Dopamine depletion leads to pathological synchronization of distinct basal ganglia loops in the beta band

• Main Authors: Ahmadipour, M. (Author), Mannella, R. (Author), Mazzoni, A. (Author), Ortone, A. (Author), Vergani, A.A (Author)
• Format: Article
• Language: English
• Published: NLM (Medline) 2023
• Subjects: Basal Ganglia; basal ganglion; dopamine; Dopamine; globus pallidus; Globus Pallidus; human; Humans; Parkinson disease; Parkinson Disease; physiology; subthalamic nucleus; Subthalamic Nucleus
• Online Access: View Fulltext in Publisher; View in Scopus
• ISBN: 15537358 (ISSN)
• DOI: 10.1371/journal.pcbi.1010645

Motor symptoms of Parkinson's Disease (PD) are associated with dopamine deficits and pathological oscillation of basal ganglia (BG) neurons in the β range ([12-30] Hz). However, how dopamine depletion affects the oscillation dynamics of BG nuclei is still unclear. With a spiking neurons model, we here capture the features of BG nuclei interactions leading to oscillations in dopamine-depleted condition. We highlight that both the loop between subthalamic nucleus (STN) and Globus Pallidus pars externa (GPe) and the loop between striatal fast spiking and medium spiny neurons and GPe display resonances in the β range, and synchronize to a common β frequency through interaction. Crucially, the synchronization depends on dopamine depletion: the two loops are largely independent for high levels of dopamine, but progressively synchronize as dopamine is depleted due to the increased strength of the striatal loop. The model is validated against recent experimental reports on the role of cortical inputs, STN and GPe activity in the generation of β oscillations. Our results highlight the role of the interplay between the GPe-STN and the GPe-striatum loop in generating sustained β oscillations in PD subjects, and explain how this interplay depends on the level of dopamine. This paves the way to the design of therapies specifically addressing the onset of pathological β oscillations. Copyright: © 2023 Ortone et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.