RT Journal Article
SR Electronic
T1 Cellular Plasticity for Group I mGluR-Mediated Epileptogenesis
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3497
OP 3507
DO 10.1523/JNEUROSCI.5447-08.2009
VO 29
IS 11
A1 Riccardo Bianchi
A1 Shih-Chieh Chuang
A1 Wangfa Zhao
A1 Steven R. Young
A1 Robert K. S. Wong
YR 2009
UL http://www.jneurosci.org/content/29/11/3497.abstract
AB Stimulation of group I metabotropic glutamate receptors (mGluRs) by the agonist (S)-dihydroxyphenylglycine in the hippocampus transforms normal neuronal activity into prolonged epileptiform discharges. The conversion is long lasting in that epileptiform discharges persist after washout of the inducing agonist and serves as a model of epileptogenesis. The group I mGluR model of epileptogenesis took on special significance because epilepsy associated with fragile X syndrome (FXS) may be caused by excessive group I mGluR signaling. At present, the plasticity mechanism underlying the group I mGluR-mediated epileptogenesis is unknown. ImGluR(V), a voltage-gated cationic current activated by group I mGluR agonists in CA3 pyramidal cells in the hippocampus, is a possible candidate. ImGluR(V) activation is associated with group I mGluR agonist-elicited epileptiform discharges. For ImGluR(V) to play a role in epileptogenesis, long-term activation of the current must occur after group I mGluR agonist exposure or synaptic stimulation. We observed that ImGluR(V), once induced by group I mGluR agonist stimulation in CA3 pyramidal cells, remained undiminished for hours after agonist washout. In slices prepared from FXS model mice, repeated stimulation of recurrent CA3 pyramidal cell synapses, effective in eliciting mGluR-mediated epileptiform discharges, also induced long-lasting ImGluR(V) in CA3 pyramidal cells. Similar to group I mGluR-mediated prolonged epileptiform discharges, persistent ImGluR(V) was no longer observed in preparations pretreated with inhibitors of tyrosine kinase, of extracellular signal-regulated kinase 1/2, or of mRNA protein synthesis. The results indicate that ImGluR(V) is an intrinsic plasticity mechanism associated with group I mGluR-mediated epileptogenesis.