Obligatory Role of NR2A for Metaplasticity in Visual Cortex
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Light deprivation lowers the threshold for long-term depression (LTD) and long-term potentiation (LTP) in visual cortex by a process termed metaplasticity, but the mechanism is unknown. The decreased LTD/P threshold correlates with a decrease in the ratio of NR2A to NR2B subunits of cortical NMDA receptors (NMDARs) and a slowing of NMDAR-mediated excitatory postsynaptic currents (EPSCs). However, whether and how changes in NR2 subunit expression contribute to LTD and LTP have been controversial. In the present study, we used an NR2A knockout (KO) mouse to examine the role of this subunit in the experience-dependent modulation of NMDAR properties, LTD, and LTP. We found that deletion of NR2A abrogates the effects of visual experience on NMDAR EPSCs and prevents metaplasticity of LTP and LTD. These data support the hypothesis that experience-dependent changes in NR2A/B are functionally significant and yield a mechanism for an adjustable synaptic modification threshold in visual cortex.
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An increased NR2A/NR2B ratio translates into a higher threshold for induction of LTP and conversely a state that is more favorable for induction of LTD.
“The resulting increased NR2A/NR2B ratio translates into a higher threshold for induction of LTP and conversely a state that is more favorable for induction of LTD.118, 119”
From A role for synaptic plasticity in the adolescent development of executive function (2013) · cites this paper as [118]
The NR2A/NR2B ratio is an important determinant of NMDA receptor signaling.
“Given that the NR2A/NR2B ratio appears to be an important determinant of NMDA receptor signaling”
From Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125b and miR-132 (2010) · cites this paper as Philpot et al., 2007
Cites
Monyer, H., Burnashev, N., Laurie, D. J., Sakmann, B., & Seeburg, P. H. (1994) · Neuron · doi:10.1016/0896-6273(94)90210-0 · Cited by 2,989 · see citing works
Bienenstock, E., Cooper, L., & Munro, P. (1982) · The Journal of Neuroscience · doi:10.1523/jneurosci.02-01-00032.1982 · Cited by 2,896 · see citing works
Heteromeric NMDA receptors: molecular and functional distinction of subtypes
Monyer, H., Sprengel, R., Schoepfer, R., Herb, A., Higuchi, M., Lomeli, H., Burnashev, N., Sakmann, B., & Seeburg, P. H. (1992) · Science · doi:10.1126/science.256.5060.1217 · Cited by 2,541 · see citing works
Metaplasticity: the plasticity of synaptic plasticity
Abraham, W. C., & Bear, M. F. (1996) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)80018-x · Cited by 1,783 · see citing works
Self-citationProteomic analysis of NMDA receptor–adhesion protein signaling complexes
Husi, H., Ward, M. A., Choudhary, J. S., Blackstock, W. P., & Grant, S. G. N. (2000) · Nature Neuroscience · doi:10.1038/76615 · Cited by 1,194 · see citing works
Changing subunit composition of heteromeric NMDA receptors during development of rat cortex
Sheng, M., Cummings, J., Roldan, L. A., Jan, Y. N., & Jan, L. Y. (1994) · Nature · doi:10.1038/368144a0 · Cited by 1,170 · see citing works
Role of NMDA Receptor Subtypes in Governing the Direction of Hippocampal Synaptic Plasticity
Liu, L., Wong, T. P., Pozza, M. F., Lingenhoehl, K., Wang, Y., Sheng, M., Auberson, Y. P., & Wang, Y. T. (2004) · Science · doi:10.1126/science.1096615 · Cited by 1,106 · see citing works
Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor ε1 subunit
Sakimura, K., Kutsuwada, T., Ito, I., Manabe, T., Takayama, C., Kushiya, E., Yagi, T., Aizawa, S., Inoue, Y., Sugiyama, H., et al. (1995) · Nature · doi:10.1038/373151a0 · Cited by 859 · see citing works
Activity-Dependent Decrease in NMDA Receptor Responses During Development of the Visual Cortex
Carmignoto, G., & Vicini, S. (1992) · Science · doi:10.1126/science.1279803 · Cited by 716 · see citing works
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 · see citing works
Massey, P. V., Johnson, B. E., Moult, P. R., Auberson, Y. P., Brown, M. W., Molnár, E., Collingridge, G. L., & Bashir, Z. I. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1697-04.2004 · Cited by 693 · see citing works
A critical period for long-term potentiation at thalamocortical synapses
Crair, M. C., & Malenka, R. C. (1995) · Nature · doi:10.1038/375325a0 · Cited by 691 · see citing works
Functional and Pharmacological Differences Between Recombinant N -Methyl- d -Aspartate Receptors
Vicini, S., Wang, J. F., Li, J. H., Zhu, W. J., Wang, Y. H., Luo, J. H., Wolfe, B. B., & Grayson, D. R. (1998) · Journal of Neurophysiology · doi:10.1152/jn.1998.79.2.555 · Cited by 674 · see citing works
