Protein Synthesis Is Required for the Enhancement of Long-Term Potentiation and Long-Term Memory by Spaced Training
Abstract
Spaced training is generally more effective than massed training for learning and memory, but the molecular mechanisms underlying this trial spacing effect remain poorly characterized. One potential molecular basis for the trial spacing effect is the differential modulation, by distinct temporal patterns of neuronal activity, of protein synthesis-dependent processes that contribute to the expression of specific forms of synaptic plasticity in the mammalian brain. Long-term potentiation (LTP) is a type of synaptic modification that may be important for certain forms of memory storage in the mammalian brain. To explore the role of protein synthesis in the trial spacing effect, we assessed the protein synthesis dependence of hippocampal LTP induced by 100-Hz tetraburst stimulation delivered to mouse hippocampal slices in either a temporally massed (20-s interburst interval) or spaced (5-min interburst interval) fashion. To extend our studies to the behavioral level, we trained mice in fear conditioning using either a massed or spaced training protocol and examined the sensitivity of long-term memory to protein synthesis inhibition. Larger LTP was induced by spaced stimulation in hippocampal slices. This improvement of synaptic potentiation following temporally spaced synaptic stimulation in slices was attenuated by bath application of an inhibitor of protein synthesis. Further, the maintenance of LTP induced by spaced synaptic stimulation was more sensitive to disruption by anisomycin than the maintenance of LTP elicited following massed stimulation. Temporally spaced behavioral training improved long-term memory for contextual but not for cued fear conditioning, and this enhancement of memory for contextual fear was also protein synthesis dependent. Our data reveal that altering the temporal spacing of synaptic stimulation and behavioral training improved hippocampal LTP and enhanced contextual long-term memory. From a broad perspective, these results suggest that the recruitment of protein synthesis-dependent processes important for long-term memory and for long-lasting forms of LTP can be modulated by the temporal profiles of behavioral training and synaptic stimulation.
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LTP that persists for several hours or more requires translation and transcription, which is reliant on transcription factors such as CREB.
“LTP that persists for several hours or more requires translation and transcription50,51, which is reliant on key transcription factors such as cyclic AMP-responsive element (CRE)-binding protein (CREB)52.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [51]
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
LeDoux, J. E. (2000) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.23.1.155 · Cited by 8,444 · 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
Synaptic Plasticity and Memory: An Evaluation of the Hypothesis
Martin, S. J., Grimwood, P. D., & Morris, R. G. M. (2000) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.23.1.649 · Cited by 2,794 · see citing works
Memory deficits associated with senescence: A neurophysiological and behavioral study in the rat.
Barnes, C. A. (1979) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0077579 · Cited by 2,088 · see citing works
Bourtchuladze, R., Frenguelli, B., Blendy, J., Cioffi, D., Schutz, G., & Silva, A. J. (1994) · Cell · doi:10.1016/0092-8674(94)90400-6 · Cited by 1,800 · see citing works
Protein synthesis and memory: A review.
