Different Training Procedures Recruit Either One or Two Critical Periods for Contextual Memory Consolidation, Each of Which Requires Protein Synthesis and PKA
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We have used a combined genetic and pharmacological approach to define the time course of the requirement for protein kinase A (PKA) and protein synthesis in long-term memory for contextual fear conditioning in mice. The time course of amnesia in transgenic mice that express R(AB) and have genetically reduced PKA activity in the hippocampus parallels that observed both in mice treated with inhibitors of PKA and mice treated with inhibitors of protein synthesis. This PKA- and protein synthesis-dependent memory develops between 1 hr and 3 hr after training. By injecting the protein synthesis inhibitor anisomycin or the PKA inhibitor Rp-cAMPs at various times after training, we find that depending on the nature of training, contextual memory has either one or two brief consolidation periods requiring synthesis of new proteins, and each of these also requires PKA. Weak training shows two time periods of sensitivity to inhibitors of protein synthesis and PKA, whereas stronger training exhibits only one. These studies underscore the parallel dependence of long-term contextual memory on protein synthesis and PKA and suggest that different training protocols may recruit a common signaling pathway in distinct ways.
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cAMP-PKA-dependent memory formation for contextual fear conditioning is selectively sensitive to inhibition of PKA and protein synthesis within specific time windows after training (immediately or 4 h).
“Also, cAMP-PKA-dependent memory formation for contextual fear conditioning is selectively sensitive to the inhibition of PKA and protein synthesis when this inhibition occurs within specific time windows after training, i.e., immediately or 4 h after training (128).”
From About Sleep's Role in Memory (2013) · cites this paper as [128]
The section “A Weak Training Protocol Reveals Two Sensitive Periods” reports that, after a single CS/US pairing, inhibition of either protein synthesis or PKA impaired contextual memory when given immediately or 4 hours after training. The claim omits the training-strength qualification: the paper reports only an immediate sensitive period after stronger training, with no significant effect at 4 hours. (LLM, conf=0.88)
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Cites
Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning.
Phillips, R. G., & LeDoux, J. E. (1992) · Behavioral Neuroscience · doi:10.1037/0735-7044.106.2.274 · Cited by 3,292 · see citing works
Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons
Frey, U., Huang, Y.-Y., & Kandel, E. R. (1993) · Science · doi:10.1126/science.8389057 · Cited by 1,218 · see citing works
Logue, S. F., Paylor, R., & Wehner, J. M. (1997) · Behavioral Neuroscience · doi:10.1037/0735-7044.111.1.104 · Cited by 385 · 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
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Research works printed but not linked: 3
- Bernabeu, R., L. Bevilaqua, P. Ardenghi., E. Bromberg, P. Schmitz, M. Bianchin, I. Izquierdo, and J. Medina. 1997. Involvement of hippocampal cAMP/cAMP-dependent protein kinase signaling pathways in a late memory consolidation phase of aversively motivated learning in rats. Proc. Natl. Acad. Sci. 94: 7041-7046.
- Davis, H.P. and L.R. Squire. 1984. Protein synthesis and memory: A review. Psychol. Bull. 96: 518-559.
- Franklin, K.B. and G. Paxinos. 1997. The mouse brain in stereotaxic coordinates. Academic Press, San Diego, CA.
Cited by
Sorted by citations
LeDoux, J. E. (2000) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.23.1.155 · Cited by 8,444 · see citing works
Rasch, B., & Born, J. (2013) · Physiological Reviews · doi:10.1152/physrev.00032.2012 · Cited by 2,783 · see citing works
“, immediately or 4 h after training (128).”
