Abstract

Central thalamic deep brain stimulation (CT-DBS) has been proposed as an experimental therapeutic approach to produce consistent sustained regulation of forebrain arousal for several neurological diseases. We investigated local field potentials (LFPs) induced by CT-DBS from the thalamic central lateral nuclei (CL) and the striatum as potential biomarkers for the enhancement of lever-pressing skill learning. LFPs were simultaneously recorded from multiple sites in the CL, ventral striatum (Vstr), and dorsal striatum (Dstr). LFP oscillation power and functional connectivity were assessed and compared between the CT-DBS and sham control groups. The theta and alpha LFP oscillations were significantly increased in the CL and striatum in the CT-DBS group. Furthermore, interhemispheric coherences between bilateral CL and striatum were increased in the theta band. Additionally, enhancement of c-Fos activity, dopamine D2 receptor (Drd2), and α4-nicotinic acetylcholine receptor (α4-nAChR) occurred after CT-DBS treatment in the striatum and hippocampus. CT-DBS strengthened thalamic-striatal functional connectivity, which demonstrates that the inter-regional connectivity enhancement might contribute to synaptic plasticity in the striatum. Altered dopaminergic and cholinergic receptors resulted in modulation of striatal synaptic plasticity's ability to regulate downstream signaling cascades for higher brain functions of lever-pressing skill learning.

Highlights

  • Deep brain stimulation (DBS) is a potent therapeutic approach of electrical stimulation through electrodes implanted in specific regions to modulate abnormal neuronal activities that contribute to neurological diseases and psychiatric disorders (Kolb et al, 1983; Overbeek et al, 2013; Williams and Okun, 2013; Schlaepfer and Bewernick, 2014)

  • To examine whether Central thalamic deep brain stimulation (CT-DBS) has an effect on cognitive function, we developed a water reward-related lever-pressing learning for the rats

  • There were no significant power spectral density (PSD) differences in the central lateral nuclei (CL), ventral striatum (Vstr), and dorsal striatum (Dstr) between before and after the reward-related lever-pressing learning in the sham control group as shown in the upper row of Figure 2 (∗P > 0.0125, Wilcoxon signed-rank tests with a Bonferroni correction, N = 10)

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Summary

INTRODUCTION

Deep brain stimulation (DBS) is a potent therapeutic approach of electrical stimulation through electrodes implanted in specific regions to modulate abnormal neuronal activities that contribute to neurological diseases and psychiatric disorders (Kolb et al, 1983; Overbeek et al, 2013; Williams and Okun, 2013; Schlaepfer and Bewernick, 2014). Studies have shown that DBS mediates neurological changes and behavioral improvement, and interval stimulation of the medial temporal lobe and the memory formation-related region with specific frequencies and critical timing is important for memory processing (Suthana et al, 2012; Fell et al, 2013; Lee et al, 2013). Based on the anatomical connections of CT with the striatum, we were interested in the direct electrical stimulation of CT that altered the changes in functional connectivity for the targeted Vstr and Dstr, the stimulation site of CT, which improved the skill learning process. We hypothesized that functional connectivity could be enhanced by CT-DBS treatment in the reward and skill learning-related brain areas. Regulation of the synaptic dopaminergic and cholinergic systems are required for lever-pressing skill learning

MATERIALS AND METHODS
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DISCUSSION

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