Davis, H. P., & Squire, L. R. (1984) · Psychological Bulletin · doi:10.1037/0033-2909.96.3.518 · Cited by 1,505 · 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
Self-citationThe MAPK cascade is required for mammalian associative learning
Atkins, C. M., Selcher, J. C., Petraitis, J. J., Trzaskos, J. M., & Sweatt, J. D. (1998) · Nature Neuroscience · doi:10.1038/2836 · Cited by 1,083 · see citing works
Induction of a dominant negative CREB transgene specifically blocks long-term memory in Drosophila
Yin, J. C. P., Wallach, J. S., Del Vecchio, M., Wilder, E. L., Zhou, H., Quinn, W. G., & Tully, T. (1994) · Cell · doi:10.1016/0092-8674(94)90399-9 · Cited by 959 · see citing works
Genetic dissection of consolidated memory in Drosophila
Tully, T., Preat, T., Boynton, S. C., & Del Vecchio, M. (1994) · Cell · doi:10.1016/0092-8674(94)90398-0 · Cited by 924 · see citing works
Jones, M. W., Errington, M. L., French, P. J., Fine, A., Bliss, T., Garel, S., Charnay, P., Bozon, B., Laroche, S., & Davis, S. (2001) · Nature Neuroscience · doi:10.1038/85138 · Cited by 899 · see citing works
Impey, S., Obrietan, K. H., Wong, S. T., Poser, S., Yano, S., Wayman, G. A., Deloulme, J., Chan, G. C. ‐., & Storm, D. R. (1998) · Neuron · doi:10.1016/s0896-6273(00)80602-9 · Cited by 889 · see citing works
Requirement of a Critical Period of Transcription for Induction of a Late Phase of LTP
Nguyen, P. V., Abel, T., & Kandel, E. R. (1994) · Science · doi:10.1126/science.8066450 · Cited by 888 · see citing works
Self-citationA Requirement for the Mitogen-activated Protein Kinase Cascade in Hippocampal Long Term Potentiation
English, J. D., & Sweatt, J. D. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.31.19103 · Cited by 860 · see citing works
Frey, U., Krug, M., Reymann, K. G., & Matthies, H. (1988) · Brain Research · doi:10.1016/0006-8993(88)90008-x · Cited by 806 · see citing works
Behavioral studies of Pavlovian conditioning
Rescorla, R. A. (1988) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.11.030188.001553 · Cited by 715 · see citing works
Yin, J. C. P., Del Vecchio, M., Zhou, H., & Tully, T. (1995) · Cell · doi:10.1016/0092-8674(95)90375-5 · Cited by 642 · see citing works
Bach, M. E., Barad, M., Son, H., Zhuo, M., Lü, Y.-F., Shih, R., Mansuy, I. M., Hawkins, R. D., & Kandel, E. R. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.9.5280 · Cited by 561 · see citing works
Roberson, E. D., English, J. D., Adams, J. P., Selcher, J. C., Kondratick, C. M., & Sweatt, J. D. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-11-04337.1999 · Cited by 542 · see citing works
Bourtchouladze, R., Abel, T., Berman, N., Gordon, R., Lapidus, K., & Kandel, E. R. (1998) · Learning & Memory · doi:10.1101/lm.5.4.365 · Cited by 525 · see citing works
Self-citationMayford, M. R., Wang, J., Kandel, E. R., & O’Dell, T. J. (1995) · Cell · doi:10.1016/0092-8674(95)90009-8 · Cited by 523 · see citing works
Josselyn, S. A., Shi, C., Carlezon, W. A., Neve, R. L., Nestler, E. J., & Davis, M. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-07-02404.2001 · Cited by 451 · see citing works
Schafe, G. E., Nadel, N. V., Sullivan, G. M., Harris, A. Z., & LeDoux, J. E. (1999) · Learning & Memory · doi:10.1101/lm.6.2.97 · Cited by 407 · see citing works
Spaced stimuli stabilize MAPK pathway activation and its effects on dendritic morphology
Wu, G., Deisseroth, K. A., & Tsien, R. W. (2001) · Nature Neuroscience · doi:10.1038/83976 · Cited by 389 · see citing works
Hippocampus and context in classical conditioning
Holland, P. C., & Bouton, M. E. (1999) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(99)80027-0 · Cited by 377 · see citing works
Theoretical Implications of the Spacing Effect 1
Hintzman, D. L. (2024) · Routledge eBooks · doi:10.4324/9781032722375-5 · Cited by 364 · see citing works
Spaced training induces normal long-term memory in CREB mutant mice
Kogan, J. H., Frankland, P. W., Blendy, J. A., Coblentz, J., Marowitz, Z., Schütz, G., & Silva, A. J. (1997) · Current Biology · doi:10.1016/s0960-9822(06)00022-4 · Cited by 350 · see citing works
Targeting of the CREB gene leads to up‐regulation of a novel CREB mRNA isoform.
