METABOTROPIC GLUTAMATE-RECEPTOR MEDIATED LONG-TERM DEPRESSION IN DEVELOPING HIPPOCAMPUS

The effects of bath application of the metabotropic glutamate receptor (mGluR) agonist 1S,3R-1-aminocyclopentane-1 ,3-dicarboxylic acid (ACP D, 10 mu M) were studied at the Schaffer collateral-CA1 synapse in hip pocampal slices from rats of 8-33 days postnatal age. In immature anim als (8-12 days) ACPD induced a biphasic response characterized by an a cute decrease in field EPSP slope (similar to 50-60% of baseline) in t he presence of the agonist, followed by long-term depression (LTD, sim ilar to 75-80% of baseline) after washout. In animals older than 20 da ys, ACPD induced a slow onset potentiation or minimal change. Both the acute depression and LTD were blocked by the mGluR antagonist alpha-m ethyl-4-carboxyphenyl glycine (MCPG). ACPD-induced LTD was blocked by the N-methyl-D-aspartate receptor (NMDAR) antagonists D(-)-2-amino-5 p hosphopentanoic acid (APS) and dizocilpine maleate (MK-801), and by et hanol. Glutamic pyruvic transaminase, an enzyme that selectively metab olizes endogenous extracellular glutamate, also blocked LTD suggesting that the requisite NMDA currents were tonically activated by extracel lular rather than synaptically released glutamate. ACPD-induced LTD wa s blocked by staurosporine, indicating a requirement for serine-threon ine kinase activation, and was unaffected by the L-type voltage sensit ive calcium channel blocker nitrendipine and the A1 adenosine receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT). Because mGluR-me diated LTD was observed only in immature CA1, mGluRs may play a role i n hippocampal development, perhaps by contributing to synapse pruning in a temporally restricted fashion. (C) 1997 Elsevier Science Ltd.