Introduction: MicroRNAs (miRNAs) are a class of small non-coding RNA molecules negatively regulating gene expression at post-transcriptional level, and playing an important role in the regulation of development and aging of many tissues and organs including the central nervous system (CNS).CREB, a key nuclear factor in hippocampal neurons on which many signal pathways converged, plays a crucial role in learning and memory.Recent studies found that miR-181a is rich in mature nerve cells, and bioinformatic analysis showed that CREB1 mRNA 3UTR contains complementary sequence to the miR-181a seed region.Thus, it is possible that microRNA-181a is a negative regulator fur CREB 1 expression in neurons.The aim of the present was to test this hypothesis and observe the function of the microRNA in IGF-l-induced activation of CREB1 expression.Methods: (1) A dual luciferase detection system vas used to check the direct binding of miR-181a to CREB1 mRNA 3-UTR sequence in rat PC12 cell line.(2) The function of microRNA-181a was assessed by RT-PCR and Western analyses for expression of CREB1 in PC12 cell transfccted with miR-181a mimics (50nM, 100nM)or miR-181a inhibitor (100 nM, 200 nM).(3) MicroRNA-181a and CREB1 was detected with quantitative RTPCR and Western blot in PC12 cells stimulated by IGF-1 (50 ng/mL).(4) The relationship of miRNA-181a and CREB1 expression to IGF-1 was confirmed in hippocampi of newborn and adult Lewis rats with miRNA microarray, quantitative RT-PCR and Western blot.Result: (1) Co-transfection of miR-181a mimic and pGL3CCREB1/3UTR (luciferase vectors containing the CREB1-mRNA 3UTR of rat) repressed the luciferaseactivity,but this coud not be observed when miR-181 a mimic was replaced by scramble miRNA or pGL3C-CREB 1/3UTR by its mutant, indica ting a specific binding of miR-181 a to the CREB 1-mRNA.(2) Transfection with miR-181 a mimics downregulated, but that with miR-181a inhibitor upregulated the expression of CREB1 in PC12 cells.(3)A decreased miR-181 a expression with upregulated CREB 1 was observed in IGF-1 stimulated proliferating PC 12cells.(4) The hippocampal levels of IGF-Ⅰ and CREB1 were significantly higher in adult Lewis rats comparing to the newborns, while miR-181a expression was lower.Conclusion: This study demonstrated that miR-181a can inhibit expression of CREB 1 by specifically targeting its mRNA;and the IGF-1-induced activation of CREB 1 may be involved in a repressed expression the micro-RNA.