Interrogating basal ganglia circuit function in Parkinson's disease and dystonia

Sumarac, S.; Spencer, K. A.; Steiner, L. A.; Fearon, C.; Haniff, E.; Kuhn, A. A.; Hodaie, M.; Kalia, S. K.; Lozano, A. M.; Fasano, A.; Hutchison, W. D.; Milosevic, L.

doi:10.1101/2023.08.26.554666

bioRxiv · 10.1101/2023.08.26.554666

Interrogating basal ganglia circuit function in Parkinson's disease and dystonia

Sumarac, S.·Spencer, K. A.·Steiner, L. A.·Fearon, C.·Haniff, E.·Kuhn, A. A.·Hodaie, M.·Kalia, S. K.·Lozano, A. M.·Fasano, A.·Hutchison, W. D.·Milosevic, L.

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Abstract

BackgroundThe dichotomy between the hypo-versus hyperkinetic nature of Parkinsons disease (PD) and dystonia, respectively, is thought to be reflected in the underlying basal ganglia pathophysiology. ObjectiveInvestigate differences in globus pallidus internus (GPi) neuronal activity, and short- and long-term plasticity of direct pathway projections. ResultsGPi neurons were slower, burstier, and less regular in dystonia. In PD, symptom severity positively correlated with the power of low-beta frequency spiketrain oscillations. In dystonia, symptom severity negatively correlated with firing rate, and positively correlated with neuronal variability and the power of theta frequency spiketrain oscillations. Dystonia was moreover associated with less long-term plasticity and slower synaptic depression. ConclusionWe substantiated claims of hyper-versus hypofunctional GPi output in PD versus dystonia, and provided cellular-level validation of the pathological nature of theta and low-beta oscillations in respective disorders. Such circuit changes may be underlain by disease-related differences in plasticity of striato-pallidal synapses.

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Sumarac, S., Spencer, K. A., Steiner, L. A., Fearon, C., Haniff, E., Kuhn, A. A., Hodaie, M., Kalia, S. K., Lozano, A. M., Fasano, A., Hutchison, W. D., Milosevic, L.. 2023-08-28. Interrogating basal ganglia circuit function in Parkinson's disease and dystonia. https://doi.org/10.1101/2023.08.26.554666

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