Intracellular studies of the interaction between paired-pulse facilitation and the delayed phase of long-term potentiation in the hippocampus.

The mechanisms of the early (up to 1 h) and late (up to 3 h) phases of long-term potentiation were studied by analyzing the interaction between long-term potentiation and presynaptic paired-pulse facilitation. "Minimal" excitatory postsynaptic potentials were measured in pyramidal neurons in field CA1 of rat hippocampal slices in conditions of paired-pulse stimulation of the radial layer. In most neurons, paired-pulse facilitation decreased after induction of long-term potentiation, and this reduction lasted throughout the recording period (up to 3.5 h). Changes in paired-pulse facilitation correlated with the extent of long-term facilitation and with the initial level of paired-pulse facilitation, and the extent of facilitation depended on the initial level of paired-pulse facilitation. This latter relationship was different for the early and late phases of long-term potentiation and increased with time. Overall, the data obtained here demonstrate a significant role for presynaptic mechanisms in maintaining both the early and late phases of long-term potentiation. It is suggested that the basic mechanism of the early phase of potentiation is an increase in the probability that transmitter will be released, which also leads to an increase in the number of effective release sites, due to transformation of "presynaptically quiet" synapses into effective synapses. It is proposed that the development of the late phase is based on simultaneous pre- and postsynaptic structural transformations which increase the number of synaptically active zones.