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J Neurophysiol 96: 613-621, 2006. First published March 22, 2006; doi:10.1152/jn.00105.2006
0022-3077/06 $8.00
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Cellular Mechanisms Preventing Sustained Activation of Cortex During Subcortical High-Frequency Stimulation

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

Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, Canada

Submitted 31 January 2006; accepted in final form 8 March 2006

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.

Address for reprint requests and other correspondence: Z.H.T. Kiss, Heritage Medical Research Building, Room 182A, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1 (E-mail: zkiss{at}ucalgary.ca)




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