Objective: The aim of our study was to investigate neuronal network activity in the basal ganglia (BG) and cerebellum (CB) in Rapid-Onset Dystonia-Parkinsonism (RDP).

Background: RDP is a rare neurological disease caused by ATP1A3 mutation. Symptoms are characterized by the sudden onset of both dystonia and parkinsonism, which manifest after stressful events and remain stable. Currently, there are no treatment options. Ouabain is a highly selective toxin, blocking the a3-subunit activity of a Na⁺-/K⁺-ATPase that can be used to model RDP in rodents. Recent studies showed that an Ouabain infusion into BG induces parkinsonism, whereas dystonia can be generated by an infusion into CB. A combined infusion at both sites induces dystonia-parkinsonism similar to the human disease. Prior publications support that disease symptoms in RDP are mediated by a combined dysfunction of BG and CB. However, the underlying network disorder has not been sufficiently explored so far.

Method: We infused Ouabain in rats by osmotic pumps either in the CB, striatum (STR) or at both places simultaneously. Motor behavior was scored using published rating systems. After the onset of symptoms, we performed parallel in vivo recordings of local field potentials (LFP) under urethane anesthesia from the primary cortex (M1), deep cerebellar nuclei (DCN) and substantia nigra reticulata (SNr). Data was compared with untreated controls.

Results: Rats with Ouabain infusion into CB developed severe dystonia. Peak frequency power and coherence showed a highly significant increase in gamma activity (55-80 Hz) in all recorded network nuclei compared to the controls (Average peaks [Hz] M1: 65, SNr: 66, DCN: 65). In contrast striatal Ouabain infusion resulted in akinetic animals. Analysis of the LFPs revealed a significant increase in beta oscillations (13-30 Hz, peak frequencies [Hz] DCN: 19, SNr: 20, M1: 22). In addition, we observed a significant decrease in the gamma power. Rats with a combined infusion into STR/CB developed dystonia-parkinsonism. Beta power was increased in the DCN, whereas gamma activity decreased in M1, SNr and DCN. Coherence analysis demonstrated a significant elevation of beta activity between CB and BG. However, gamma coherence was significantly reduced.

Conclusion: In our animal model of RDP gamma oscillations were related to dystonic symptoms, whereas beta oscillations were related to parkinsonism and dystonia-parkinsonism.

« Back to 2023 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/pathological-neuronal-oscillations-in-an-animal-model-of-rapid-onset-dystonia-parkinsonism/