title: Axonal failure during high frequency stimulation of rat subthalamic nucleus.
abstract: 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.
authors.affiliation: Institute of Physiology and Pathophysiology, University of Erlangen-Nürnberg, Universitätsstraße 17, 91054 Erlangen, Germany.
authors.forename: Fang
authors.initials: F
authors.lastname: Zheng
authors.forename: Katja
authors.initials: K
authors.lastname: Lammert
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Nixdorf-Bergweiler
authors.forename: Frank
authors.initials: F
authors.lastname: Steigerwald
authors.forename: Jens
authors.initials: J
authors.lastname: Volkmann
authors.forename: Christian
authors.initials: C
authors.lastname: Alzheimer
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000502:physiology*; D046690:Deep Brain Stimulation; D004298:Dopamine / Q000378:metabolism; D055724:Electrophysiological Phenomena / Q000187:drug effects / Q000502:physiology; D020392:Entopeduncular Nucleus / Q000166:cytology / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D058787:GABA-A Receptor Antagonists / Q000493:pharmacokinetics; D058788:GABA-B Receptor Antagonists / Q000494:pharmacology; D007736:Kynurenic Acid / Q000494:pharmacology; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors; D013378:Substantia Nigra / Q000166:cytology / Q000502:physiology; D020531:Subthalamic Nucleus / Q000166:cytology / Q000502:physiology*; D055366:Synaptic Potentials / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013696:Temperature
chemical_list: D004298:Dopamine; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D007736:Kynurenic Acid; D010852:Picrotoxin; D011188:Potassium; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2