Abstract

Long-term potentiation (LTP) is an experimental procedure that shares certain mechanisms with neuronal learning and memory processes and represents a well-known example of synaptic plasticity. LTP consists of an increase of the synaptic response to a control stimulus following the presentation of a high-frequency stimulation (HFS) train to an afferent pathway. This technique is studied mostly in the hippocampus due to the latter’s high susceptibility and its laminar nature which facilitates the location of defined synapses. Although most preceding studies have been performed in vitro, we have developed an experimental approach to carry out these experiments in alert behaving animals. The main goal of this study was to confirm the existence of synaptic changes in strength in synapses that are post-synaptic to the one presented with the HFS. We recorded field excitatory post-synaptic potentials (fEPSPs) evoked in five hippocampal synapses, from both hemispheres, of adult male mice. HFS was presented to the perforant pathway (PP). We characterized input/output curves, paired-pulse stimulation, and LTP of these synapses. We also performed depth-profile recordings to determine differences in fEPSP latencies. Collected data indicate that the five selected synapses have similar basic electrophysiological properties, a fact that enables an easier comparison of LTP characteristics. Importantly, we observed the presence of significant LTP in the contralateral CA1 (cCA1) area following the control stimulation of non-HFS-activated pathways. These results indicate that LTP appears as a physiological process present in synapses located far away from the HFS-stimulated afferent pathway.

Highlights

  • Long-term potentiation (LTP) of synaptic strength is an experimentally induced technique commonly used for studying the mechanisms involved in learning and memory processes, since changes in synaptic efficacy of both events share many properties with respect to the underlying physiological, cellular, and molecular phenomena (Bliss and Collingridge, 1993; Gruart et al, 2006)

  • The electrophysiological study presented here demonstrates that LTP experimentally induced by high-frequency stimulation (HFS) in the perforant pathway (PP) transsynaptically propagates to the contralateral hippocampal CA1 area across the CA3-contralateral CA1 (cCA1) projection

  • It is evidenced the longer latency of field excitatory post-synaptic potentials (fEPSPs) evoked in the cCA1 area by PP stimulation, suggestive of a disynaptic projection, and by the presence of LTP in the CA3-cCA1 synapse not evoked by previous direct HFS of the CA3 area

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Summary

Introduction

LTP of synaptic strength is an experimentally induced technique commonly used for studying the mechanisms involved in learning and memory processes, since changes in synaptic efficacy of both events share many properties with respect to the underlying physiological, cellular, and molecular phenomena (Bliss and Collingridge, 1993; Gruart et al, 2006). The well-defined intrinsic circuit of the hippocampus and its specific ultrastructural organization in layers (Witter et al, 2000; Shepherd, 2004) have allowed an extensive and detailed study of LTP properties and putative functions (Collingridge et al, 1992; Bortolotto and Collingridge, 1993; Matsuzaki et al, 2004; Gruart et al, 2015; Volianskis et al, 2015; Korte and Schmitz, 2016; Fassin et al, 2020) Most of these earlier studies describe only the effects of LTP in synaptic sites in direct contact (i.e., monosynaptic) with an activated afferent pathway, leaving further transsynaptic sites completely unexplored. There are already studies carried out in behaving rats suggesting the presence of experimentally evoked transsynaptic LTP in hippocampal-tocontralateral medial prefrontal cortex (Taylor et al, 2016) and entorhinal cortex-to-contralateral dentate nucleus (Krug et al, 2001) circuits

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