INDUCIBLE AND REVERSIBLE GENE-EXPRESSION WITH THE RTTA SYSTEM FOR THESTUDY OF MEMORY

To obtain rapidly inducible and reversible expression of transgenes in the forebrain of the mouse, we have combined the reverse tetracycline -controlled trans-activator (rtTA) system with the CaMKll alpha promot er. We show that doxycycline induces maximal gene expression in neuron s of the forebrain within 6 days and that this expression can be rever sed by removal of doxycycline. Using calcineurin as a test transgene, we show that doxycycline-induced expression impairs both an intermedia te form of LTP (l-LTP) in the hippocampus and the storage of spatial m emory. The reversibility of the rtTA system in turn allowed us to exam ine the effects of the transgene on memory retrieval after normal stor age had occurred. This examination suggests that retrieval requires so me of the same molecular components required for storage.