CONTROL OF MEMORY FORMATION THROUGH REGULATED EXPRESSION OF A CAMKII TRANSGENE

One of the major limitations in the use of genetically modified mice f or 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 sy stem to achieve both regional and temporal control of transgene expres sion, Expression of an activated calcium-independent form of calcium-c almodulin-dependent dent kinase II (CaMKII) resulted in a loss of hipp ocampal long-term potentiation in response to 10-hertz stimulation and a deficit in spatial memory, a form of explicit memory, Suppression o f transgene expression reversed both the physiological and the memory deficit, When the transgene was expressed at high levels in the latera l 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 bot h explicit and implicit memory storage,in a manner that is independent of its potential role in development.