Experience-dependent modification of synaptic plasticity in visual cortex
Kirkwood, A., Rioult, M., & Bear, M. (1996) · Nature · doi:10.1038/381526a0 · Cited by 666 · see citing works
Self-citationNR2A Subunit Expression Shortens NMDA Receptor Synaptic Currents in Developing Neocortex
Flint, A. C., Maisch, U. S., Weishaupt, J. H., Kriegstein, A. R., & Monyer, H. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-07-02469.1997 · Cited by 615 · see citing works
Rapid, experience-dependent expression of synaptic NMDA receptors in visual cortex in vivo
Quinlan, E., Philpot, B. D., Huganir, R., & Bear, M. (1999) · Nature Neuroscience · doi:10.1038/7263 · Cited by 614 · see citing works
Self-citationA developmental change in NMDA receptor-associated proteins at hippocampal synapses
Sans, N., Petralia, R. S., Wang, Y.-X., Blahos, J., Hell, J. W., & Wenthold, R. J. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-03-01260.2000 · Cited by 537 · see citing works
Developmental regulation of NMDA receptor-mediated synaptic currents at a central synapse
Hestrin, S. (1992) · Nature · doi:10.1038/357686a0 · Cited by 518 · see citing works
Zeng, H., Chattarji, S., Barbarosie, M., Rondi-Reig, L., Philpot, B. D., Miyakawa, T., Bear, M. F., & Tonegawa, S. (2001) · Cell · doi:10.1016/s0092-8674(01)00585-2 · Cited by 498 · see citing works
Self-citationKutsuwada, T., Sakimura, K., Manabe, T., Takayama, C., Katakura, N., Kushiya, E., Natsume, R., Watanabe, M., Inoue, Y., Yagi, T., et al. (1996) · Neuron · doi:10.1016/s0896-6273(00)80051-3 · Cited by 498 · see citing works
Roles of NMDA NR2B Subtype Receptor in Prefrontal Long-Term Potentiation and Contextual Fear Memory
Zhao, M., Toyoda, H., Lee, Y., Wu, L., Ko, S. W., Zhang, X.-H., Jia, Y., Shum, F. W. F., Xu, H., Li, B.-M., et al. (2005) · Neuron · doi:10.1016/j.neuron.2005.08.014 · Cited by 495 · see citing works
NMDA receptors in the visual cortex of young kittens are more effective than those of adult cats
Tsumoto, T., Hagihara, K., Sato, H., & Hata, Y. (1987) · Nature · doi:10.1038/327513a0 · Cited by 440 · see citing works
Philpot, B. D., Sekhar, A. K., Shouval, H., & Bear, M. (2001) · Neuron · doi:10.1016/s0896-6273(01)00187-8 · Cited by 440 · see citing works
Self-citationHollingsworth, E. B., McNeal, E., Burton, J. L., Williams, R., Daly, J. W., & Creveling, C. R. (1985) · Journal of Neuroscience · doi:10.1523/jneurosci.05-08-02240.1985 · Cited by 408 · see citing works
Ligand affinities at recombinant receptors depend on subunit composition
Laurie, D., & Seeburg, P. H. (1994) · European Journal of Pharmacology Molecular Pharmacology · doi:10.1016/0922-4106(94)90058-2 · Cited by 386 · see citing works
Potentiation of cortical inhibition by visual deprivation
Maffei, A., Nataraj, K., Nelson, S. B., & Turrigiano, G. G. (2006) · Nature · doi:10.1038/nature05079 · Cited by 383 · see citing works
Quinlan, E. M., Olstein, D. H., & Bear, M. F. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.22.12876 · Cited by 382 · see citing works
Self-citationIncreased contribution of NR2A subunit to synaptic NMDA receptors in developing rat cortical neurons
Stocca, G., & Vicini, S. (1998) · The Journal of Physiology · doi:10.1111/j.1469-7793.1998.013bu.x · Cited by 369 · see citing works
Lack of NMDA Receptor Subtype Selectivity for Hippocampal Long-Term Potentiation
Berberich, S., Punnakkal, P., Jensen, V., Pawlak, V., Seeburg, P. H., Hvalby, Ø., & Köhr, G. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.1905-05.2005 · Cited by 304 · see citing works
Assembly with the NR1 Subunit Is Required for Surface Expression of NR3A-Containing NMDA Receptors
Pérez‐Otaño, I., Schulteis, C. T., Contractor, A., Lipton, S. A., Trimmer, J. S., Sucher, N. J., & Heinemann, S. F. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-04-01228.2001 · Cited by 287 · see citing works
NMDA Receptor Subunit-Dependent [Ca2+] Signaling in Individual Hippocampal Dendritic Spines
Sobczyk, A., Scheuß, V., & Svoboda, K. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.1221-05.2005 · Cited by 280 · see citing works
Priestley, T., Laughton, P., Myers, J., Bourdellès, B. L., Kerby, J., & Whiting, P. J. (1995) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)10541-5 · Cited by 262 · see citing works
Bidirectional synaptic plasticity: from theory to reality
Bear, M. F. (2003) · Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences · doi:10.1098/rstb.2002.1255 · Cited by 260 · see citing works
