Temporal Features of Gamma Activity of Hyper-direct Pathway Regulated by Dopamine Receptors in the Dyskinetic Rat.

Abstract

Cortico-thalamic projections (the hyper-direct pathway) are implicated in levodopa-induced dyskinesia (LID), a challenging complication in the advanced stages of Parkinson's disease (PD). Excessive beta and gamma activity in PD and LID has frequently been reported in recent cross-sectional studies. We aimed to investigate the temporal features of beta and gamma activity in the hyper-direct pathway during the development of PD and LID in rats, as well as the regulatory role of the dopamine receptors DI (D1Rs) and DIII (D3Rs) in these disorders. We recorded motor behavior and electrophysiological data during the development of PD and LID, and after interventions with D1R and D3R antagonists and agonists. We demonstrated exaggerated beta-band activity in the PD state and excessive gamma-band activity during on-state dyskinesia. Subsequently, process-dependent increased beta activity correlated with bradykinesia during PD modeling, while process-dependent increased gamma activity correlated with dyskinesia under the cumulative effects of levodopa during on-state dyskinesia. Finally, both D1Rs and D3Rs were found to be involved in regulating dyskinesia and gamma activity. Dynamic oscillations are closely associated with motor behavior, and mapping dynamic oscillations may be associated with optimizing deep brain stimulation parameters and developing personalized neurotherapeutic targeting. Moreover, D1Rs and D3Rs may ameliorate dyskinesia by mediating gamma oscillations.