U. S. (2011) · Neural Networks · doi:10.1016/j.neunet.2011.05.001 · Cited by 25 · see citing works
The chemical organization of signaling interactions
Bhalla, U. S. (2002) · Bioinformatics · doi:10.1093/bioinformatics/18.6.855 · Cited by 20 · see citing works
Rack, M., Xhonneux-Cremers, B., Schraermeyer, U., & Stieve, H. (1994) · Experimental Eye Research · doi:10.1006/exer.1994.1063 · Cited by 15 · see citing works
Modeling of spatially‐restricted intracellular signaling
Neves, S. R. (2011) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.155 · Cited by 6 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [5]Malenka RC Bear MF LTP and LTD: an embarrassment of riches Neuron 2004 44 5 21 15450156
- [53]Kim M Colocalization of PKA with adenylyl cyclase enhances PKA activity during L-LTP induction PLoS Comput Biol 2011 7 e1002085 21738458 PMC3127802
Cited by
Sorted by citations
A physical view of computational neurodynamics
Ma, J., Yang, Z., Yang, L., & Tang, J. (2019) · Journal of Zhejiang University. Science A · doi:10.1631/jzus.a1900273 · Cited by 173 · see citing works
Effects of pyrethroids on brain development and behavior: Deltamethrin
Pitzer, E. M., Williams, M. T., & Vorhees, C. V. (2021) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2021.106983 · Cited by 99 · see citing works
Sathe, G. J., Mangalaparthi, K. K., Jain, A., Darrow, J. A., Troncoso, J. C., Albert, M., Moghekar, A., & Pandey, A. (2020) · OMICS A Journal of Integrative Biology · doi:10.1089/omi.2019.0191 · Cited by 36 · see citing works
Gallimore, A., Aricescu, A., Yuzaki, M., & Calinescu, R. (2016) · PLoS Comput. Biol. · doi:10.1371/journal.pcbi.1004664 · Cited by 21 · see citing works
Wang, M., Jiang, L., Chen, H., & Cheng, L. (2019) · Medical Science Monitor · doi:10.12659/msm.913542 · Cited by 15 · see citing works
Gallimore, A. R., Hepburn, I., Georgiev, S. V., Rizzoli, S. O., & Schutter, E. D. (2025) · Science Advances · doi:10.1126/sciadv.adq6477 · Cited by 13 · see citing works
G-protein coupled receptors and synaptic plasticity in sleep deprivation
Parmar, S., Tadavarty, R., & Sastry, B. R. (2021) · World Journal of Psychiatry · doi:10.5498/wjp.v11.i11.954 · Cited by 11 · see citing works
Makadia, H. K., Anderson, W. D., Fey, D., Sauter, T., Schwaber, J. S., & Vadigepalli, R. (2015) · Biophysical Journal · doi:10.1016/j.bpj.2014.11.1851 · Cited by 9 · see citing works
Molecular Physiology of the Neuronal Synapse
Ramírez-Expósito, M. J., Cueto-Ureña, C., & Martínez-Martos, J. M. (2026) · Current Issues in Molecular Biology · doi:10.3390/cimb48010088 · Cited by 6 · see citing works
“However, parameter estimation and sensitivity analysis in spatial models (reaction-diffusion networks) remain significantly more difficult than in single-compartment models [71].”
Schmalz, J., & Kumar, G. (2021) · Journal of Computational Neuroscience · doi:10.1007/s10827-021-00793-6 · Cited by 4 · see citing works
Analysis of proteins in computational models of synaptic plasticityPreprint
Heil, K. F., Wysocka, E., Sorokina, O., Kotaleski, J. H., Simpson, T. I., Armstrong, J. D., & Sterratt, D. C. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/254094 · Cited by 5 · see citing works
Sarkar, A., Srinivasan, K., Datusalia, A. K., & Sharma, S. S. (2026) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.70248 · Cited by 2 · see citing works
Sotiriou, E., Angelatou, F., & Papatheodoropoulos, C. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/593095
Novel Optogenetic Approach Reveals a Function of cGMP in Synaptic Plasticity and Memory
Borovac, J. (2019) · TSpace (University of Toronto)
Schorova, L. (2018) · theses.fr (ABES) · doi:10.70675/a30a505az5e81z4089za24azcf43d27e33ce
Miftakhov, R., Fortygina, P., Zuzina, A., Balaban, P., & Borodinova, A. (2026) · Scientific Reports · doi:10.1038/s41598-026-56373-0
- Authors
- Blackwell, K. T., & Jedrzejewska‐Szmek, J.
- Affiliations
- George Mason University (US)
- Molecular Neuroscience Department The Krasnow Institute for Advanced Studies, George Mason University Fairfax VA USA
- Corresponding author
- Blackwell, Kim T.
- ORCID
- Blackwell, Kim T.
- Venue
- WIREs Systems Biology and Medicine
- Publisher
- Wiley
- Published
- 2013-09-09
- Volume
- 5
- Issue
- 6
- Pages
- 717-731
- ISSN
- 1939-005X (ISSN-L)
- 1939-5094
- PMC
- PMC3947422
- OpenAlex
- W2146433357
- Cited by
- 17
- References
- 112
- Citations by year
- 2026: 3 · 2025: 1 · 2021: 3 · 2020: 1 · 2019: 4 · 2018: 2 · 2016: 1 · 2015: 1 · 2014: 1
- FWCI
- 0.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- WIREs Systems Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (NIH R01 AA18066)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- synaptic plasticity, neuronal signaling pathways, reaction-diffusion networks, ERK activation, hippocampal neurons, anchoring proteins, synaptic potentiation and depression, transmembrane receptors, computational modeling of signaling, parameter estimation, sensitivity analysis, live-cell imaging
- MeSH terms
- Animals, Computer Simulation, Humans, Models, Neurological, Synaptic Transmission, Neuronal Plasticity, Software, MAP Kinase Signaling System, Systems Biology
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