Blendy, J. A., Kaestner, K. H., Schmid, W., Gass, P., & Schütz, G. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00447.x · Cited by 223 · see citing works
The influence of duration of protein synthesis inhibition on memory
Flood, J. F., Rosenzweig, M. R., Bennett, E. L., & Orme, A. E. (1973) · Physiology & Behavior · doi:10.1016/0031-9384(73)90221-7 · Cited by 216 · see citing works
Deficits in Memory Tasks of Mice with CREB Mutations Depend on Gene DosagePreprint
Gass, P., Wolfer, D. P., Balschun, D., Rudolph, D., Frey, U., Lipp, H.-P., & Schütz, G. (1998) · Learning & Memory · doi:10.1101/lm.5.4.274 · Cited by 210 · see citing works
Ebbinghaus, H. (1996) · University of Toronto eBooks · Cited by 203 · see citing works
Trial and intertrial durations in Pavlovian conditioning: Issues of learning and performance.
Lattal, K. M. (1999) · Journal of Experimental Psychology Animal Behavior Processes · doi:10.1037/0097-7403.25.4.433 · Cited by 112 · see citing works
Self-citationBehavioral analysis of CREB αΔ mutation on a B6/129 F1 hybrid background
Graves, L. A., Dalvi, A., Lucki, I., Blendy, J. A., & Abel, T. G. (2002) · Hippocampus · doi:10.1002/hipo.10003 · Cited by 109 · see citing works
Self-citationRammes, G., Steckler, T., Kresse, A. E., Schütz, G., Zieglgänsberger, W., & Lutz, B. (2000) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2000.00108.x · Cited by 100 · see citing works
Doyère, V., & Laroche, S. (1992) · Hippocampus · doi:10.1002/hipo.450020106 · Cited by 98 · see citing works
Nguyen, P., Duffy, S. N., & Young, J. Z. (2000) · Journal of Neurophysiology · doi:10.1152/jn.2000.84.5.2484 · Cited by 88 · see citing works
Self-citationWoo, N. H., Duffy, S. N., Abel, T. G., & Nguyen, P. (2000) · Journal of Neurophysiology · doi:10.1152/jn.2000.84.6.2739 · Cited by 48 · see citing works
Self-citationMemory: Old questions, new perspectives
Eichenbaum, H. (1997) · Current Biology · doi:10.1016/s0960-9822(06)00021-2 · Cited by 14 · see citing works
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Cited by
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Optimizing inhibitory learning during exposure therapy
Craske, M. G., Kircanski, K., Zelikowsky, M., Mystkowski, J., Chowdhury, N., & Baker, A. (2008) · Behaviour Research and Therapy · doi:10.1016/j.brat.2007.10.003 · Cited by 1,607 · see citing works
BDNF: A key regulator for protein synthesis-dependent LTP and long-term memory?
Lü, Y., Christian, K. M., & Lu, B. (2007) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2007.08.018 · Cited by 768 · see citing works
Bekinschtein, P., Cammarota, M., Igaz, L. M., Bevilaqua, L. R. M., Izquierdo, I., & Medina, J. H. (2007) · Neuron · doi:10.1016/j.neuron.2006.11.025 · Cited by 633 · see citing works
Cascade Models of Synaptically Stored Memories
Fusi, S., Drew, P. J., & Abbott, L. F. (2005) · Neuron · doi:10.1016/j.neuron.2005.02.001 · Cited by 569 · see citing works
Translational Regulatory Mechanisms in Persistent Forms of Synaptic Plasticity
Kelleher, R. J., Govindarajan, A., & Tonegawa, S. (2004) · Neuron · doi:10.1016/j.neuron.2004.09.013 · Cited by 592 · see citing works
Maier, M., Ballester, B. R., & Verschure, P. F. M. J. (2019) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2019.00074 · Cited by 528 · 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
Self-citationTargeting the CREB pathway for memory enhancers
Tully, T., Bourtchouladze, R., Scott, R., & Tallman, J. F. (2003) · Nature Reviews Drug Discovery · doi:10.1038/nrd1061 · Cited by 355 · see citing works
A clustered plasticity model of long-term memory engrams.
