Selective attenuation of afferent synaptic transmission as a mechanism of thalamic deep brain stimulation-induced tremor arrest

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

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

Deep brain stimulation (DBS) of the ventrolateral thalamus stops several forms of tremor. Microelectrode recordings in the human thalamus have revealed tremor cells that fire synchronous with electromyographic tremor. The efficacy of DBS likely depends on its ability to modify the activity of these tremor cells either synaptically by stopping afferent tremor signals or by directly altering the intrinsic membrane currents of the neurons. To test these possibilities, whole-cell patch-clamp recordings of ventral thalamic neurons were obtained from rat brain slices. DBS was simulated (sDBS) using extracellular constant current pulse trains (125 Hz, 60-80 μs, 0.25-5 mA, 1-30 s) applied through a bipolar electrode. Using a paired-pulse protocol, we first established that thalamocortical relay neurons receive converging input from multiple independent afferent fibers. Second, although sDBS induced homosynaptic depression of EPSPs along its own pathway, it did not alter the response from a second independent pathway. Third, in contrast to the subthalamic nucleus, sDBS in the thalamus failed to inhibit the rebound potential and the persistent Na+ current but did activate the I h current. Finally, in eight patients undergoing thalamic DBS surgery for essential tremor, microstimulation was most effective in alleviating tremor when applied in close proximity to recorded tremor cells. However, stimulation could still suppress tremor at distances incapable of directly spreading to recorded tremor cells. These complementary data indicate that DBS may induce a "functional deafferentation" of afferent axons to thalamic tremor cells, thereby preventing tremor signal propagation in humans.

Original languageEnglish (US)
Pages (from-to)841-850
Number of pages10
JournalJournal of Neuroscience
Volume26
Issue number3
DOIs
StatePublished - Jan 18 2006

Keywords

  • Deep brain stimulation
  • Essential tremor
  • High-frequency stimulation
  • Paired pulse
  • Synaptic depression
  • Thalamus

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Selective attenuation of afferent synaptic transmission as a mechanism of thalamic deep brain stimulation-induced tremor arrest'. Together they form a unique fingerprint.

  • Cite this