Pattern and predictability in memory formation: From molecular mechanisms to clinical relevance
Open accessAbstract
Most long-term memories are formed as a consequence of multiple experiences. The temporal spacing of these experiences is of considerable importance: experiences distributed over time (spaced training) are more easily encoded and remembered than either closely spaced experiences, or a single prolonged experience (massed training). In this article, we first review findings from studies in animal model systems that examine the cellular and molecular properties of the neurons and circuits in the brain that underlie training pattern sensitivity during long-term memory (LTM) formation. We next focus on recent findings which have begun to elucidate the mechanisms that support inter-trial interactions during the induction of LTM. Finally, we consider the implications of these findings for developing therapeutic strategies to address questions of direct clinical relevance.
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Spaced training leads to improved memory in invertebrates such as Aplysia californica, Drosophila melanogaster and bees, and in rodents and non-human primates.
“Spaced training also leads to improved memory in invertebrates, such as the mollusk Aplysia californica11–14, Drosophila melanogaster15,16 and bees17, and in rodents18,19 and non-human primates20,21.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [11]
In response to each 5-HT pulse, PKA activity increases rapidly and decays rapidly.
“In response to each 5-HT pulse, PKA activity increases rapidly and decays rapidly (FIG. 4c).”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [11]
MAPK activity rises and decays more slowly, not peaking until ~45 minutes after a pulse.
“MAPK activity rises and decays more slowly, not peaking until ~45 minutes after a pulse.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [11]
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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
Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B
Klunk, W. E., Engler, H., Nordberg, A., Wang, Y., Blomqvist, G., Holt, D. P., Bergström, M., Savitcheva, I., Huang, G., Estrada, S., et al. (2004) · Annals of Neurology · doi:10.1002/ana.20009 · Cited by 4,496 · 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
Memory: A Contribution to Experimental Psychology
Ebbinghaus, H. (2013) · Annals of Neurosciences · doi:10.5214/ans.0972.7531.200408 · Cited by 2,827 · see citing works
Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133
Gonzalez, G. A., & Montminy, M. (1989) · Cell · doi:10.1016/0092-8674(89)90013-5 · Cited by 2,464 · see citing works
Distributed practice in verbal recall tasks: A review and quantitative synthesis.
Cepeda, N. J., Pashler, H., Vul, E., Wixted, J. T., & Rohrer, D. (2006) · Psychological Bulletin · doi:10.1037/0033-2909.132.3.354 · Cited by 1,888 · cited 2× · see citing works
“In humans, the benefits of spaced training for memory formation in young healthy adults are well documented (for a recent meta-analysis see Cepeda et al., 2006), and also appear to benefit learning throughout the lifespan.”
BackgroundMemory: A contribution to experimental psychology.
Ebbinghaus, H. (1913) · doi:10.1037/10011-000 · Cited by 1,645 · see citing works
Silva, A. J., Kogan, J. H., Frankland, P. W., & Kida, S. (1998) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.21.1.127 · Cited by 1,462 · see citing works
Memory; a contribution to experimental psychology,
Ebbinghaus, H., Bussenius, C. E., & Ruger, H. A. (n.d.) · University of Michigan Library Repository · Cited by 1,281 · see citing works
Bito, H., Deisseroth, K. A., & Tsien, R. W. (1996) · Cell · doi:10.1016/s0092-8674(00)81816-4 · Cited by 1,123 · see citing works
The 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
The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation
Tidyman, W. E., & Rauen, K. A. (2009) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2009.04.001 · Cited by 780 · see citing works
Diamond, D. M., Campbell, A. M., Park, C. R., Halonen, J., & Zoladz, P. R. (2007) · Neural Plasticity · doi:10.1155/2007/60803 · Cited by 762 · see citing works
Dash, P. K., Hochner, B., & Kandel, E. R. (1990) · Nature · doi:10.1038/345718a0 · Cited by 747 · see citing works
PET imaging of amyloid deposition in patients with mild cognitive impairment
Forsberg, A., Engler, H., Almkvist, O., Blomquist, G., Hagman, G., Wall, A. E., Ringheim, A., Långström, B., & Nordberg, A. K. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.03.029 · Cited by 725 · see citing works
Toward a molecular definition of long-term memory storage
Bailey, C. H., Bartsch, D., & Kandel, E. R. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.13445 · Cited by 691 · see citing works
Synaptic plasticity in the hippocampus: LTP and LTD
Malenka, R. C. (1994) · Cell · doi:10.1016/0092-8674(94)90517-7 · Cited by 655 · 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
Long-Term Sensitization of a Defensive Withdrawal Reflex in <i>Aplysia</i>
Pinsker, H. M., Hening, W. A., Carew, T. J., & Kandel, E. R. (1973) · Science · doi:10.1126/science.182.4116.1039 · Cited by 606 · see citing works
Self-citationLearning Concepts and Categories: Is Spacing the “Enemy of Induction”?
