Modulation of direct pathway regulates motor symmetry in the unilateral 6-OHDA rat model of PD

Parkinson's disease (PD) is characterized by progressive dopaminergic depletion in the striatum leading to motor deficits that often manifest with asymmetry. In this study, we investigated the role of optogenetic activation of the direct pathway in its ability to reestablish motor function and regulate oscillatory activity in cortex-basal ganglia loops. Rats received a unilateral injection of 6-OHDA into the medial forebrain bundle, followed by the delivery of adeno-associated viruses (AAVs) that specifically transduced Dopamine-1-Receptor-positive medium spiny neurons (DRD1-neurons). Using this method, we delivered red-shifted ChrimsonR to the dorsolateral striatum of the affected hemisphere. Our behavioral assessments included the cylinder test, T-maze, runway, and open field. To reestablish symmetry of body posture and movement, we explored various optogenetic stimulation frequencies and amplitudes, including closed-loop strategies targeting different phases of the beta band from real-time M2 ECOG signals. Our study suggests that using motor symmetry as behavioral feedback could help optimizing neuromodulation approaches for clinical translation in PD.