Govindarajan, A., Kelleher, R. J., & Tonegawa, S. (2006) · Nature reviews. Neuroscience · doi:10.1038/nrn1937 · Cited by 355 · 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
Self-citationRegulation of hippocampal synaptic plasticity by cyclic AMP-dependent protein kinases
Nguyen, P., & Woo, N. H. (2003) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2003.12.003 · Cited by 324 · see citing works
Self-citationThe right time to learn: Mechanisms and optimization of spaced learning
Smolen, P., Zhang, Y., & Byrne, J. H. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2015.18 · Cited by 326 · see citing works
Interleukin‐6: a cytokine to forget
Balschun, D., Wetzel, W., del Rey, A., Pitossi, F. J., Schneider, H., Zuschratter, W., & Besedovsky, H. O. (2004) · The FASEB Journal · doi:10.1096/fj.04-1625fje · Cited by 317 · see citing works
Pavlik, P. I., & Anderson, J. R. (2005) · Cognitive Science · doi:10.1207/s15516709cog0000_14 · Cited by 312 · see citing works
(2010) · Psychology of Learning and Motivation · doi:10.1016/s0079-7421(10)53003-2 · Cited by 255 · see citing works
Persistent Phosphorylation by Protein Kinase Mζ Maintains Late-Phase Long-Term Potentiation
Serrano, P. A., Yao, Y., & Sacktor, T. C. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.5132-04.2005 · Cited by 220 · see citing works
Molecular Mechanisms of the Memory Trace
Asok, A., Leroy, F., Rayman, J. B., & Kandel, E. R. (2018) · Trends in Neurosciences · doi:10.1016/j.tins.2018.10.005 · Cited by 213 · see citing works
Gelinas, J. N., & Nguyen, P. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4175-04.2005 · Cited by 205 · see citing works
Self-citationTo Favor Survival Under Food Shortage, the Brain Disables Costly Memory
Plaçais, P.-Y., & Préat, T. (2013) · Science · doi:10.1126/science.1226018 · Cited by 202 · see citing works
Early consolidation of instrumental learning requires protein synthesis in the nucleus accumbens
Hernandez, P. J., Sadeghian, K., & Kelley, A. E. (2002) · Nature Neuroscience · doi:10.1038/nn973 · Cited by 186 · see citing works
A new chapter in the field of memory: adult hippocampal neurogenesis
Koehl, M., & Abrous, D. N. (2011) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2011.07609.x · Cited by 183 · see citing works
Sisti, H. M., Glass, A. L., & Shors, T. J. (2007) · Learning & Memory · doi:10.1101/lm.488707 · Cited by 188 · see citing works
O'Dell, T. J., Connor, S. A., Guglietta, R., & Nguyen, P. V. (2015) · Learning & Memory · doi:10.1101/lm.031088.113 · Cited by 163 · see citing works
Self-citationWhat Can Medical Education Learn From the Neurobiology of Learning?
Friedlander, M. J., Andrews, L., Armstrong, E. G., Aschenbrenner, C. A., Kass, J. S., Ogden, P. E., Schwartzstein, R. M., & Viggiano, T. R. (2011) · Academic Medicine · doi:10.1097/acm.0b013e31820dc197 · Cited by 160 · see citing works
Temporally massed CS presentations generate more fear extinction than spaced presentations.
