Interactions among paired-pulse facilitation and post-tetanic and long-term potentiation in the mossy fiber-CA3 pathway in rat hippocampus.

Long-term potentiation (LTP) observed at the synapses of mossy fiber-CA3 (MF-CA3) pathway differs from that observed at the Schaffer collateral-CA1 pathway (SC-CA1), in being independent of N-methyl-D-aspartate (NMDA) receptors. The induction and expression mechanisms of MF-CA3 LTP remain to be determined. We have compared the occurrence and magnitude of LTP with that of two other indicators of presynaptic plasticity, post-tetanic potentiation (PTP) and paired-pulse facilitation in control brain slices from young rats and in slices treated with phorbol-12, 13-diacetate (PDAc), a protein kinase C activator. Paired-pulse facilitation is a potentiation of the second of two responses at intervals of tens of milliseconds and is due to a presynaptic calcium increase. Tetanic stimulation of mossy fibers induced LTP is area CA3 in only 64% of slices. In those slices that showed LTP, the size of the PTP was significantly greater than in those slices that did not, and the degree of correlation between LTP and PTP amplitude overall was r = 0.7. The degree of paired-pulse facilitation before tetanic stimulation was also positively correlated to the occurrence and magnitude of LTP and PTP after tetanic stimulation. The correlation coefficient between PTP and PPF was 0.749 for all slices studied, while that between LTP and PPF was 0.835 overall. Application of PDAc potentiated synaptic transmission and abolished paired-pulse facilitation (control ratio of second to first response, 2.1; after PDAc ratio 0.8) and LTP. PTP was absent at the control stimulus intensity in PDAc, but was apparent if the stimulus intensity was reduced to give a response of the same amplitude as before administration of PDAc. Stable LTP was also accompanied by a marked decrease in paired-pulse facilitation. These data suggest that MF-CA3 LTP, PTP and paired-pulse facilitation share common mechanisms and are all at least primarily of presynaptic origin. The occurrence of large paired-pulse facilitation or PTP is a predictor of a preparation which will show LTP. It is likely that presynaptic [Ca2+]i is an essential factor in LTP, PTP and paired-pulse facilitation, as well as the potentiation induced by application of PDAc, but the factors which determine whether or not [Ca2+]i rises following these various stimuli are not clear from the techniques used in these investigations.