Effect of High-Frequency Stimulation of the Subthalamic Nucleus on Subthalamic Neurons: An Intracellular Study

Abstract

Background/Aims: The precise mechanism of action of deep brain stimulation in the subthalamic nucleus (STN) for the treatment of Parkinson’s disease and epilepsy is unknown. In the present study, the intracellular effects on STN neurons following high-frequency stimulation (HFS) of STN were examined to test the hypothesis that HFS results in either an increase or a decrease in neuronal action potential generation. Methods: Intracellular electrophysiological recordings were made in the rat STN neurons in in vitro slice preparations. A concentric bipolar stimulating electrode was placed in the STN, and electrical stimulation (duration, 100–2000 ms; amplitude, 10–500 µA, and frequency, 10–200 Hz) was delivered while simultaneously recording intracellularly from a STN neuron using a sharp electrode. Results: HFS of STN resulted in the generation of excitatory postsynaptic potentials and an increase in action potential firing during the stimulation period followed by a period of poststimulation inhibition of firing in STN neurons. The degree of increase in action potentials from HFS was critically dependent on the frequency of electrical stimulation, i.e. at approximately 100–140 Hz, maximal increase was obtained, but at 200 Hz, the activity was blocked. Interestingly, the duration of poststimulation inhibition of firing was dependent on the duration of stimulation, i.e. the longer the HFS, the longer the inhibition. Conclusions: These results suggest that the mechanism of action of deep brain stimulation involves initial excitation followed by later inhibition of STN neurons at a cellular level rather than primary inhibition, as previously hypothesized.