Transient Mitogen-Activated Protein Kinase Activation Is Confined to a Narrow Temporal Window Required for the Induction of Two-Trial Long-Term Memory in Aplysia

Philips, Gary T.; Tzvetkova, Ekaterina I.; Carew, Thomas J.

doi:10.1523/jneurosci.4262-07.2007

Cited by 67Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchNeurobiology and Insect Physiology Research

Transient Mitogen-Activated Protein Kinase Activation Is Confined to a Narrow Temporal Window Required for the Induction of Two-Trial Long-Term Memory in Aplysia

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Philips, Gary T., Tzvetkova, Ekaterina I., Carew, Thomas J.·2007·The Journal of Neuroscience

DOI 10.1523/jneurosci.4262-07.2007PMC PMC6673619

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Abstract

Although it is commonly appreciated that spaced training is superior to massed training in memory formation, the molecular mechanisms underlying this feature of memory are largely unknown. We previously described the selective benefit of multiple spaced (vs massed) training trials in the induction of long-term memory (LTM) for sensitization in Aplysia californica. We now report that LTM can be induced with only two spaced training trials [tail shocks (TSs)] when the second TS is administered 45 min after the first. In contrast, spacing intervals of 15 and 60 min are ineffective. This surprisingly narrow permissive training window for two-trial LTM is accompanied by an equally narrow window of transient mitogen-activated protein kinase (MAPK) activation, a necessary signaling molecule for LTM induction, at 45 min after a single TS. Thus, the transient recruitment of MAPK following a single TS may provide a narrow molecular window for two-trial LTM formation.

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The 45-minute optimum for LTS in Aplysia californica was associated with activation of MAPK.
“The 45-minute optimum was associated with activation of MAPK.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [66]
Following either a single 5-HT pulse or a single electric shock, MAPK activation peaked at or near 45 minutes post-trial; thus, a 45-minute interval might optimally reinforce the effects of MAPK.
“Following either a single 5-HT pulse or a single electric shock, MAPK activation peaked at or near 45 minutes post-trial12,66; thus, a 45-minute interval might optimally reinforce the effects of MAPK.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [66]
In Aplysia californica, when two electric shocks were given to induce LTS, maximal LTS was produced when the inter-stimulus interval was 45 minutes; LTS was not produced with intervals of 15 or 60 minutes.
“In experiments with A. californica, when two electric shocks were given to induce LTS, maximal LTS was produced when the inter-stimulus interval was 45 minutes. LTS was not produced with intervals of 15 or 60 minutes66.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [66]
ERK is activated more slowly, with maximal activation about 45 min after a single trial.
“In contrast, ERK is activated more slowly with maximal activation occurring about 45 min after a single trial7.”
From Computational design of enhanced learning protocols (2012) · cites this paper as [7]
The non-uniform distribution of interstimulus intervals in the Enhanced protocol was in marked contrast to the fixed intervals used in previous protocols for behavioral training in Aplysia.
“Interestingly, the non-uniform distribution of ISIs in the Enhanced protocol was in marked contrast to the fixed intervals used in previous protocols for behavioral training in Aplysia6,7,10.”
From Computational design of enhanced learning protocols (2012) · cites this paper as [7]

