Tonic and phasic release of glutamate and acetylcholine neurotransmission in sub-regions of the rat prefrontal cortex using enzyme-based microelectrode arrays

J Neurosci Methods. 2011 Nov 15;202(2):199-208. doi: 10.1016/j.jneumeth.2011.08.020. Epub 2011 Aug 27.


The medial prefrontal cortex (mPFC) is an area of the brain critical for higher cognitive processes and implicated in disorders of the CNS such as drug addiction, depression and schizophrenia. Glutamate and acetylcholine are neurotransmitters that are essential for cortical functioning, yet little is known about the dynamic function of these neurotransmitters in subregions of the mPFC. In these studies we used a novel microelectrode array technology to measure resting levels (tonic release) of glutamate and acetylcholine as well as KCl-evoked release (stimulated phasic release) in the mPFC of the anesthetized rat to further our understanding of both tonic and phasic neurotransmission in the cingulate cortex, prelimbic cortex, and infralimbic cortex of the mPFC. Studies revealed homogeneity of tonic and phasic signaling among brain subregions for each neurotransmitter. However, resting levels of glutamate were significantly higher as compared to acetylcholine levels in all subregions. Additionally, KCl-evoked acetylcholine release in the cingulate cortex (7.1 μM) was significantly greater than KCl-evoked glutamate release in any of the three subregions (Cg1, 2.9 μM; PrL, 2.0 μM; IL, 1.8 μM). Interestingly, the time for signal decay following KCl-evoked acetylcholine release was significantly longer by an average of 240% as compared to KCL-evoked glutamate release for all three brain subregions. Finally, we observed a negative relationship between acetylcholine resting levels and KCl-evoked release in the Cg1. These data suggest a homogenous distribution of both glutamatergic and acetylcholinergic innervation in the mPFC, with alterations in tonic and phasic release regulation accounting for differences between these neurotransmitters.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylcholine / analysis
  • Acetylcholine / metabolism*
  • Animals
  • Electrochemical Techniques / instrumentation
  • Electrochemical Techniques / methods*
  • Glutamic Acid / analysis
  • Glutamic Acid / metabolism*
  • Male
  • Microelectrodes / standards*
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism*
  • Rats
  • Rats, Inbred F344
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Time Factors


  • Glutamic Acid
  • Acetylcholine