Altered synaptic plasticity in a mouse model of fragile X mental retardation.
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.
Huber
Kimberly M
KM
Department of Neuroscience, Howard Hughes Medical Institute, Brown University, Providence, RI 02912, USA.
Gallagher
Sean M
SM
Warren
Stephen T
ST
Bear
Mark F
MF
D000818:Animals; D004195:Disease Models, Animal; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009473:Neuronal Plasticity / Q000502:physiology*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins; D013569:Synapses / Q000502:physiology*; D014158:Transcription, Genetic
D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human; C497684:Fmr1 protein, mouse