Control of memory formation through regulated expression of a CaMKII transgene
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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The tetracycline-regulated expression system has been used in mice for inducible expression of genes from the TRE promoter in response to tTA or rtTA activation.
“The tetracycline (Tet)-regulated expression system has been used in mice for inducible expression of genes from the TRE (tetracycline response element, also called tetO) promoter in response to tTA (Tet-Off) or rtTA (Tet-On) activation (Garner et al., 2012; Gossen and Bujard, 1992; Mayford et al., 1996; Reijmers et al., 2007; Urlinger et al., 2000).”
From Transgenic mice for intersectional targeting of neural sensors and effectors with high specificity and performance (2015) · cites this paper as Mayford et al., 1996
Camk2a-tTA is restricted to forebrain excitatory neurons and striatal medium spiny neurons.
“Camk2a-tTA is restricted to forebrain excitatory neurons and striatal medium spiny neurons.”
From Transgenic mice for intersectional targeting of neural sensors and effectors with high specificity and performance (2015) · cites this paper as Mayford et al., 1996
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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
- Semantic Scholar
- 8133e8d6024af49f2f869510542f0066de92c8a8
- 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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