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Deep brain stimulation-guided optogenetic rescue of parkinsonian symptoms
Deep brain stimulation (DBS) of the subthalamic nucleus is a symptomatic treatment of Parkinson’s disease but benefits only to a minority of patients due to stringent eligibility criteria. To investigate new targets for less invasive therapies, we aimed at elucidating key mechanisms supporting deep...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220902/ https://www.ncbi.nlm.nih.gov/pubmed/32404907 http://dx.doi.org/10.1038/s41467-020-16046-6 |
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author | Valverde, Sébastien Vandecasteele, Marie Piette, Charlotte Derousseaux, Willy Gangarossa, Giuseppe Aristieta Arbelaiz, Asier Touboul, Jonathan Degos, Bertrand Venance, Laurent |
author_facet | Valverde, Sébastien Vandecasteele, Marie Piette, Charlotte Derousseaux, Willy Gangarossa, Giuseppe Aristieta Arbelaiz, Asier Touboul, Jonathan Degos, Bertrand Venance, Laurent |
author_sort | Valverde, Sébastien |
collection | PubMed |
description | Deep brain stimulation (DBS) of the subthalamic nucleus is a symptomatic treatment of Parkinson’s disease but benefits only to a minority of patients due to stringent eligibility criteria. To investigate new targets for less invasive therapies, we aimed at elucidating key mechanisms supporting deep brain stimulation efficiency. Here, using in vivo electrophysiology, optogenetics, behavioral tasks and mathematical modeling, we found that subthalamic stimulation normalizes pathological hyperactivity of motor cortex pyramidal cells, while concurrently activating somatostatin and inhibiting parvalbumin interneurons. In vivo opto-activation of cortical somatostatin interneurons alleviates motor symptoms in a parkinsonian mouse model. A computational model highlights that a decrease in pyramidal neuron activity induced by DBS or by a stimulation of cortical somatostatin interneurons can restore information processing capabilities. Overall, these results demonstrate that activation of cortical somatostatin interneurons may constitute a less invasive alternative than subthalamic stimulation. |
format | Online Article Text |
id | pubmed-7220902 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-72209022020-05-15 Deep brain stimulation-guided optogenetic rescue of parkinsonian symptoms Valverde, Sébastien Vandecasteele, Marie Piette, Charlotte Derousseaux, Willy Gangarossa, Giuseppe Aristieta Arbelaiz, Asier Touboul, Jonathan Degos, Bertrand Venance, Laurent Nat Commun Article Deep brain stimulation (DBS) of the subthalamic nucleus is a symptomatic treatment of Parkinson’s disease but benefits only to a minority of patients due to stringent eligibility criteria. To investigate new targets for less invasive therapies, we aimed at elucidating key mechanisms supporting deep brain stimulation efficiency. Here, using in vivo electrophysiology, optogenetics, behavioral tasks and mathematical modeling, we found that subthalamic stimulation normalizes pathological hyperactivity of motor cortex pyramidal cells, while concurrently activating somatostatin and inhibiting parvalbumin interneurons. In vivo opto-activation of cortical somatostatin interneurons alleviates motor symptoms in a parkinsonian mouse model. A computational model highlights that a decrease in pyramidal neuron activity induced by DBS or by a stimulation of cortical somatostatin interneurons can restore information processing capabilities. Overall, these results demonstrate that activation of cortical somatostatin interneurons may constitute a less invasive alternative than subthalamic stimulation. Nature Publishing Group UK 2020-05-13 /pmc/articles/PMC7220902/ /pubmed/32404907 http://dx.doi.org/10.1038/s41467-020-16046-6 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Valverde, Sébastien Vandecasteele, Marie Piette, Charlotte Derousseaux, Willy Gangarossa, Giuseppe Aristieta Arbelaiz, Asier Touboul, Jonathan Degos, Bertrand Venance, Laurent Deep brain stimulation-guided optogenetic rescue of parkinsonian symptoms |
title | Deep brain stimulation-guided optogenetic rescue of parkinsonian symptoms |
title_full | Deep brain stimulation-guided optogenetic rescue of parkinsonian symptoms |
title_fullStr | Deep brain stimulation-guided optogenetic rescue of parkinsonian symptoms |
title_full_unstemmed | Deep brain stimulation-guided optogenetic rescue of parkinsonian symptoms |
title_short | Deep brain stimulation-guided optogenetic rescue of parkinsonian symptoms |
title_sort | deep brain stimulation-guided optogenetic rescue of parkinsonian symptoms |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220902/ https://www.ncbi.nlm.nih.gov/pubmed/32404907 http://dx.doi.org/10.1038/s41467-020-16046-6 |
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