Within the hippocampus, electrophysiological and immunohistochemical studies showed that metabotropic glutamate receptor subtype 5 (mGluR5) is the major postsynaptic mGluR expressed in CA1 pyramidal neurons. To better understand the role of mGluR5 in ischemia-induced neuronal death, whole-cell patch-clamp recordings using hippocampal slices were performed to investigate the functional change of mGluR5 in CA1 pyramidal neurons following transient global ischemia. Our results indicated that 6 to 24 h after global ischemia, mGluR5-induced cationic currents and mGluR5-mediated enhancement of NMDA-evoked currents in CA1 pyramidal neurons were significantly reduced. Further TaqMan real-time quantitative RT-PCR assay showed that mGluR5 mRNA expression in hippocampal CA1 region or single CA1 pyramidal neurons was significantly downregulated following ischemic insults. The present study suggests that transient global ischemia downregulates mGluR5 function of CA1 pyramidal neurons by decreasing mGluR5 mRNA and that the resulting reduced mGluR5-mediated excitotoxicity could contribute to the survival of CA1 pyramidal neurons after ischemic insult.