Rapid microelectrode measurements and the origin and regulation of extracellular glutamate in rat prefrontal cortex

Erin R. Hascup, Kevin N. Hascup, Michelle Stephens, Francois Pomerleau, Peter Huettl, Alain Gratton, Greg A. Gerhardt

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

Abstract

Glutamate in the prefrontal cortex (PFC) plays a significant role in several mental illnesses, including schizophrenia, addiction and anxiety. Previous studies on PFC glutamate-mediated function have used techniques that raise questions on the neuronal versus astrocytic origin of glutamate. The present studies used enzyme-based microelectrode arrays to monitor second-by-second resting glutamate levels in the PFC of awake rats. Locally applied drugs were employed in an attempt to discriminate between the neuronal or glial components of the resting glutamate signal. Local application of tetrodotoxin (sodium channel blocker), produced a significant (∼40%) decline in resting glutamate levels. In addition significant reductions in extracellular glutamate were seen with locally applied ω-conotoxin (MVIIC; ∼50%; calcium channel blocker), and the mGluR2/3 agonist, LY379268 (∼20%), and a significant increase with the mGluR2/3 antagonist LY341495 (∼40%), effects all consistent with a large neuronal contribution to the resting glutamate levels. Local administration of D,L-threo-β-benzyloxyaspartate (glutamate transporter inhibitor) produced an ∼120% increase in extracellular glutamate levels, supporting that excitatory amino acid transporters, which are largely located on glia, modulate clearance of extracellular glutamate. Interestingly, local application of (S)-4-carboxyphenylglycine (cystine/glutamate antiporter inhibitor), produced small, non-significant bi-phasic changes in extracellular glutamate versus vehicle control. Finally, pre-administration of tetrodotoxin completely blocked the glutamate response to tail pinch stress. Taken together, these results support that PFC resting glutamate levels in rats as measured by the microelectrode array technology are at least 40-50% derived from neurons. Furthermore, these data support that the impulse flow-dependent glutamate release from a physiologically -evoked event is entirely neuronally derived.

Original languageEnglish
Pages (from-to)1608-1620
Number of pages13
JournalJournal of Neurochemistry
Volume115
Issue number6
DOIs
StatePublished - Dec 2010

Keywords

  • basal
  • chronic
  • d, l -threo-β- benzyloxyaspartate
  • freely moving
  • tetrodotoxin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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