title: Synaptic plasticity in rat subthalamic nucleus induced by high-frequency stimulation.
abstract: The technique of deep brain stimulation (DBS) has become a preferred surgical choice for the treatment of advanced Parkinson's disease. The subthalamic nucleus (STN) is presently the most promising target for such DBS. In this study, whole-cell patch-clamp recordings were made from 46 STN neurons in rat brain slices to examine the effect of high-frequency stimulation (HFS) of the STN on glutamatergic synaptic transmission in STN neurons. HFS, consisting of trains of stimuli at a frequency of 100 Hz for 1 min, produced three types of synaptic plasticity in 17 STN neurons. First, HFS of the STN induced short-term potentiation (STP) of evoked postsynaptic current (EPSC) amplitude in four neurons. STP was associated with a reduction in the EPSC paired-pulse ratio, suggesting a presynaptic site of action. Second, HFS of the STN generated long-term potentiation (LTP) of EPSC amplitude in eight neurons. Although the EPSC paired-pulse ratio was reduced transiently in the first 2 min following HFS, ratios measured 6-20 min after HFS were unchanged from control. This suggests that LTP is maintained by a postsynaptic mechanism. Third, HFS produced long-term depression (LTD) of EPSC amplitude in five STN neurons. LTD was associated with a significant increase in EPSC paired-pulse ratios, indicating a presynaptic site of action. These results suggest that HFS can produce long-term changes in the efficacy of synaptic transmission in the STN. HFS-induced synaptic plasticity might be one mechanism underlying the effectiveness of DBS in the STN as a treatment of advanced Parkinson's disease.
authors.affiliation: Department of Neurology, Oregon Health and Science University, Portland, Oregon 97239, USA.
authors.forename: Ke-Zhong
authors.initials: KZ
authors.lastname: Shen
authors.forename: Zi-Tao
authors.initials: ZT
authors.lastname: Zhu
authors.forename: Adam
authors.initials: A
authors.lastname: Munhall
authors.forename: Steven W
authors.initials: SW
authors.lastname: Johnson
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001933:Brain Stem / Q000502:physiology; D004558:Electric Stimulation / Q000379:methods*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020531:Subthalamic Nucleus / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D010852:Picrotoxin; D014633:Valine; C056639:2-amino-5-phosphopentanoic acid