Cited by 1,159Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersAmino Acid Enzymes and Metabolism

NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders

Lau, C. Geoffrey, Zukin, R. Suzanne·2007·Nature Reviews Neuroscience

Abstract

The number and subunit composition of synaptic N-methyl-D-aspartate receptors (NMDARs) are not static, but change in a cell- and synapse-specific manner during development and in response to neuronal activity and sensory experience. Neuronal activity drives not only NMDAR synaptic targeting and incorporation, but also receptor retrieval, differential sorting into the endosomal-lysosomal pathway and lateral diffusion between synaptic and extrasynaptic sites. An emerging concept is that activity-dependent, bidirectional regulation of NMDAR trafficking provides a dynamic and potentially powerful mechanism for the regulation of synaptic efficacy and remodelling, which, if dysregulated, can contribute to neuropsychiatric disorders such as cocaine addiction, Alzheimer's disease and schizophrenia.

Integrity signals

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Crossref · 10.1038/nrn2153

Cites

154 of 154 references verified0 citation errors · 0 not checkable

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  • Overactivity of NMDA receptors causing excitotoxicity is a proposed underlying mechanism for epilepsy, dementia, and stroke.

    “Overactivity of NMDA receptors causing excitotoxicity is a proposed underlying mechanism for epilepsy, dementia, and stroke, whereas low activity produces symptoms of schizophrenia.2–4”
  • Low activity of NMDA receptors produces symptoms of schizophrenia.

    “Overactivity of NMDA receptors causing excitotoxicity is a proposed underlying mechanism for epilepsy, dementia, and stroke, whereas low activity produces symptoms of schizophrenia.2–4”
  • The persisting amnesia in patients who recover from anti-NMDA-receptor encephalitis is compatible with disruption of the mechanisms of synaptic plasticity, thought to underlie learning and memory, in which NMDA receptors play a key part.

    “This feature is compatible with disruption of the mechanisms of synaptic plasticity, thought to underlie learning and memory, in which the NMDA receptors play a key part.4”

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Authors
Lau, C. G., & Zukin, R. S.
Affiliations
Albert Einstein College of Medicine (US)
Corresponding author
Zukin, R. Suzanne
Venue
Nature Reviews Neuroscience
Published
2007-06
Volume
8
Issue
6
Pages
413-426
ISSN
  • 1471-003X (ISSN-L)
  • 1471-0048
OpenAlex
W1985241009
Cited by
1,159
References
154
Citations by year
2026: 27 · 2025: 27 · 2024: 35 · 2023: 50 · 2022: 39 · 2021: 60 · 2020: 54 · 2019: 70 · 2018: 75 · 2017: 66 · 2016: 51 · 2015: 78 · 2014: 70 · 2013: 69 · 2012: 89
FWCI
6.05
Type
journal article
Language
en
Open access
closed
Locations
  • Nature reviews. Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (NS-20752, R01NS020752)
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, receptor trafficking, synaptic plasticity, postsynaptic density, receptor subunit composition, synaptic targeting, endolysosomal pathway, extrasynaptic receptors, activity-dependent regulation, cocaine dependence, Alzheimer's disease, schizophrenia, neuropsychiatric disorders
MeSH terms
Animals, Mental Disorders, Brain, Endocytosis, Humans, Synaptic Transmission, Neuronal Plasticity, Synapses, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Protein Transport

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