RT Journal Article SR Electronic T1 Serotonin-Mediated Synapsin Expression Is Necessary for Long-Term Facilitation of the Aplysia Sensorimotor Synapse JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 18401 OP 18411 DO 10.1523/JNEUROSCI.2816-11.2011 VO 31 IS 50 A1 Anne K. Hart A1 Diasinou Fioravante A1 Rong-Yu Liu A1 Gregg A. Phares A1 Leonard J. Cleary A1 John H. Byrne YR 2011 UL http://www.jneurosci.org/content/31/50/18401.abstract AB Serotonin (5-HT)-induced long-term facilitation (LTF) of the Aplysia sensorimotor synapse depends on enhanced gene expression and protein synthesis, but identification of the genes whose expression and regulation are necessary for LTF remains incomplete. In this study, we found that one such gene is synapsin, which encodes a synaptic vesicle-associated protein known to regulate short-term synaptic plasticity. Both synapsin mRNA and protein levels were increased by 5-HT. Upregulation of synapsin protein occurred in presynaptic sensory neurons at neurotransmitter release sites. To investigate the molecular mechanisms underlying synapsin regulation, we cloned the promoter region of Aplysia synapsin, and found that the synapsin promoter contained a cAMP response element (CRE), raising the possibility that the transcriptional activator CRE-binding protein 1 (CREB1) mediates 5-HT-induced regulation of synapsin. Indeed, binding of CREB1 to the synapsin promoter was increased following treatment with 5-HT. Furthermore, increased acetylation of histones H3 and H4 and decreased association of histone deacetylase 5 near the CRE site are consistent with transcriptional activation by CREB1. RNA interference (RNAi) targeting synapsin mRNA blocked the 5-HT-induced increase in synapsin protein levels and LTF; in the absence of 5-HT treatment, basal synapsin levels were unaffected. These results indicate that the 5-HT-induced regulation of synapsin levels is necessary for LTF and that this regulation is part of the cascade of synaptic events involved in the consolidation of memory.