STUDIES ON THE ROLE OF METABOTROPIC GLUTAMATE RECEPTORS IN LONG-TERM POTENTIATION - SOME METHODOLOGICAL CONSIDERATIONS

There has been considerable interest recently in trying to elucidate the roles of metabotropic glutamate receptors (mGluRs) in the induction of long-term potentiation (LTP) in area CA1 of rat hippocampal slices. This has come about principally because of the development of specific mGluR agonists and antagonists. Recently we reported that the competitive mGluR antagonist (+)-alpha-methyl-4-carboxyphenylglycine (MCPG) blocks the induction of LTP but not short-term potentiation (STP). We describe here the dose-dependency of the MCPG block; there is no effect at 100 mu M while at 200 mu M the block of LTP is normally complete but STP is spared. A higher concentration of MCPG (500 mu M) has the same effect as 200 mu M. We have also reported recently that high-frequency (tetanic) stimulation conditions a pathway such that MCPG fails to block the induction of subsequent LTP. We illustrate here that the conditioning effect of a tetanus lasts at least 6 h. We show how the pathway can be conditioned, without any persistent change in the synaptic response, by delivering tetanic stimulation in the presence of the specific NMDA receptor antagonist D-2-amino-5-phosphonopentanoate (AP5). The pathway can subsequently be deconditioned by delivering low-frequency stimulation (900 shocks at 2 Hz) so that MCPG blocks the induction of subsequent LTP. We also have reported that the specific mGluR agonist 1-aminocyclopentane-(1S,3R)-dicarboxylate (ACPD) can induce LTP without the need for STP. We now report the surprising observation that ACPD-induced LTP is prevented reversibly under conditions in which the slice is submerged below the bathing medium. One consequence of submerging the slice, which might account for the difference, is acidification of the tissue.