Cited by 1,550Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchNeurogenesis and neuroplasticity mechanisms

Control of memory formation through regulated expression of a CaMKII transgene

Mayford, Mark, Bach, Mary Elizabeth, Huang, Yan-You, Wang, Lei, Hawkins, Robert D., Kandel, Eric R.·1996·Science

Abstract

One of the major limitations in the use of genetically modified mice for studying cognitive functions is the lack of regional and temporal control of gene function. To overcome these limitations, a forebrain-specific promoter was combined with the tetracycline transactivator system to achieve both regional and temporal control of transgene expression. Expression of an activated calcium-independent form of calcium-calmodulin-dependent kinase II (CaMKII) resulted in a loss of hippocampal long-term potentiation in response to 10-hertz stimulation and a deficit in spatial memory, a form of explicit memory. Suppression of transgene expression reversed both the physiological and the memory deficit. When the transgene was expressed at high levels in the lateral amygdala and the striatum but not other forebrain structures, there was a deficit in fear conditioning, an implicit memory task, that also was reversible. Thus, the CaMKII signaling pathway is critical for both explicit and implicit memory storage, in a manner that is independent of its potential role in development.

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Crossref · 10.1126/science.274.5293.1678

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Authors
Mayford, M., Bach, M. E., Huang, Y.-Y., Wang, L., Hawkins, R. D., & Kandel, E. R.
Affiliations
Howard Hughes Medical Institute (US)
Corresponding author
Kandel, Eric R.
Venue
Science
Published
1996-12-06
Volume
274
Issue
5293
Pages
1678-1683
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2011029903
Cited by
1,550
References
38
Citations by year
2026: 25 · 2025: 25 · 2024: 42 · 2023: 30 · 2022: 39 · 2021: 35 · 2020: 34 · 2019: 37 · 2018: 40 · 2017: 44 · 2016: 43 · 2015: 54 · 2014: 54 · 2013: 57 · 2012: 62
FWCI
46.45
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
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
CaMKII, memory formation, hippocampal long-term potentiation, spatial memory, fear conditioning, declarative memory, implicit memory, transgene expression regulation, lateral amygdala, striatum, calcium/calmodulin-dependent kinase II
MeSH terms
Amygdala, Animals, Brain, Conditioning, Psychological, Corpus Striatum, Doxycycline, Fear, Hippocampus, Memory, Mice, Inbred C57BL, Mice, Transgenic, Neuronal Plasticity, Promoter Regions, Genetic, Signal Transduction, Gene Expression Regulation, Enzymologic, Prosencephalon, Long-Term Potentiation, Calcium-Calmodulin-Dependent Protein Kinases, Genes, Reporter, Maze Learning, Transgenes, Mice, Calcium-Calmodulin-Dependent Protein Kinase Type 2

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