Metabotropic glutamate receptor activation causes a rapid redistribution of AMPA receptors

Electrophysiology, immunostaining and time lapse imaging techniques were em ployed to study the mechanism of long-term depression (LTD) induced by DHPG , a specific group I metabotropic glutamate receptor (mGluR) agonist. Exper iments were performed in primary hippocampal culture or in the CAI area of acute rat hippocampal slices. In agreement with previous results by others, we show that DHPG (200 muM, 10 min) can induce LTD (DHPG-LTD) in acute sli ces, in the presence or absence of synaptic inhibition. In addition, in vol tage clamp whole cell experiments we find that accompanying the reduction i n the evoked excitatory postsynaptic current (EPSC), miniature EPSC amplitu de and frequency are reduced. Similar results were obtained in cultured neu rons. Immunostaining and time lapse imaging showed a long-lasting loss of A MPA receptors from the membrane surface of cultured neurons after DHPG trea tment. which appears to occur in only a subset of the puncta. Further elect rophysiological recordings on slices showed that blocking postsynaptic endo cytosis by introducing a blocking peptide named D15 in recording pipettes a bolished the DHPG-LTD. In conclusion, these data suggest that LTD induced b y mGluR activation is due to a rapid removal of AMPA receptors from the pos tsynaptic membrane. (C) 2001 Elsevier Science Ltd. All rights reserved.