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

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 he...

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Autores principales: Ortone, Andrea, Vergani, Alberto Arturo, Ahmadipour, Mahboubeh, Mannella, Riccardo, Mazzoni, Alberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10168586/
https://www.ncbi.nlm.nih.gov/pubmed/37104542
http://dx.doi.org/10.1371/journal.pcbi.1010645
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author Ortone, Andrea
Vergani, Alberto Arturo
Ahmadipour, Mahboubeh
Mannella, Riccardo
Mazzoni, Alberto
author_facet Ortone, Andrea
Vergani, Alberto Arturo
Ahmadipour, Mahboubeh
Mannella, Riccardo
Mazzoni, Alberto
author_sort Ortone, Andrea
collection PubMed
description 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.
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spelling pubmed-101685862023-05-10 Dopamine depletion leads to pathological synchronization of distinct basal ganglia loops in the beta band Ortone, Andrea Vergani, Alberto Arturo Ahmadipour, Mahboubeh Mannella, Riccardo Mazzoni, Alberto PLoS Comput Biol Research Article 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. Public Library of Science 2023-04-27 /pmc/articles/PMC10168586/ /pubmed/37104542 http://dx.doi.org/10.1371/journal.pcbi.1010645 Text en © 2023 Ortone et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ortone, Andrea
Vergani, Alberto Arturo
Ahmadipour, Mahboubeh
Mannella, Riccardo
Mazzoni, Alberto
Dopamine depletion leads to pathological synchronization of distinct basal ganglia loops in the beta band
title Dopamine depletion leads to pathological synchronization of distinct basal ganglia loops in the beta band
title_full Dopamine depletion leads to pathological synchronization of distinct basal ganglia loops in the beta band
title_fullStr Dopamine depletion leads to pathological synchronization of distinct basal ganglia loops in the beta band
title_full_unstemmed Dopamine depletion leads to pathological synchronization of distinct basal ganglia loops in the beta band
title_short Dopamine depletion leads to pathological synchronization of distinct basal ganglia loops in the beta band
title_sort dopamine depletion leads to pathological synchronization of distinct basal ganglia loops in the beta band
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10168586/
https://www.ncbi.nlm.nih.gov/pubmed/37104542
http://dx.doi.org/10.1371/journal.pcbi.1010645
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