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

We have investigated the effects of administration of exogenous glutamate receptor agonists on the amplitude of field excitatory post-synaptic 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 which persisted for over 90 min. L-Glutamate induced potentiation was blocked by either D(-)-2-amino-5-phosphonopentanoic acid (40 mu M) or by (RS)-alpha-methyl-4-carboxyphenylglycine (500 mu M). In slices in which synaptic long-term potentiation had been saturated, iontophoretically applied L-glutamate did not induce further potentiation, but reset the fEPSP amplitude back to control levels. Iontophoretic administration of N-methyl-D-aspartate (NMDA) evoked a transient potentiation which decayed back to control levels within 90 min whereas bath perfusion of NMDA (50 mu M) evoked a persistent depression. Bath perfusion of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA, 50 mu M) evoked no persistent effects. Bath administration of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD, 50 or 100 mu M) caused a short term depression of the fEPSP and no significant persistent effects. Perfusion of 100 mu M ACPD in medium containing 1 mu M picrotoxin caused a much smaller short term depression of the fEPSP and this was followed by a gradually developing and persistent potentiation. Bath perfusion of spermidine (250 mu M) and D-serine (200 mu M) merely prolonged the time course of the iontophoretic NMDA induced potentiation, whereas administration of NMDA in the presence of 50 mu M ACPD evoked a rapidly initiated potentiation which remained stable throughout the recording period. The results may reflect a requirement for coactivation of metabotropic and NMDA receptors in the induction of LTP.