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Inducible Molecular Switches for the Study of Long-Term Potentiation

Gaël Hédou and Isabelle M. Mansuy
Philosophical Transactions: Biological Sciences
Vol. 358, No. 1432, Long-term Potentiation: Enhancing Neuroscience for 30 Years (Apr. 29, 2003), pp. 797-804
Published by: Royal Society
Stable URL: http://www.jstor.org/stable/3558181
Page Count: 8
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Inducible Molecular Switches for the Study of Long-Term Potentiation
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Abstract

This article reviews technical and conceptual advances in unravelling the molecular bases of long-term potentiation (LTP), learning and memory using genetic approaches. We focus on studies aimed at testing a model suggesting that protein kinases and protein phosphatases balance each other to control synaptic strength and plasticity. We describe how gene 'knock-out' technology was initially exploited to disrupt the Ca2+/calmodulin-dependent protein kinase II α (CaMKII α) gene and how refined knock-in techniques later allowed an analysis of the role of distinct phosphorylation sites in CaMKII. Further to gene recombination, regulated gene expression using the tetracycline-controlled transactivator and reverse tetracycline-controlled transactivator systems, a powerful new means for modulating the activity of specific molecules, has been applied to CaMKII α and the opposing protein phosphatase calcineurin. Together with electro-physiological and behavioural evaluation of the engineered mutant animals, these genetic methodologies have helped gain insight into the molecular mechanisms of plasticity and memory. Further technical developments are, however, awaited for an even higher level of finesse.

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