Kornell, N., & Bjork, R. A. (2008) · Psychological Science · doi:10.1111/j.1467-9280.2008.02127.x · Cited by 602 · see citing works
Bartsch, D., Ghirardi, M., Skehel, P. A., Karl, K. A., Herder, S. P., Chen, M., Bailey, C. H., & Kandel, E. R. (1995) · Cell · doi:10.1016/0092-8674(95)90213-9 · Cited by 572 · see citing works
Martin, K. C., Michael, D., Rose, J. C., Barad, M., Casadio, A., Zhu, H., & Kandel, E. R. (1997) · Neuron · doi:10.1016/s0896-6273(00)80330-x · Cited by 545 · see citing works
C/EBP is an immediate-early gene required for the consolidation of long-term facilitation in Aplysia
Alberini, C. M., Ghirardl, M., Metz, R., & Kandel, E. R. (1994) · Cell · doi:10.1016/0092-8674(94)90386-7 · Cited by 523 · see citing works
Mayford, M., Siegelbaum, S. A., & Kandel, E. R. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005751 · Cited by 500 · see citing works
Huang, Y.-Y., & Kandel, E. R. (1994) · Learning & Memory · doi:10.1101/lm.1.1.74 · Cited by 476 · see citing works
Protein phosphatase 1 is a molecular constraint on learning and memory
Genoux, D., Haditsch, U., Knobloch, M., Michalon, A., Storm, D., & Mansuy, I. M. (2002) · Nature · doi:10.1038/nature00928 · Cited by 472 · see citing works
Malleret, G., Haditsch, U., Genoux, D., Jones, M. W., Bliss, T. V. P., Vanhoose, A. M., Weitlauf, C., Kandel, E. R., Winder, D. G., & Mansuy, I. M. (2001) · Cell · doi:10.1016/s0092-8674(01)00264-1 · Cited by 470 · 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
CREB's control of intrinsic and synaptic plasticity: implications for CREB-dependent memory models
Benito, E., & Barco, Á. (2010) · Trends in Neurosciences · doi:10.1016/j.tins.2010.02.001 · Cited by 450 · see citing works
Barad, M., Bourtchouladze, R., Winder, D. G., Golan, H. M., & Kandel, E. R. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.15020 · Cited by 431 · see citing works
The consolidation of new but not reactivated memory requires hippocampal C/EBPβ
Taubenfeld, S. M., Milekic, M. H., Monti, B., & Alberini, C. M. (2001) · Nature Neuroscience · doi:10.1038/90520 · Cited by 420 · see citing works
Rest Interval between Sets in Strength Training
de Salles, B. F., Junior, R. F. S., Miranda, F., Novaes, J. D. S., Lemos, A., & Willardson, J. M. (2009) · Sports Medicine · doi:10.2165/11315230-000000000-00000 · Cited by 403 · see citing works
CREB and the formation of long-term memory
Yin, J. C. P., & Tully, T. P. (1996) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(96)80082-1 · Cited by 399 · see citing works
Guzowski, J. F. (2002) · Hippocampus · doi:10.1002/hipo.10010 · Cited by 392 · see citing works
Bartsch, D., Casadio, A., Karl, K. A., Serodio, P., & Kandel, E. R. (1998) · Cell · doi:10.1016/s0092-8674(00)81752-3 · Cited by 373 · see citing works
Synaptic plasticity in the hippocampus
Bliss, T. (1979) · Trends in Neurosciences · doi:10.1016/0166-2236(79)90019-5 · Cited by 351 · see citing works
Winder, D. G., Mansuy, I. M., Osman, M., Moallem, T. M., & Kandel, E. R. (1998) · Cell · doi:10.1016/s0092-8674(00)80896-x · Cited by 351 · 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
Abraham, W. C., Logan, B. J., Greenwood, J. M., & Dragunow, M. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-21-09626.2002 · Cited by 338 · 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
Memory Suppressor Genes: Inhibitory Constraints on the Storage of Long-Term Memory
Abel, T. G., Martin, K. C., Bartsch, D., & Kandel, E. R. (1998) · Science · doi:10.1126/science.279.5349.338 · Cited by 316 · see citing works
Long-term potentiation: What's learning got to do with it?
