Inducible and reversible gene expression with the rtTA system for the study of memory.
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.
Mansuy
I M
IM
Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, New York 10032, USA.
Winder
D G
DG
Moallem
T M
TM
Osman
M
M
Mayford
M
M
Hawkins
R D
RD
Kandel
E R
ER
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D019703:Calcineurin / Q000235:genetics; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology*; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000187:drug effects; D011401:Promoter Regions, Genetic; D016548:Prosencephalon / Q000187:drug effects* / Q000378:metabolism; D013752:Tetracycline / Q000494:pharmacology*; D015534:Trans-Activators / Q000096:biosynthesis / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D015534:Trans-Activators; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019703:Calcineurin; D013752:Tetracycline; D004318:Doxycycline