These authors contributed equally to this work.
Rapid microelectrode measurements and the origin and regulation of extracellular glutamate in rat prefrontal cortex
Article first published online: 19 NOV 2010
© 2010 The Authors. Journal of Neurochemistry © 2010 International Society for Neurochemistry
Journal of Neurochemistry
Volume 115, Issue 6, pages 1608–1620, December 2010
How to Cite
Hascup, E. R., Hascup, K. N., Stephens, M., Pomerleau, F., Huettl, P., Gratton, A. and Gerhardt, G. A. (2010), Rapid microelectrode measurements and the origin and regulation of extracellular glutamate in rat prefrontal cortex. Journal of Neurochemistry, 115: 1608–1620. doi: 10.1111/j.1471-4159.2010.07066.x
- Issue published online: 1 DEC 2010
- Article first published online: 19 NOV 2010
- Accepted manuscript online: 22 OCT 2010 01:10PM EST
- Received June 28, 2010; revised manuscript received October 1, 2010; accepted October 5, 2010.
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J. Neurochem. (2010) 115, 1608–1620.
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.