Shors, T. J., & Matzel, L. D. (1997) · Behavioral and Brain Sciences · doi:10.1017/s0140525x97001593 · Cited by 314 · see citing works
Cammarota, M., Bevilaqua, L. R., Ardenghi, P. G., Paratcha, G., de Stein, M. L., Izquierdo, I., & Medina, J. H. (2000) · Molecular Brain Research · doi:10.1016/s0169-328x(99)00329-0 · Cited by 310 · see citing works
Long-Term Habituation of a Defensive Withdrawal Reflex in <i>Aplysia</i>
Carew, T. J., Pinsker, H. M., & Kandel, E. R. (1972) · Science · doi:10.1126/science.175.4020.451 · Cited by 294 · see citing works
Self-citationVillemagne, V. L., Pike, K. E., Darby, D., Maruff, P. T., Savage, G. R., Ng, S., Ackermann, U., Cowie, T., Currie, J. N., Chan, S. G., et al. (2008) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2008.02.008 · Cited by 291 · see citing works
More than synaptic plasticity: role of nonsynaptic plasticity in learning and memory
Mozzachiodi, R., & Byrne, J. H. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.10.001 · Cited by 273 · see citing works
MOTIVATING AUTISTIC CHILDREN THROUGH STIMULUS VARIATION
Dunlap, G., & Koegel, R. L. (1980) · Journal of Applied Behavior Analysis · doi:10.1901/jaba.1980.13-619 · Cited by 266 · see citing works
Spaced retrieval: Absolute spacing enhances learning regardless of relative spacing.
Karpicke, J. D., & Kaminske, A. N. (2011) · Journal of Experimental Psychology Learning Memory and Cognition · doi:10.1037/a0023436 · Cited by 263 · see citing works
Trial and intertrial durations in autoshaping.
Gibbon, J., Baldock, M. D., Locurto, C., Gold, L., & Terrace, H. S. (1977) · Journal of Experimental Psychology Animal Behavior Processes · doi:10.1037/0097-7403.3.3.264 · Cited by 260 · see citing works
Castellucci, V. F., Blumenfeld, H., Goelet, P., & Kandel, E. R. (1989) · Journal of Neurobiology · doi:10.1002/neu.480200102 · Cited by 232 · see citing works
Spacing practice sessions across days benefits the learning of motor skills
Shea, C. H., Lai, Q., Black, C., & Park, J.-H. (2000) · Human Movement Science · doi:10.1016/s0167-9457(00)00021-x · Cited by 224 · see citing works
Common molecular mechanisms in explicit and implicit memory
Barco, Á., Bailey, C. H., & Kandel, E. R. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03870.x · Cited by 217 · see citing works
Rubinstein–Taybi syndrome: clinical and molecular overview
Roelfsema, J. H., & Peters, D. J. M. (2007) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399407000415 · Cited by 217 · see citing works
Activity-Dependent Transport of the Transcriptional Coactivator CRTC1 from Synapse to Nucleus
Ch’ng, T. H., Uzgil, B., Lin, P., Avliyakulov, N. K., O’Dell, T. J., & Martin, K. C. (2012) · Cell · doi:10.1016/j.cell.2012.05.027 · Cited by 206 · see citing works
Protein Phosphatase 1 Regulates the Histone Code for Long-Term Memory
Koshibu, K., Gräff, J., Beullens, M., Heitz, F. D., Berchtold, D., Russig, H. D., Farinelli, M., Bollen, M., & Mansuy, I. M. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.3610-09.2009 · Cited by 202 · see citing works
Synaptic evidence for the efficacy of spaced learning
Kramár, E. A., Babayan, A. H., Gavin, C. F., Cox, C. D., Jafari, M., Gall, C. M., Rumbaugh, G., & Lynch, G. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1120700109 · Cited by 192 · see citing works
Spacing as the friend of both memory and induction in young and older adults.
Kornell, N., Castel, A. D., Eich, T. S., & Bjork, R. A. (2010) · Psychology and Aging · doi:10.1037/a0017807 · Cited by 179 · see citing works
Kovács, K. A., Steullet, P., Steinmann, M., Kim, Q., Magistretti, P. J., Halfon, O., & Cardinaux, J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0607524104 · Cited by 179 · see citing works
Molecular Mechanisms Underlying a Unique Intermediate Phase of Memory in Aplysia
Sutton, M. A., Masters, S. E., Bagnall, M. W., & Carew, T. J. (2001) · Neuron · doi:10.1016/s0896-6273(01)00342-7 · Cited by 178 · see citing works
Self-citationSlow oscillations in two pairs of dopaminergic neurons gate long-term memory formation in Drosophila
Plaçais, P.-Y., Trannoy, S., Isabel, G., Aso, Y., Siwanowicz, I., Belliart-Guérin, G., Vernier, P., Birman, S., Tanimoto, H., & Préat, T. (2012) · Nature Neuroscience · doi:10.1038/nn.3055 · Cited by 178 · see citing works
Visualizing Long-Term Memory Formation in Two Neurons of the <i>Drosophila</i> Brain
Chen, C.-C., Wu, J.-K., Lin, H.-W., Pai, T.-P., Fu, T.-F., Wu, C.-L., Tully, T., & Chiang, A.-S. (2012) · Science · doi:10.1126/science.1212735 · Cited by 171 · see citing works
Roberson, E. D., & Sweatt, J. D. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.48.30436 · Cited by 160 · see citing works
The Phosphatase SHP2 Regulates the Spacing Effect for Long-Term Memory Induction
Pagani, M. R., Oishi, K., Gelb, B. D., & Zhong, Y. (2009) · Cell · doi:10.1016/j.cell.2009.08.033 · Cited by 157 · see citing works
Operant Conditioning in Lymnaea: Evidence for Intermediate- and Long-term MemoryPreprint
Lukowiak, K., Adatia, N., Krygier, D. S., & Syed, N. I. (2000) · Learning & Memory · doi:10.1101/lm.7.3.140 · Cited by 154 · see citing works
Involvement of LTP in memory: Are we “searching under the street light”?
