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http://hdl.handle.net/1843/56636| Type: | Artigo de Periódico |
| Title: | Optogenetic Stimulation of the M2 Cortex Reverts Motor Dysfunction in a Mouse Model of Parkinson’s Disease |
| Authors: | 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 |
| Abstract: | 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. |
| Subject: | Encéfalo Cognição Movimento Optogenética Córtex Pré-Frontal |
| language: | eng |
| metadata.dc.publisher.country: | Brasil |
| Publisher: | Universidade Federal de Minas Gerais |
| Publisher Initials: | UFMG |
| metadata.dc.publisher.department: | ICB - DEPARTAMENTO DE PATOLOGIA ICB - INSTITUTO DE CIÊNCIAS BIOLOGICAS MED - DEPARTAMENTO DE PEDIATRIA |
| Rights: | Acesso Aberto |
| metadata.dc.identifier.doi: | https://doi.org/10.1523/JNEUROSCI.2277-18.2019 |
| URI: | http://hdl.handle.net/1843/56636 |
| Issue Date: | 24-Apr-2019 |
| metadata.dc.url.externa: | https://www.jneurosci.org/content/39/17/3234 |
| metadata.dc.relation.ispartof: | The Journal of Neuroscience |
| Appears in Collections: | Artigo de Periódico |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| Optogenetic Stimulation of the M2 Cortex Reverts Motor Dysfunction in a Mouse Model of Parkinson’s Disease.pdf | 4.93 MB | Adobe PDF | View/Open |
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