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

被认为是长期记忆的细胞基础的长期神经元可塑性变化是新的蛋白质合成依赖事件。在研究与点燃建立相关的分子的过程中，我发现在刺激后点燃的大脑中，ICER(可诱导的环磷酸腺苷早期抑制物)基因的表达一过性上调。此外，在恐惧条件反射和条件性恐惧反应后，杏仁核中ICER mRNA的表达也有所增加。由于ICER被认为是Cre介导的基因转录的抑制因子，该转录因子可能参与了神经元可塑性变化和恐惧学习过程中基因表达的下调。在PC12细胞中，ICER mRNA被生长因子和dBcAMP诱导，ICER的过表达抑制了细胞突起的生长，提示ICER是细胞分化的重要调节因子。动态的基因调控应该发生在记忆巩固和细胞分化过程中。DNA芯片技术使我们能够系统地筛选在记忆巩固过程中表达水平发生变化的mRNAs。我发现在恐惧条件作用后，杏仁核中有15个基因上调。因此，在恐惧条件作用期间，杏仁核中基因表达的变化是动态发生的。这些基因可能对长时记忆的分子机制至关重要。

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.