Control of memory formation through regulated expression of a CaMKII transgene

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

Research output: Contribution to journalArticle

995 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1678-1683
Number of pages6
JournalScience
Volume274
Issue number5293
DOIs
StatePublished - Dec 6 1996
Externally publishedYes

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Calcium-Calmodulin-Dependent Protein Kinases
Transgenes
Prosencephalon
Calcium
Critical Pathways
Trans-Activators
Long-Term Potentiation
Memory Disorders
Tetracycline
Amygdala
Cognition
Fear
Genes

ASJC Scopus subject areas

  • General

Cite this

Mayford, M., Bach, M. E., Huang, Y. Y., Wang, L., Hawkins, R. D., & Kandel, E. R. (1996). Control of memory formation through regulated expression of a CaMKII transgene. Science, 274(5293), 1678-1683. https://doi.org/10.1126/science.274.5293.1678

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.

In: Science, Vol. 274, No. 5293, 06.12.1996, p. 1678-1683.

Research output: Contribution to journalArticle

Mayford, M, Bach, ME, Huang, YY, Wang, L, Hawkins, RD & Kandel, ER 1996, 'Control of memory formation through regulated expression of a CaMKII transgene', Science, vol. 274, no. 5293, pp. 1678-1683. https://doi.org/10.1126/science.274.5293.1678
Mayford, Mark ; Bach, Mary Elizabeth ; Huang, Yan You ; Wang, Lei ; Hawkins, Robert D. ; Kandel, Eric R. / Control of memory formation through regulated expression of a CaMKII transgene. In: Science. 1996 ; Vol. 274, No. 5293. pp. 1678-1683.
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