Introduction: Recently, the cerebellum has gained increasing attention for its ambiguous role in Parkinson’s disease (PD). Interrogation of this motor system is necessary and may lead to innovative candidates for therapeutics. Here, we examine the evolution of spatiospectral dynamics in basal ganglia (BG) and cerebellar nuclei.
Methods: Sprague-dawley rats received an injection of 6-hydroxydopamine (6-OHDA) in the right median forebrain bundle to induce a hemi-parkinsonian model. Animals underwent a second surgery to insert ten recording electrodes: bilaterally into the striatum, primary motor cortex, substantia nigra pars reticulata, lateral cerebellar dentate nucleus (DN), and cerebellar lobule 7/8. Local field potential (LFP) recordings were collected at baseline and following injection with benserazide (12mg/kg) and/or levodopa (6mg/kg) each week for eight consecutive weeks. Post-mortem cresyl violet (CV) and tyrosine hydroxylase (TH) staining were performed for assessment of electrode location and parkinsonian model confirmation, respectively. LFPs were analyzed with NeuroExplorer, statistics were performed with GraphPad Prism, and tissue was analyzed with ImageJ.
Results: Beta oscillations (13-35 Hz) emerged in the ipsilateral striatum of 6-OHDA animals at six weeks post-craniotomy. However, distinct changes in spectral dynamics did not occur in the DN of 6-OHDA animals until ten weeks, when increases in theta (4-8 Hz), alpha (8-12 Hz), and beta power were observed bilaterally. When treated with levodopa, striatal beta oscillations significantly improved at six weeks compared to untreated animals (p=0.0298), and beta (p=0.0177) and alpha (p=0.0464) oscillations decreased in the ipsilateral DN at ten weeks.
Conclusion : This is the first time spectral dynamics in BG and cerebellum are investigated longitudinally in a PD model. These observations provide better insight regarding the dynamic engagement of the cerebellum during dopamine depletion and replacement therapy. This provides context for better understanding the role of the cerebellum in PD pathophysiology, as well as its potential as a therapeutic target.
.jpg)
