POTENTIATION OF SYNAPTIC TRANSMISSION IN THE RAT HIPPOCAMPAL SLICE BYEXOGENOUS L-GLUTAMATE AND SELECTIVE L-GLUTAMATE RECEPTOR SUBTYPE AGONISTS

We have investigated the effects of administration of exogenous glutam ate receptor agonists on the amplitude of field excitatory post-synapt ic potentials (fEPSPs) evoked in the CA1 region of the rat hippocampal slice by stimulation of the Schaffer collateral-commissural fibres. L -Glutamate applied by iontophoresis or by bath perfusion (50 mu M for 5 min) evoked a slowly rising increase in the amplitude of the fESPS w hich persisted for over 90 min. L-Glutamate induced potentiation was b locked by either D(-)-2-amino-5-phosphonopentanoic acid (40 mu M) or b y (RS)-alpha-methyl-4-carboxyphenylglycine (500 mu M). In slices in wh ich synaptic long-term potentiation had been saturated, iontophoretica lly applied L-glutamate did not induce further potentiation, but reset the fEPSP amplitude back to control levels. Iontophoretic administrat ion of N-methyl-D-aspartate (NMDA) evoked a transient potentiation whi ch decayed back to control levels within 90 min whereas bath perfusion of NMDA (50 mu M) evoked a persistent depression. Bath perfusion of l pha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA, 50 mu M) evoked no persistent effects. Bath administration of (1S,3R)-1-aminoc yclopentane-1,3-dicarboxylic acid (ACPD, 50 or 100 mu M) caused a shor t term depression of the fEPSP and no significant persistent effects. Perfusion of 100 mu M ACPD in medium containing 1 mu M picrotoxin caus ed a much smaller short term depression of the fEPSP and this was foll owed by a gradually developing and persistent potentiation. Bath perfu sion of spermidine (250 mu M) and D-serine (200 mu M) merely prolonged the time course of the iontophoretic NMDA induced potentiation, where as administration of NMDA in the presence of 50 mu M ACPD evoked a rap idly initiated potentiation which remained stable throughout the recor ding period. The results may reflect a requirement for coactivation of metabotropic and NMDA receptors in the induction of LTP.