Barnes, C. A. (1995) · Neuron · doi:10.1016/0896-6273(95)90166-3 · Cited by 153 · see citing works
The Soma of RPeD1 Must Be Present for Long-Term Memory Formation of Associative Learning inLymnaea
Scheibenstock, A., Krygier, D. S., Haque, Z., Syed, N. I., & Lukowiak, K. (2002) · Journal of Neurophysiology · doi:10.1152/jn.2002.88.4.1584 · Cited by 143 · see citing works
Vlach, H. A., & Sandhofer, C. M. (2012) · Child Development · doi:10.1111/j.1467-8624.2012.01781.x · Cited by 142 · see citing works
Cerebral Protein Synthesis Inhibitors Block Long-Term Memory
Barondes, S. H. (1970) · International review of neurobiology · doi:10.1016/s0074-7742(08)60061-6 · Cited by 133 · see citing works
Tsao, J. C. I., & Craske, M. G. (2000) · Behavior Therapy · doi:10.1016/s0005-7894(00)80026-x · Cited by 131 · see citing works
Fasting Launches CRTC to Facilitate Long-Term Memory Formation in <i>Drosophila</i>
Hirano, Y., Masuda, T., Naganos, S., Matsuno, M., Ueno, K., Miyashita, T., Horiuchi, J., & Saitoe, M. (2013) · Science · doi:10.1126/science.1227170 · Cited by 129 · see citing works
Mauelshagen, J., Sherff, C. M., & Carew, T. J. (1998) · Learning & Memory · doi:10.1101/lm.5.3.246 · Cited by 129 · see citing works
Self-citationMüller, U., & Carew, T. J. (1998) · Neuron · doi:10.1016/s0896-6273(00)80660-1 · Cited by 128 · see citing works
Self-citationBalota, D. A., Duchek, J. M., Sergent-Marshall, S. D., & Roediger, H. L., III (2006) · Psychology and Aging · doi:10.1037/0882-7974.21.1.19 · Cited by 127 · see citing works
van Giezen, A. E., Arensman, E., Spinhoven, P., & Wolters, G. (2005) · Clinical Psychology Review · doi:10.1016/j.cpr.2005.04.011 · Cited by 127 · see citing works
Sharma, S. K., Sherff, C. M., Shobe, J., Bagnall, M. W., Sutton, M. A., & Carew, T. J. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-09-03899.2003 · Cited by 125 · see citing works
Self-citationSutton, M. A., Ide, J., Masters, S. E., & Carew, T. J. (2002) · Learning & Memory · doi:10.1101/lm.44802 · Cited by 125 · see citing works
Self-citationLong-Term Memory of an Operantly Conditioned Respiratory Behaviour Pattern in Lymnaea Stagnalis
Lukowiak, K., Cotter, R., Westly, J., Ringseis, E. L., Spencer, G. E., & Syed, N. I. (1998) · Journal of Experimental Biology · doi:10.1242/jeb.201.6.877 · Cited by 123 · see citing works
Beck, C. D. O., Schroeder, B., & Davis, R. L. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-08-02944.2000 · Cited by 120 · see citing works
αCaMKII autophosphorylation contributes to rapid learning but is not necessary for memory
Irvine, E. E., Vernon, J., & Giese, K. P. (2005) · Nature Neuroscience · doi:10.1038/nn1431 · Cited by 119 · see citing works
Requirement of TORC1 for Late-Phase Long-Term Potentiation in the Hippocampus
Zhou, Y., Wu, H., Li, S., Chen, Q., Cheng, X., Zheng, J., Takemori, H., & Xiong, Z. (2006) · PLoS ONE · doi:10.1371/journal.pone.0000016 · Cited by 119 · see citing works
Verb Learning in Children With SLI
Riches, N. G., Tomasello, M., & Conti‐Ramsden, G. (2005) · Journal of Speech Language and Hearing Research · doi:10.1044/1092-4388(2005/097 · Cited by 118 · see citing works
Aversive olfactory learning and associative long-term memory in Caenorhabditis elegansPreprint
Amano, H., & MARUYAMA, I. N. (2011) · Learning & Memory · doi:10.1101/lm.2224411 · Cited by 113 · see citing works
Teaching in small portions dispersed over time enhances long-term knowledge retention
Raman, M., Mclaughlin, K., Violato, C., Rostom, A., Allard, J., & Coderre, S. (2010) · Medical Teacher · doi:10.3109/01421590903197019 · Cited by 112 · see citing works
Parametric and genetic analysis of Drosophila appetitive long‐term memory and sugar motivation
Colomb, J., Kaiser, L., Chabaud, M.-A., & Préat, T. (2009) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2009.00482.x · Cited by 108 · see citing works
Sangha, S., Scheibenstock, A., McComb, C., & Lukowiak, K. (2003) · Journal of Experimental Biology · doi:10.1242/jeb.00301 · Cited by 108 · see citing works
Wüstenberg, D., Gerber, B., & Menzel, R. (1998) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1998.00319.x · Cited by 105 · see citing works