Self-citationNeyton, J., & Paoletti, P. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.5242-05.2006 · Cited by 245 · see citing works
Morishita, W., Lü, W., Smith, G. B., Nicoll, R. A., Bear, M. F., & Malenka, R. C. (2006) · Neuropharmacology · doi:10.1016/j.neuropharm.2006.07.005 · Cited by 235 · see citing works
Self-citationSteigerwald, F., Schulz, T. W., Schenker, L. T., Kennedy, M., Seeburg, P., & Köhr, G. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-12-04573.2000 · Cited by 204 · see citing works
Kadotani, H., Hirano, T., Masugi, M., Nakamura, K., Nakao, K., Katsuki, M., & Nakanishi, S. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-24-07859.1996 · Cited by 196 · see citing works
Evidence for Altered NMDA Receptor Function as a Basis for Metaplasticity in Visual Cortex
Philpot, B. D., Espinosa, J. S., & Bear, M. F. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-13-05583.2003 · Cited by 191 · see citing works
Self-citationNMDAR EPSC kinetics do not regulate the critical period for LTP at thalamocortical synapses
Barth, A. L., & Malenka, R. C. (2001) · Nature Neuroscience · doi:10.1038/85070 · Cited by 183 · see citing works
Lu, H., Gonzalez, E., & Crair, M. C. (2001) · Neuron · doi:10.1016/s0896-6273(01)00501-3 · Cited by 180 · see citing works
Fagiolini, M., Katagiri, H., Miyamoto, H., Mori, H., Grant, S. G. N., Mishina, M., & Hensch, T. K. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0536089100 · Cited by 178 · see citing works
Gardoni, F., Schrama, L. H., Kamal, A., Gispen, W. H., Cattabeni, F., & Luca, M. D. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-05-01501.2001 · Cited by 174 · see citing works
Weitlauf, C., Honse, Y., Auberson, Y. P., Mishina, M., Lovinger, D. M., & Winder, D. G. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2388-05.2005 · Cited by 170 · see citing works
Fonseca, R., Nägerl, U. V., Morris, R., & Bonhoeffer, T. (2004) · Neuron · doi:10.1016/j.neuron.2004.10.033 · Cited by 160 · see citing works
Kirson, E. D., & Yaari, Y. (1996) · The Journal of Physiology · doi:10.1113/jphysiol.1996.sp021779 · Cited by 147 · see citing works
Inhibitory Control of LTP and LTD: Stability of Synapse Strength
Steele, P. M., & Mauk, M. D. (1999) · Journal of Neurophysiology · doi:10.1152/jn.1999.81.4.1559 · Cited by 129 · see citing works
Eye opening induces a rapid dendritic localization of PSD-95 in central visual neurons
Yoshii, A., Sheng, M., & Constantine‐Paton, M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0335785100 · Cited by 111 · see citing works
Exon 5 and Spermine Regulate Deactivation of NMDA Receptor Subtypes
Rumbaugh, G., Prybylowski, K., Wang, J. F., & Vicini, S. (2000) · Journal of Neurophysiology · doi:10.1152/jn.2000.83.3.1300 · Cited by 109 · see citing works
Functional Repression of cAMP Response Element in 6-Hydroxydopamine-treated Neuronal Cells*
Chalovich, E. M., Zhu, J.-H., Caltagarone, J., Bowser, R., & Chu, C. T. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602632200 · Cited by 108 · see citing works
Calcineurin acts via the C-terminus of NR2A to modulate desensitization of NMDA receptors
Krupp, J., Vissel, B., Thomas, C. G., Heinemann, S. F., & Westbrook, G. L. (2002) · Neuropharmacology · doi:10.1016/s0028-3908(02)00031-x · Cited by 108 · see citing works
Fox, K. D., Daw, N. W., Sato, H., & Czepita, D. (1992) · Journal of Neuroscience · doi:10.1523/jneurosci.12-07-02672.1992 · Cited by 107 · see citing works
Chen, W. S., & Bear, M. F. (2006) · Neuropharmacology · doi:10.1016/j.neuropharm.2006.07.003 · Cited by 105 · see citing works
Self-citationMorikawa, E., Mori, H., Kiyama, Y., Mishina, M., Asano, T., & Kirino, T. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-23-09727.1998 · Cited by 99 · see citing works
Genetic and epigenetic regulation of NMDA receptor expression in the rat visual cortex
Nase, G., Weishaupt, J. H., Stern, P., Singer, W., & Monyer, H. (1999) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1999.00859.x · Cited by 92 · see citing works
Shi, J., Townsend, M., & Constantine‐Paton, M. (2000) · Neuron · doi:10.1016/s0896-6273(00)00089-1 · Cited by 92 · see citing works
Philpot, B. D., Weisberg, M. P., Ramos, M. S., Sawtell, N. B., Tang, Y., Tsien, J. Z., & Bear, M. F. (2001) · Neuropharmacology · doi:10.1016/s0028-3908(01)00136-8 · Cited by 85 · see citing works
Self-citationCompeting for MemoryHippocampal LTP under Regimes of Reduced Protein Synthesis
Fonseca, R., Nägerl, U. V., MORRIS, R., & Bonhoeffer, T. (2004) · Neuron · doi:10.1016/s0896-6273(04)00713-5 · Cited by 77 · see citing works
Distinct Spatio‐temporal Distributions of the NMDA Receptor Channel Subunit mRNAs in the Brain
