Synaptic Plasticity in Rat Subthalamic Nucleus Induced by High-Frequency Stimulation

Ke Zhong Shen, Zi Tao Zhu, Adam Munhall, Steven W. Johnson

Research output: Contribution to journalArticle

78 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)314-319
Number of pages6
JournalSynapse
Volume50
Issue number4
DOIs
StatePublished - Dec 15 2003

    Fingerprint

Keywords

  • EPSC
  • Long-term depression
  • Long-term potentiation
  • Short-term potentiation

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this