Inducible and reversible gene expression with the rtTA system for the study of memory.

Mansuy IM, Winder DG, Moallem TM, Osman M, Mayford M, Hawkins RD, Kandel ER
Neuron. 1998 21 (2): 257-65

PMID: 9728905 · DOI:10.1016/s0896-6273(00)80533-4

To obtain rapidly inducible and reversible expression of transgenes in the forebrain of the mouse, we have combined the reverse tetracycline-controlled transactivator (rtTA) system with the CaMKIIalpha promoter. We show that doxycycline induces maximal gene expression in neurons of the forebrain within 6 days and that this expression can be reversed by removal of doxycycline. Using calcineurin as a test transgene, we show that doxycycline-induced expression impairs both an intermediate form of LTP (I-LTP) in the hippocampus and the storage of spatial memory. The reversibility of the rtTA system in turn allowed us to examine the effects of the transgene on memory retrieval after normal storage had occurred. This examination suggests that retrieval requires some of the same molecular components required for storage.

MeSH Terms (17)

Animals Anti-Bacterial Agents Calcineurin Calcium-Calmodulin-Dependent Protein Kinases Calcium-Calmodulin-Dependent Protein Kinase Type 2 Dose-Response Relationship, Drug Doxycycline Gene Expression Regulation Maze Learning Memory Mice Mice, Transgenic Neural Pathways Promoter Regions, Genetic Prosencephalon Tetracycline Trans-Activators

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