The interplay of small noncoding RNAs,mRNAs,and proteins has been shown to play crucial roles in almost all cellular processes.miRNAs are small noncoding RNAs capable of regulating gene expression at the post-transcriptional level.A growing body of evidence demonstrated that miR-124 can regulate the levels of CREB,the transcriptional switch critical for converting short-to long term facilitation.miR-124 was exclusively present presynaptically in a sensory-motor synapse where it constrains serotonin-induced synaptic facilitation through regulation of the transcriptional factor CREB.However,the basic mechanism by how miR-124 affects the LTM is still not understood.To explore the physiological significance of miR-124 in regulating formation of long-term memory,we present a reduced model of miR-124 biogenesis network,in which miR-124 inhibits its regulator CREB and CREB enhances miR-124.We also explore its dynamics by using bifurcation analysis.The dynamics of this simple network architecture indicates that,as the concentration of 5HT increases,the system undergoes a transition from monostability to bistability.In particular,we show that CREB can reach high level for only once 5HT pulse with the lower levels of miR-124.Moreover,the ratio of degradation rates of miR-124 and CREB is critical for the switching sensitivity and resistance to stimulus fluctuations.These findings may highlight why miR-124 provides an inhibitory constraint on synaptic plasticity and long-term facilitation through the regulation of CREB.We hope this research can facilitate the development of approaches to exploit this regulatory pathway by manipulating miR-124 for novel treatments of human diseases.