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Overview of glutamatergic neurotransmission in the nervous system
Journal article   Open access   Peer reviewed

Overview of glutamatergic neurotransmission in the nervous system

Mark J Niciu, Benjamin Kelmendi and Gerard Sanacora
Pharmacology, biochemistry and behavior, Vol.100(4), pp.656-664
2012
DOI: 10.1016/j.pbb.2011.08.008
PMCID: PMC3253893
PMID: 21889952
url
https://www.ncbi.nlm.nih.gov/pmc/articles/3253893View
Open Access

Abstract

This introductory article to the special edition on glutamate neurotransmission in neuropsychiatric disorders provides an overview of glutamate neurotransmitter system physiology and pharmacology. Glutamate was only relatively recently recognized as the major excitatory neurotransmitter in the mammalian brain, in part due to its ubiquitous nature and diverse metabolic roles within the CNS. The extremely high concentration of glutamate in brain tissue paired with its excitotoxic potential requires tight physiological regulation of extracellular glutamate levels and receptor signaling in order to assure optimal excitatory neurotransmission but limits excitotoxic damage. In order to achieve this high level of control, the system has developed a complex physiology with multiple regulatory processes modulating glutamate metabolism, release, receptor signaling, and uptake. The basic physiology of the various regulatory components of the system including the rich receptor pharmacology is briefly reviewed. Potential contributions from each of the system's components to the pathophysiology of neuropsychiatric illnesses are briefly discussed, as are the many new pharmacological targets for drug development provided by the system, especially as they pertain to the proceeding preclinical and clinical articles in this issue.
AMPA NMDA Metabotropic Glutamate Transporter Psychiatry EAAT

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