Watanabe, M., Inoue, Y., Sakimura, K., & Mishina, M. (1993) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1993.tb38099.x · Cited by 72 · see citing works
Fu, Z., Logan, S. M., & Vicini, S. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2004.079467 · Cited by 39 · see citing works
Effect of longer periods of dark rearing on NMDA receptors in cat visual cortex
Czepita, D., Reid, S. N. M., & Daw, N. W. (1994) · Journal of Neurophysiology · doi:10.1152/jn.1994.72.3.1220 · Cited by 38 · see citing works
Intracellular Domains of NR2 Alter Calcium-Dependent Inactivation of N-Methyl-d-aspartate Receptors
Vissel, B., Krupp, J., Heinemann, S. F., & Westbrook, G. L. (2002) · Molecular Pharmacology · doi:10.1124/mol.61.3.595 · Cited by 36 · see citing works
Increased Exon 5 Expression Alters Extrasynaptic NMDA Receptors in Cerebellar Neurons
Prybylowski, K., Rumbaugh, G., Wolfe, B. B., & Vicini, S. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0751140.x · Cited by 26 · see citing works
Flagged first, then by citations
1 of the 63 references couldn’t be matched to a known paper.
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NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease
Paoletti, P., Bellone, C., & Zhou, Q. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3504 · Cited by 2,523 · see citing works
Synaptic Plasticity: Multiple Forms, Functions, and Mechanisms
Citri, A., & Malenka, R. C. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301559 · Cited by 2,323 · see citing works
NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders
Lau, C. G., & Zukin, R. S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2153 · Cited by 1,159 · see citing works
Metaplasticity: tuning synapses and networks for plasticity
Abraham, W. C. (2008) · Nature reviews. Neuroscience · doi:10.1038/nrn2356 · Cited by 1,119 · see citing works
Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125b and miR-132
Edbauer, D., Neilson, J. R., Foster, K. A., Wang, C.-F., Seeburg, D. P., Batterton, M. N., Tada, T., Dolan, B. M., Sharp, P. A., & Sheng, M. (2010) · Neuron · doi:10.1016/j.neuron.2010.01.005 · Cited by 735 · see citing works
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 721 · see citing works
Synaptic mechanisms for plasticity in neocortex
Feldman, D. E. (2009) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.051508.135516 · Cited by 704 · see citing works
Regulation of NMDA receptor subunit expression and its implications for LTD, LTP, and metaplasticity
Yashiro, K., & Philpot, B. D. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.07.046 · Cited by 649 · see citing works
Self-citationThe Hippocampal Formation in Schizophrenia
Tamminga, C. A., Stan, A. D., & Wagner, A. D. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2010.09081187 · Cited by 583 · see citing works
A role for synaptic plasticity in the adolescent development of executive function
Selemon, L. D. (2013) · Translational Psychiatry · doi:10.1038/tp.2013.7 · Cited by 439 · see citing works
“The resulting increased NR2A/NR2B ratio translates into a higher threshold for induction of LTP and conversely a state that is more favorable for induction of LTD.(118,119)”
BackgroundInfluentialKantrowitz, J. T., & Javitt, D. C. (2010) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2010.04.006 · Cited by 397 · see citing works
The BCM theory of synapse modification at 30: interaction of theory with experiment
Cooper, L. N., & Bear, M. F. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3353 · Cited by 395 · see citing works
Self-citationHomeostatic Regulation of Eye-Specific Responses in Visual Cortex during Ocular Dominance Plasticity
Mrsic-Flogel, T. D., Hofer, S. B., Ohki, K., Reid, R. C., Bonhoeffer, T., & Hübener, M. (2007) · Neuron · doi:10.1016/j.neuron.2007.05.028 · Cited by 330 · see citing works
Ube3a is required for experience-dependent maturation of the neocortex
Yashiro, K., Riday, T. T., Condon, K. H., Roberts, A. C., Bernardo, D. R., Prakash, R., Weinberg, R. J., Ehlers, M. D., & Philpot, B. D. (2009) · Nature Neuroscience · doi:10.1038/nn.2327 · Cited by 328 · see citing works
Self-citationMetaplasticity in Human Cortex
Müller‐Dahlhaus, F., & Ziemann, U. (2014) · The Neuroscientist · doi:10.1177/1073858414526645 · Cited by 246 · 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
Self-citationDistinct Roles of NR2A and NR2B Cytoplasmic Tails in Long-Term Potentiation
Foster, K. A., McLaughlin, N., Edbauer, D., Phillips, M., Bolton, A., Constantine-Paton, M., & Sheng, M. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4022-09.2010 · Cited by 219 · see citing works
