title: High-frequency stimulation of the subthalamic nucleus silences subthalamic neurons: a possible cellular mechanism in Parkinson's disease.
abstract: The subthalamic nucleus participates in the control of movement and is considered a surgical target in the treatment of parkinsonian symptoms. Using the rat brain in vitro slice technique we show that sustained high-frequency (>100 Hz) electrical stimulation (i.e., 'tetanic stimulation') of the nucleus, as used in humans to treat Parkinson's disease, silenced subthalamic neurons. Two main cell types were identified. 'Tonic cells' (68%) showed delayed inward rectification, fired continuously, switched to bursting and stopped firing when strongly depolarized with injected current. Tetanic stimulation of the nucleus induced a steady depolarization (approximately 18 mV) that triggered action potentials at a high rate followed by bursts and finally (approximately 25 s) totally silenced tonic cells. The control tonic activity was recovered rapidly (<10 s) after ending stimulation. 'Phasic cells' (25%) discharged a single initial brief burst of action potentials both when depolarized by prolonged current injection and tetanic stimulation and did not show inward rectification. An infrequent cell type called 'phasic-tonic' (7%) showed a mixed discharge. We suggest that the silencing effect of tetanic stimulation is not a frequency-dependent presynaptic depression and could result from the gradual inactivation of Na+-mediated action potentials. These findings suggest that the remission of parkinsonian symptoms by treatment with high-frequency electrical stimulation of the subthalamic nucleus in humans may primarily reside on its capacity to suppress the action potential activity of subthalamic neurons.
authors.affiliation: Neurologi;a Experimental, Unidad Asociada al Instituto Cajal, CSIC, Depto. de Investigación, Hospital Ramón y Cajal, Ctra. Colmenar, 28034, Madrid, Spain. carlos.magarinos@hrc.es
authors.forename: C
authors.initials: C
authors.lastname: Magariños-Ascone
authors.forename: J H
authors.initials: JH
authors.lastname: Pazo
authors.forename: O
authors.initials: O
authors.lastname: Macadar
authors.forename: W
authors.initials: W
authors.lastname: Buño
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D048429:Cell Size / Q000502:physiology; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D004558:Electric Stimulation; D004599:Electric Stimulation Therapy; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010300:Parkinson Disease / Q000503:physiopathology* / Q000628:therapy; D051381:Rats; D015222:Sodium Channels / Q000502:physiology; D020531:Subthalamic Nucleus / Q000166:cytology / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D015222:Sodium Channels