Pineda, V. V., Athos, J., Wang, H., Celver, J. P., Ippolito, D. L., Boulay, G., Birnbaumer, L., & Storm, D. R. (2004) · Neuron · doi:10.1016/s0896-6273(03)00813-4 · Cited by 104 · see citing works
Nomoto, M., Takeda, Y., Uchida, S., Mitsuda, K., Enomoto, H., Saito, K., Choi, T., Watabe, A. M., Kobayashi, S., Masushige, S., et al. (2012) · Molecular Brain · doi:10.1186/1756-6606-5-8 · Cited by 103 · see citing works
Abrahams, J., & Camp, C. J. (1993) · Clinical Gerontologist · doi:10.1300/j018v12n03_06 · Cited by 102 · see citing works
Lynch, G., Kramár, E. A., Babayan, A. H., Rumbaugh, G., & Gall, C. M. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.07.006 · Cited by 97 · see citing works
Mechanism for long-term memory formation when synaptic strengthening is impaired
Radwanska, K., Medvedev, N. I., Pereira, G. S., Engmann, O., Thiede, N., Moraes, M. F. D., Villers, A., Irvine, E. E., Maunganidze, N. S., Pyza, E. M., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1109680108 · Cited by 97 · see citing works
αCaMKII autophosphorylation: a fast track to memory
Irvine, E. E., von Hertzen, L. S. J., Plattner, F., & Giese, K.-P. (2006) · Trends in Neurosciences · doi:10.1016/j.tins.2006.06.009 · Cited by 92 · see citing works
Changes in neuronal excitability serve as a mechanism of long-term memory for operant conditioning
Mozzachiodi, R., Lorenzetti, F. D., Baxter, D. A., & Byrne, J. H. (2008) · Nature Neuroscience · doi:10.1038/nn.2184 · Cited by 89 · see citing works
Using Spaced Retrieval as an Intervention During Speech-Language Therapy
Brush, J., & Camp, C. J. (1998) · Clinical Gerontologist · doi:10.1300/j018v19n01_05 · Cited by 80 · see citing works
Computational design of enhanced learning protocols
Zhang, Y., Liu, R.-Y., Heberton, G. A., Smolen, P., Baxter, D. A., Cleary, L. J., & Byrne, J. H. (2012) · Nature Neuroscience · doi:10.1038/nn.2990 · Cited by 80 · see citing works
Localized Neuronal Outgrowth Induced by Long-Term Sensitization Training in<i>Aplysia</i>
Wainwright, M. L., Zhang, H., Byrne, J. H., & Cleary, L. J. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-10-04132.2002 · Cited by 78 · see citing works
Spacing effects on implicit memory tests.
Greene, R. L. (1990) · Journal of Experimental Psychology Learning Memory and Cognition · doi:10.1037/0278-7393.16.6.1004 · Cited by 77 · 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
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
Philips, G. T., Ye, X., Kopec, A. M., & Carew, T. J. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.5561-12.2013 · Cited by 70 · see citing works
Self-citationPhilips, G. T., Tzvetkova, E. I., & Carew, T. J. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4262-07.2007 · Cited by 67 · see citing works
Self-citationGerber, B., Wüstenberg, D., Schütz, A., & Menzel, R. (1998) · Neurobiology of Learning and Memory · doi:10.1006/nlme.1997.3801 · Cited by 67 · 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
Haslam, C., Hodder, K. I., & Yates, P. (2011) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/13803395.2010.533155 · Cited by 63 · see citing works
Intermediate-term processes in memory formation
Stough, S., Shobe, J. L., & Carew, T. J. (2006) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2006.10.009 · Cited by 62 · see citing works
Self-citationEffects of Very Short Rest Periods on Hormonal Responses to Resistance Exercise in Men
Rahimi, R., Qaderi, M., Faraji, H., & Boroujerdi, S. S. (2010) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0b013e3181ddb265 · Cited by 61 · see citing works
Liu, R.-Y., Cleary, L. J., & Byrne, J. H. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.5071-10.2011 · Cited by 60 · see citing works
Sharma, S. K., Bagnall, M. W., Sutton, M. A., & Carew, T. J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0830994100 · Cited by 57 · see citing works
Self-citationGoverover, Y., Hillary, F. G., Chiaravalloti, N. D., Arango‐Lasprilla, J. C., & DeLuca, J. (2008) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/13803390802287042 · Cited by 54 · see citing works
Hopper, T. L., Mahendra, N., Kim, E., Azuma, T., Bayles, K. A., Cleary, S., & Tomoeda, C. K. (2005) · Journal of medical speech-language pathology · Cited by 52 · see citing works