Emerging roles of metaplasticity in behaviour and disease
Hulme, S. R., Jones, O. D., & Abraham, W. C. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2013.03.007 · Cited by 204 · see citing works
Metabotropic NMDA receptor function is required for β-amyloid–induced synaptic depression
Kessels, H. W. H. G., Nabavi, S., & Malinow, R. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1219605110 · Cited by 196 · see citing works
Homeostatic and Nonhomeostatic Modulation of Learning in Human Motor Cortex
Jung, P., & Ziemann, U. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.0222-09.2009 · Cited by 191 · see citing works
Matta, J. A., Ashby, M. C., Sanz-Clemente, A., Roche, K. W., & Isaac, J. T. R. (2011) · Neuron · doi:10.1016/j.neuron.2011.02.045 · Cited by 191 · see citing works
The role of metaplasticity mechanisms in regulating memory destabilization and reconsolidation
Finnie, P. S. B., & Nader, K. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.03.008 · Cited by 189 · see citing works
Homeostatic plasticity and STDP: keeping a neuron's cool in a fluctuating world
Watt, A. J. (2010) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2010.00005 · Cited by 189 · see citing works
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Lee, M.-C., Yasuda, R., & Ehlers, M. (2010) · Neuron · doi:10.1016/j.neuron.2010.05.015 · Cited by 185 · see citing works
Bidirectional synaptic mechanisms of ocular dominance plasticity in visual cortex
Smith, G. B., Heynen, A. J., & Bear, M. F. (2008) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2008.0198 · Cited by 175 · see citing works
Self-citationLisman, J. E. (2017) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0260 · Cited by 165 · see citing works
EphB Controls NMDA Receptor Function and Synaptic Targeting in a Subunit-Specific Manner
Nolt, M. J., Lin, Y., Hruska, M., Murphy, J. A., Sheffler-Collins, S. I., Kayser, M. S., Passer, J. Z., Bennett, M. V. L., Zukin, R. S., & Dalva, M. B. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0282-11.2011 · Cited by 161 · see citing works
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Murakami, T., Müller‐Dahlhaus, F., Lu, M., & Ziemann, U. (2012) · The Journal of Physiology · doi:10.1113/jphysiol.2012.238519 · Cited by 149 · see citing works
Glutamate Dysfunction in Hippocampus: Relevance of Dentate Gyrus and CA3 Signaling
Tamminga, C. A., Southcott, S. A., Sacco, C., Wagner, A. D., & Ghose, S. (2012) · Schizophrenia Bulletin · doi:10.1093/schbul/sbs062 · Cited by 144 · see citing works
Regulation of NMDA receptor Ca2+ signalling and synaptic plasticity
Lau, C. G., Takeuchi, K., Rodenas-Ruano, A., Takayasu, Y., Murphy, J., Bennett, M. V. L., & Zukin, R. S. (2009) · Biochemical Society Transactions · doi:10.1042/bst0371369 · Cited by 138 · see citing works
Alcohol Exposure Alters NMDAR Function in the Bed Nucleus of the Stria Terminalis
Kash, T. L., Baucum, A. J., Conrad, K. L., Colbran, R. J., & Winder, D. G. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2009.69 · Cited by 133 · see citing works
The development of human visual cortex and clinical implications
Siu, C. R., & Murphy, K. M. (2018) · Eye and Brain · doi:10.2147/eb.s130893 · Cited by 131 · see citing works
Spine microdomains for postsynaptic signaling and plasticity
Newpher, T. M., & Ehlers, M. D. (2009) · Trends in Cell Biology · doi:10.1016/j.tcb.2009.02.004 · Cited by 140 · see citing works
Jiang, Y., Jakovcevski, M., Bharadwaj, R., Connor, C., Schroeder, F. A., Lin, C. L., Straubhaar, J., Martin, G., & Akbarian, S. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.1314-10.2010 · Cited by 118 · see citing works
Cooke, S. F., & Bear, M. F. (2013) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2013.0284 · Cited by 114 · see citing works
Self-citationXu, Z., Chen, R., Gu, Q.-H., Yan, J.-Z., Wang, S., Liu, S., & Lü, W. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.1014-09.2009 · Cited by 115 · see citing works
Cho, K. K. A., Khibnik, L. A., Philpot, B. D., & Bear, M. F. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808104106 · Cited by 114 · see citing works
Self-citationThe intersection of stress and reward: BNST modulation of aversive and appetitive states
Ch’ng, S. S., Fu, J., Brown, R. M., McDougall, S. J., & Lawrence, A. J. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2018.01.005 · Cited by 111 · see citing works
Seeburg, D. P., & Sheng, M. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1853-08.2008 · Cited by 106 · see citing works