Cain, C. K., Blouin, A. M., & Barad, M. (2003) · Journal of Experimental Psychology Animal Behavior Processes · doi:10.1037/0097-7403.29.4.323 · Cited by 144 · see citing works
Regulation of Protein Kinase Mζ Synthesis by Multiple Kinases in Long-Term Potentiation
Kelly, M., Crary, J. F., & Sacktor, T. C. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.5612-06.2007 · Cited by 144 · see citing works
Park, P., Volianskis, A., Sanderson, T. M., Bortolotto, Z. A., Jane, D. E., Zhuo, M., Kaang, B., & Collingridge, G. L. (2013) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2013.0131 · Cited by 134 · see citing works
Hypoxia‐induced phrenic long‐term facilitation: emergent properties
Devinney, M. J., Huxtable, A. G., Nichols, N. L., & Mitchell, G. S. (2013) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12085 · Cited by 135 · see citing works
Agboada, D., Mosayebi-Samani, M., Kuo, M., & Nitsche, M. A. (2020) · Brain stimulation · doi:10.1016/j.brs.2020.04.009 · Cited by 131 · see citing works
The effect of distributed practice: Neuroscience, cognition, and education
Gerbier, É., & Toppino, T. C. (2015) · Trends in Neuroscience and Education · doi:10.1016/j.tine.2015.01.001 · Cited by 108 · see citing works
Protein synthesis-dependent long-term functional plasticity: methods and techniques
Sajikumar, S., Navakkode, S., & Frey, J. U. (2005) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2005.08.009 · Cited by 106 · see citing works
Acute Hypertension Induces Oxidative Stress in Brain Tissues
Poulet, R., Gentile, M. T., Vecchione, C., Distaso, M., Aretini, A., Fratta, L., Russo, G., Echart, C., Maffei, A., Simoni, M. G. D., et al. (2005) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600188 · Cited by 106 · see citing works
Maren, S., Ferrario, C. R., Corcoran, K. A., Desmond, T. J., & Frey, K. A. (2003) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2003.03063.x · Cited by 102 · see citing works
Fulton, D. J., Kemenes, I., Andrew, R., & Benjamin, P. R. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.03970.x · Cited by 103 · see citing works
Making long-term memories in minutes: a spaced learning pattern from memory research in education
Kelley, P., & Whatson, T. S. (2013) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00589 · Cited by 106 · 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
Zhang, W., Wang, P., Sha, H., Ni, J., Li, M., & Gu, G.-J. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-8640-x · Cited by 96 · see citing works
Brightwell, J. J., Smith, C. A., Neve, R. L., & Colombo, P. J. (2007) · Learning & Memory · doi:10.1101/lm.395407 · Cited by 95 · see citing works
Datta, S., Li, G., & Auerbach, S. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06166.x · Cited by 99 · see citing works
Wang, X., Luo, Y.-X., He, Y.-Y., Li, F.-Q., Shi, H.-S., Xue, L.-F., Xue, Y.-X., & Lu, L. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.1264-10.2010 · Cited by 88 · see citing works
Differential translation and fragile X syndrome
Vanderklish, P. W., & Edelman, G. M. (2005) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2005.00134.x · Cited by 81 · 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
Self-citationOKAMOTO, T., Endo, S., Shirao, T., & Nagao, S. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.1151-11.2011 · Cited by 76 · see citing works
Ulloor, J., & Datta, S. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03378.x · Cited by 89 · see citing works
Zago, M., Bosco, G., Maffei, V., Iosa, M., Ivanenko, Y. P., & Lacquaniti, F. (2004) · Journal of Neurophysiology · doi:10.1152/jn.00833.2004 · 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-citationCalixto, E., Thiels, E., Klann, E., & Barrionuevo, G. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-12-04842.2003 · Cited by 69 · see citing works
Mechanisms of Musculoskeletal Physiotherapy
Zusman, M. (2004) · Physical Therapy Reviews · doi:10.1179/108331904225003973 · Cited by 71 · see citing works
Protein Synthesis Is Required for Synaptic Immunity to Depotentiation
Woo, N. H., & Nguyen, P. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-04-01125.2003 · Cited by 67 · see citing works
Self-citationDo memories consolidate to persist or do they persist to consolidate?
