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Cited by 94Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchMemory Processes and Influences

Memory Erasure Experiments Indicate a Critical Role of CaMKII in Memory Storage

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Rossetti, Tom, Banerjee, Somdeb, Kim, Chris, Leubner, Megan, Lamar, Casey, Gupta, Pooja, Lee, Bomsol, Neve, Rachael +1 more·2017·Neuron
DOI 10.1016/j.neuron.2017.09.010PMC PMC5634137
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Abstract

The abundant synaptic protein CaMKII is necessary for long-term potentiation (LTP) and memory. However, whether CaMKII is required only during initial processes or whether it also mediates memory storage remains unclear. The most direct test of a storage role is the erasure test. In this test, a putative memory molecule is inhibited after learning. The key prediction is that this should produce persistent memory erasure even after the inhibitory agent is removed. We conducted this test using transient viral (HSV) expression of dominant-negative CaMKII-alpha (K42M) in the hippocampus. This produced persistent erasure of conditioned place avoidance. As an additional test, we found that expression of activated CaMKII (T286D/T305A/T306A) impaired place avoidance, a result not expected if a process other than CaMKII stores memory. Our behavioral results, taken together with prior experiments on LTP, strongly support a critical role of CaMKII in LTP maintenance and memory storage.

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  • NMDAR-dependent LTP has been most tightly associated with intact animal behavioral memory.

    “Additionally, NMDAR-dependent LTP has been most tightly associated with intact animal behavioral memory (19, 43–46).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [46]

    The Introduction (page unavailable) describes NMDA-initiated LTP in hippocampal CA1 as a candidate memory mechanism. The Discussion (page unavailable) says that interference with CaMKII can erase both LTP and memory, supporting a link between them. But the paper does not establish the comparative claim that NMDAR-dependent LTP is *most tightly* associated with behavioral memory in intact animals; it cautions that LTP is difficult to observe during learning. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Transiently silencing CaMKII in mice after learning a behavior erases the memory.

    “For instance, recent experiments (46) using the viral expression of the catalytically dead CaMKII K42M mutant, which acts in a dominant-negative manner (444), have found that transiently silencing CaMKII in mice after learning a behavior erases the memory (46).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [46]

    The Results report that transient expression of dominant-negative CaMKII after learning substantially impaired retention of conditioned place avoidance, with the mutant no longer present at testing. However, the Results and Methods identify the animals as rats, not mice, so the claim gives the wrong species. (LLM, conf=0.91)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

  • Synaptic memory and CaMKII

    Nicoll, R. A., & Schulman, H. (2023) · Physiological Reviews · doi:10.1152/physrev.00034.2022 · Cited by 126 · see citing works

    “For instance, recent experiments (46) using the viral expression of the catalytically dead CaMKII K42M mutant, which acts in a dominant-negative manner (444), have found that transiently silencing CaMKII in mice after learning a behavior erases the memory (46).”
    Background

Authors
Rossetti, T., Banerjee, S., Kim, C., Leubner, M., Lamar, C., Gupta, P., Lee, B., Neve, R., & Lisman, J.
Affiliations
  • Brandeis University (US)
  • Massachusetts General Hospital (US)
Corresponding author
Lisman, John
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2017-09
Volume
96
Issue
1
Pages
207-216.e2
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2017.09.010
PMC
PMC5634137
OpenAlex
W2758121911
Cited by
94
References
18
Citations by year
2026: 5 · 2025: 5 · 2024: 6 · 2023: 14 · 2022: 12 · 2021: 8 · 2020: 11 · 2019: 11 · 2018: 19 · 2017: 3
FWCI
6.90
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NIH (U01NS090583, R56NS096710, R01DA043195, R01NS103168)
  • NSF (1526941)
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
CaMKII, memory storage, memory erasure, long-term potentiation, conditioned place avoidance, hippocampus, synaptic plasticity
MeSH terms
Animals, Avoidance Learning, Conditioning, Psychological, Hippocampus, Male, Memory, Phosphorylation, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2

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