Levodopa differentially modulates spectral features in cerebellum and basal ganglia in a rodent model of Parkinson's disease.

Abstract

The cerebellum has largely remained overlooked for its role in Parkinson's disease (PD). Interrogation of this motor system may reveal innovative targets for therapeutics for PD. Here, we investigate longitudinal changes in spatiospectral dynamics in basal ganglia (BG) and cerebellar nuclei to characterize altered patterns of neural activity in both motor-related brain areas in a rodent model of PD. To do so, we used the unilateral 6-hydroxydopamine (6-OHDA) rat model and recorded local field potentials (LFP) before and during treatment with levodopa and benserazide from three to six weeks post-lesion. Beta oscillations (13-35 Hz) emerged in the ipsilateral striatum of hemiparkinsonian animals at three weeks, whereas beta, theta (4-8 Hz) and alpha (8-12 Hz) oscillations appeared in the DN at six weeks. Levodopa decreased striatal beta oscillations at six weeks post-lesion (p = 0.003) compared to untreated PD animals but did not affect theta oscillations in the striatum and dentate nucleus at this time. These findings suggest that the cerebellum may play a variable role in PD depending on dopamine status: a mirroring/pathologic role during dopamine depletion and a compensatory role during dopamine replacement. This is the first time spectral dynamics in BG and cerebellum have been investigated longitudinally in a PD model, and our findings provide clearer insight regarding the dynamic engagement of the cerebellum during dopamine depletion and replacement therapy. A better understanding about the role of the cerebellum in PD pathophysiology may unmask future targets for therapeutic development.