High frequency stimulation abolishes thalamic network oscillations: An electrophysiological and computational analysis

Kendall H Lee, Frederick L. Hitti, Su-Youne Chang, Dongchul C. Lee, David W. Roberts, Cameron C. McIntyre, James C. Leiter

Research output: Contribution to journalArticle

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Abstract

Deep brain stimulation (DBS) of the thalamus has been demonstrated to be effective for the treatment of epilepsy. To investigate the mechanism of action of thalamic DBS, we examined the effects of high frequency stimulation (HFS) on spindle oscillations in thalamic brain slices from ferrets. We recorded intracellular and extracellular electrophysiological activity in the nucleus reticularis thalami (nRt) and in thalamocortical relay (TC) neurons in the lateral geniculate nucleus, stimulated the slice using a concentric bipolar electrode, and recorded the level of glutamate within the slice. HFS (100 Hz) of TC neurons generated excitatory post-synaptic potentials, increased the number of action potentials in both TC and nRt neurons, reduced the input resistance, increased the extracellular glutamate concentration, and abolished spindle wave oscillations. HFS of the nRt also suppressed spindle oscillations. In both locations, HFS was associated with significant and persistent elevation in extracellular glutamate levels and suppressed spindle oscillations for many seconds after the cessation of stimulation. We simulated HFS within a computational model of the thalamic network, and HFS also disrupted spindle wave activity, but the suppression of spindle activity was short-lived. Simulated HFS disrupted spindle activity for prolonged periods of time only after glutamate release and glutamate-mediated activation of a hyperpolarization- activated current (I h) was incorporated into the model. Our results suggest that the mechanism of action of thalamic DBS as used in epilepsy may involve the prolonged release of glutamate, which in turn modulates specific ion channels such as I h, decreases neuronal input resistance, and abolishes thalamic network oscillatory activity.

Original languageEnglish (US)
Article number046001
JournalJournal of Neural Engineering
Volume8
Issue number4
DOIs
StatePublished - Aug 2011

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Glutamic Acid
Brain
Neurons
Thalamus
Deep Brain Stimulation
Epilepsy
Geniculate Bodies
Synaptic Potentials
Ferrets
Chemical activation
Ion Channels
Electrodes
Action Potentials
Ions
Therapeutics

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cellular and Molecular Neuroscience

Cite this

High frequency stimulation abolishes thalamic network oscillations : An electrophysiological and computational analysis. / Lee, Kendall H; Hitti, Frederick L.; Chang, Su-Youne; Lee, Dongchul C.; Roberts, David W.; McIntyre, Cameron C.; Leiter, James C.

In: Journal of Neural Engineering, Vol. 8, No. 4, 046001, 08.2011.

Research output: Contribution to journalArticle

Lee, Kendall H ; Hitti, Frederick L. ; Chang, Su-Youne ; Lee, Dongchul C. ; Roberts, David W. ; McIntyre, Cameron C. ; Leiter, James C. / High frequency stimulation abolishes thalamic network oscillations : An electrophysiological and computational analysis. In: Journal of Neural Engineering. 2011 ; Vol. 8, No. 4.
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