Inhibition of Neuronal Firing in the Human Substantia Nigra Pars Reticulata in Response to High-Frequency Microstimulation Aids Localization of the Subthalamic Nucleus
Deep brain stimulation (DBS) has been playing an increasing role in the treatment of various movement disorders with the most common being Parkinson’s disease (PD). Currently, the preferred target for treating PD motor symptoms is the subthalamic nucleus (STN). Microelectrode recordings are frequently used to aid in the determination of the optimal target for implanting the DBS electrode. Changes in cellular activity are typically used to detect the borders of the STN during microelectrode recordings. Although the dorsal border of the STN is usually clear, its ventral border with the substantia nigra pars reticulata (SNr) is sometimes more difficult to identify. Our previous studies of the effects of microstimulation in the internal globus pallidus (GPi), which is functionally similar to SNr, and STN revealed that firing in GPi but not STN neurons is readily inhibited by low current stimulation through an adjacent microelectrode. The aim of the current study was to examine and compare the aftereffects of local high-frequency microstimulation through the recording electrode on the firing of STN and SNr neurons to determine whether this might be a useful technique for differentiating STN from SNr. Neurons in the SNr and STN were identified as well isolated high-amplitude spikes and were stimulated extracellulary through the recording microelectrode with 0.5-s trains of high-frequency (200 Hz) and low current (<5 μA). In the majority (89%) of SNr neurons, this type of stimulation led to a period of inhibition lasting several hundreds of milliseconds following the end of the train. A much smaller proportion of STN neurons (9%) was similarly affected by this type of stimulation. These findings indicate that almost all SNr neurons but few STN neurons display prolonged inhibition following very low current microstimulation through the recording electrode. This characteristic provides a useful additional finding that can be used to identify the border between STN and SNr.