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

1, The quantal mechanism underlying the expression of longterm potenti ation (LTP) was studied in the mossy-fiber( mf) synapses of the rat hi ppocampus. Whole-cell recordings were used to measure the excitatory p ostsynaptic currents(EPSCs) before and after LTP induction in brain sl ices maintained at 31+/-1 degrees C. 2. Evoked EPSCs were recorded fro m 473 CA3 pyramidal neurons. The mf synapses were stimulated using pai red pulses (40-ms interpulse interval) repeated every 2-10 s. At least 400 pairs of mf responses were obtained before and during the express ion of LTP, which was produced by high-frequency (100 Hz) mf stimulati on. Sufficiently stationary data were obtained from five neurons that exhibited LTP and that also satisfied strict criteria and procedures t hat are necessary for eliciting and identifying unitary mf responses. 3. Three independent lines of evidence implicated a presynaptic compon ent to the mechanism underlying mf LTP. The first was based on a graph ical version of the classical method of variance. The graphical varian ce (GV) method was evaluated by clamping the cell at two different hol ding potentials during paired-pulse facilitation (PPF). The results in dicated that the GV method can distinguish changes in mean quantal con tent m and mean quantal size g in rat mf synapses. The same analysis, when applied to PPF before and after LTP induction, indicated that bot h result from an increase in In. 4. The second line of evidence was ba sed on the classical method of failures. Consistent with the inference that mf LTP is due to an increase in m, there was a statistically sig nificant reduction in the number of quantal release failures. A graphi cal version of the method of failures similarly indicated that both PP F 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 th at these were quantal failures and not stimulation failures. 5. The th ird line of evidence was based on the relationship between LTP and PPF . In three of the five cells there was a statistically significant int eraction between PPF and LTP, suggesting that the same quantal paramet er was affected in both cases. Interestingly, the interaction was not significant in the two other cells, suggesting that the interaction te st alone may not furnish a reliable guide to the locus of LTP expressi on in these synapses. For the three cells in which an interaction betw een PPF and LTP was observed, the GV results were consistent with the hypothesis that the probability of transmitter release was the shared quantal parameter.