BackgroundThe organization of recent and remote memories
Frankland, P. W., & Bontempi, B. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1607 · Cited by 2,138 · see citing works
The Emotional Brain, Fear, and the Amygdala
LeDoux, J. (2003) · Cellular and Molecular Neurobiology · doi:10.1023/a:1025048802629 · Cited by 1,818 · see citing works
Translational control of long-lasting synaptic plasticity and memory
Costa-Mattioli, M., Sossin, W. S., Klann, E., & Sonenberg, N. (2009) · Neuron · doi:10.1016/j.neuron.2008.10.055 · Cited by 944 · see citing works
Sleep, learning, and dreams: off-line memory reprocessing
Stickgold, R., Hobson, J. A., Fosse, R., & Fosse, M. (2001) · Science · doi:10.1126/science.1063530 · Cited by 762 · 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
Schafe, G. E., & LeDoux, J. E. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-18-j0003.2000 · Cited by 611 · see citing works
Synaptic plasticity in the lateral amygdala: a cellular hypothesis of fear conditioning
Blair, H. T., Schafe, G. E., Bauer, E. P., Rodrigues, S. M., & LeDoux, J. E. (2001) · Learning & Memory · doi:10.1101/lm.30901 · Cited by 610 · see citing works
Memory consolidation of Pavlovian fear conditioning: a cellular and molecular perspective
Schafe, G. E., Nader, K., Blair, H. T., & LeDoux, J. E. (2001) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)01969-x · Cited by 510 · see citing works
Molecular mechanisms underlying emotional learning and memory in the lateral amygdala
Rodrigues, S. M., Schafe, G. E., & LeDoux, J. E. (2004) · Neuron · doi:10.1016/j.neuron.2004.09.014 · Cited by 491 · see citing works
Sleep deprivation selectively impairs memory consolidation for contextual fear conditioning
Graves, L. A., Heller, E. A., Pack, A. I., & Abel, T. (2003) · Learning & Memory · doi:10.1101/lm.48803 · Cited by 476 · see citing works
Self-citationEffects of D-cycloserine on extinction of conditioned freezing.
Ledgerwood, L., Richardson, R., & Cranney, J. (2003) · Behavioral Neuroscience · doi:10.1037/0735-7044.117.2.341 · Cited by 388 · see citing works
Alonso, M., Vianna, M. R. M., Depino, A. M., Mello e Souza, T., Pereira, P., Szapiro, G., Viola, H., Pitossi, F., Izquierdo, I., & Medina, J. H. (2002) · Hippocampus · doi:10.1002/hipo.10035 · Cited by 339 · see citing works
Seeking a Spotless Mind: Extinction, Deconsolidation, and Erasure of Fear Memory
Maren, S. (2011) · Neuron · doi:10.1016/j.neuron.2011.04.023 · Cited by 259 · see citing works
“Consistentwith thisaim,several investigatorshavenowshownthat fearmemory is inhibitedby systemic posttraining protein synthesis inhibition (Bourtchouladze et al., 1998; Lattal and Abel, 2001).”
BackgroundBDNF activates mTOR to regulate GluR1 expression required for memory formation
Slipczuk, L., Bekinschtein, P., Katche, C., Cammarota, M., Izquierdo, I., & Medina, J. H. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006007 · Cited by 246 · see citing works
Through the looking glass: Differential noradenergic modulation of prefrontal cortical function
Arnsten, A. F. T. (2000) · Neural Plasticity · doi:10.1155/np.2000.133 · Cited by 229 · see citing works
Dysregulation of Protein Kinase A Signaling in the Aged Prefrontal Cortex
Ramos, B. P., Birnbaum, S. G., Lindenmayer, I., Newton, S. S., Duman, R. S., & Arnsten, A. F. T. (2003) · Neuron · doi:10.1016/s0896-6273(03)00694-9 · Cited by 218 · see citing works
Sleep and memory: a molecular perspective
Graves, L. (2001) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)01744-6 · Cited by 216 · see citing works
Scharf, M. T., Woo, N. H., Lattal, K. M., Young, J. Z., Nguyen, P. V., & Abel, T. (2002) · Journal of Neurophysiology · doi:10.1152/jn.2002.87.6.2770 · Cited by 204 · see citing works
Self-citationChapter 6 Regulation of hippocampus-dependent memory by cyclic AMP-dependent protein kinase