Medina, J. H., Bekinschtein, P., Cammarota, M., & Izquierdo, I. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.02.006 · Cited by 65 · see citing works
Raber, J., Arzy, S., Bertolus, J. B., Depue, B., Haas, H. E., Hofmann, S. G., Kangas, M., Kensinger, E., Lowry, C. A., Marusak, H. A., et al. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.03.015 · Cited by 62 · see citing works
Cortical plasticity and rehabilitation
Moucha, R., & Kilgard, M. P. (2006) · Progress in brain research · doi:10.1016/s0079-6123(06)57007-4 · Cited by 62 · see citing works
Generalization of Dynamics Learning Across Changes in Movement Amplitude
Mattar, A. A. G., & Ostry, D. J. (2010) · Journal of Neurophysiology · doi:10.1152/jn.00886.2009 · Cited by 62 · see citing works
A role for ERKII in synaptic pattern selectivity on the time‐scale of minutes
Ajay, S. M., & Bhalla, U. S. (2004) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2004.03725.x · Cited by 64 · see citing works
Guilding, C., McNair, K., Stone, T. W., & MORRIS, B. J. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.05238.x · Cited by 62 · see citing works
The molecular memory code and synaptic plasticity: A synthesis
Gershman, S. J. (2023) · Biosystems · doi:10.1016/j.biosystems.2022.104825 · Cited by 61 · see citing works
Aziz, W., Wang, W., Kesaf, S., Mohamed, A. A., Fukazawa, Y., & Shigemoto, R. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303317110 · Cited by 60 · see citing works
Transducer of regulated CREB and late phase long‐term synaptic potentiation
Wu, H., Zhou, Y., & Xiong, Z. (2007) · FEBS Journal · doi:10.1111/j.1742-4658.2007.05891.x · Cited by 58 · see citing works
Woldemichael, B. T., Jawaid, A., Kremer, E. A., Gaur, N., Krol, J., Marchais, A., & Mansuy, I. M. (2016) · Nature Communications · doi:10.1038/ncomms12594 · Cited by 56 · see citing works
Wu, J.-K., Tai, C., Feng, K.-L., Chen, S., Chen, C., & Chiang, A. (2017) · Scientific Reports · doi:10.1038/s41598-017-07600-2 · Cited by 56 · see citing works
Wilkerson, J. R., Satriotomo, I., Baker‐Herman, T. L., Watters, J. J., & Mitchell, G. S. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.5539-07.2008 · Cited by 54 · see citing works
Activation of phasic pontine-wave generator: A mechanism for sleep-dependent memory processing
Datta, S. (2006) · Sleep and Biological Rhythms · doi:10.1111/j.1479-8425.2006.00202.x · Cited by 54 · see citing works
Woo, N. H., Abel, T. G., & Nguyen, P. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2002.02260.x · Cited by 52 · see citing works
Self-citationMaddox, G. B. (2016) · Journal of Cognitive Psychology · doi:10.1080/20445911.2016.1181637 · Cited by 50 · see citing works
“Silent” Metaplasticity of the Late Phase of Long-Term Potentiation Requires Protein PhosphatasesPreprint
Woo, N. H., & Nguyen, P. (2002) · Learning & Memory · doi:10.1101/lm.498402 · Cited by 50 · see citing works
Self-citationSaha, S. G., & Datta, S. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04166.x · Cited by 49 · see citing works
Molecular Determinants of the Spacing Effect
Naqib, F., Sossin, W. S., & Farah, C. A. (2012) · Neural Plasticity · doi:10.1155/2012/581291 · Cited by 49 · see citing works
Evolution of Motor Memory During the Seconds After Observation of Motor Error
Huang, V. S., & Shadmehr, R. (2007) · Journal of Neurophysiology · doi:10.1152/jn.01281.2006 · Cited by 48 · see citing works
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Popovych, O. V., Xenakis, M. N., & Tass, P. A. (2015) · PLoS ONE · doi:10.1371/journal.pone.0117205 · Cited by 48 · see citing works
Kapeli, K., & Yeo, G. W.-M. (2012) · Frontiers in Neuroscience · doi:10.3389/fnins.2012.00144 · Cited by 47 · see citing works
Early onset of behavioral alterations in senescence-accelerated mouse prone 8 (SAMP8)
Yanai, S., & Endo, S. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.04.026 · Cited by 47 · see citing works
Transcriptional Control of Synaptic Plasticity by Transcription Factor NF-κB
Engelmann, C., & Haenold, R. (2016) · Neural Plasticity · doi:10.1155/2016/7027949 · Cited by 46 · see citing works
Mavanji, V., Ulloor, J., Saha, S. G., & Datta, S. (2004) · SLEEP · doi:10.1093/sleep/27.7.1282 · Cited by 45 · see citing works
