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NR2B subunit in the prefrontal cortex: A double-edged sword for working memory function and psychiatric disorders
Journal article   Open access   Peer reviewed

NR2B subunit in the prefrontal cortex: A double-edged sword for working memory function and psychiatric disorders

Sarah A Monaco, Yelena Gulchina and Wen-Jun Gao
Neuroscience and biobehavioral reviews, v 56, pp 127-138
Sep 2015
PMID: 26143512
url
https://doi.org/10.1016/j.neubiorev.2015.06.022View
Published, Version of Record (VoR) Open

Abstract

Mental Disorders - pathology Peptide Fragments - metabolism Animals Humans Prefrontal Cortex - metabolism Receptors, N-Methyl-D-Aspartate - metabolism Memory, Short-Term - physiology
The prefrontal cortex (PFC) is a brain region featured with working memory function. The exact mechanism of how working memory operates within the PFC circuitry is unknown, but persistent neuronal firing recorded from prefrontal neurons during a working memory task is proposed to be the neural correlate of this mnemonic encoding. The PFC appears to be specialized for sustaining persistent firing, with N-methyl-D-aspartate (NMDA) receptors, especially slow-decay NR2B subunits, playing an essential role in the maintenance of sustained activity and normal working memory function. However, the NR2B subunit serves as a double-edged sword for PFC function. Because of its slow kinetics, NR2B endows the PFC with not only "neural psychic" properties, but also susceptibilities for neuroexcitotoxicity and psychiatric disorders. This review aims to clarify the interplay among working memory, the PFC, and NMDA receptors; demonstrate the importance of NR2B in the maintenance of persistent activity; understand the risks and vulnerabilities of how NR2B is related to the development of neuropsychiatric disorders; identify gaps that currently exist in our understanding of these processes; and provide insights regarding future directions that may clarify these issues. We conclude that the PFC is a specialized brain region with distinct delayed maturation, unique neuronal circuitry, and characteristic NMDA receptor function. The unique properties and development of NMDA receptors, especially enrichment of NR2B subunits, endow the PFC with not only the capability to generate sustained activity for working memory, but also serves as a major vulnerability to environmental insults and risk factors for psychiatric disorders.

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Web of Science research areas
Behavioral Sciences
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