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Bidirectional Optogenetic Modulation of the Subthalamic Nucleus in a Rodent Model of Parkinson’s Disease

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a range of motor symptoms. Treatments are focused on dopamine replacement therapy or deep brain stimulation (DBS). The subthalamic nucleus (STN) is a common target for DBS treatment of PD. However, the function of the STN in n...

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Autores principales: Xie, Caroline, Power, John, Prasad, Asheeta A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9152094/
https://www.ncbi.nlm.nih.gov/pubmed/35655750
http://dx.doi.org/10.3389/fnins.2022.848821
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author Xie, Caroline
Power, John
Prasad, Asheeta A.
author_facet Xie, Caroline
Power, John
Prasad, Asheeta A.
author_sort Xie, Caroline
collection PubMed
description Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a range of motor symptoms. Treatments are focused on dopamine replacement therapy or deep brain stimulation (DBS). The subthalamic nucleus (STN) is a common target for DBS treatment of PD. However, the function of the STN in normal conditions and pathology is poorly understood. Here, we show in rats that optogenetic modulation of STN neuronal activity exerts bidirectional control of motor function, where inhibition of the STN increases movement and STN activation decreases movement. We also examined the effect of bidirectional optogenetic manipulation STN neuronal activity under dopamine depleted condition using the bilateral rodent 6-hydroxydopamine (6-OHDA) model of Parkinson’s disease. Optogenetic inhibition of the STN in the absence of dopamine had no impact on motor control yet STN excitation led to pronounced abnormal involuntary movement. Administration of levodopa rescued the abnormal involuntary movements induced by STN excitation. Although dopamine and STN dysfunction are well established in PD pathology, here we demonstrate simultaneous STN over activity and loss of dopamine lead to motor deficits. Moreover, we show the dysfunction of the STN is dependent on dopamine. This study provides evidence that the loss of dopamine and the over activity of the STN are key features of PD motor deficits. These results provide insight into the STN pathology in PD and therapeutic mechanism of targeting the STN for the treatment for PD.
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spelling pubmed-91520942022-06-01 Bidirectional Optogenetic Modulation of the Subthalamic Nucleus in a Rodent Model of Parkinson’s Disease Xie, Caroline Power, John Prasad, Asheeta A. Front Neurosci Neuroscience Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a range of motor symptoms. Treatments are focused on dopamine replacement therapy or deep brain stimulation (DBS). The subthalamic nucleus (STN) is a common target for DBS treatment of PD. However, the function of the STN in normal conditions and pathology is poorly understood. Here, we show in rats that optogenetic modulation of STN neuronal activity exerts bidirectional control of motor function, where inhibition of the STN increases movement and STN activation decreases movement. We also examined the effect of bidirectional optogenetic manipulation STN neuronal activity under dopamine depleted condition using the bilateral rodent 6-hydroxydopamine (6-OHDA) model of Parkinson’s disease. Optogenetic inhibition of the STN in the absence of dopamine had no impact on motor control yet STN excitation led to pronounced abnormal involuntary movement. Administration of levodopa rescued the abnormal involuntary movements induced by STN excitation. Although dopamine and STN dysfunction are well established in PD pathology, here we demonstrate simultaneous STN over activity and loss of dopamine lead to motor deficits. Moreover, we show the dysfunction of the STN is dependent on dopamine. This study provides evidence that the loss of dopamine and the over activity of the STN are key features of PD motor deficits. These results provide insight into the STN pathology in PD and therapeutic mechanism of targeting the STN for the treatment for PD. Frontiers Media S.A. 2022-05-17 /pmc/articles/PMC9152094/ /pubmed/35655750 http://dx.doi.org/10.3389/fnins.2022.848821 Text en Copyright © 2022 Xie, Power and Prasad. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Xie, Caroline
Power, John
Prasad, Asheeta A.
Bidirectional Optogenetic Modulation of the Subthalamic Nucleus in a Rodent Model of Parkinson’s Disease
title Bidirectional Optogenetic Modulation of the Subthalamic Nucleus in a Rodent Model of Parkinson’s Disease
title_full Bidirectional Optogenetic Modulation of the Subthalamic Nucleus in a Rodent Model of Parkinson’s Disease
title_fullStr Bidirectional Optogenetic Modulation of the Subthalamic Nucleus in a Rodent Model of Parkinson’s Disease
title_full_unstemmed Bidirectional Optogenetic Modulation of the Subthalamic Nucleus in a Rodent Model of Parkinson’s Disease
title_short Bidirectional Optogenetic Modulation of the Subthalamic Nucleus in a Rodent Model of Parkinson’s Disease
title_sort bidirectional optogenetic modulation of the subthalamic nucleus in a rodent model of parkinson’s disease
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9152094/
https://www.ncbi.nlm.nih.gov/pubmed/35655750
http://dx.doi.org/10.3389/fnins.2022.848821
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