TY - JOUR
T1 - Whisker stimulation-dependent translation of FMRP in the barrel cortex requires activation of type I metabotropic glutamate receptors
AU - Todd, Peter K.
AU - Malter, James S.
AU - Mack, Kenneth J.
N1 - Funding Information:
This work was funded by NIH grants to JSM and KJM and a grant from FRAXA to KJM.
PY - 2003/2/20
Y1 - 2003/2/20
N2 - 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.
AB - 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.
KW - Barrel cortex
KW - Dendritic protein synthesis
KW - Experience dependent plasticity
KW - Fragile X syndrome
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U2 - 10.1016/S0169-328X(02)00657-5
DO - 10.1016/S0169-328X(02)00657-5
M3 - Article
C2 - 12591163
AN - SCOPUS:0037456073
SN - 0169-328X
VL - 110
SP - 267
EP - 278
JO - Molecular Brain Research
JF - Molecular Brain Research
IS - 2
ER -