Abstract

The hippocampus plays an important role in learning and memory. Synaptic plasticity in the hippocampus, short-term and long-term, is postulated to be a neural substrate of memory trace. Paired-pulse stimulation is a standard technique for evaluating a form of short-term synaptic plasticity in rodents. However, evidence is lacking for paired-pulse responses in the primate hippocampus. In the present study, we recorded paired-pulse responses in the dentate gyrus of monkeys while stimulating to the medial part of the perforant path at several inter-pulse intervals (IPIs) using low and high stimulus intensities. When the stimulus intensity was low, the first pulse produced early strong depression (at IPIs of 10–30 ms) and late slight depression (at IPIs of 100–1000 ms) of field excitatory postsynaptic potentials (fEPSPs) generated by the second pulse, interposing no depression IPIs (50–70 ms). When the stimulus intensity was high, fEPSPs generated by the second pulse were depressed by the first pulse at all IPIs except for the longest one (2000 ms). Population spikes (PSs) generated by the second pulse were completely blocked or strongly depressed at shorter IPIs (10–100 or 200 ms, respectively), while no depression or slight facilitation occurred at longer IPIs (500–2000 ms). Administration of diazepam slightly increased fEPSPs, while it decreased PSs produced by the first pulse. It also enhanced the facilitation of PSs produced by the second stimulation at longer IPIs. The present results, in comparison with previous studies using rodents, indicate that paired-pulse responses of fEPSPs in the monkey are basically similar to those of rodents, although paired-pulse responses of PSs in the monkey are more delayed than those in rodents and have a different sensitivity to diazepam.

Highlights

  • The hippocampus is important for certain classes of learning and memory [1,2,3]

  • local field potentials (LFPs) started to appear on the oscilloscope as a small positive deflection at a stimulus intensity between 50–100 mA (Fig. 1 Aa and B)

  • The evoked LFPs increased as the stimulus intensity increased: the slope of field excitatory postsynaptic potentials (fEPSPs) became steeper, and a negative notch (PS) started to appear (Fig. 1 Ab and B)

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Summary

Introduction

Synaptic plasticity in the hippocampus is hypothesized to be a neural substrate of the mnemonic process [4,5]. There are several forms of synaptic plasticity, including short-term and long-term types. Paired-pulse stimulation is a standard technique for the evaluation of short-term synaptic plasticity, and its effects in the hippocampus and their underlying mechanisms have been intensively investigated using rodents. It is known that paired-pulse facilitation (PPF) and paired-pulse depression (PPD) appear in the dentate gyrus of rats in a manner dependent on stimulation sites, stimulus intensities and inter-pulse intervals (IPIs) [6,7,8,9,10,11]. The paired-pulse test has often been used in the dentate gyrus of rats to characterize the effect of anesthetic or antianxiety drugs on GABAergic inhibition [e.g., 12,13,17]

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