USING PAIRED-PULSE FACILITATION TO PROBE THE MECHANISMS FOR LONG-TERMPOTENTIATION (LTP)

Paired-pulse facilitation (PPF) of excitatory synaptic transmission at Schaffer collateral synapses in the hippocampus was examined in relat ionship to long-term potentiation (LTP). PPF is a relatively simple-to -measure presynaptic form of synaptic plasticity. It is hypothesized t hat if the expression of LTP includes a presynaptic component, then PP F and LTP may interfere with one another. When averaged over more than 100 experiments, we observed no change in average PPF with LTP, as re ported previously by a number of investigators. When individual experi ments were analyzed, however, PPF significantly increased or decreased with LTP in direct relation to the initial value of PPF. There was al so a linear relationship between the change in PPF and the magnitude o f LTP. The PPF changes were specific to LTP and presynaptic in origin as they were input-specific and persisted with low concentrations of C NQX, GABA(A) and GABA(B) antagonists, different interstimulus interval s, and different Ca2+ concentrations. To understand the interaction be tween LTP and PPF, we constructed a simple model of LTP in which poten tial contributions by increases in three synaptic parameters were exam ined: the number of neurotransmitter release sires (n), the probabilit y of release (p), and the postsynaptic unit potential (q) The data wer e fit by a model in which there were increases in n that changed the a verage p of the population, but not by a model that increased p or q a lone. This is the first experimental evidence for an increase in the n umber of release sites with LTP, which could be due to pre- or postsyn aptic mechanisms.