ROLE OF A TRANSCRIPTION FACTOR (CREB) IN MEMORY PROCESSES

Memory storage includes a short-term phase (STM) which requires the ph osphorylation of pre-existing proteins, and a long-term phase (LTM) wh ich needs the novel synthesis of RNA and proteins. Cyclic AMP and a sp ecific transcription factor (cAMP response element binding protein or CREB) play a central role in the formation oft TM in aplysia, drosophi la and mice. Following its phosphorylation by protein kinase A, CREB b inds to the enhancer element CRE which is located in the upstream regi on of cAMP-responsive genes, thus triggering transcription. Some of th e newly-synthesized proteins are additional transcription factors that ultimately give rise to the activation of late response genes, whose products are responsible for the modification of synaptic efficacy lea ding to LTM. In aplysia, CREB activation has been interfered with by m icroinjection of CRE containing oligonucleotides into cultured neurons . Under these conditions LTM is blocked while STM remains unchanged In drosophila, CREB function has been disrupted using a reverse genetic approach. Thus, LTM has been specifically blocked by the induced expre ssion of a CREB repressor isoform, and enhanced by the induced express ion of an activator isoform. In mouse, the role of CREB has been confi rmed by behavioural analyses of a knock-out line with a targeted mutat ion in the CREB gene. In these mutants, learning and STM are normal, w hereas LTM is disrupted. On the whole, the data suggest that encoding of long arm memories involve highly conserved molecular mechanisms.