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

Kimberly M. Huber, Sean M. Gallagher, Stephen T. Warren, Mark F. Bear

Research output: Contribution to journalArticle

902 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7746-7750
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number11
DOIs
StatePublished - May 28 2002

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Fragile X Mental Retardation Protein
Neuronal Plasticity
Intellectual Disability
Fragile X Syndrome
Metabotropic Glutamate Receptors
Mammals
Hippocampus
Depression
Messenger RNA
Mutation
Brain
Genes
Proteins

ASJC Scopus subject areas

  • Genetics
  • General

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Altered synaptic plasticity in a mouse model of fragile X mental retardation. / Huber, Kimberly M.; Gallagher, Sean M.; Warren, Stephen T.; Bear, Mark F.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 11, 28.05.2002, p. 7746-7750.

Research output: Contribution to journalArticle

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