Elsevier

Neuroscience

Volume 76, Issue 3, 11 December 1996, Pages 829-843
Neuroscience

Changes in paired-pulse facilitation correlate with induction of long-term potentiation in area CA1 of rat hippocampal slices

https://doi.org/10.1016/S0306-4522(96)00342-9Get rights and content

Abstract

The phenomenon of long-term potentiation is widely used as an experimental model of memory. An approach that has been used to study its underlying mechanisms is to analyse its interaction with presynaptic paired-pulse facilitation. Several studies found no evidence for an interaction in the CA1 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, initial slopes of field potentials in area CA1 were measured in rat hippocampal slices. “Conventional” long-term potentiation was induced by high-frequency (100 Hz) afferent tetanization of the testing input. “Associative” long-term potentiation was induced by combining lower frequency (40 Hz) tetanization of a testing input with high-frequency tetanization of a second input. The paired-pulse facilitation ratio decreased in the majority of experiments in which long-term potentiation was induced conventionally, but it decreased, increased or did not change after inducing associative potentiation. Decreases in the paired-pulse facilitation correlated inversely with the initial (pre-tetanic) facilitation ratio. A more detailed regression analysis suggests that this correlation results from two other correlations: (i) that between changes in paired-pulse facilitation and the magnitude of long-term potentiation, and (ii) that between initial paired-pulse facilitation and the magnitude of long-term potentiation. The first correlation prevailed during the initial 10 min following tetanization, while the second prevailed 40–60 min later.

A post-tetanic decrease in paired-pulse facilitation is evidence for an involvement of presynaptic mechanisms in the maintenance of long-term potentiation. The lack of significant changes 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 been inconsistent. The present study suggests that the early (10–20 min) and late (>40–50 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 following scheme of involvement of several mechanisms in long-term potentiation maintenance is proposed. The early phase includes two major mechanisms: 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 increased number of postsynaptic receptors. The later phase of long-term potentiation is attributed to an increase in the number of transmitter zones, presumably due to structural modifications.

Section snippets

Preparation

Hippocampal slices (500 μm thick) were prepared from adult male Wistar rats (250–350 g) killed by a blow to the neck, according to standard methods.[30]Cuts between CA3 and CA1 regions were routinely made to reduce polysynaptic excitation. The recordings were made in a submerged chamber perfused with media containing (in mM): 124 NaCl, 3 KCl, 1.3 MgSO4, 2.4 CaCl2, 1.25 KH2PO4, 26 NaHCO3, 10 glucose, saturated with O2/CO2 (95%/5%) at 32°C at a rate of 2.7 ml/min.

Recording and stimulation

Field potentials were recorded from

Decrease of paired-pulse facilitation following induction of long-term potentiaition by a single tetanic train

A result from the first series of experiments in which a single conditioning tetanic train was used is illustrated in Fig. 1. The tetanus (Fig. 1A, arrow) significantly increased the slopes of both the first (Fig. 1A, open circles) and second (Fig. 1A, closed circles) responses. The increase in the field potential slope persisted throughout the post-tetanic recording period (at least 1 h). Note that the apparent peak amplitude of field potential could diminish following the tetanus (compare

Decrease of paired-pulse facilitation following long-term potentiation induction

The present data, together with previously published studies,34, 59, 71confirm that PPF did not always change following induction of LTP in CA1. It did not change when the initial PPF ratio and the magnitude of LTP were small. On the other hand, similar to previous studies,34, 59, 71the present data showed a strong reduction of PPF following induction of robust LTP, especially for the cases with high initial PPF. This finding is supported by correlation analyses described in this (Fig. 6) and

Conclusions

Recordings of field potentials from the CA1 region of hippocampal slices confirmed that PPF often decreased after LTP induction. Several reasons were put forward to explain why such decreases might be small and might have been missed in previous studies, particularly when the magnitude of LTP was small. The existence of an inverse correlation between initial PPF and changes in PPF which has been reported previously was also confirmed and shown to derive from two other correlations, between

Acknowledgements

We thank Dr M. Volgushev for helpful comments. This work was supported by grants from the International Science Foundation (ISF), the Russian Foundation of Basic Research (RFBR), the Deutsche Forschungsgemeinschaft (DFG) and the International Association for Promotion of Cooperation with New Independent States (INTAS).

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