The time window hypothesis: Spacing effects
Rovee‐Collier, C., Evancio, S., & Earley, L. A. (1995) · Infant Behavior and Development · doi:10.1016/0163-6383(95)90008-x · Cited by 49 · see citing works
Parsons, R. G., & Davis, M. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.0939-12.2012 · 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
Wittstock, S., Kaatz, H., & Menzel, R. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-04-01379.1993 · Cited by 48 · see citing works
A new frontier in spaced retrieval memory training for persons with Alzheimer's disease
Small, J. A. (2012) · Neuropsychological Rehabilitation · doi:10.1080/09602011.2011.640468 · Cited by 41 · see citing works
Gettinger, M., Bryant, N. D., & Fayne, H. R. (1982) · The Journal of Special Education · doi:10.1177/002246698201600407 · Cited by 41 · see citing works
PKC Differentially Translocates during Spaced and Massed Training in<i>Aplysia</i>
Farah, C. A., Weatherill, D., Dunn, T. W., & Sossin, W. S. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.1533-09.2009 · Cited by 38 · see citing works
Goverover, Y., Arango‐Lasprilla, J. C., Hillary, F. G., Chiaravalloti, N. D., & DeLuca, J. (2009) · American Journal of Occupational Therapy · doi:10.5014/ajot.63.5.543 · Cited by 37 · see citing works
Hart, A. K., Fioravante, D., Liu, R., Phares, G. A., Cleary, L. J., & Byrne, J. H. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.2816-11.2011 · Cited by 36 · see citing works
Enhancing memory formation by altering protein phosphorylation balance
Rosenegger, D. G., Parvez, K., & Lukowiak, K. (2008) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2008.06.005 · Cited by 34 · see citing works
Effect of spaced repetitions on amnesia patients' recall and recognition performance.
Cermak, L. S., Verfaellie, M. H., Lanzoni, S. M., Mather, M., & Chase, K. A. (1996) · Neuropsychology · doi:10.1037/0894-4105.10.2.219 · Cited by 31 · see citing works
Diminished But Not Forgotten: Effects of Aging on Magnitude of Spacing Effect Benefits
Simone, P. M., Bell, M. C., & Cepeda, N. J. (2012) · The Journals of Gerontology Series B · doi:10.1093/geronb/gbs096 · Cited by 31 · see citing works
Place learning in the Morris water task: Making the memory stickPreprint
Bolding, K. A., & Rudy, J. W. (2006) · Learning & Memory · doi:10.1101/lm.146106 · Cited by 30 · see citing works
Deficit in Long-Term Synaptic Plasticity Is Rescued by a Computationally Predicted Stimulus Protocol
Liu, R.-Y., Zhang, Y., Baxter, D. A., Smolen, P., Cleary, L. J., & Byrne, J. H. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.0643-13.2013 · Cited by 29 · see citing works
Xia, S. (1998) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(98)00060-4 · Cited by 29 · see citing works
Philips, G. T., Sherff, C. M., Menges, S. A., & Carew, T. J. (2011) · Learning & Memory · doi:10.1101/lm.2125311 · Cited by 29 · see citing works
Self-citationHopper, T. L., Drefs, S., Bayles, K. A., Tomoeda, C. K., & Dinu, I. A. (2009) · Neuropsychological Rehabilitation · doi:10.1080/09602010902937590 · Cited by 27 · see citing works
Nonuniform effects of reinstatement within the time window
Galluccio, L., & Rovee‐Collier, C. (2005) · Learning and Motivation · doi:10.1016/j.lmot.2005.01.002 · Cited by 27 · see citing works
Structural changes and the storage of long-term memory inAplysia
Bailey, C. H. (1999) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y99-072 · Cited by 25 · see citing works
Klapdor, K., & van der Staay, F. J. (1998) · Physiology & Behavior · doi:10.1016/s0031-9384(98)00003-1 · Cited by 24 · see citing works
Ye, X., Shobe, J. L., Sharma, S. K., Marina, A., & Carew, T. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808110105 · Cited by 24 · see citing works
Self-citationCoomber, C. J. (1998) · Neural Computation · doi:10.1162/089976698300017070 · Cited by 23 · see citing works
Comparing fixed- and randomized-interval spaced retrieval in anomia treatment
Morrow, K. L., & Fridriksson, J. (2005) · Journal of Communication Disorders · doi:10.1016/j.jcomdis.2005.05.001 · Cited by 22 · see citing works
Reexamination of contextual conditioning with massed versus distributed unconditioned stimuli.
