Abstract
Both the subthalamic nucleus (STN) and the globus pallidus pars interna (GPi) are major targets for neuromodulation therapy for movement disorders. An example of such a therapy is deep brain stimulation (DBS). The striatum is the primary target for pharmacological treatment of these disorders. To further our understanding of both the functional relationships among motor nuclei and the mechanisms of therapies for movement disorders, it is important to clarify how changing the neuronal activity of one target, either by medication or by artificial electrical stimulation, affects the other connected nuclei. To investigate this point, we recorded single‐unit activity from tonically active neurons (TANs), which are putative cholinergic interneurons in the striatum, of healthy monkeys (Macaca fuscata) during electrical stimulation of the STN or GPi. Both STN stimulation and GPi stimulation reduced the TAN spike rate. Local infusion of a D2 receptor antagonist in the striatum blocked the reduction in spike rate induced by STN stimulation but not that induced by GPi stimulation. Further, STN stimulation induced phasic dopamine release in the striatum as revealed by in vivo fast‐scan cyclic voltammetry. These results suggest the presence of multiple, strong functional relationships among the STN, GPi, and striatum that have different pathways and imply distinct therapeutic mechanisms for STN‐ and GPi‐DBS.
Highlights
The basal ganglia and cerebral cortex are thought to constitute a parallel, closed-loop system, the so-called cortico-basal-ganglia circuit (Alexander et al, 1986)
We here demonstrate that electrical stimulation of either the subthalamic nucleus (STN) or the globus pallidus pars interna (GPi) influences tonically active neuron (TAN) activity
Dopamine is crucial for the TAN response to STN stimulation but not for the response to GPi stimulation, the latter instead being dependent on GABAergic mechanisms
Summary
The basal ganglia and cerebral cortex are thought to constitute a parallel, closed-loop system, the so-called cortico-basal-ganglia circuit (Alexander et al, 1986). In this model, the subthalamic nucleus (STN) and the globus pallidus pars interna (GPi) are considered the basal ganglia’s input and output structures, respectively. The STN receives cortical information both directly and indirectly and receives inputs from brainstem nuclei such as the pedunculopontine nucleus (Kita et al, 2014). The associated peer review process communications can be found in the online version of this article. Transmitted to the GPi/SNr from the STN return to the cerebral cortex via the thalamus. Several studies have reported that changing STN or GPi activity affects cortical activity (Devos et al, 2002, 2004; Yang et al, 2015), which leads to alterations in movement or behavior (Reymann et al, 2013; Piron et al, 2016)
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