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A specialized NMDA receptor function in layer 5 recurrent microcircuitry of the adult rat prefrontal cortex

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Wang, Huaixing, Stradtman, George G., Wang, Xiao-Jing, Gao, Wen-Jun·2008·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0804318105PMC PMC2575498

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Abstract

In the prefrontal cortex, NMDA receptors are important for normal prefrontal functions such as working memory, and their dysfunction plays a key role in the pathological processes of psychiatric disorders such as schizophrenia. Little is known, however, about the synaptic properties of NMDA receptors in the local circuits of recurrent excitation, a leading candidate mechanism underlying working memory. We investigated the NMDA receptor-mediated currents at monosynaptic connections between pairs of layer 5 pyramidal neurons. We found that NMDA receptor-mediated currents at prefrontal synapses in the adult, but not young, rats exhibit a twofold longer decay time-constant and temporally summate a train of stimuli more effectively, compared to those in the primary visual cortex. Experiments with pharmacological, immunocytochemical, and biochemical approaches further suggest that, in the adult animals, neurons express significantly more NR2B subunits in the prefrontal cortex than the visual cortex. The NR2B-rich synapses in the prefrontal circuitry may be critically implicated in online cognitive computations and plasticity in learning, as well as psychiatric disorders.

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Authors: Wang, H., Stradtman, G. G., Wang, X.-J., & Gao, W.-J.
Affiliations: Drexel University (US)
Yale University (US)
ORCID: Wang, Huaixing
Wang, Xiao-Jing
Gao, Wen-Jun
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2008-10-28
Volume: 105
Issue: 43
Pages: 16791-16796
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.0804318105
PMC: PMC2575498
OpenAlex: W2064286037
Cited by: 199
References: 39
Citations by year: 2026: 7 · 2025: 3 · 2024: 9 · 2023: 6 · 2022: 8 · 2021: 15 · 2020: 12 · 2019: 9 · 2018: 15 · 2017: 10 · 2016: 16 · 2015: 14 · 2014: 20 · 2013: 17 · 2012: 11
FWCI: 3.85
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Drexel University
National Alliance for Research on Schizophrenia and Depression
National Institutes of Health (NIH-R01)
College of Medicine, Drexel University
National Institute of Mental Health (R21MH079117, R01MH062349, MH232307, R01MH085666)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Keywords: NMDA receptor, prefrontal cortex, layer 5 pyramidal neurons, monosynaptic connections, NR2B subunit, synaptic plasticity, working memory, temporal summation, primary visual cortex, schizophrenia, adult rats
MeSH terms: Animals, Synaptic Transmission, Synapses, Receptors, N-Methyl-D-Aspartate, Prefrontal Cortex, Pyramidal Cells, Rats

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A specialized NMDA receptor function in layer 5 recurrent microcircuitry of the adult rat prefrontal cortex

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