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Carpenter, S. K. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-809324-5.21054-7 · Cited by 45 · see citing works
Gold, P. E. (2008) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2007.12.005 · Cited by 44 · see citing works
FXR1P Limits Long-Term Memory, Long-Lasting Synaptic Potentiation, and De Novo GluA2 Translation
Cook, D., Nuro, E., Jones, E. V., Altimimi, H. F., Farmer, W. T., Gandin, V., Hanna, E., Zong, R.-T., Barbon, A., Nelson, D. L., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.10.028 · Cited by 43 · see citing works
Connor, S. A., Wang, Y. T., & Nguyen, P. (2011) · The Journal of Physiology · doi:10.1113/jphysiol.2011.209379 · Cited by 42 · see citing works
Self-citationMarballi, K. K., & Gallitano, A. L. (2018) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2018.00023 · Cited by 40 · see citing works
Contributions of extracellular-signal regulated kinase 1/2 activity to the memory trace
Ramos, S. O., Feld, M., & Fustiñana, M. S. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.988790 · Cited by 41 · see citing works
Impaired hippocampal LTP in inbred mouse strains can be rescued by β‐adrenergic receptor activation
Schimanski, L. A., Ali, D. W., Baker, G. B., & Nguyen, P. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05376.x · Cited by 37 · see citing works
Self-citationMechanism of seizure-induced retrograde amnesia
Naik, A. A., Sun, H., Williams, C. L., Weller, D. S., Zhu, J., & Kapur, J. (2020) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2020.101984 · Cited by 37 · see citing works
Parallels between spacing effects during behavioral and cellular learning
Kornmeier, J., & Sosic-Vasic, Z. (2012) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2012.00203 · Cited by 37 · see citing works
Abate, G., Colazingari, S., Accoto, A., Conversi, D., & Bevilacqua, A. (2018) · Behavioural Brain Research · doi:10.1016/j.bbr.2018.02.011 · Cited by 36 · see citing works
Chapter 1 Genetic Dissection of Neural Circuits and Behavior in Mus musculus
Havekes, R., & Abel, T. G. (2009) · Advances in genetics · doi:10.1016/s0065-2660(09)65001-x · Cited by 35 · see citing works
Self-citation‘Alzheimer-like’ pathology in a murine model of arterial hypertension
Carnevale, D., & Lembo, G. (2011) · Biochemical Society Transactions · doi:10.1042/bst0390939 · Cited by 33 · see citing works
Persistent LTP without triggered protein synthesis
Abbas, A.-K., Dozmorov, M., Li, R., Huang, F.-S., Hellberg, F., Danielson, J., Tian, Y., Ekström, J., Sandberg, M., & Wigström, H. (2009) · Neuroscience Research · doi:10.1016/j.neures.2008.10.008 · Cited by 42 · see citing works
Genes associated with cognitive performance in the Morris water maze: an RNA-seq study
Reshetnikov, V. V., Kisaretova, P. E., Ershov, N., Shulyupova, A. S., Oshchepkov, D. Y., Klimova, N. V., Ivanchikhina, A. V., Merkulova, T. I., & Bondar, N. P. (2020) · Scientific Reports · doi:10.1038/s41598-020-78997-6 · Cited by 32 · see citing works
The effect of rest breaks on human sensorimotor adaptation
Bock, O. L., Thomas, M., & Grigorova, V. (2005) · Experimental Brain Research · doi:10.1007/s00221-005-2231-z · Cited by 33 · see citing works
The trial-spacing effect in olfactory patterning discriminations in honeybees
Deisig, N., Sandoz, J., Giurfa, M., & Lachnit, H. (2006) · Behavioural Brain Research · doi:10.1016/j.bbr.2006.10.019 · Cited by 33 · see citing works
Kojima, N., Sakamoto, T., Endo, S., & Niki, H. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.03955.x · Cited by 33 · see citing works
Kelley, J. B., Anderson, K. L., Altmann, S. L., & Itzhak, Y. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.11.005 · Cited by 32 · see citing works
Colón-Cesario, M., Wang, J., Ramos, X., Garcia, H. G., Davila, J., Laguna, J., Rosado, C., & de Ortı́z, S. P. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.3050-05.2006 · Cited by 32 · see citing works
LRRK2 at Striatal Synapses: Cell-Type Specificity and Mechanistic Insights
Skelton, P. D., Tokars, V. L., & Parisiadou, L. (2022) · Cells · doi:10.3390/cells11010169 · Cited by 31 · see citing works
Temporal phases of long-term potentiation (LTP): myth or fact?
