Altered synaptic plasticity in a mouse model of fragile X mental retardation

被引:1026
作者
Huber, KM
Gallagher, SM
Warren, ST
Bear, MF [1 ]
机构
[1] Brown Univ, Howard Hughes Med Inst, Dept Neurosci, Providence, RI 02912 USA
[2] Emory Univ, Howard Hughes Med Inst, Dept Human Genet, Atlanta, GA 30322 USA
[3] Emory Univ, Howard Hughes Med Inst, Dept Biochem, Atlanta, GA 30322 USA
[4] Emory Univ, Howard Hughes Med Inst, Dept Pediat, Atlanta, GA 30322 USA
关键词
D O I
10.1073/pnas.122205699
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Fragile X syndrome, the most common inherited form of human mental retardation, is caused by mutations of the Fmr1 gene that encodes the fragile X mental retardation protein (FMRP). Biochemical evidence indicates that FMRP binds a subset of mRNAs and acts as a regulator of translation. However, the consequences of FMRP loss on neuronal function in mammals remain unknown. Here we show that a form of protein synthesis-dependent synaptic plasticity, long-term depression triggered by activation of metabotropic glutamate receptors, is selectively enhanced in the hippocampus of mutant mice lacking FMRP. This finding indicates that FMRP plays an important functional role in regulating activity-dependent synaptic plasticity in the brain and suggests new therapeutic approaches for fragile X syndrome.
引用
收藏
页码:7746 / 7750
页数:5
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