Axonal failure during high frequency stimulation of rat subthalamic nucleus

J Physiol. 2011 Jun 1;589(Pt 11):2781-93. doi: 10.1113/jphysiol.2011.205807. Epub 2011 Apr 11.


Deep brain stimulation (DBS) has been established as an effective surgical therapy for advanced Parkinson's disease (PD) and gains increasing acceptance for otherwise intractable neuropsychiatric diseases such as major depression or obsessive–compulsive disorders. In PD, DBS targets predominantly the subthalamic nucleus (STN) and relieves motor deficits only at high frequency (>100 Hz). In contrast to the well-documented clinical efficacy of DBS, its underlying principle remains enigmatic spawning a broad and, in part, contradictory spectrum of suggested synaptic and non-synaptic mechanisms within and outside STN. Here we focused on a crucial, but largely neglected issue in this controversy, namely the axonal propagation of DBS within and away from STN. In rat brain slices preserving STN projections to substantia nigra (SN) and entopeduncular nucleus (EP, the rodent equivalent of internal globus pallidus), STN-DBS disrupted synaptic excitation onto target neurons through an unexpected failure of axonal signalling. The rapid onset and, upon termination of DBS, recovery of this effect was highly reminiscent of the time course of DBS in the clinical setting. We propose that DBS-induced suppression of axonal projections from and to STN serves to shield basal ganglia circuitry from pathological activity arising in or amplified by this nucleus.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Axons / physiology*
  • Deep Brain Stimulation*
  • Dopamine / metabolism
  • Electrophysiological Phenomena / drug effects
  • Electrophysiological Phenomena / physiology
  • Entopeduncular Nucleus / cytology
  • Entopeduncular Nucleus / physiology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • GABA-A Receptor Antagonists / pharmacokinetics
  • GABA-B Receptor Antagonists / pharmacology
  • Kynurenic Acid / pharmacology
  • Neural Conduction / drug effects
  • Neural Conduction / physiology*
  • Neuronal Plasticity / physiology
  • Neurons / drug effects
  • Neurons / physiology
  • Patch-Clamp Techniques
  • Picrotoxin / pharmacology
  • Potassium / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Substantia Nigra / cytology
  • Substantia Nigra / physiology
  • Subthalamic Nucleus / cytology
  • Subthalamic Nucleus / physiology*
  • Synaptic Potentials / drug effects
  • Synaptic Potentials / physiology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Temperature


  • GABA-A Receptor Antagonists
  • GABA-B Receptor Antagonists
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 2
  • Picrotoxin
  • Kynurenic Acid
  • Potassium
  • Dopamine