Maintenance of thalamic epileptiform activity depends on the astrocytic glutamate-glutamine cycle

J Neurophysiol. 2009 Nov;102(5):2880-8. doi: 10.1152/jn.00476.2009. Epub 2009 Sep 9.


The generation of prolonged neuronal activity depends on the maintenance of synaptic neurotransmitter pools. The astrocytic glutamate-glutamine cycle is a major mechanism for recycling the neurotransmitters GABA and glutamate. Here we tested the effect of disrupting the glutamate-glutamine cycle on two types of neuronal activity patterns in the thalamus: sleep-related spindles and epileptiform oscillations. In recording conditions believed to induce glutamine scarcity, epileptiform oscillations showed a progressive reduction in duration that was partially reversible by the application of exogenous glutamine (300 muM). Blocking uptake of glutamine into neurons with alpha-(methylamino) isobutyric acid (5 mM) caused a similar reduction in oscillation duration, as did blocking neuronal GABA synthesis with 3-mercaptoproprionic acid (10 muM). However, comparable manipulations did not affect sleep spindles. Together, these results support a crucial role for the glutamate-glutamine cycle in providing the neurotransmitters necessary for the generation of epileptiform activity and suggest potential therapeutic approaches that selectively reduce seizure activity but maintain normal neuronal activity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Mercaptopropionic Acid / pharmacology
  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Analysis of Variance
  • Animals
  • Astrocytes / drug effects
  • Astrocytes / physiology*
  • Bicuculline / analogs & derivatives
  • Bicuculline / pharmacology
  • Convulsants / pharmacology
  • Female
  • Glutamic Acid / metabolism*
  • Glutamic Acid / pharmacology
  • Glutamine / metabolism*
  • Glutamine / pharmacology
  • Male
  • Neurons / drug effects
  • Neurons / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Thalamus / cytology*
  • Time Factors


  • Convulsants
  • Glutamine
  • Glutamic Acid
  • bicuculline methiodide
  • 3-Mercaptopropionic Acid
  • Bicuculline