THE ROLE OF ICER, INDUCIBLE ISOFORM OF CRE TRANSCRIPTION FACTOR ON NEURONAL SYNAPTICITY, LEARNING AND MEMORY

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Long-term neuronal plastic changes that are thought to be a cellular basis for long-term memory are newly protein-synthesis-dependent events. During a course of the study for identification of the molecules involved in the establishment of kindling, I found that ICER (inducible cyclic AMP early repressor) mRNA was transiently up-regulated in the kindled brain after the stimulation. Furthermore, increase in ICER mRNA was also observed in the amygdala after the fear conditioning and after the conditioned fear responses. Since ICER is thought to be a repressor of CRE-mediated gene transcription, this transcription factor might be involved in the down-regulation of gene expression during neuronal plastic changes and fear learning. In the PC12 cells, ICER mRNA is induced by growth factor and dBcAMP.Overexpression of ICER attenuated neurite growth of cells after such treatments, suggesting that ICER is an important regulator for cell differentiation. Dynamic gene regulation should occur during memory consolidation, as well as during cell differentiation. DNA chip technology allows us to screen systematically the mRNAs whose levels of expression are changed during memory consolidation. I found 15 genes that are up-regulated in the amygdala after fear conditioning. Thus, changes in the expression of genes dynamically occur in the amygdala during fear conditioning. These genes might be critical for molecular mechanism of long-term memory.