Cocaine-induced metaplasticity in the nucleus accumbens: Silent synapse and beyond
Lee, B. R., & Dong, Y. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.12.033 · Cited by 103 · see citing works
Mechanisms of heterosynaptic metaplasticity
Hulme, S. R., Jones, O. D., Raymond, C. R., Sah, P., & Abraham, W. C. (2013) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2013.0148 · Cited by 103 · see citing works
Wills, T. A., Klug, J. R., Silberman, Y., Baucum, A. J., Weitlauf, C., Colbran, R. J., Delpire, E., & Winder, D. G. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113820109 · Cited by 98 · see citing works
Roles of NR2A and NR2B in the Development of Dendritic Arbor MorphologyIn Vivo
Ewald, R. C., Keuren‐Jensen, K. R. V., Aizenman, C. D., & Cline, H. T. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.5078-07.2008 · Cited by 95 · see citing works
Activity-dependent synaptic plasticity modulates the critical phase of brain development
Chaudhury, S., Sharma, V., Kumar, V., Nag, T. C., & Wadhwa, S. (2015) · Brain and Development · doi:10.1016/j.braindev.2015.10.008 · Cited by 92 · see citing works
Primary motor cortical metaplasticity induced by priming over the supplementary motor area
Hamada, M., Hanajima, R., Terao, Y., Okabe, S., Nakatani‐Enomoto, S., Furubayashi, T., Matsumoto, H., Shirota, Y., Ohminami, S., & Ugawa, Y. (2009) · The Journal of Physiology · doi:10.1113/jphysiol.2009.179101 · Cited by 86 · see citing works
Long-lasting and transgenerational effects of an environmental enrichment on memory formation
Arai, J. A., & Feig, L. A. (2010) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2010.11.003 · Cited by 84 · see citing works
Hardt, O. M., Nader, K., & Wang, Y.-T. (2013) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2013.0141 · Cited by 82 · see citing works
Glycine transport inhibitors in the treatment of schizophrenia
Javitt, D. C. (2012) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-25758-2_12 · Cited by 83 · see citing works
Spatial memory formation induces recruitment of NMDA receptor and PSD‐95 to synaptic lipid rafts
Delint‐Ramírez, I., Salcedo‐Tello, P., & Bermúdez‐Rattoni, F. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05523.x · Cited by 79 · see citing works
Hippocampal Metaplasticity Induced by Deficiency in the Extracellular Matrix Glycoprotein Tenascin-R
Bukalo, O., Schachner, M., & Dityatev, A. E. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.1022-07.2007 · Cited by 80 · see citing works
Gene Expression Switching of Receptor Subunits in Human Brain Development
Bar-Shira, O., Maor, R., & Chechik, G. (2015) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1004559 · Cited by 69 · see citing works
Santucci, D. M., & Raghavachari, S. (2008) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000208 · Cited by 71 · see citing works
Alcohol Inhibits NR2B-Containing NMDA Receptors in the Ventral Bed Nucleus of the Stria Terminalis
Kash, T. L., Matthews, R. T., & Winder, D. G. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301504 · Cited by 71 · see citing works
John, R. A., Milozzi, A., Tsarev, S. A., Brönnimann, R., Boehme, S. C., Wu, E., Shorubalko, I., Kovalenko, M. V., & Ielmini, D. (2022) · Science Advances · doi:10.1126/sciadv.ade0072 · Cited by 70 · see citing works
Pelkey, K. A., Topolnik, L., Yuan, X.-Q., Lacaille, J.-C., & McBain, C. J. (2008) · Neuron · doi:10.1016/j.neuron.2008.11.018 · Cited by 69 · see citing works
Experience-dependent changes in NMDA receptor composition at mature central synapses
Kopp, C., Longordo, F., & Lüthi, A. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2007.03.014 · Cited by 69 · see citing works
Experience-dependent homeostatic synaptic plasticity in neocortex
Whitt, J. L., Petrus, E., & Lee, H. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.02.016 · Cited by 66 · see citing works
Calcium-Dependent But Action Potential-Independent BCM-Like Metaplasticity in the Hippocampus
Hulme, S. R., Jones, O. D., Ireland, D. R., & Abraham, W. C. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.0634-12.2012 · Cited by 70 · see citing works
Volkmann, R. A., Fanger, C. M., Anderson, D. R., Sirivolu, V. R., Paschetto, K. A., Gordon, E., Virginio, C., Gleyzes, M., Buisson, B., Steidl, E., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0148129 · Cited by 64 · see citing works
Ding, X., Cai, J., Li, S., Liu, X., Wan, Y., & Xing, G. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.10.025 · Cited by 64 · see citing works
