The NMDA receptor may participate in widespread suppression of circuit level neural activity, in addition to a similarly prominent role in circuit level activation

Behavioural Brain Research
Paul J Fitzgerald

Abstract

The N-methyl-d-aspartate receptor (NMDAR) plays a critical role in glutamatergically mediated neurotransmission, and thereby affects a wide range of brain circuits and important behavioral functions, not limited to learning and memory. While glutamate is classically considered to be the brain's principal excitatory neurotransmitter, there is also evidence the NMDAR plays a "functionally inhibitory" role, not in that it directly hyperpolarizes neurons but rather it suppresses circuit level neural activity, including through activation of GABAergic interneurons. This paper reviews data on the NMDAR "suppression" hypothesis (while also examining circuit level activation), with a focus on the following 6 lines of evidence: (1) epilepsy studies, (2) neurotoxicity studies, (3) mouse knockout studies of particular receptor subunits, (4) electrophysiological studies, (5) 2-deoxyglucose studies, and (6) functional brain imaging studies. For many of these lines of evidence, the review focuses on data from two well-characterized NMDAR antagonists, ketamine and phencyclidine. Also, evidence regarding the NMDAR and schizophrenia, including the psychotomimetic properties of ketamine and phencyclidine, cuts across several of the lines of evid...Continue Reading

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Citations

Feb 9, 2013·Journal of Lipid Research·Cheryl Ackert-BicknellRon Korstanje
Sep 14, 2012·Expert Opinion on Drug Discovery·Angelo Bifone, Alessandro Gozzi
Oct 23, 2013·Pharmacological Reports : PR·Władysław LasońKonrad Rejdak
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Aug 3, 2013·Journal of Affective Disorders·Paul J Fitzgerald
Apr 12, 2014·Frontiers in Psychiatry·Maria R DauvermannThomas W J Moorhead
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Dec 13, 2018·Journal of Autism and Developmental Disorders·Jerry Stuger
Jan 29, 2020·The International Journal of Neuropsychopharmacology·Jing SunHongbo Guo

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