The Origin and Neuronal Function ofIn VivoNonsynaptic Glutamate

• DOI: 10.1523/jneurosci.22-20-09134.2002
• Publication Date: 2018-04-05T22:55:21Z
• Authors: David A. Baker; Zheng-Xiong Xi; Hui Shen; Chad J. Swanson; Peter W. Kalivas
• Keywords: Male; Neurons; Dopamine; Microdialysis; Glutamic Acid; In Vitro Techniques; Receptors, Metabotropic Glutamate; Cyclic AMP-Dependent Protein Kinases; Synaptic Transmission; Corpus Striatum; Rats; Rats, Sprague-Dawley; 03 medical and health sciences; 0302 clinical medicine; Synapses; Excitatory Amino Acid Agonists; Animals; Carrier Proteins; Extracellular Space; Excitatory Amino Acid Antagonists

Basal extracellular glutamate sampled in vivo is present micromolar concentrations the space outside synaptic cleft, and neither origin nor function of this known. This report reveals that blockade release from cystine-glutamate antiporter produced a significant decrease (60%) extrasynaptic levels rat striatum, whereas voltage-dependent Na+ Ca2+ channels relatively minimal changes (0-30%). indicates primary striatum arises nonvesicular by antiporter. By measuring [35S]cystine uptake, it was shown similar to vesicular release, activity negatively regulated group II metabotropic receptors (mGluR2/3) via cAMP-dependent protein kinase mechanism. Extracellular derived regulate dopamine. Infusion mGluR2/3 antagonist (RS)-1-amino-5-phosphonoindan-1-carboxylic acid (APICA) increased levels, previous prevented APICA-induced rise glutamate. suggests released source endogenous tone on mGluR2/3. Blockade also an increase dopamine reversed infusing agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxlylate, indicating antiporter-derived can modulate transmission heteroreceptors. These results suggest both transmission.