Blackmore, D. G., Turpin, F. R., Palliyaguru, T., Evans, H. T., Chicoteau, A., Lee, W., Pelekanos, M., Nguyen, N., Song, J. H., Sullivan, R., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01129-7 · Cited by 63 · see citing works
Spolidoro, M., Putignano, E., Munafò, C., Maffei, L., & Pizzorusso, T. (2012) · Cerebral Cortex · doi:10.1093/cercor/bhr158 · Cited by 58 · see citing works
Fong, M., Mitchell, D. E., Duffy, K. R., & Bear, M. F. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1613279113 · Cited by 56 · see citing works
Self-citationNMDA Receptors and Brain Development
Ewald, R. C., & Cline, H. T. (2008) · Frontiers in neuroscience · doi:10.1201/9781420044157.ch1 · Cited by 57 · see citing works
Dendritic GluN2A Synthesis Mediates Activity-Induced NMDA Receptor Insertion
Swanger, S. A., He, Y. A., Richter, J. D., & Bassell, G. J. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.0289-13.2013 · Cited by 55 · see citing works
Regulation of synaptic plasticity in hippocampal area CA2
Carstens, K. E., & Dudek, S. M. (2019) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2018.07.008 · Cited by 55 · see citing works
Zhao, J.-P., & Constantine‐Paton, M. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.3153-07.2007 · Cited by 55 · see citing works
Rivolta, D., Castellanos, N. P., Stawowsky, C., Helbling, S., Wibral, M., Grützner, C., Koethe, D., Birkner, K., Kranaster, L., Enning, F., et al. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.3752-13.2014 · Cited by 55 · see citing works
Thomson, A. C., & Sack, A. T. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.599918 · Cited by 55 · see citing works
Sengpiel, F. (2007) · Current Biology · doi:10.1016/j.cub.2007.06.017 · Cited by 53 · see citing works
D1/D5Modulation of Synaptic NMDA Receptor Currents
Varela, J. A., Hirsch, S. J., Chapman, D. E., Leverich, L. S., & Greene, R. W. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.4746-08.2009 · Cited by 52 · see citing works
Shakib, M. A., Gao, Z., & Lamuta, C. (2023) · ACS Applied Electronic Materials · doi:10.1021/acsaelm.3c00654 · Cited by 51 · see citing works
Limits on lability: boundaries of reconsolidation and the relationship to metaplasticity
Zhang, J. J., Haubrich, J., Bernabo, M., Finnie, P. S. B., & Nader, K. (2018) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2018.02.018 · Cited by 50 · see citing works
Linking NMDA Receptor Synaptic Retention to Synaptic Plasticity and Cognition
Franchini, L., Stanic, J., Ponzoni, L., Mellone, M., Carrano, N., Musardo, S., Zianni, E., Olivero, G., Marcello, E. E., Pittaluga, A., et al. (2019) · iScience · doi:10.1016/j.isci.2019.08.036 · Cited by 50 · see citing works
Targeting metaplasticity mechanisms to promote sustained antidepressant actions
Brown, K. A., & Gould, T. D. (2024) · Molecular Psychiatry · doi:10.1038/s41380-023-02397-1 · Cited by 49 · see citing works
Hwang, H., Szucs, M. J., Ding, L. J., Allen, A., Ren, X., Haensgen, H., Gao, F., Rhim, H., Andrade, A., Pan, J. Q., et al. (2021) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.07.014 · Cited by 49 · see citing works
Gustin, R. M., Shonesy, B. C., Robinson, S. L., Rentz, T. J., Baucum, A. J., Jalan‐Sakrikar, N., Winder, D. G., Stanwood, G. D., & Colbran, R. J. (2011) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2011.05.006 · Cited by 48 · see citing works
Stoneham, E. T., Sanders, E. M., Sanyal, M., & Dumas, T. C. (2010) · Biological Bulletin · doi:10.1086/bblv219n2p81 · Cited by 47 · see citing works
Ahn, K.-C., Bernier, B. E., Harnett, M. T., & Morikawa, H. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.4453-09.2010 · Cited by 44 · see citing works
Lack of Pannexin 1 Alters Synaptic GluN2 Subunit Composition and Spatial Reversal Learning in Mice
Gajardo, I., Salazar, C., López-Espíndola, D., Estay, C., Flores‐Muñoz, C., Elgueta, C., González‐Jamett, A. M., Martı́nez, A. D., Muñoz, P., & Ardiles, Á. O. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00114 · Cited by 43 · see citing works
Amblyopia: New molecular/pharmacological and environmental approaches
Stryker, M. P., & Löwel, S. (2018) · Visual Neuroscience · doi:10.1017/s0952523817000256 · Cited by 44 · see citing works
de Marchena, J., Roberts, A. C., Middlebrooks, P. G., Valakh, V., Yashiro, K., Wilfley, L. R., & Philpot, B. D. (2008) · Journal of Neurophysiology · doi:10.1152/jn.90290.2008 · Cited by 44 · see citing works
Self-citationGoh, W. W. B., Sergot, M. J., Sng, J., & Wong, L. (2013) · Journal of Proteome Research · doi:10.1021/pr301127f · Cited by 43 · see citing works
NR2A at CA1 Synapses Is Obligatory for the Susceptibility of Hippocampal Plasticity to Sleep Loss
