Objective: We recorded the single-unit activity of striatal cholinergic interneurons of healthy monkeys during high-frequency stimulation (HFS) of the subthalamic nucleus (STN) and globus pallidus (GPi) and also measured dopamine release during stimulation of these targets to examine the therapeutic mechanisms of deep brain stimulation (DBS) using electrophysiological, pharmacological, and electrochemical methods.

Background: DBS of STN and GPi is an established surgical therapy for patients with Parkinson’s disease (PD). Inconsistent DBS efficacy may result from limited understanding of the therapeutic mechanisms such as the contribution of striatal cholinergic interneurons.

Methods: Neuronal activity of tonically active neurons (TANs) in the putamen was extracellularly recorded during STN- and GPi-HFS (130 Hz; 60 µs; 0.4 mA and 0.1 mA for 30 s and 10 s, respectively) in three healthy monkeys. To examine the neurotransmitter pathways that are involved in regulating TAN activity, we locally injected several receptor modulators and assessed their influence on the activity. Furthermore, we measured real-time dopamine release using fast-scan cyclic voltammetry during STN-HFS.

Results: We measured the spiking activities of 96 TANs during STN-HFS and 25 during GPi-HFS. Both STN- and GPi-HFS reduced the interneuron spike rate (86% of recorded neurons during STN-HFS and 79% during GPi-HFS, p < 0.05, Mann–Whitney U test). Striatal infusion of a D2 receptor antagonist blocked the reduction in the spike rate that was induced by STN-HFS but not by GPi-HFS. STN-HFS, not GPi-HFS, induced phasic dopamine release in the striatum, as revealed by in vivo voltammetry.

Conclusions: These results indicate reduced striatal cholinergic tone in response to DBS and suggest distinct therapeutic mechanisms for STN- and GPi-DBS. Furthermore, STN-DBS efficacy may depend on a preserved striatal dopaminergic signaling, suggesting that STN-DBS should be considered for early stage PD.

This work is partially presented at 5th Asian and Oceanian Parkinson’s disease and Movement disorders Congress 2015.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/role-of-dopamine-and-gaba-during-subthalamic-and-pallidal-deep-brain-stimulation-evidence-of-dopamine-release-during-subthalamic-deep-brain-stimulation/