Cellular mechanisms preventing sustained activation of cortex during subcortical high-frequency stimulation

Karl J. Iremonger, Trent R. Anderson, Bin Hu, Zelma H.T. Kiss

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


Axonal excitation has been proposed as a key mechanism in therapeutic brain stimulation. In this study we examined how high-frequency stimulation (HFS) of subcortical white matter tracts projecting to motor cortex affects downstream postsynaptic responses in cortical neurons. Whole cell recordings were performed in the primary motor cortex (M1) and ventral thalamus of rat brain slices. In M1, neurons showed only an initial depolarization in response to HFS, after which the membrane potential returned to prestimulation levels. The prolonged suppression of excitation during stimulation was neither associated with GABAergic inhibition nor complete action potential failure in stimulated axons. Instead we found that HFS caused a depression of excitatory synaptic currents in postsynaptic neurons that was specific to the stimulated subcortical input. These data are consistent with the hypothesis that axonal HFS produces a functional deafferentation of postsynaptic targets likely from depletion of neurotransmitter.

Original languageEnglish (US)
Pages (from-to)613-621
Number of pages9
JournalJournal of neurophysiology
Issue number2
StatePublished - 2006

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology


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