Cited by 97Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchNeurogenesis and neuroplasticity mechanisms

Mechanism for long-term memory formation when synaptic strengthening is impaired

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Radwanska, Kasia, Medvedev, Nikolay I., Pereira, Grace S., Engmann, Olivia, Thiede, Nina, Moraes, Marcio F. D., Villers, Agnes, Irvine, Elaine E. +8 more·2011·Proceedings of the National Academy of Sciences

Abstract

Long-term memory (LTM) formation has been linked with functional strengthening of existing synapses and other processes including de novo synaptogenesis. However, it is unclear whether synaptogenesis can contribute to LTM formation. Here, using α-calcium/calmodulin kinase II autophosphorylation-deficient (T286A) mutants, we demonstrate that when functional strengthening is severely impaired, contextual LTM formation is linked with training-induced PSD95 up-regulation followed by persistent generation of multiinnervated spines, a type of synapse that is characterized by several presynaptic terminals contacting the same postsynaptic spine. Both PSD95 up-regulation and contextual LTM formation in T286A mutants required signaling by the mammalian target of rapamycin (mTOR). Furthermore, we show that contextual LTM resists destabilization in T286A mutants, indicating that LTM is less flexible when synaptic strengthening is impaired. Taken together, we suggest that activation of mTOR signaling, followed by overexpression of PSD95 protein and synaptogenesis, contributes to formation of invariant LTM when functional strengthening is impaired.

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  • NMDAR-dependent LTP is greatly impaired when T286 is replaced by T286A.

    “Foremost are data, now long accepted, that NMDAR-dependent LTP is greatly impaired when T286 is replaced by T286A (43, 121, 381–384).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [384]

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Authors
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., Ris, L., Szymańska, M., Lipiński, M., Kaczmarek, L., Stewart, M. G., & Giese, K. P.
Affiliations
  • Institute of Psychiatry, King's College London, London SE5 9NU, United Kingdom;
  • The Open University (GB)
  • Universidade Federal de Minas Gerais (BR)
  • King's College London (GB)
  • University of Freiburg (DE)
  • University of Mons (BE)
  • University College London (GB)
  • Jagiellonian University (PL)
  • Instytut Biologii Doświadczalnej im. Marcelego Nenckiego (PL)
Venue
Proceedings of the National Academy of Sciences
Published
2011-10-24
Volume
108
Issue
45
Pages
18471-18475
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2110813649
Cited by
97
References
35
Citations by year
2026: 1 · 2025: 4 · 2024: 8 · 2023: 8 · 2022: 8 · 2021: 8 · 2020: 9 · 2019: 7 · 2018: 8 · 2017: 7 · 2016: 1 · 2015: 9 · 2014: 6 · 2013: 7 · 2012: 4
FWCI
3.09
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (submittedVersion)
  • ORBi UMONS (submittedVersion)
Funders
National Institute of Mental Health (R01MH087463)
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
long-term memory formation, synaptic strengthening, synaptogenesis, calcium/calmodulin-dependent protein kinase II, PSD-95, mTOR signaling, contextual memory, memory stability
MeSH terms
Disks Large Homolog 4 Protein, Animals, Hippocampus, Membrane Proteins, Phosphorylation, Synapses, Up-Regulation, Genes, Immediate-Early, Sirolimus, Mice, Guanylate Kinases, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Memory, Long-Term, TOR Serine-Threonine Kinases

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