NMDA Receptors in the Central Nervous System

• Type of Material: Article
• Authors: Kasper B. Hansen, University of Montana; Feng Yi, University of Montana; Riley Perszyk, Emory University; Frank S. Menniti, MindImmune Therapeutics Inc; Stephen Traynelis, Emory University
• Language: English
• Date: 2017-01-01
• Publisher: Humana Press Inc.
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © Springer Science+Business Media LLC 2017.
• Final Published Version (URL): http://dx.doi.org/10.1007/978-1-4939-7321-7_1
• Title of Journal or Parent Work: NMDA Receptors: Methods and Protocols
• Volume: 1677
• Start Page: 1
• End Page: 80
• Grant/Funding Information: This work was supported by grants from National Institutes of Health to S.F.T. (NS036654 and NS065371) and K.B.H. (GM103546 and NS097536).
• Keywords: Calcium dependent; Neurosciences; Partial agonist action; Biochemistry & Molecular Biology; Life Sciences & Biomedicine; Nigra pars compacta; Protein Kinase II; Cerebellar mossy fiber; Ligand binding domain; Neurosciences & Neurology; D-Asparate receptor; Biochemical Research Methods; Long-term potentiation; Science & Technology; Positive allosteric motivation; Subunit specific potentiation
• Research Categories: Health Sciences, Pharmacy; Biology, Neuroscience; Biology, Molecular; Engineering, Biomedical

Abstract

NMDA-type glutamate receptors are ligand-gated ion channels that mediate a major component of excitatory neurotransmission in the central nervous system (CNS). They are widely distributed at all stages of development and are critically involved in normal brain functions, including neuronal development and synaptic plasticity. NMDA receptors are also implicated in the pathophysiology of numerous neurological and psychiatric disorders, such as ischemic stroke, traumatic brain injury, Alzheimer’s disease, epilepsy, mood disorders, and schizophrenia. For these reasons, NMDA receptors have been intensively studied in the past several decades to elucidate their physiological roles and to advance them as therapeutic targets. Seven NMDA receptor subunits exist that assemble into a diverse array of tetrameric receptor complexes, which are differently regulated, have distinct regional and developmental expression, and possess a wide range of functional and pharmacological properties. The diversity in subunit composition creates NMDA receptor subtypes with distinct physiological roles across neuronal cell types and brain regions, and enables precise tuning of synaptic transmission. Here, we will review the relationship between NMDA receptor structure and function, the diversity and significance of NMDA receptor subtypes in the CNS, as well as principles and rules by which NMDA receptors operate in the CNS under normal and pathological conditions.