The maintenance of long‐term memory in the hippocampus depends on the interaction between N‐ethylmaleimide‐sensitive factor and GluA2
Abstract
The maintenance of established memories has recently been shown to involve the stabilization of GluA2-containing AMPA receptors (GluA2/AMPARs) at postsynaptic membranes. Previous studies have suggested that N-ethylmaleimide-sensitive factor (NSF) regulates the stabilization of AMPARs at the synaptic membrane. We therefore disrupted the interaction between GluA2 and NSF in the dorsal hippocampus and examined its effect on the maintenance of object location and contextual fear memory. We used two interference peptides, pep2m and pepR845A, that have been shown to block the binding of NSF to GluA2 and reduce GluA2 synaptic content. Either peptide disrupted consolidated memory, and these effects persisted for at least 5 or 28 days after peptide administration. Following peptide administration and long-term memory disruption, rats were able to acquire new memories. Memory acquisition or consolidation was not impaired when pepR845A was given immediately before the training sessions. Blocking GluA2 endocytosis with the peptide GluA23Y prevented the memory impairment effect of pepR845A. Taken together, our results indicate that the persistence of long-term memory depends on the maintenance of a steady-state level of synaptic GluA2/AMPARs, which requires the interaction of NSF with GluA2.
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Maintenance of long-term OPP memory required GluA2/AMPA-R stabilization.
“Maintenance of long-term OPP memory required GluA2/AMPA-R stabilization”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Migues et al., 2014
Cites
Söllner, T. H., Bennett, M., Whiteheart, S., Scheller, R., & Rothman, J. (1993) · Cell · doi:10.1016/0092-8674(93)90376-2 · Cited by 1,922 · see citing works
Schemas and Memory Consolidation.
Tse, D., Langston, R. F., Kakeyama, M., Bethus, I., Spooner, P. A., Wood, E. R., Witter, M. P., & Morris, R. G. M. (2007) · Science · doi:10.1126/science.1135935 · Cited by 1,244 · see citing works
The Involvement of the Anterior Cingulate Cortex in Remote Contextual Fear Memory
Frankland, P., Bontempi, B., Talton, L., Kaczmarek, L., & Silva, A. J. (2004) · Science · doi:10.1126/science.1094804 · Cited by 952 · see citing works
Storage of spatial information by the maintenance mechanism of LTP
Pastalkova, E., Serrano, P., Pinkhasova, D., Wallace, E., Fenton, A. A., & Sacktor, T. C. (2006) · Science · doi:10.1126/science.1128657 · Cited by 848 · see citing works
Cellular and Systems Reconsolidation in the Hippocampus
Dębiec, J., LeDoux, J. E., & Nader, K. (2002) · Neuron · doi:10.1016/s0896-6273(02)01001-2 · Cited by 758 · see citing works
Self-citationRole of AMPA Receptor Cycling in Synaptic Transmission and Plasticity
Lüscher, C., Xia, H., Beattie, E. C., Carroll, R. C., von Zastrow, M., Malenka, R. C., & Nicoll, R. A. (1999) · Neuron · doi:10.1016/s0896-6273(00)81119-8 · Cited by 692 · see citing works
Time-dependent reorganization of brain circuitry underlying long-term memory storage
Bontempi, B., Laurent-Demir, C., Destrade, C., & Jaffard, R. (1999) · Nature · doi:10.1038/23270 · Cited by 673 · see citing works
Distinct components of spatial learning revealed by prior training and NMDA receptor blockade
Bannerman, D. M., Good, M. A., Butcher, S. P., Ramsay, M., & Morris, R. G. M. (1995) · Nature · doi:10.1038/378182a0 · Cited by 551 · see citing works
Dynamics of Retrieval Strategies for Remote Memories
Goshen, I., Brodsky, M., Prakash, R., Wallace, J. L., Gradinaru, V., Ramakrishnan, C., & Deisseroth, K. A. (2011) · Cell · doi:10.1016/j.cell.2011.09.033 · Cited by 546 · see citing works
NSF Binding to GluR2 Regulates Synaptic Transmission
Nishimune, A., Isaac, J. T. R., Molnár, E., Noël, J., Nash, S. R., Tagaya, M., Collingridge, G. L., Nakanishi, S., & Henley, J. M. (1998) · Neuron · doi:10.1016/s0896-6273(00)80517-6 · Cited by 544 · see citing works
