Optogenetic Stimulation of the M2 Cortex Reverts Motor Dysfunction in a Mouse Model of Parkinson’s Disease

• Autor(a) principal: Luiz Alexandre Viana Magno
• Data de Publicação: 2019
• Outros Autores: 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
• 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
• topic: Brain stimulation; Cognition; Movement; Optogenetics; Parkinson’s disorder; Prefrontal cortex; Encéfalo; Cognição; Movimento; Optogenética; Córtex Pré-Frontal

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.