Modulation of Long-Term Potentiation in the CA1 Area of Rat Hippocampus by Platelet-Activating Factor

Abstract

We have previously shown that platelet-activating factor (PAF: l-O-alkyl-2-sn-3-glycerophosphocholine) selectively augments EPSCs in cultured hippocampal neurons by a presynaptic mechanism, suggesting that this agent could be involved in hippocampal long-term potentiation (LTP). We have also examined the possible involvement of PAF in LTP in the CA1 region of rat hippocampal slices using the hydrolysis resistant analog, methyl-carbamyl-PAF (C-PAF), and PAF receptor antagonists. When 2 μM BN--52021, a synaptosomal PAF receptor antagonist, was applied, LTP was inhibited and 20 min application of 1 μM MC-PAF in the absence of tetanic stimulation produced a slowly developing potentiation of extracellular recorded EPSP’s which persisted for more than 2h. Extra- or intracellular administration of C-PAF also appears to slow the washout of LTP-generating ability which occurs during whole-cell recording, making it possible to induce LTP for as long as 60 min after cell penetration. A decrease in extracellular magnesium (0.1 mM) for 15 min induced LTP which was not inhibited by a PAF antagonist, indicating the existence of PAF dependent and independent LTP. These data suggest that PAF and PAF activated process are important in LTP and modulate the threshold for LTP induction.