Control of Memory Formation Through Regulated Expression of a CaMKII Transgene

TLDR

One of the major limitations in using genetically modified mice for cognitive studies is the lack of regional and temporal control of gene function. To overcome this, a forebrain‑specific promoter was combined with a tetracycline transactivator system to achieve both regional and temporal control of transgene expression. Activated CaMKII expression abolished hippocampal LTP and spatial memory, while suppression restored these functions; high expression in the lateral amygdala and striatum similarly impaired fear conditioning, demonstrating that CaMKII signaling is essential for both explicit and implicit memory storage independent of developmental effects.

Abstract

One of the major limitations in the use of genetically modified mice for 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 system to achieve both regional and temporal control of transgene expression. Expression of an activated calcium-independent form of calcium-calmodulin-dependent kinase II (CaMKII) resulted in a loss of hippocampal long-term potentiation in response to 10-hertz stimulation and a deficit in spatial memory, a form of explicit memory. Suppression of transgene expression reversed both the physiological and the memory deficit. When the transgene was expressed at high levels in the lateral 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 both explicit and implicit memory storage, in a manner that is independent of its potential role in development.