RT Journal Article
SR Electronic
T1 Prolonged Epileptiform Discharges Induced by Altered Group I Metabotropic Glutamate Receptor-Mediated Synaptic Responses in Hippocampal Slices of a Fragile X Mouse Model
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8048
OP 8055
DO 10.1523/JNEUROSCI.1777-05.2005
VO 25
IS 35
A1 Chuang, Shih-Chieh
A1 Zhao, Wangfa
A1 Bauchwitz, Robert
A1 Yan, Qijiang
A1 Bianchi, Riccardo
A1 Wong, Robert K. S.
YR 2005
UL http://www.jneurosci.org/content/25/35/8048.abstract
AB 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.