Whisker stimulation-dependent translation of FMRP in the barrel cortex requires activation of type I metabotropic glutamate receptors

Peter K. Todd, James S. Malter, Kenneth J. Mack

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Fragile X syndrome is a common inherited cause of mental retardation that results from the absence of the Fragile X Mental Retardation Protein (FMRP), an RNA binding protein thought to regulate translation of bound mRNAs, including its own. Previous studies in our laboratory have shown that FMRP expression increases in the barrel cortex of the rat after unilateral whisker stimulation, a model of experience dependent plasticity. This increase in protein is restricted to sub-cellular fractions enriched for synaptic or poly-ribosomal complexes. Here, we demonstrate that these increases are not accompanied by a change in FMR-1 mRNA levels and that they are blocked by the protein synthesis inhibitor cycloheximide in a dose dependent manner. Whisker stimulation dependent expression of FMRP is also abolished by pharmacological blockade of either NMDA receptors (MK-801, 0.25 mg/kg) or type I metabotropic glutamate receptors (AIDA, 5 mg/kg). In primary cortical neurons, activation of type I mGluRs leads to an increase in FMRP expression that is not effected by blockade of NMDA receptors. Taken together, these studies show that experience regulates FMRP production in vivo at the level of translation and supports a role for FMRP in metabotropic glutamate receptor mediated synaptic plasticity.

Original languageEnglish (US)
Pages (from-to)267-278
Number of pages12
JournalMolecular Brain Research
Volume110
Issue number2
DOIs
StatePublished - Feb 20 2003

Fingerprint

Fragile X Mental Retardation Protein
Vibrissae
Metabotropic Glutamate Receptors
N-Methyl-D-Aspartate Receptors
Metabotropic Glutamate 5 Receptor
Fragile X Syndrome
Neuronal Plasticity
Protein Synthesis Inhibitors
RNA-Binding Proteins
Dizocilpine Maleate
Protein Biosynthesis
Cycloheximide
Protein Binding
Intellectual Disability
Pharmacology
Neurons
Messenger RNA

Keywords

  • Barrel cortex
  • Dendritic protein synthesis
  • Experience dependent plasticity
  • Fragile X syndrome

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Whisker stimulation-dependent translation of FMRP in the barrel cortex requires activation of type I metabotropic glutamate receptors. / Todd, Peter K.; Malter, James S.; Mack, Kenneth J.

In: Molecular Brain Research, Vol. 110, No. 2, 20.02.2003, p. 267-278.

Research output: Contribution to journalArticle

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