Abel, T., & Nguyen, P. V. (2008) · Progress in Brain Research · doi:10.1016/s0079-6123(07)00006-4 · Cited by 198 · see citing works
Self-citationWeber-Stadlbauer, U., Richetto, J., Labouesse, M. A., Bohacek, J., Mansuy, I. M., & Meyer, U. (2017) · Molecular Psychiatry · doi:10.1038/mp.2016.41 · Cited by 170 · see citing works
Systemic inhibition of mammalian target of rapamycin inhibits fear memory reconsolidation
Blundell, J., Kouser, M., & Powell, C. M. (2008) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2007.12.004 · Cited by 162 · see citing works
Decoding material-specific memory reprocessing during sleep in humans
Schönauer, M., Alizadeh, S., Jamalabadi, H., Abraham, A., Pawlizki, A., & Gais, S. (2017) · Nature Communications · doi:10.1038/ncomms15404 · Cited by 139 · see citing works
Artinian, J., McGauran, A. T., De Jaeger, X., Mouledous, L., Frances, B., & Roullet, P. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06262.x · Cited by 145 · see citing works
Prince, T.-M., Wimmer, M., Choi, J., Havekes, R., Aton, S., & Abel, T. (2014) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2013.11.021 · Cited by 142 · see citing works
REM sleep deprivation affects extinction of cued but not contextual fear conditioning
Silvestri, A. J. (2005) · Physiology & Behavior · doi:10.1016/j.physbeh.2004.11.011 · Cited by 124 · see citing works
Taylor, J. R., Birnbaum, S., Ubriani, R., & Arnsten, A. F. T. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-18-j0001.1999 · Cited by 120 · see citing works
Hippocampal reactivation extends for several hours following novel experience
Giri, B., Miyawaki, H., Mizuseki, K., Cheng, S., & Diba, K. (2019) · The Journal of Neuroscience · doi:10.1523/jneurosci.1950-18.2018 · Cited by 99 · see citing works
Hagewoud, R., Whitcomb, S. N., Heeringa, A. N., Havekes, R., Koolhaas, J. M., & Meerlo, P. (2010) · Sleep · doi:10.1093/sleep/33.10.1315 · Cited by 99 · see citing works
CA1 hippocampal network activity changes during sleep-dependent memory consolidation
Ognjanovski, N., Maruyama, D., Lashner, N., Zochowski, M., & Aton, S. J. (2014) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2014.00061 · Cited by 81 · see citing works
Animal Studies on the Role of Sleep in Memory: From Behavioral Performance to Molecular Mechanisms
Havekes, R., Meerlo, P., & Abel, T. (2015) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2015_369 · Cited by 78 · see citing works
Self-citationSpatiotemporally resolved protein synthesis as a molecular framework for memory consolidation
Shrestha, P., & Klann, E. (2022) · Trends in Neurosciences · doi:10.1016/j.tins.2022.01.004 · Cited by 54 · see citing works
- Authors
- Bourtchouladze, R., Abel, T., Berman, N., Gordon, R., Lapidus, K., & Kandel, E. R.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Learning & Memory
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1998-09-01
- Volume
- 5
- Issue
- 4
- Pages
- 365-374
- ISSN
- 1072-0502 (ISSN-L)
- 1549-5485
- PMC
- PMC311273
- OpenAlex
- W1949317008
- Cited by
- 525
- References
- 4
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 9 · 2023: 9 · 2022: 14 · 2021: 11 · 2020: 15 · 2019: 19 · 2018: 22 · 2017: 22 · 2016: 26 · 2015: 24 · 2014: 23 · 2013: 21 · 2012: 26
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Learning & Memory (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health
- 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
- contextual fear conditioning, memory consolidation, protein synthesis, protein kinase A, anisomycin, Rp-cAMPS, hippocampus, training protocols, long-term memory
- MeSH terms
- Acoustic Stimulation, Cyclic AMP, Amnesia, Animals, Anisomycin, Avoidance Learning, Conditioning, Operant, Electroshock, Enzyme Inhibitors, Hippocampus, Memory, Mice, Transgenic, Protein Synthesis Inhibitors, Thionucleotides, Time Factors, Cyclic AMP-Dependent Protein Kinases, Mice
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