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Altered Dynamic Information Flow through the Cortico-Basal Ganglia Pathways Mediates Parkinson’s Disease Symptoms
Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by dopamine deficiency. To elucidate network-level changes through the cortico-basal ganglia pathways in PD, we recorded neuronal activity in PD monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. We applied e...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Oxford University Press
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568006/ https://www.ncbi.nlm.nih.gov/pubmed/34268560 http://dx.doi.org/10.1093/cercor/bhab164 |
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author | Chiken, Satomi Takada, Masahiko Nambu, Atsushi |
author_facet | Chiken, Satomi Takada, Masahiko Nambu, Atsushi |
author_sort | Chiken, Satomi |
collection | PubMed |
description | Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by dopamine deficiency. To elucidate network-level changes through the cortico-basal ganglia pathways in PD, we recorded neuronal activity in PD monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. We applied electrical stimulation to the motor cortices and examined responses in the internal (GPi) and external (GPe) segments of the globus pallidus, the output and relay nuclei of the basal ganglia, respectively. In the normal state, cortical stimulation induced a triphasic response composed of early excitation, inhibition, and late excitation in the GPi and GPe. In the PD state, cortically evoked inhibition in the GPi mediated by the cortico-striato-GPi “direct” pathway was largely diminished, whereas late excitation in the GPe mediated by the cortico-striato-GPe-subthalamo (STN)-GPe pathway was elongated. l-DOPA treatment ameliorated PD signs, particularly akinesia/bradykinesia, and normalized cortically evoked responses in both the GPi and GPe. STN blockade by muscimol injection ameliorated the motor deficit and unmasked cortically evoked inhibition in the GPi. These results suggest that information flow through the direct pathway responsible for the initiation of movements is largely reduced in PD and fails to release movements, resulting in akinesia/bradykinesia. Restoration of the information flow through the direct pathway recovers execution of voluntary movements. |
format | Online Article Text |
id | pubmed-8568006 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-85680062021-11-05 Altered Dynamic Information Flow through the Cortico-Basal Ganglia Pathways Mediates Parkinson’s Disease Symptoms Chiken, Satomi Takada, Masahiko Nambu, Atsushi Cereb Cortex Original Article Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by dopamine deficiency. To elucidate network-level changes through the cortico-basal ganglia pathways in PD, we recorded neuronal activity in PD monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. We applied electrical stimulation to the motor cortices and examined responses in the internal (GPi) and external (GPe) segments of the globus pallidus, the output and relay nuclei of the basal ganglia, respectively. In the normal state, cortical stimulation induced a triphasic response composed of early excitation, inhibition, and late excitation in the GPi and GPe. In the PD state, cortically evoked inhibition in the GPi mediated by the cortico-striato-GPi “direct” pathway was largely diminished, whereas late excitation in the GPe mediated by the cortico-striato-GPe-subthalamo (STN)-GPe pathway was elongated. l-DOPA treatment ameliorated PD signs, particularly akinesia/bradykinesia, and normalized cortically evoked responses in both the GPi and GPe. STN blockade by muscimol injection ameliorated the motor deficit and unmasked cortically evoked inhibition in the GPi. These results suggest that information flow through the direct pathway responsible for the initiation of movements is largely reduced in PD and fails to release movements, resulting in akinesia/bradykinesia. Restoration of the information flow through the direct pathway recovers execution of voluntary movements. Oxford University Press 2021-07-16 /pmc/articles/PMC8568006/ /pubmed/34268560 http://dx.doi.org/10.1093/cercor/bhab164 Text en © The Author(s) 2021. Published by Oxford University Press. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Original Article Chiken, Satomi Takada, Masahiko Nambu, Atsushi Altered Dynamic Information Flow through the Cortico-Basal Ganglia Pathways Mediates Parkinson’s Disease Symptoms |
title | Altered Dynamic Information Flow through the Cortico-Basal Ganglia Pathways Mediates Parkinson’s Disease Symptoms |
title_full | Altered Dynamic Information Flow through the Cortico-Basal Ganglia Pathways Mediates Parkinson’s Disease Symptoms |
title_fullStr | Altered Dynamic Information Flow through the Cortico-Basal Ganglia Pathways Mediates Parkinson’s Disease Symptoms |
title_full_unstemmed | Altered Dynamic Information Flow through the Cortico-Basal Ganglia Pathways Mediates Parkinson’s Disease Symptoms |
title_short | Altered Dynamic Information Flow through the Cortico-Basal Ganglia Pathways Mediates Parkinson’s Disease Symptoms |
title_sort | altered dynamic information flow through the cortico-basal ganglia pathways mediates parkinson’s disease symptoms |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568006/ https://www.ncbi.nlm.nih.gov/pubmed/34268560 http://dx.doi.org/10.1093/cercor/bhab164 |
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