Longordo, F., Kopp, C., Mishina, M., Luján, R., & Lüthi, A. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.1215-09.2009 · Cited by 42 · see citing works
Circadian gating of neuronal functionality: a basis for iterative metaplasticity1
Iyer, R., Wang, T. A., & Gillette, M. U. (2014) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2014.00164 · Cited by 41 · see citing works
Park, C. S., Elgersma, Y., Grant, S. G. N., & Morrison, J. H. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.09.075 · Cited by 41 · see citing works
Metaplasticity contributes to memory formation in the hippocampus
Crestani, A. P., Krueger, J. N., Barragan, E. V., Nakazawa, Y., Nemes, S. E., Quillfeldt, J. A., Gray, J. A., & Wiltgen, B. J. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0096-7 · Cited by 40 · see citing works
Kanold, P. O., Kim, Y. A., GrandPré, T., & Shatz, C. J. (2009) · The Journal of Physiology · doi:10.1113/jphysiol.2009.171215 · Cited by 39 · see citing works
Adaptive control of synaptic plasticity integrates micro- and macroscopic network function
Scott, D. N., & Frank, M. J. (2022) · Neuropsychopharmacology · doi:10.1038/s41386-022-01374-6 · Cited by 39 · see citing works
Genetic control of experience‐dependent plasticity in the visual cortex
Heimel, J. A., Hermans, J. M., Sommeijer, J.-P., & Levelt, C. N. (2008) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2008.00431.x · Cited by 38 · see citing works
METAPLASTICITY: NEW INSIGHTS THROUGH ELECTROPHYSIOLOGICAL INVESTIGATIONS
Mockett, B. G., & Hulme, S. R. (2008) · Journal of Integrative Neuroscience · doi:10.1142/s0219635208001782 · Cited by 37 · see citing works
Zhang, X., Yan, X., Zhang, B., Yang, Q., Ye, M., Cao, W., Qiang, W.-B., Zhu, L.-J., Du, Y.-L., Xu, X., et al. (2015) · Cell Research · doi:10.1038/cr.2015.75 · Cited by 36 · see citing works
Khanas, A., Hébert, C., Becerra, L., Portier, X., & Jedrecy, N. (2022) · Advanced Electronic Materials · doi:10.1002/aelm.202200421 · Cited by 35 · see citing works
Sidorov, M. S., Kaplan, E. S., Osterweil, E. K., Lindemann, L., & Bear, M. F. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1512878112 · Cited by 33 · see citing works
Self-citationMoraga‐Amaro, R., González, H., Ugalde, V., Donoso-Ramos, J. P., Quintana-Donoso, D., Lara, M., Morales, B., Rojas, P., Pacheco, R., & Stehberg, J. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.12.018 · Cited by 35 · see citing works
Augmenting LTP-Like Plasticity in Human Motor Cortex by Spaced Paired Associative Stimulation
Müller‐Dahlhaus, F., Lücke, C., Lu, M., Arai, N., Fuhl, A., Herrmann, E. M., & Ziemann, U. (2015) · PLoS ONE · doi:10.1371/journal.pone.0131020 · Cited by 35 · see citing works
Dynamic Regulation of NMDA Receptor Transmission
Gambrill, A. C., Storey, G. P., & Barría, A. (2010) · Journal of Neurophysiology · doi:10.1152/jn.00457.2010 · Cited by 34 · see citing works
Dumas, T. C. (2010) · Hippocampus · doi:10.1002/hipo.20881 · Cited by 33 · see citing works
Advances in understanding visual cortex plasticity
McCoy, P. A., Huang, H., & Philpot, B. D. (2009) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2009.05.010 · Cited by 33 · see citing works
Self-citation
- Authors
- Philpot, B. D., Cho, K. K. A., & Bear, M. F.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Bear, Mark F.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2007-02
- Volume
- 53
- Issue
- 4
- Pages
- 495-502
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC1847797
- OpenAlex
- W2161352090
- Cited by
- 207
- References
- 63
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 5 · 2023: 5 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 7 · 2018: 15 · 2017: 9 · 2016: 5 · 2015: 11 · 2014: 14 · 2013: 18 · 2012: 13
- FWCI
- 9.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- National Institute of Mental Health (P50MH058880)
- National Eye Institute (R01EY012309)
- National Institute of Neurological Disorders and Stroke (P01NS039321)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- metaplasticity, NR2A subunit, long-term depression, long-term potentiation, visual cortex, light deprivation, experience-dependent synaptic plasticity, excitatory postsynaptic currents
- MeSH terms
- Action Potentials, Analysis of Variance, Animals, Animals, Newborn, Brain Chemistry, Dark Adaptation, Dose-Response Relationship, Radiation, Electric Stimulation, Gene Expression Regulation, Mice, Inbred C57BL, Neuronal Plasticity, Neurons, Synaptosomes, Visual Cortex, Receptors, N-Methyl-D-Aspartate, Mice, Knockout, Patch-Clamp Techniques, Mice, In Vitro Techniques
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