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Subunit-Specific NMDA Receptor Trafficking to Synapses

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Barria, Andres, Malinow, Roberto·2002·Neuron

DOI 10.1016/s0896-6273(02)00776-6

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Abstract

To elucidate mechanisms controlling the number and subunit composition of synaptic NMDA-Rs in hippocampal slice neurons, the NR1, NR2A, and NR2B subunits were optically and electrophysiologically tagged. The NR2 subunit directs delivery of receptors to synapses with different rules controlling NR2A and NR2B. Synaptic incorporation of NR2B-containing receptors is not limited by synaptic transmission nor enhanced by increased subunit expression. NR2A-containing receptors whose expression normally increases with age replace synaptic NR2B-containing receptors. Replacement is enhanced by increased NR2A expression and requires synaptic activity. Surprisingly, spontaneously released transmitter acting on synaptic NMDA-Rs is sufficient for replacement and reduces NMDA-R responses. Thus, as with AMPA-Rs, synaptic trafficking of NMDA-Rs is tightly regulated and has subunit-specific rules with functionally important consequences.

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Authors: Barria, A., & Malinow, R.
Affiliations: Cold Spring Harbor Laboratory (US)
Corresponding author: Malinow, Roberto
ORCID: Malinow, Roberto
Venue: Neuron
Publisher: Elsevier BV
Published: 2002-07
Volume: 35
Issue: 2
Pages: 345-353
ISSN: 0896-6273 (ISSN-L)
DOI: 10.1016/s0896-6273(02)00776-6
OpenAlex: W2030377743
Cited by: 515
References: 151
Citations by year: 2026: 5 · 2025: 14 · 2024: 16 · 2023: 12 · 2022: 14 · 2021: 14 · 2020: 17 · 2019: 22 · 2018: 12 · 2017: 15 · 2016: 26 · 2015: 27 · 2014: 28 · 2013: 23 · 2012: 23
FWCI: 10.46
Type: journal article
Language: en
Open access: bronze
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www.elsevier.com/open-access/userlicense/1.0/ (vor, 4034 d)
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Locations: Neuron (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords: NMDA receptor, receptor trafficking, NR2A, NR2B, NR1, subunit composition, hippocampal neurons, spontaneous neurotransmission, receptor subunit expression, synaptic plasticity
MeSH terms: Animals, Animals, Newborn, Cell Compartmentation, Cells, Cultured, Dendrites, Dose-Response Relationship, Drug, Hippocampus, Indicators and Reagents, Luminescent Proteins, Membrane Potentials, Mutation, Synaptic Transmission, Organ Culture Techniques, Recombinant Fusion Proteins, Synapses, Receptors, N-Methyl-D-Aspartate, Pyramidal Cells, Excitatory Amino Acid Antagonists, Protein Transport, Sodium Channel Blockers, Green Fluorescent Proteins

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Subunit-Specific NMDA Receptor Trafficking to Synapses

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