Synaptic plasticity in rat subthalamic nucleus induced by high‐frequency stimulation

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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. Synapse 50:314–319, 2003.