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This version was published on April 1, 2008
The Neuroscientist, Vol. 14, No. 2, 171-181 (2008)
DOI: 10.1177/1073858407308518
© 2008 SAGE Publications

Regulation of Synaptic Transmission by Ambient Extracellular Glutamate

David E. Featherstone

Department of Biological Sciences, University of Illinois at Chicago, def{at}uic.edu

Scott A. Shippy

Department of Chemistry, University of Illinois at Chicago

Many neuroscientists assume that ambient extracellular glutamate concentrations in the nervous system are biologically negligible under nonpathological conditions. This assumption is false. Hundreds of studies over several decades suggest that ambient extracellular glutamate levels in the intact mammalian brain are ~0.5 to ~5 µM. This has important implications. Glutamate receptors are desensitized by glutamate concentrations significantly lower than needed for receptor activation; 0.5 to 5 µM of glutamate is high enough to cause constitutive desensitization of most glutamate receptors. Therefore, most glutamate receptors in vivo may be constitutively desensitized, and ambient extracellular glutamate and receptor desensitization may be potent but generally unrecognized regulators of synaptic transmission. Unfortunately, the mechanisms regulating ambient extracellular glutamate and glutamate receptor desensitization remain poorly understood and understudied. NEUROSCIENTIST 14(2):171—181, 2008. DOI: 10.1177/1073858407308518

Key Words: Glutamate • Synaptic • Synapse • Glutamate receptor • Ambient extracellular glutamate


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