A comparison of paired-pulse facilitation of AMPA and NMDA receptor-mediated excitatory postsynaptic currents in the hippocampus

Paired-pulse facilitation of excitatory synaptic transmission was investigated in the CA1 region of rat hippocampal slices using whole-cell patch-clamp recording. To optimise the measurement of excitatory synaptic transmission, γ-amino-butyric acid (GABA)-mediated synaptic inhibition was eliminated using both GABAA and GABAB antagonists. Pure α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or N-methyl-d-aspartate (NMDA) receptor-mediated excitatory postsynaptic currents (EPSCs) were then isolated pharmacologically. Paired-pulse facilitation of either AMPA or NMDA receptor-mediated EPSCs (EPSCA and EPSCN, respectively) was investigated using two stimuli of identical strength delivered at intervals of between 25 and 1000 ms. The paired-pulse facilitation profiles of both EPSCA and EPSCN were similar. Pairedpulse facilitation of EPSCA was independent of holding potential. In contrast paired-pulse facilitation of EPSCN was markedly voltage-dependent; maximum facilitation was recorded at hyperpolarised membrane potentials. At positive membrane potentials there was little or no paired-pulse facilitation and, in most neurones, pairedpulse depression was observed. Voltage-dependence of paired-pulse facilitation of EPSCN was similar in the presence or nominal absence of Mg2+ in the bathing medium, and was unaffected by extensive dialysis of neurones with 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA). These data are consistent with a presynaptic locus for paired-pulse facilitation of EPSCA. However, paired-pulse facilitation of EPSCN involves postsynaptic factors.