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Review
. 2019 May 21;3:2398212819848213.
doi: 10.1177/2398212819848213. eCollection Jan-Dec 2019.

Persistent Memories of Long-Term Potentiation and the N-methyl-d-aspartate Receptor

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Free PMC article
Review

Persistent Memories of Long-Term Potentiation and the N-methyl-d-aspartate Receptor

Tvp Bliss et al. Brain Neurosci Adv. .
Free PMC article

Abstract

In this article, we describe our involvement in the early days of research into long-term potentiation. We start with a description of the early experiments conducted in Oslo and London where long-term potentiation was first characterised. We discuss the ways in which the molecular pharmacology of glutamate receptors control the induction and expression of long-term potentiation and its counterpart, long-term depression. We then go on to summarise the extraordinary advances in understanding the cellular mechanisms of synaptic plasticity that have taken place in the subsequent half century. Finally, the increasing evidence that impaired long-term potentiation is a core feature of many brain disorders (LToPathies) is addressed by way of a few selected examples.

Keywords: Hippocampus; long-term potentiation (LTP); synaptic plasticity.

Conflict of interest statement

Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
The first experiment by Bliss and Lømo, performed in the autumn of 1968, on the effects of high-frequency stimulation on synaptic responses in the hippocampus of the anaesthetised rabbit. Because of drifting baselines, this figure was not included in Bliss and Lømo (1973), but the long-lasting potentiation of the responses in the tetanised pathway (filled circles) can be clearly seen. The moribund control pathway was coaxed back to life by repeated trains at the end of the experiment.
Figure 2.
Figure 2.
An experiment from the study that first investigated the effects of glutamate receptor subtypes on the induction and expression of LTP (Collingridge et al., 1983b). Synaptic transmission was recorded from the CA1 cell body region of a rat hippocampal slice in response to stimulation of Schaffer collateral/commissural fibres and drugs applied ionophoretically into the dendritic region. γ-d-glutamlyglycine (DGG), which is an AMPAR and NMDAR antagonist, inhibited synaptic transmission and the induction of LTP, in response to a single tetanus (100 Hz, 1s; marked by arrow). A subsequent tetanus, delivered after washout of DGG, induced a substantial LTP. 2-amino-5-phosphonopentanoate (APV), a selective NMDAR antagonist, had no effect on this LTP. When the stimulus was reduced and a third tetanus delivered little synaptic plasticity was induced. A fourth tetanus delivered after washout of APV induced additional LTP, which was followed for a further 45 min.

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References

    1. Abdou K, Shehata M, Choko K, et al. (2018) Synapse-specific representation of the identity of overlapping memory engrams. Science 360(6394): 1227–1231. - PubMed
    1. Abraham WC. (2003) How long will long-term potentiation last? Philosophical Transactions of the Royal Society of London: Series B, Biological Sciences 358(1432): 735–744. - PMC - PubMed
    1. Abraham WC, Bear MF. (1996) Metaplasticity: The plasticity of synaptic plasticity. Trends in Neurosciences 19(4): 126–130. - PubMed
    1. Aggleton JP, Morris RGM. (2018) Memory: Looking back and looking forward. Brain and Neuroscience Advances. Epub ahead of print 1 January DOI: 10.1177/2398212818794830. - DOI - PMC - PubMed
    1. Alford S, Frenguelli BG, Schofield JG, et al. (1993) Characterization of Ca2+ signals induced in hippocampal CA1 neurones by the synaptic activation of NMDA receptors. Journal of Physiology 469(1): 693–716. - PMC - PubMed

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