Journal
JOURNAL OF NEUROSCIENCE
Volume 25, Issue 35, Pages 8048-8055Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1777-05.2005
Keywords
mGluR; epilepsy; FMRP; fragile X; synaptic plasticity; synchronization
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Funding
- NINDS NIH HHS [R56 NS035481, R01 NS035481, NS35481] Funding Source: Medline
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Mutations in FMR1, which encodes the fragile X mental retardation protein ( FMRP), are the cause of fragile X syndrome (FXS), an X-linked mental retardation disorder. Inactivation of the mouse gene Fmr1 confers a number of FXS-like phenotypes including an enhanced susceptibility to epileptogenesis during development. We find that in a FXS mouse model, in which the function of FMRP is suppressed, synaptically released glutamate induced prolonged epileptiform discharges resulting from enhanced group I metabotropic glutamate receptor (mGluR)-mediated responses in hippocampal slices. The induction of the group I mGluR-mediated, prolonged epileptiform discharges was inhibited in preparations that were pretreated with inhibitors of ERK1/2 ( extracellular signal-regulated kinase 1/2) phosphorylation or of mRNA translation, and their maintenance was suppressed by group I mGluR antagonists. The results suggest that FMRP plays a key role in the control of signaling at the recurrent glutamatergic synapses in the hippocampus. The absence of this control causes the synaptically activated group I mGluRs to elicit translation-dependent epileptogenic activities.
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