Regulation of NMDA receptor subunit expression and its implications for LTD, LTP, and metaplasticity

Yashiro, Koji; Philpot, Benjamin D.

doi:10.1016/j.neuropharm.2008.07.046

Cited by 649Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersAmino Acid Enzymes and Metabolism

Regulation of NMDA receptor subunit expression and its implications for LTD, LTP, and metaplasticity

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Yashiro, Koji, Philpot, Benjamin D.·2008·Neuropharmacology

DOI 10.1016/j.neuropharm.2008.07.046PMC PMC2590778

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Abstract

NMDA-type glutamate receptors (NMDARs) mediate many forms of synaptic plasticity. These tetrameric receptors consist of two obligatory NR1 subunits and two regulatory subunits, usually a combination of NR2A and NR2B. In the neonatal neocortex NR2B-containing NMDARs predominate, and sensory experience facilitates a developmental switch in which NR2A levels increase relative to NR2B. In this review, we clarify the roles of NR2 subunits in synaptic plasticity, and argue that a primary role of this shift is to control the threshold, rather than determining the direction, for modifying synaptic strength. We also discuss recent studies that illuminate the mechanisms regulating NR2 subunits, and suggest that the NR2A/NR2B ratio is regulated by multiple means, which may control the ratio both locally at individual synapses and globally in a cell-wide manner. Finally, we use the visual cortex as a model system to illustrate how activity-dependent modifications in the NR2A/NR2B ratio may contribute to the development of cortical functions.

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An increased NR2A/NR2B ratio translates into a higher threshold for induction of LTP and conversely a state that is more favorable for induction of LTD.
“The resulting increased NR2A/NR2B ratio translates into a higher threshold for induction of LTP and conversely a state that is more favorable for induction of LTD.118, 119”
From A role for synaptic plasticity in the adolescent development of executive function (2013) · cites this paper as [119]
Section 6 says an elevated NR2A/NR2B ratio is hypothesized to require stronger stimulation for LTP and to allow a wider range of weaker stimulation to induce LTD. It also says the existing data suggest a high ratio favors LTD over LTP, but notes caveats. The citing sentence presents this proposed relationship as an established consequence. (LLM, conf=0.85)
Experimental — accuracy not yet measured
The drop in miR-125b may contribute to the induction of NR2A protein expression at the post-transcriptional level.
“During this period miR-125b levels dropped ~50% (Supplemental Figure S6B), which may contribute to the induction of NR2A protein expression at the post-transcriptional level (Yashiro and Philpot, 2008).”
From Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125b and miR-132 (2010) · cites this paper as Yashiro and Philpot, 2008

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Mower GD 1991b The effect of dark rearing on the time course of the critical period in cat visual cortex Dev Brain Res 58 151 158 2029762
Philpot BD Bear MF Abraham WC 1999 Metaplasticity: the plasticity of synaptic plasticity Katz PS Beyond Neurotransmission: Neuromodulation and its importance for information flow Oxford University Press U.K., Oxford

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Authors: Yashiro, K., & Philpot, B. D.
Affiliations: University of North Carolina at Chapel Hill (US)
Corresponding author: Yashiro, Koji
Philpot, Benjamin D.
ORCID: Philpot, Benjamin D.
Venue: Neuropharmacology
Publisher: Elsevier BV
Published: 2008-12
Volume: 55
Issue: 7
Pages: 1081-1094
ISSN: 0028-3908 (ISSN-L)
DOI: 10.1016/j.neuropharm.2008.07.046
PMC: PMC2590778
OpenAlex: W1968024448
Cited by: 649
References: 175
Citations by year: 2026: 16 · 2025: 20 · 2024: 26 · 2023: 16 · 2022: 22 · 2021: 35 · 2020: 27 · 2019: 31 · 2018: 52 · 2017: 36 · 2016: 43 · 2015: 36 · 2014: 51 · 2013: 59 · 2012: 53
FWCI: 3.47
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuropharmacology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
UNC Libraries
Funders: Whitehall Foundation
National Eye Institute (R01EY018323)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD040127)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Keywords: NMDA receptor subunit expression, synaptic plasticity, long-term depression, long-term potentiation, metaplasticity, visual cortex development, NR1 subunit, activity-dependent regulation, neocortex
MeSH terms: Animals, Cerebral Cortex, Humans, Kinetics, Neuronal Plasticity, Visual Cortex, Receptors, N-Methyl-D-Aspartate, Long-Term Potentiation

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Regulation of NMDA receptor subunit expression and its implications for LTD, LTP, and metaplasticity

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