title: Activation of Metabotropic Glutamate Receptors in Conjunction with Postsynaptic Depolarization Triggers a Long-Term Depression of the N-Methyl-D-Aspartate Receptor-Mediated Synaptic Potential in the Rat Hippocampus.
abstract: The mechanism responsible for long-term depression (LTD) of pharmacologically isolated N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsynaptic potential (EPSP(NMDA)) was studied. Intracellular recordings were made from CA1 cells of rat hippocampal slices in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (10 &mgr;M) and picrotoxin (50 &mgr;M), which block non-NMDA and GABA(A) receptors, respectively. Intracellular injections of depolarizing pulses (500 ms, 0.3-0.7 nA) at 1 Hz for 5 min in the absence of synaptic stimulation caused a persistent increase in the amplitude of EPSP(NMDA). However, coupling postsynaptic depolarization with synaptic activity induced LTD. The EPSP(NMDA) LTD could be blocked by L-2-amino-3-phosphonopropionic acid (50 &mgr;M) or (RS)-alpha-methyl-4-carboxyphenylglycine (200 &mgr;M), specific antagonists for metabotropic glutamate receptors (mGluR). Furthermore, application of trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD, 50 &mgr;M), a specific mGluR agonist, in conjunction with postsynaptic depolarizing elicited LTD. In contrast, the mGluR agonists quisqualate or t-ACPD when given alone produced a sustained enhancement of EPSP(NMDA). Finally, coupled depolarization did not evoke LTD in slices pretreated with the protein kinase C (PKC) inhibitor calphostin c (60 nM). The present results demonstrate that activation of mGluR is necessary for the induction of LTD of EPSP(NMDA) and suggest that NMDA receptors are subject to bidirectional regulation by mGluR. Furthermore, the induction of LTD is likely to involve the stimulation of PKC. Copyright 1995 S. Karger AG, Basel
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan, Taiwan, Republic of China.
authors.forename: P.-W.
authors.initials: PW
authors.lastname: Gean
authors.forename: F.-C.
authors.initials: FC
authors.lastname: Chang
authors.forename: P.-L.
authors.initials: PL
authors.lastname: Yi
authors.forename: J.-H.
authors.initials: JH
authors.lastname: Lin
authors.forename: J.-J.
authors.initials: JJ
authors.lastname: Tsai