Optogenetic Stimulation of the M2 Cortex Reverts Motor Dysfunction in a Mouse Model of Parkinson’s Disease
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFMG |
Texto Completo: | https://doi.org/10.1523/JNEUROSCI.2277-18.2019 http://hdl.handle.net/1843/56636 https://orcid.org/0000-0002-7081-8401 |
Resumo: | Neuromodulation of deep brain structures (deep brain stimulation)isthe current surgical procedurefortreatment of Parkinson’s disease (PD). Less studied is the stimulation of cortical motor areas to treat PD symptoms, although also known to alleviate motor disturbances in PD.We were ableto showthat optogenetic activation of secondary (M2) motor cortex improves motorfunctions in dopamine-depleted male mice. The stimulated M2 cortex harbors glutamatergic pyramidal neurons that project to subcortical structures, critically involved inmotor control, andmakes synaptic contactswithdopaminergic neurons. Strikingly, optogenetic activation ofM2 neurons or axonsinto the dorsomedial striatum increases striatal levels of dopamine and evokes locomotor activity. We found that dopamine neurotransmission sensitizes the locomotor behavior elicited by activation of M2 neurons. Furthermore, combination of intranigral infusion of glutamatergic antagonists and circuit specific optogenetic stimulation revealed that behavioral response depended on the activity of M2 neurons projecting to SNc. Interestingly, repeated M2 stimulation combined with L-DOPA treatment produced an unanticipated improvement in working memory performance, which was absent in control mice under L-DOPA treatment only. Therefore, the M2-basal ganglia circuit is critical for the assembly of the motor and cognitive function, and this study demonstrates a therapeutic mechanism for cortical stimulation in PD that involves recruitment of long-range glutamatergic projection neurons. |
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2023-07-18T20:23:17Z2023-07-18T20:23:17Z2019-04-24391732343248https://doi.org/10.1523/JNEUROSCI.2277-18.20190270-6474http://hdl.handle.net/1843/56636https://orcid.org/0000-0002-7081-8401Neuromodulation of deep brain structures (deep brain stimulation)isthe current surgical procedurefortreatment of Parkinson’s disease (PD). Less studied is the stimulation of cortical motor areas to treat PD symptoms, although also known to alleviate motor disturbances in PD.We were ableto showthat optogenetic activation of secondary (M2) motor cortex improves motorfunctions in dopamine-depleted male mice. The stimulated M2 cortex harbors glutamatergic pyramidal neurons that project to subcortical structures, critically involved inmotor control, andmakes synaptic contactswithdopaminergic neurons. Strikingly, optogenetic activation ofM2 neurons or axonsinto the dorsomedial striatum increases striatal levels of dopamine and evokes locomotor activity. We found that dopamine neurotransmission sensitizes the locomotor behavior elicited by activation of M2 neurons. Furthermore, combination of intranigral infusion of glutamatergic antagonists and circuit specific optogenetic stimulation revealed that behavioral response depended on the activity of M2 neurons projecting to SNc. Interestingly, repeated M2 stimulation combined with L-DOPA treatment produced an unanticipated improvement in working memory performance, which was absent in control mice under L-DOPA treatment only. Therefore, the M2-basal ganglia circuit is critical for the assembly of the motor and cognitive function, and this study demonstrates a therapeutic mechanism for cortical stimulation in PD that involves recruitment of long-range glutamatergic projection neurons.engUniversidade Federal de Minas GeraisUFMGBrasilICB - DEPARTAMENTO DE PATOLOGIAICB - INSTITUTO DE CIÊNCIAS BIOLOGICASMED - DEPARTAMENTO DE PEDIATRIAThe Journal of NeuroscienceEncéfaloCogniçãoMovimentoOptogenéticaCórtex Pré-FrontalBrain stimulationCognitionMovementOptogeneticsParkinson’s disorderPrefrontal cortexOptogenetic Stimulation of the M2 Cortex Reverts Motor Dysfunction in a Mouse Model of Parkinson’s Diseaseinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://www.jneurosci.org/content/39/17/3234Luiz Alexandre Viana MagnoAlexander BirbrairDébora Marques MirandaMarco Aurélio Romano-silvaHelia Tenza-ferrerMélcar CollodettiMatheus Felipe Guimarães AguiarAna Paula Carneiro RodriguesRodrigo Souza da SilvaJoice do Prado SilvaNycolle Ferreira NicolauDaniela Valadão Freitas Rosaapplication/pdfinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGLICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/56636/1/License.txtfa505098d172de0bc8864fc1287ffe22MD51ORIGINALOptogenetic Stimulation of the M2 Cortex Reverts Motor Dysfunction in a Mouse Model of Parkinson’s Disease.pdfOptogenetic Stimulation of the M2 Cortex Reverts Motor Dysfunction in a Mouse Model of Parkinson’s Disease.pdfapplication/pdf5047986https://repositorio.ufmg.br/bitstream/1843/56636/2/Optogenetic%20Stimulation%20of%20the%20M2%20Cortex%20Reverts%20Motor%20Dysfunction%20in%20a%20Mouse%20Model%20of%20Parkinson%e2%80%99s%20Disease.pdf8d997d17e6d436f46427e675b5013183MD521843/566362023-07-18 17:23:18.007oai:repositorio.ufmg.br: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Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-07-18T20:23:18Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
dc.title.pt_BR.fl_str_mv |
