Deficits in LTP facilitation by 5-HT2A receptor antagonist in a mouse model for fragile X syndrome

• 作 者: XUZhao-hui;MALan;ZHAOMing-gao;
• 机 构: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, C
• 出 处: 中国药理学会第十一次全国学术会议
• 发表日期: 2011年期

　　Fragile X syndrome (FXS) is a common inherited mental retardation caused by the lack of fragile X mental retardation protein (FMRP) due to silencing of the Fmr1 gene.Here, we report that FMRP is involved in serotonin (5-HT) modulation of synaptic potentiation.Pharmacological inhibition of 5-HT2A receptor (5-HT2AR) by R-96544 facilitated the induction of long-term potentiation (LTP) in the anterior cingulate cortex (ACC) of the wild-type (WT) mice.The facilitation of LTP by R-96544 depended on the activation of NMDARs and elevated postsynaptic Ca2 + concentrations, indicating the postsynaptic mechanism underlying the LTP induction.However, the LTP facilitation by R-96544 was reduced in the ACC of the Fmr1 knock-out (KO) mice.Furthermore, AMPA receptor subtype 1 (GluR1) surface expression in response to 5-HT2AR inhibition was impaired in the cultured ACC neurons from Fmr1 KO mice.Together, these findings suggest that FMRP is involved in serotonin receptor signaling and contributes to GluR1 sutface expression induced by 5-HT2AR inactivation.