%0 Journal Article
%T Extracellular Glutamate Exposure Facilitates Group I mGluR-Mediated Epileptogenesis in the Hippocampus
%A Riccardo Bianchi
%A Robert K.S. Wong
%A Shih-Chieh Chuang
%A Steven R. Young
%A Wangfa Zhao
%J The Journal of Neurosience
%D 2015
%R 10.1523/JNEUROSCI.1944-14.2015
%X Stimulation of group I mGluRs elicits several forms of translation-dependent neuronal plasticity including epileptogenesis. The translation process underlying plasticity induction is controlled by repressors including the fragile X mental retardation protein (FMRP). In the absence of FMRP-mediated repression, a condition that occurs in a mouse model ( Fmr1 £¿/£¿) of fragile X syndrome, group I mGluR-activated translation is exaggerated causing enhanced seizure propensity. We now show that glutamate exposure (10 ¦Ìm for 30 min) reduced FMRP levels in wild-type mouse hippocampal slices. Downregulation of FMRP was dependent on group I mGluR activation and was blocked by a proteasome inhibitor (MG-132). Following glutamate exposure, synaptic stimulation induced prolonged epileptiform discharges with properties similar to those observed in Fmr1 £¿/£¿ preparations. In both cases, prolonged epileptiform discharges were blocked by group I mGluR antagonists (LY367385 + MPEP) and their induction was prevented by protein synthesis inhibitor (anisomycin). The results suggest that stimulation of group I mGluRs during glutamate exposure caused proteolysis of FMRP. Reduction of FMRP led to enhanced synaptic group I mGluR-mediated translation. Elevated translation facilitated the recruitment of group I mGluR-mediated prolonged epileptiform discharges
%U http://www.jneurosci.org/content/35/1/308