CHANGES IN PAIRED-PULSE FACILITATION CORRELATE WITH INDUCTION OF LONG-TERM POTENTIATION IN AREA CA1 OF RAT HIPPOCAMPAL SLICES

The phenomenon of long-term potentiation is widely used as an experime ntal model of memory. An approach that has been used to study its unde rlying mechanisms is to analyse its interaction with presynaptic paire d-pulse Facilitation. Several studies found no evidence for an interac tion in the CAl hippocampal area, whereas other data, for example from quantal analysis, suggested that presynaptic mechanisms contribute to the maintenance of long-term potentiation. In the present study, init ial slopes of field potentials in area CAl were measured in rat hippoc ampal slices. ''Conventional'' long-term potentiation was induced by h igh-frequency (100 Hz) afferent tetanization of the testing input. ''A ssociative'' long-term potentiation was induced by combining lower fre quency (40 Hz) tetanization of a testing input with high-frequency tet anization of a second input. The paired-pulse facilitation ratio decre ased in the majority of experiments in which long-term potentiation wa s induced conventionally, but it decreased, increased or did not chang e after inducing associative potentiation. Decreases in the paired-pul se facilitation correlated inversely with the initial (pre-tetanic) fa cilitation ratio. A more detailed regression analysis suggests that th is correlation results from two other correlations: (i) that between c hanges in paired-pulse facilitation and the magnitude of long-term pot entiation, and (ii) that between initial paired-pulse facilitation and the magnitude of long-term potentiation. The first correlation prevai led during tile initial 10 min following tetanization, while the secon d prevailed 40-60 min later.A post-tetanic decrease in paired-pulse fa cilitation is evidence for an involvement of presynaptic mechanisms in the maintenance of long-term potentiation. The lack of significant ch anges in some studies could be due to the inclusion in the analyses of experiments with long-term potentiation of small magnitude, in which changes in paired-pulse facilitation ratios would have beer, inconsist ent. The present study suggests that the early (10-20 min) and late (4 0-50 min) phases of long-term potentiation were mediated by different mechanisms, with a mixture of these mechanisms during the intermediate period. On the basis of the present and previous studies, the followi ng scheme of involvement of several mechanisms in long-term potentiati on maintenance is proposed. The early phase includes two major mechani sms: an increase in the probability of transmitter release, leading to an apparent increase in the number of effective release sites, and an increase in efficacy of one transmitter quantum, probably due to an i ncreased number of postsynaptic receptors. The later phase of long-ter m potentiation is attributed to an increase in the number of transmitt er zones, presumably due to structural modifications. Copyright (C) 19 96 IBRO.