Optogenetic Stimulation of the M2 Cortex Reverts Motor Dysfunction in a Mouse Model of Parkinson’s Disease |
title |
Optogenetic Stimulation of the M2 Cortex Reverts Motor Dysfunction in a Mouse Model of Parkinson’s Disease |
spellingShingle |
Optogenetic Stimulation of the M2 Cortex Reverts Motor Dysfunction in a Mouse Model of Parkinson’s Disease Luiz Alexandre Viana Magno Brain stimulation Cognition Movement Optogenetics Parkinson’s disorder Prefrontal cortex Encéfalo Cognição Movimento Optogenética Córtex Pré-Frontal |
title_short |
Optogenetic Stimulation of the M2 Cortex Reverts Motor Dysfunction in a Mouse Model of Parkinson’s Disease |
title_full |
Optogenetic Stimulation of the M2 Cortex Reverts Motor Dysfunction in a Mouse Model of Parkinson’s Disease |
title_fullStr |
Optogenetic Stimulation of the M2 Cortex Reverts Motor Dysfunction in a Mouse Model of Parkinson’s Disease |
title_full_unstemmed |
Optogenetic Stimulation of the M2 Cortex Reverts Motor Dysfunction in a Mouse Model of Parkinson’s Disease |
title_sort |
Optogenetic Stimulation of the M2 Cortex Reverts Motor Dysfunction in a Mouse Model of Parkinson’s Disease |
author |
Luiz Alexandre Viana Magno |
author_facet |
Luiz Alexandre Viana Magno Alexander Birbrair Débora Marques Miranda Marco Aurélio Romano-silva Helia Tenza-ferrer Mélcar Collodetti Matheus Felipe Guimarães Aguiar Ana Paula Carneiro Rodrigues Rodrigo Souza da Silva Joice do Prado Silva Nycolle Ferreira Nicolau Daniela Valadão Freitas Rosa |
author_role |
author |
author2 |
Alexander Birbrair Débora Marques Miranda Marco Aurélio Romano-silva Helia Tenza-ferrer Mélcar Collodetti Matheus Felipe Guimarães Aguiar Ana Paula Carneiro Rodrigues Rodrigo Souza da Silva Joice do Prado Silva Nycolle Ferreira Nicolau Daniela Valadão Freitas Rosa |
author2_role |
author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Luiz Alexandre Viana Magno Alexander Birbrair Débora Marques Miranda Marco Aurélio Romano-silva Helia Tenza-ferrer Mélcar Collodetti Matheus Felipe Guimarães Aguiar Ana Paula Carneiro Rodrigues Rodrigo Souza da Silva Joice do Prado Silva Nycolle Ferreira Nicolau Daniela Valadão Freitas Rosa |
dc.subject.por.fl_str_mv |
Brain stimulation Cognition Movement Optogenetics Parkinson’s disorder Prefrontal cortex |
topic |
Brain stimulation Cognition Movement Optogenetics Parkinson’s disorder Prefrontal cortex Encéfalo Cognição Movimento Optogenética Córtex Pré-Frontal |
dc.subject.other.pt_BR.fl_str_mv |
Encéfalo Cognição Movimento Optogenética Córtex Pré-Frontal |
description |
Neuromodulation of deep brain structures (deep brain stimulation)isthe current surgical procedurefortreatment of Parkinson’s disease (PD). Less studied is the stimulation of cortical motor areas to treat PD symptoms, although also known to alleviate motor disturbances in PD.We were ableto showthat optogenetic activation of secondary (M2) motor cortex improves motorfunctions in dopamine-depleted male mice. The stimulated M2 cortex harbors glutamatergic pyramidal neurons that project to subcortical structures, critically involved inmotor control, andmakes synaptic contactswithdopaminergic neurons. Strikingly, optogenetic activation ofM2 neurons or axonsinto the dorsomedial striatum increases striatal levels of dopamine and evokes locomotor activity. We found that dopamine neurotransmission sensitizes the locomotor behavior elicited by activation of M2 neurons. Furthermore, combination of intranigral infusion of glutamatergic antagonists and circuit specific optogenetic stimulation revealed that behavioral response depended on the activity of M2 neurons projecting to SNc. Interestingly, repeated M2 stimulation combined with L-DOPA treatment produced an unanticipated improvement in working memory performance, which was absent in control mice under L-DOPA treatment only. Therefore, the M2-basal ganglia circuit is critical for the assembly of the motor and cognitive function, and this study demonstrates a therapeutic mechanism for cortical stimulation in PD that involves recruitment of long-range glutamatergic projection neurons. |
publishDate |
2019 |
dc.date.issued.fl_str_mv |
2019-04-24 |
dc.date.accessioned.fl_str_mv |
2023-07-18T20:23:17Z |
dc.date.available.fl_str_mv |
2023-07-18T20:23:17Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1843/56636 |
dc.identifier.doi.pt_BR.fl_str_mv |
https://doi.org/10.1523/JNEUROSCI.2277-18.2019 |
dc.identifier.issn.pt_BR.fl_str_mv |
0270-6474 |
dc.identifier.orcid.pt_BR.fl_str_mv |
https://orcid.org/0000-0002-7081-8401 |
url |
https://doi.org/10.1523/JNEUROSCI.2277-18.2019 http://hdl.handle.net/1843/56636 https://orcid.org/0000-0002-7081-8401 |
identifier_str_mv |
0270-6474 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
The Journal of Neuroscience |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais |
dc.publisher.initials.fl_str_mv |
UFMG |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
ICB - DEPARTAMENTO DE PATOLOGIA ICB - INSTITUTO DE CIÊNCIAS BIOLOGICAS MED - DEPARTAMENTO DE PEDIATRIA |
publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais |
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reponame:Repositório Institucional da UFMG instname:Universidade Federal de Minas Gerais (UFMG) instacron:UFMG |
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Universidade Federal de Minas Gerais (UFMG) |
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