Lee, S. H., Liu, L., Wang, Y. T., & Sheng, M. (2002) · Neuron · doi:10.1016/s0896-6273(02)01024-3 · Cited by 441 · see citing works
Self-citationInteraction of the N-Ethylmaleimide–Sensitive Factor with AMPA Receptors
Song, I., Kamboj, S. K., Xia, J., Dong, H., Liao, D., & Huganir, R. L. (1998) · Neuron · doi:10.1016/s0896-6273(00)80548-6 · Cited by 398 · see citing works
Kim, C., Chung, H. J., Lee, H., & Huganir, R. L. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.211132798 · Cited by 358 · see citing works
Rapid Erasure of Long-Term Memory Associations in the Cortex by an Inhibitor of PKMζ
Shema, R., Sacktor, T. C., & Dudai, Y. (2007) · Science · doi:10.1126/science.1144334 · Cited by 353 · see citing works
Extracellular interactions between GluR2 and N-cadherin in spine regulation
Saglietti, L., Dequidt, C., Kamieniarz, K., Rousset, M.-C., Valnegri, P., Thoumine, O., Beretta, F., Fagni, L., Choquet, D., Sala, C., et al. (2007) · Neuron · doi:10.1016/j.neuron.2007.04.012 · Cited by 341 · see citing works
Noël, J., Ralph, G. S., Pickard, L., Williams, J., Molnár, E., Uney, J. B., Collingridge, G. L., & Henley, J. M. (1999) · Neuron · doi:10.1016/s0896-6273(00)80786-2 · Cited by 299 · see citing works
PKMζ maintains memories by regulating GluR2-dependent AMPA receptor trafficking
Migues, P. V., Hardt, O., Wu, D. C., Gamache, K., Sacktor, T. C., Wang, Y. T., & Nader, K. (2010) · Nature Neuroscience · doi:10.1038/nn.2531 · Cited by 283 · see citing works
Self-citationPKMζ Maintains Spatial, Instrumental, and Classically Conditioned Long-Term Memories
Serrano, P., Friedman, E., Kenney, J., Taubenfeld, S., Zimmerman, J. M., Hanna, J., Alberini, C., Kelley, A., Maren, S., Rudy, J., et al. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060318 · Cited by 273 · see citing works
Yao, Y., Kelly, M. T., Sajikumar, S., Serrano, P. A., Tian, D., Bergold, P. J., Frey, J. U., & Sacktor, T. C. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0223-08.2008 · Cited by 268 · see citing works
Subunit Rules Governing the Sorting of Internalized AMPA Receptors in Hippocampal Neurons
Lee, S. H., Simonetta, A., & Sheng, M. (2004) · Neuron · doi:10.1016/j.neuron.2004.06.015 · Cited by 268 · see citing works
Gardner, S. M., Takamiya, K., Xia, J., Suh, J., Johnson, R. C., Yu, S., & Huganir, R. L. (2005) · Neuron · doi:10.1016/j.neuron.2005.02.026 · Cited by 245 · see citing works
Rocca, D. L., Martin, S., Jenkins, E. L., & Hanley, J. (2008) · Nature Cell Biology · doi:10.1038/ncb1688 · Cited by 228 · see citing works
NSF ATPase and α-/β-SNAPs Disassemble the AMPA Receptor-PICK1 Complex
Hanley, J. G., Khatri, L., Hanson, P. I., & Ziff, E. B. (2002) · Neuron · doi:10.1016/s0896-6273(02)00638-4 · Cited by 197 · see citing works
Lin, D.-T., & Huganir, R. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.1750-07.2007 · Cited by 186 · see citing works
PICK1 is a calcium‐sensor for NMDA‐induced AMPA receptor trafficking
Hanley, J. G., & Henley, J. M. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600801 · Cited by 162 · see citing works
Cong, M., Perry, S. J., Hu, L. A., Hanson, P. I., Claing, A., & Lefkowitz, R. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106087200 · Cited by 138 · see citing works
A mechanism underlying AMPA receptor trafficking during cerebellar long-term potentiation
Kakegawa, W., & Yuzaki, M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508910102 · Cited by 109 · see citing works
Inhibition of PKMζ in Nucleus Accumbens Core Abolishes Long-Term Drug Reward Memory
Li, Y.-Q., Xue, Y.-X., He, Y., Li, F., Xue, L., Xu, C., Sacktor, T. C., Shaham, Y., & Lü, L. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.5884-10.2011 · Cited by 104 · see citing works
Araki, Y., Lin, D.-T., & Huganir, R. L. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006584107 · Cited by 92 · see citing works
Protein kinase Mzeta maintains fear memory in the amygdala but not in the hippocampus.
