title: Neurotransmitter release from high-frequency stimulation of the subthalamic nucleus.
abstract: OBJECTIVE
  High-frequency stimulation (HFS) delivered through implanted electrodes in the subthalamic nucleus (STN) has become an established treatment for Parkinson disease (PD). The precise mechanism of action of deep brain stimulation (DBS) in the STN is unknown, however. In the present study, the authors tested the hypothesis that HFS within the STN changes neuronal action potential firing rates during the stimulation period by modifying neurotransmitter release.
  
  
  METHODS
  Intracellular electrophysiological recordings were obtained using sharp electrodes in rat STN neurons in an in vitro slice preparation. A concentric bipolar stimulating electrode was placed in the STN slice, and electrical stimulation (pulse width 50-100 microsec, duration 100-2000 msec, amplitude 10-500 microA, and frequency 10-200 Hz) was delivered while simultaneously obtaining intracellular recordings from an STN neuron. High-frequency stimulation of the STN either generated excitatory postsynaptic potentials (EPSPs) and increased the action potential frequency or it generated inhibitory postsynaptic potentials and decreased the action potential frequency of neurons within the STN. These effects were blocked after antagonists to glutamate and gamma-aminobutyric acid were applied to the tissue slice, indicating that HFS resulted in the release of neurotransmitters. Intracellular recordings from substantia nigra pars compacta (SNc) dopaminergic neurons during HFS of the STN revealed increased generation of EPSPs and increased frequency of action potentials in SNc neurons.
  
  
  CONCLUSIONS
  During HFS of STN neurons the mechanism of DBS may involve the release of neurotransmitters rather than the primary electrogenic inhibition of neurons.
authors.affiliation: Section of Neurosurgery, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA. kendall.h.lee@hitchcock.org
authors.forename: Kendall H
authors.initials: KH
authors.lastname: Lee
authors.forename: Su-Youne
authors.initials: SY
authors.lastname: Chang
authors.forename: David W
authors.initials: DW
authors.lastname: Roberts
authors.forename: Uhnoh
authors.initials: U
authors.lastname: Kim
mesh_terms: D000818:Animals; D046508:Culture Techniques; D004298:Dopamine / Q000378:metabolism; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D008297:Male; D008564:Membrane Potentials; D009474:Neurons / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020531:Subthalamic Nucleus / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D018377:Neurotransmitter Agents; D004298:Dopamine