Williams, D. A., Frame, K. A., & LoLordo, V. M. (1991) · Journal of Experimental Psychology Animal Behavior Processes · doi:10.1037//0097-7403.17.2.202 · Cited by 20 · see citing works
Intermediate-Term Memory is Modulated by the Circadian Clock
Lyons, L. C., Green, C. L., & Eskin, A. (2008) · Journal of Biological Rhythms · doi:10.1177/0748730408325359 · Cited by 19 · see citing works
Rogers, R. F., Talk, A. C., & Matzel, L. D. (1994) · Behavioral Neuroscience · doi:10.1037/0735-7044.108.6.1030 · Cited by 19 · see citing works
Massed versus spaced visuospatial memory in cognitively healthy young and older adults
Jackson, C. E., Maruff, P. T., & Snyder, P. J. (2012) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2012.04.005 · Cited by 15 · see citing works
Anticholinesterase amnesia as a function of massed or spaced retest.
Deutsch, J. A., & Rocklin, K. W. (1972) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0033318 · Cited by 12 · see citing works
Biochemical mechanisms of memory storage.
Alkon, D. L., & Naito, S. (1986) · PubMed · Cited by 11 · see citing works
Reexamination of contextual conditioning with massed versus distributed unconditioned stimuli.
Williams, D. A., Frame, K. A., & LoLordo, V. M. (1991) · Journal of Experimental Psychology Animal Behavior Processes · doi:10.1037/0097-7403.17.2.202 · Cited by 11 · see citing works
Grassi, J. R. (1971) · Journal of Learning Disabilities · doi:10.1177/002221947100400501 · Cited by 9 · see citing works
Flagged first, then by citations
1 of the 145 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Janiszewski C Noel H Sawyer AG 2003 A Meta-analysis of the Spacing Effect in Verbal Learning: Implications for Research on Advertising Repetition and Consumer Memory Journal of Consumer Research 30 138 149
- Landauer TK Bjork RA 1978 Optimum rehearsal patterns and name learning London Academic Press
Cited by
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The 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
Reward signal in a recurrent circuit drives appetitive long-term memory formation
Ichinose, T., Aso, Y., Yamagata, N., Abe, A., Rubin, G. M., & Tanimoto, H. (2015) · eLife · doi:10.7554/elife.10719 · Cited by 162 · 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
Storkel, H., Voelmle, K. A., Fierro, V., Flake, K., Fleming, K. K., & Romine, R. (2017) · Language, Speech & Hearing Services in Schools · doi:10.1044/2016_lshss-16-0014 · Cited by 62 · see citing works
Kukushkin, N. V., & Carew, T. J. (2017) · Neuron · doi:10.1016/j.neuron.2017.05.029 · Cited by 68 · see citing works
Self-citationSpinal metaplasticity in respiratory motor control
Fields, D. P., & Mitchell, G. S. (2015) · Frontiers in Neural Circuits · doi:10.3389/fncir.2015.00002 · Cited by 62 · see citing works
Sustained Hypoxia Elicits Competing Spinal Mechanisms of Phrenic Motor Facilitation
Devinney, M. J., Nichols, N. L., & Mitchell, G. S. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.4122-15.2016 · Cited by 45 · see citing works
Spacing Effects on Learning and Memory ☆
Carpenter, S. K. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-809324-5.21054-7 · Cited by 45 · see citing works
Fast Cerebellar Reflex Circuitry Requires Synaptic Vesicle Priming by Munc13-3
Netrakanti, P. R., Cooper, B. H., Dere, E., Poggi, G., Winkler, D., Brose, N., & Ehrenreich, H. (2015) · The Cerebellum · doi:10.1007/s12311-015-0645-0 · Cited by 36 · see citing works
Behavioral and neural mechanisms by which prior experience impacts subsequent learning
Parsons, R. G. (2017) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2017.11.008 · Cited by 33 · see citing works
Kopec, A. M., Philips, G. T., & Carew, T. J. (2015) · Neuron · doi:10.1016/j.neuron.2015.04.025 · Cited by 32 · see citing works
Self-citationHistone deacetylase inhibition facilitates massed pattern-induced synaptic plasticity and memoryPreprint
Pandey, K. R., Sharma, K. P., & Sharma, S. K. (2015) · Learning & Memory · doi:10.1101/lm.039289.115 · Cited by 16 · see citing works
Spaced training improves learning in Ts65Dn and Ube3a mouse models of intellectual disabilities
Lauterborn, J. C., Schultz, M. N., Le, A. A., Amani, M., Friedman, A. E., Leach, P. T., Gall, C. M., LYNCH, G. S., & Crawley, J. N. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0495-5 · Cited by 15 · see citing works
Macheda, T., Roberts, K. N., Morganti, J. M., Braun, D. J., & Bachstetter, A. D. (2020) · PLoS ONE · doi:10.1371/journal.pone.0232862 · Cited by 16 · see citing works