Kwapis, J. L., Jarome, T. J., Lonergan, M. E., & Helmstetter, F. J. (2009) · Behavioral Neuroscience · doi:10.1037/a0016343 · Cited by 86 · see citing works
Zhou, Z., Hu, J., Passafaro, M., Xie, W., & Jia, Z. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.3869-10.2011 · Cited by 86 · see citing works
Hardt, O., Migues, P. V., Hastings, M., Wong, J., & Nader, K. (2010) · Hippocampus · doi:10.1002/hipo.20708 · Cited by 79 · see citing works
Self-citationSteinberg, J. P., Huganir, R. L., & Linden, D. J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408278102 · Cited by 73 · see citing works
Plk2 attachment to NSF induces homeostatic removal of GluA2 during chronic overexcitation
Evers, D. M., Matta, J. A., Hoe, H., Zarkowsky, D. S., Lee, S. H., Isaac, J. T. R., & Pak, D. T. S. (2010) · Nature Neuroscience · doi:10.1038/nn.2624 · Cited by 73 · see citing works
Multiple binding proteins suggest diverse functions for the N-ethylmaleimide sensitive factor
Whiteheart, S. W., & Matveeva, E. A. (2003) · Journal of Structural Biology · doi:10.1016/j.jsb.2003.09.015 · Cited by 64 · see citing works
NSF interaction is important for direct insertion of GluR2 at synaptic sites
Beretta, F., Sala, C., Saglietti, L., Hirling, H., Sheng, M., & Passafaro, M. (2005) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2004.11.008 · Cited by 48 · see citing works
Pauli, W. M., Clark, A. D., Guenther, H. J., O’Reilly, R. C., & Rudy, J. W. (2012) · Learning & Memory · doi:10.1101/lm.025148.111 · Cited by 44 · see citing works
Joels, G., & Lamprecht, R. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1872-10.2010 · Cited by 34 · see citing works
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- Authors
- Migues, P. V., Hardt, O., Finnie, P., Wang, Y. W., & Nader, K.
- Affiliations
- McGill University (CA)
- Department of Medicine Brain Research Center, University of British Columbia Vancouver British Columbia Canada
- Corresponding author
- Migues, Paola Virginia
- Venue
- Hippocampus
- Publisher
- Wiley
- Published
- 2014-05-02
- Volume
- 24
- Issue
- 9
- Pages
- 1112-1119
- ISSN
- 1050-9631 (ISSN-L)
- 1098-1063
- OpenAlex
- W1900605886
- Cited by
- 33
- References
- 38
- Citations by year
- 2025: 1 · 2024: 5 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 4 · 2017: 2 · 2016: 6 · 2015: 3
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hippocampus (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (MOP-123430)
- 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
- N-ethylmaleimide-sensitive factor, NSF, GluA2, AMPA receptors, memory consolidation, object location memory, contextual fear memory, dorsal hippocampus
- MeSH terms
- Animals, Endocytosis, Fear, Hippocampus, Learning, Neuropsychological Tests, Oligopeptides, Rats, Sprague-Dawley, Receptors, AMPA, Nootropic Agents, Rats, Long-Evans, Recognition, Psychology, N-Ethylmaleimide-Sensitive Proteins, Memory, Long-Term, Spatial Memory
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