Abstract
New gene expressions play an essential role in consolidation of conditioned fear memory; a form of Pavlovian conditioning between a training context (CS) and an aversive stimulus such as footshock (US). To understand the molecular mechanisms of gene expression regulation during memory consolidation, we have investigated roles of transcription factor CREB using conditional mutation. We examined the both effects of lost and gain of CREB function. Indeed, we derived transgenic mice expressing inducible CREB repressor in forebrain. Dominant negative CREB (CREBS133A) fused with tamoxifen-dependent mutant of ER ligand binding domain is expressed under the control of alpha CaMKII promoter. These transgenic mice show that activation of CREB repressor by tamoxifen leads to severe impairment of memory consolidation. In contrast, forebrain specific expression of active CREB mutant having high affinity with CBP leads to the enhancement of memory consolidation. Together, these data indicates that CREB plays essential roles in memory consolidation, and suggests that CREB functions as molecular switch to determine the strength of memory consolidation. To further understand the regulation of CREB activity during memory consolidation in vivo, we have developed the method for monitor and visualization of CREB activity using fluorescence resonance energy transfer (FRET) from CFP to YFP. Indeed, we are trying to monitor the interaction of CREB with CBP, that is essential for activation of CREB mediated transcription, and investigating the mechanism of CREB activation by various signal transduction pathways in vivo. [Jpn J Physiol 54 Suppl:S39 (2004)]
