title: The impact of NMDA receptor hypofunction on GABAergic neurons in the pathophysiology of schizophrenia.
abstract: While the dopamine hypothesis has dominated schizophrenia research for several decades, more recent studies have highlighted the role of fast synaptic transmitters and their receptors in schizophrenia etiology. Here we review evidence that schizophrenia is associated with a reduction in N-methyl-d-aspartate receptor (NMDAR) function. By highlighting postmortem, neuroimaging and electrophysiological studies, we provide evidence for preferential disruption of GABAergic circuits in the context of NMDAR hypo-activity states. The functional relationship between NMDARs and GABAergic neurons is realized at the molecular, cellular, microcircuit and systems levels. A synthesis of findings across these levels explains how NMDA-mediated inhibitory dysfunction may lead to aberrant interactions among brain regions, accounting for key clinical features of schizophrenia. This synthesis of schizophrenia unifies observations from diverse fields and may help chart pathways for developing novel diagnostics and therapeutics.
authors.affiliation: NYU Neuroscience Institute, Department of Neuroscience and Physiology, NYU Langone Medical Center, New York, NY 10016, USA.
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Cohen
authors.affiliation: NYU Neuroscience Institute, Department of Neuroscience and Physiology, NYU Langone Medical Center, New York, NY 10016, USA.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Tsien
authors.affiliation: Department of Psychiatry, NYU Langone Medical Center, 550 First Avenue, New York, NY 10016, USA; Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA.
authors.forename: Donald C
authors.initials: DC
authors.lastname: Goff
authors.affiliation: NYU Neuroscience Institute, Department of Neuroscience and Physiology, NYU Langone Medical Center, New York, NY 10016, USA; Department of Psychiatry, NYU Langone Medical Center, 550 First Avenue, New York, NY 10016, USA. Electronic address: Michael.Halassa@nyumc.org.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Halassa
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D059330:GABAergic Neurons / Q000378:metabolism*; D006801:Humans; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012559:Schizophrenia / Q000473:pathology* / Q000503:physiopathology
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate
keywords: GABA; Inhibitory interneuron; NMDA receptor; Schizophrenia