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The molecular biology of memory storage: a dialogue between genes and synapses
Kandel, E. R. (2001) · Science · doi:10.1126/science.1067020 · Cited by 3,917 · 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
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
“Subsequent studies in humans and animals have confirmed that this “spacing effect” is a general learning principle for LTM induction (Tully et al., 1994; Gerber et al., 1998; Donovan and Radosevich, 1999; Genoux et al., 2002; Sutton et al., 2002; Cepeda et al., 2006).”
Background
CREB AND MEMORY
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
Mitogen-activated protein kinases in synaptic plasticity and memory
Sweatt, J. D. (2004) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2004.04.001 · Cited by 990 · 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
A meta-analytic review of the distribution of practice effect: Now you see it, now you don’t
Donovan, J. J., & Radosevich, D. J. (1999) · Journal of Applied Psychology · doi:10.1037/0021-9010.84.5.795 · Cited by 696 · see citing works
MAP Kinase Translocates into the Nucleus of the Presynaptic Cell and Is Required for Long-Term Facilitation in Aplysia
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
A Transient, Neuron-Wide Form of CREB-Mediated Long-Term Facilitation Can Be Stabilized at Specific Synapses by Local Protein Synthesis
Casadio, A., Martin, K. C., Giustetto, M., Zhu, H., Chen, M., Bartsch, D., Bailey, C. H., & Kandel, E. R. (1999) · Cell · doi:10.1016/s0092-8674(00)81653-0 · Cited by 503 · 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
Long-Term Memory Is Facilitated by cAMP Response Element-Binding Protein Overexpression in the Amygdala
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
Habituation and Dishabituation of the Gill-Withdrawal Reflex in Aplysia
Pinsker, H. M., Kupfermann, I., Castellucci, V. F., & Kandel, E. R. (1970) · Science · doi:10.1126/science.167.3926.1740 · Cited by 431 · 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
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
Operant Reward Learning in Aplysia : Neuronal Correlates and Mechanisms
Brembs, B., Lorenzetti, F. D., Reyes, F. D., Baxter, D. A., & Byrne, J. H. (2002) · Science · doi:10.1126/science.1069434 · Cited by 338 · see citing works
Ca2+-Stimulated Adenylyl Cyclases Regulate ERK-Dependent Activation of MSK1 during Fear Conditioning
Sindreu, C. B., Scheiner, Z. S., & Storm, D. R. (2007) · Neuron · doi:10.1016/j.neuron.2006.11.024 · Cited by 192 · see citing works
Serotonin Release Evoked by Tail Nerve Stimulation in the CNS ofAplysia: Characterization and Relationship to Heterosynaptic Plasticity
Marinesco, S., & Carew, T. J. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-06-02299.2002 · Cited by 176 · see citing works
Self-citation
Differential Induction of Long-Term Synaptic Facilitation by Spaced and Massed Applications of Serotonin at Sensory Neuron Synapses of Aplysia californica
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-citation
Differential Role of Mitogen-Activated Protein Kinase in Three Distinct Phases of Memory for Sensitization inAplysia
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-citation
Interaction between Amount and Pattern of Training in the Induction of Intermediate- and Long-Term Memory for Sensitization in Aplysia
Sutton, 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-citation
Classical conditioning in Aplysia californica.
Walters, E. T., Carew, T. J., & Kandel, E. R. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.12.6675 · Cited by 112 · see citing works
Self-citation
Dynamics of Induction and Expression of Long-Term Synaptic Facilitation inAplysia
Mauelshagen, J., PARKER, G., & Carew, T. J. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-22-07099.1996 · Cited by 103 · see citing works
Self-citation
The Roles of MAPK Cascades in Synaptic Plasticity and Memory in Aplysia: Facilitatory Effects and Inhibitory Constraints: Figure 1
Sharma, S. K., & Carew, T. J. (2004) · Learning & Memory · doi:10.1101/lm.81104 · Cited by 95 · see citing works
Self-citation
Localized Neuronal Outgrowth Induced by Long-Term Sensitization Training inAplysia
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
Temporal spacing of synaptic stimulation critically modulates the dependence of LTP on cyclic AMP‐dependent protein kinase
Woo, N. H., Duffy, S. N., Abel, T., & Nguyen, P. V. (2003) · Hippocampus · doi:10.1002/hipo.10086 · Cited by 73 · see citing works
A learned change of response to inedible food in Aplysia
Susswein, A. J., & Schwarz, M. (1983) · Behavioral and Neural Biology · doi:10.1016/s0163-1047(83)90535-6 · Cited by 71 · see citing works
Temporal Determinants of Olfactory Long-Term Retention in Honeybee Classical Conditioning: Nonmonotonous Effects of the Training Trial Interval
Gerber, 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
Serotonergic Modulation in Aplysia. I. Distributed Serotonergic Network Persistently Activated by Sensitizing Stimuli
Marinesco, S., Kolkman, K. E., & Carew, T. J. (2004) · Journal of Neurophysiology · doi:10.1152/jn.00209.2004 · Cited by 64 · see citing works
Self-citation
Inhibition of calcineurin facilitates the induction of memory for sensitization in Aplysia : Requirement of mitogen-activated protein kinase
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-citation
Serotonergic Modulation in Aplysia. II. Cellular and Behavioral Consequences of Increased Serotonergic Tone
Marinesco, S., Wickremasinghe, N., Kolkman, K. E., & Carew, T. J. (2004) · Journal of Neurophysiology · doi:10.1152/jn.00210.2004 · Cited by 50 · see citing works
Self-citation
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Hu, J., Chen, Y., & Schacher, S. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2322-07.2007 · Cited by 41 · see citing works
Parallel somatic and synaptic processing in the induction of intermediate-term and long-term synaptic facilitation in Aplysia
Sherff, C. M., & Carew, T. J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402163101 · Cited by 40 · see citing works
Self-citation
Interactive contributions of intracellular calcium and protein phosphatases to massed-trials learning deficits in Hermissenda.
Muzzio, I. A., Ramirez, R. R., Talk, A. C., & Matzel, L. D. (1999) · Behavioral Neuroscience · doi:10.1037//0735-7044.113.1.103 · Cited by 17 · see citing works
Interactive contributions of intracellular calcium and protein phosphatases to massed-trials learning deficits in Hermissenda.
Muzzio, I. A., Ramirez, R. R., Talk, A. C., et al. (1999) · Behavioral Neuroscience · doi:10.1037/0735-7044.113.1.103 · Cited by 16 · see citing works
PP1 Inhibitors DepolarizeHermissendaPhotoreceptors and Reduce K+Currents
Huang, H., & Farley, J. (2001) · Journal of Neurophysiology · doi:10.1152/jn.2001.86.3.1297 · Cited by 7 · see citing works

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Authors: Philips, G. T., Tzvetkova, E. I., & Carew, T. J.
Affiliations: University of California, Irvine (US)
Image and Pervasive Access Laboratory (SG)
ORCID: Philips, Gary T.
Carew, Thomas J.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2007-12-12
Volume: 27
Issue: 50
Pages: 13701-13705
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.4262-07.2007
PMC: PMC6673619
OpenAlex: W1963487641
Cited by: 67
References: 36
Citations by year: 2026: 1 · 2024: 4 · 2023: 7 · 2022: 5 · 2021: 2 · 2020: 2 · 2018: 2 · 2017: 3 · 2016: 5 · 2015: 7 · 2014: 6 · 2013: 10 · 2012: 6
FWCI: 0.50
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 183 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Science Foundation (0444762)
National Institutes of Health
National Institute of Mental Health (R01MH041083)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
Keywords: mitogen-activated protein kinase, long-term memory, spaced training, massed training, sensitization, Aplysia californica, tail shock, temporal window, synaptic plasticity
MeSH terms: Animals, Aplysia, Behavior, Animal, Electroshock, Enzyme Activation, Memory, Neurons, Afferent, Physical Stimulation, Time Factors, Mitogen-Activated Protein Kinases

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Transient Mitogen-Activated Protein Kinase Activation Is Confined to a Narrow Temporal Window Required for the Induction of Two-Trial Long-Term Memory in Aplysia

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