Zhou, L., Zhang, Y., Liu, R.-Y., Smolen, P., Cleary, L. J., & Byrne, J. H. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.3330-14.2015 · Cited by 14 · see citing works
Zhang, Y., Smolen, P. D., Baxter, D. A., & Byrne, J. H. (2017) · eNeuro · doi:10.1523/eneuro.0373-16.2017 · Cited by 12 · see citing works
Mirisis, A. A., Alexandrescu, A., Carew, T. J., & Kopec, A. M. (2016) · AIMS neuroscience · doi:10.3934/neuroscience.2016.3.356 · Cited by 13 · see citing works
Self-citationSpaced Training Enhances Contextual Fear Memory via Activating Hippocampal 5-HT2A Receptors
Jiang, L., Wang, L., Yin, Y., Huo, M., Liu, C., Zhou, Q., Yu, D., Xu, L., & Mao, R. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00317 · Cited by 12 · see citing works
Time-dependent consolidation mechanisms of durable memory in spaced learning
Yang, Y., Huang, Z., Yang, Y., Fan, M., & Yin, D. (2025) · Communications Biology · doi:10.1038/s42003-025-07964-6 · Cited by 10 · see citing works
Plog, E., Antov, M. I., Bierwirth, P., Keil, A., & Stockhorst, U. (2021) · eNeuro · doi:10.1523/eneuro.0538-20.2021 · Cited by 9 · see citing works
Chronic nicotine exposure influences learning and memory in the honey bee
Mustard, J. A., Dobb, R., & Wright, G. A. (2023) · Journal of Insect Physiology · doi:10.1016/j.jinsphys.2023.104582 · Cited by 9 · see citing works
Neurotropic and modulatory effects of insulin-like growth factor II in Aplysia
Kukushkin, N. V., Williams, S. P., & Carew, T. J. (2019) · Scientific Reports · doi:10.1038/s41598-019-50923-5 · Cited by 9 · see citing works
Self-citationGerbier, É., & Koenig, O. (2015) · L’Année psychologique · doi:10.3917/anpsy.153.0435 · Cited by 6 · see citing works
Transcriptional analysis of a whole-body form of long-term habituation inAplysia californicaPreprint
Holmes, G., Herdegen, S., Schuon, J., Cyriac, A., Lass, J., Conte, C., Calin‐Jageman, I. E., & Calin-Jageman, R. J. (2014) · Learning & Memory · doi:10.1101/lm.036970.114 · Cited by 6 · see citing works
Pattern detection in the TGFβ cascade controls the induction of long-term synaptic plasticity
Miranda, P., Mirisis, A. A., Kukushkin, N. V., & Carew, T. J. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2300595120 · Cited by 5 · see citing works
Self-citationMueller, R. T., Carrillo, E., Wainwright, M. L., & Mozzachiodi, R. (2025) · Physiology & Behavior · doi:10.1016/j.physbeh.2025.114930 · Cited by 2 · see citing works
Intervenciones Basadas en Mindfulness: Tratamiento de las Personas Supervivientes de Trauma
Vega, B. R., Pérez, C. B., & Liria, A. F. (2016) · Revista de Psicoterapia · doi:10.33898/rdp.v27i103.101 · Cited by 2 · see citing works
Gerbier, É., & Koenig, O. (2015) · L’Année psychologique · doi:10.4074/s0003503315000159 · Cited by 3 · see citing works
Fischbach, S., Kopec, A. M., & Carew, T. J. (2014) · Learning & Memory · doi:10.1101/lm.033894.113 · Cited by 2 · see citing works
Self-citationGerbier, É., & Koenig, O. (2015) · L’Année psychologique · doi:10.4074/s000350331500305x · Cited by 1 · see citing works
Novikovskaya, A. A., Panteleeva, S. N., & Reznikova, J. I. (2019) · Experimental Psychology (Russia) · doi:10.17759/exppsy.2019120102
(2018) · Society for Neuroscience eBooks · doi:10.1523/hon.010003
Network motifs exhibiting a differential response to spaced and massed inputsPreprint
Sreejan, A., Saxena, P., & Gadgil, C. J. (2024) · Learning & Memory · doi:10.1101/lm.054012.124
- Authors
- Philips, G. T., Kopec, A. M., & Carew, T. J.
- Affiliations
- New York University (US)
- Corresponding author
- Philips, Gary T.
- Venue
- Neurobiology of Learning and Memory
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 105
- Pages
- 117-124
- ISSN
- 1074-7427 (ISSN-L)
- PMC
- PMC4020421
- OpenAlex
- W2159963075
- Cited by
- 33
- References
- 145
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 2 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 4 · 2016: 5 · 2015: 10 · 2014: 2
- FWCI
- 0.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Learning and Memory (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH094792, R01MH041083, R01MH081151)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Keywords
- long-term memory, spaced training, massed training, temporal spacing, memory formation, memory encoding, neural circuits, molecular mechanisms of memory, memory consolidation
- MeSH terms
- Animals, Humans, Learning, Neuronal Plasticity, Signal Transduction, Mice, Translational Research, Biomedical, Memory, Long-Term
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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.
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