Cited by 297Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsNeural dynamics and brain function

NMDA receptors and memory encoding

Morris, Richard G.M.·2013·Neuropharmacology

Abstract

It is humbling to think that 30 years have passed since the paper by Collingridge, Kehl and McLennan showing that one of Jeff Watkins most interesting compounds, R-2-amino-5-phosphonopentanoate (d-AP5), blocked the induction of long-term potentiation in vitro at synapses from area CA3 of the hippocampus to CA1 without apparent effect on baseline synaptic transmission (Collingridge et al., 1983). This dissociation was one of the key triggers for an explosion of interest in glutamate receptors, and much has been discovered since that collectively contributes to our contemporary understanding of glutamatergic synapses - their biophysics and subunit composition, of the agonists and antagonists acting on them, and their diverse functions in different networks of the brain and spinal cord. It can be fairly said that Collingridge et al.'s (1983) observation was the stimulus that has led, on the one hand, to structural biological work at the atomic scale describing the key features of NMDA receptors that enables their coincidence function to happen; and, on the other, to work with whole animals investigating the contributions that calcium signalling via this receptor can have on rhythmical activities controlled by spinal circuits, memory encoding in the hippocampus (the topic of this article), visual cortical plasticity, sensitization in pain, and other functions. In this article, I lay out how my then interest in long-term potentiation (LTP) as a model of memory enabled me to recognise the importance of Collingridge et al.'s discovery - and how I and my colleagues endeavoured to take things forward in the area of learning and memory. This is in some respects a personal story, and I tell it as such. The idea that NMDA receptor activation is essential for memory encoding, though not for storage, took time to develop and to be accepted. Along the way, there have been confusions, challenges, and surprises surrounding the idea that activation of NMDA receptors can trigger memory. Some of these are described and how they have been addressed and resolved. Last, I touch on some new directions of interest with respect to the functional role of the NMDA receptor in cognition. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'.

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Crossref · 10.1016/j.neuropharm.2013.04.014

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  • Enhanced glutamatergic NMDA-mediated transmission may improve memory consolidation but in excess may be neurotoxic.

    “Enhanced glutamatergic NMDA-mediated transmission may improve memory consolidation (136) but in excess may be neurotoxic (137).”

    From A brain-centric model of suicidal behavior (2020) · cites this paper as [136]

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Authors
Morris, R. G. M.
Affiliations
University of Edinburgh (GB)
Corresponding author
Morris, Richard G.M.
Venue
Neuropharmacology
Publisher
Elsevier BV
Published
2013-11
Volume
74
Pages
32-40
ISSN
0028-3908 (ISSN-L)
OpenAlex
W2027844417
Cited by
295
References
102
Citations by year
2026: 13 · 2025: 17 · 2024: 18 · 2023: 18 · 2022: 17 · 2021: 33 · 2020: 29 · 2019: 20 · 2018: 33 · 2017: 27 · 2016: 31 · 2015: 20 · 2014: 14 · 2013: 4
FWCI
2.34
Type
journal article
Language
en
Open access
closed
Locations
  • Neuropharmacology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Medical Research Council
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
Keywords
NMDA receptor, memory encoding, long-term potentiation, hippocampus, D-AP5, glutamate receptors, synaptic plasticity, learning and memory, calcium signaling, cognitive function
MeSH terms
Animals, Hippocampus, Learning, Memory, 2-Amino-5-phosphonovalerate, Receptors, N-Methyl-D-Aspartate, Long-Term Potentiation

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