Premium
Fragile X mental retardation protein is required for chemically‐induced long‐term potentiation of the hippocampus in adult mice
Author(s) -
Shang Yuze,
Wang Hansen,
Mercaldo Valentina,
Li Xiangyao,
Chen Tao,
Zhuo Min
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06314.x
Subject(s) - long term potentiation , fmr1 , fragile x syndrome , hippocampus , neuroscience , knockout mouse , nmda receptor , morris water navigation task , synaptic plasticity , metabotropic glutamate receptor , psychology , biology , receptor , medicine , psychiatry , biochemistry , fragile x , gene
Fragile X syndrome (FXS), a common form of inherited mental retardation, is caused by the lack of fragile X mental retardation protein (FMRP). The animal model of FXS, Fmr1 knockout mice, have deficits in the Morris water maze and trace fear memory tests, showing impairment in hippocampus‐dependent learning and memory. However, results for synaptic long‐term potentiation (LTP), a key cellular model for learning and memory, remain inconclusive in the hippocampus of Fmr1 knockout mice. Here, we demonstrate that FMRP is required for glycine induced LTP (Gly‐LTP) in the CA1 of hippocampus. This form of LTP requires activation of post‐synaptic NMDA receptors and metabotropic glutamateric receptors, as well as the subsequent activation of extracellular signal‐regulated kinase (ERK) 1/2. However, paired‐pulse facilitation was not affected by glycine treatment. Genetic deletion of FMRP interrupted the phosphorylation of ERK1/2, suggesting the possible role of FMRP in the regulation of the activity of ERK1/2. Our study provide strong evidences that FMRP participates in Gly‐LTP in the hippocampus by regulating the phosphorylation of ERK1/2, and that improper regulation of these signaling pathways may contribute to the learning and memory deficits observed in FXS.