QUANTAL MECHANISM OF LONG-TERM POTENTIATION IN HIPPOCAMPAL MESSY-FIBER SYNAPSES

1, The quantal mechanism underlying the expression of longterm potentiation (LTP) was studied in the mossy-fiber( mf) synapses of the rat hippocampus. Whole-cell recordings were used to measure the excitatory postsynaptic currents(EPSCs) before and after LTP induction in brain slices maintained at 31+/-1 degrees C. 2. Evoked EPSCs were recorded from 473 CA3 pyramidal neurons. The mf synapses were stimulated using paired pulses (40-ms interpulse interval) repeated every 2-10 s. At least 400 pairs of mf responses were obtained before and during the expression of LTP, which was produced by high-frequency (100 Hz) mf stimulation. Sufficiently stationary data were obtained from five neurons that exhibited LTP and that also satisfied strict criteria and procedures that are necessary for eliciting and identifying unitary mf responses. 3. Three independent lines of evidence implicated a presynaptic component to the mechanism underlying mf LTP. The first was based on a graphical version of the classical method of variance. The graphical variance (GV) method was evaluated by clamping the cell at two different holding potentials during paired-pulse facilitation (PPF). The results indicated that the GV method can distinguish changes in mean quantal content m and mean quantal size g in rat mf synapses. The same analysis, when applied to PPF before and after LTP induction, indicated that both result from an increase in In. 4. The second line of evidence was based on the classical method of failures. Consistent with the inference that mf LTP is due to an increase in m, there was a statistically significant reduction in the number of quantal release failures. A graphical version of the method of failures similarly indicated that both PPF and LTP reflect an increase in m. The amount of PPF after a quantal release failure was as large as that after a nonfailure, suggesting that these were quantal failures and not stimulation failures. 5. The third line of evidence was based on the relationship between LTP and PPF. In three of the five cells there was a statistically significant interaction between PPF and LTP, suggesting that the same quantal parameter was affected in both cases. Interestingly, the interaction was not significant in the two other cells, suggesting that the interaction test alone may not furnish a reliable guide to the locus of LTP expression in these synapses. For the three cells in which an interaction between PPF and LTP was observed, the GV results were consistent with the hypothesis that the probability of transmitter release was the shared quantal parameter.