Abbas, A.-K., Villers, A., & Ris, L. (2015) · Reviews in the Neurosciences · doi:10.1515/revneuro-2014-0072 · Cited by 29 · see citing works
Mechanism based approaches for rescuing and enhancing cognition
LYNCH, G. S. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00143 · Cited by 30 · see citing works
The Depletion–Power–Integration–Latency (DPIL) model of spaced and massed repetition
Sikström, S., & Jaber, M. Y. (2012) · Computers & Industrial Engineering · doi:10.1016/j.cie.2012.03.005 · Cited by 26 · see citing works
NEUROGENETIC DISSECTION OF CONDITIONED BEHAVIOR: EVOLUTION BY ANALOGY OR HOMOLOGY?
Dubnau, J. (2003) · Journal of Neurogenetics · doi:10.1080/01677060390441859 · Cited by 29 · see citing works
Collatz, J., Müller, C., & Steidle, J. L. M. (2006) · Learning & Memory · doi:10.1101/lm.192506 · Cited by 28 · see citing works
The computational power of the human brain
Gebicke‐Haerter, P. J. (2023) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2023.1220030 · Cited by 30 · see citing works
Wilkerson, J. R., MacFarlane, P. M., Hoffman, M. S., & Mitchell, G. S. (2007) · Biochemical Society Transactions · doi:10.1042/bst0351269 · Cited by 27 · see citing works
- Authors
- Scharf, M. T., Woo, N. H., Lattal, K. M., Young, J. Z., Nguyen, P. V., & Abel, T.
- Affiliations
- University of Pennsylvania (US)
- Physiology and
- Department of Biology and
- University of Alberta (CA)
- Venue
- Journal of Neurophysiology
- Publisher
- American Physiological Society
- Published
- 2002-06-01
- Volume
- 87
- Issue
- 6
- Pages
- 2770-2777
- ISSN
- 0022-3077 (ISSN-L)
- 1522-1598
- OpenAlex
- W2259231394
- Cited by
- 204
- References
- 39
- Citations by year
- 2026: 7 · 2025: 3 · 2024: 5 · 2023: 7 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 9 · 2017: 6 · 2016: 11 · 2015: 9 · 2014: 11 · 2013: 13 · 2012: 8
- FWCI
- 5.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurophysiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG18199, R01AG018199)
- National Institute of Mental Health (R01MH060244, MH 60244)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD026979, HD 26979)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- spaced training, massed training, long-term potentiation, protein synthesis, long-term memory, contextual fear conditioning, hippocampus, synaptic plasticity, anisomycin, memory consolidation
- MeSH terms
- Animals, Anisomycin, Conditioning, Psychological, Electric Stimulation, Fear, Female, Hippocampus, Male, Memory, Mice, Inbred C57BL, Organ Culture Techniques, Protein Synthesis Inhibitors, Synapses, Long-Term Potentiation, Excitatory Postsynaptic Potentials, Mice
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