deficits in ltp induction by 5-ht2a receptor antagonist in a mouse model for fragile x syndrome赤字ltp感应5-ht2a受体拮抗剂在脆性x综合征小鼠模型.pdfVIP

Deficits in LTP Induction by 5-HT2A Receptor Antagonist in a Mouse Model for Fragile X Syndrome 1. 1. 1. 1 2 1 1 Zhao-hui Xu , Qi Yang , Lan Ma , Shui-bing Liu , Guang-sheng Chen , Yu-mei Wu , Xiao-qiang Li , 3 1 Gang Liu *, Ming-gao Zhao * 1 Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi’an, China, 2 Department of Pathology, Xi’an Child’s Hospital, Xi’an, China, 3 Department of Orthopaedics and Traumatology, Nanjing General Hospital of Najing Military Commend, PLA, Najing, China Abstract Fragile X syndrome is a common inherited form of mental retardation caused by the lack of fragile X mental retardation protein (FMRP) because of Fmr1 gene silencing. Serotonin (5-HT) is significantly increased in the null mutants of Drosophila Fmr1, and elevated 5-HT brain levels result in cognitive and behavioral deficits in human patients. The serotonin type 2A receptor (5-HT2AR) is highly expressed in the cerebral cortex; it acts on pyramidal cells and GABAergic interneurons to modulate cortical functions. 5-HT2AR and FMRP both regulate synaptic plasticity. Therefore, the lack of FMRP may affect serotoninergic activity. In this study, we determined the involvement of FMRP in the 5-HT modulation of synaptic potentiation with the use of primary cortical neuron culture and brain slice recording. Pharmacological inhibition of 5- HT2AR by R-96544 or ketanserin facilitated long-term potentiation (LTP) in the anterior cingulate cortex (ACC) of WT mice. The prefrontal LTP induction was dependent on the activation of NMDARs and elevation of postsyna