RT Journal Article
SR Electronic
T1 Optogenetic stimulation of the M2 cortex reverts motor dysfunction in a mouse model of Parkinson's Disease
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 2277-18
DO 10.1523/JNEUROSCI.2277-18.2019
A1 Luiz Alexandre Viana Magno
A1 Helia Tenza-Ferrer
A1 Mélcar Collodetti
A1 Matheus Felipe Guimarães Aguiar
A1 Ana Paula Carneiro Rodrigues
A1 Rodrigo Souza da Silva
A1 Joice do Prado Silva
A1 Nycolle Ferreira Nicolau
A1 Daniela Valadão Freitas Rosa
A1 Alexander Birbrair
A1 Débora Marques Miranda
A1 Marco Aurélio Romano-Silva
YR 2019
UL http://www.jneurosci.org/content/early/2019/02/19/JNEUROSCI.2277-18.2019.abstract
AB Neuromodulation of deep brain structures (deep brain stimulation - DBS) is the current surgical procedure for treatment of Parkinson's disease. Less studied is the stimulation of cortical motor areas to treat PD symptoms, although also known to alleviate motor disturbances in PD. We were able to show that optogenetic activation of secondary (M2) motor cortex improves motor functions in dopamine-depleted male mice. The stimulated M2 cortex harbors glutamatergic pyramidal neurons that project to subcortical structures, critically involved in motor control, and makes synaptic contacts with dopaminergic neurons. Strikingly, optogenetic activation of M2 neurons or axons into 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 substantia nigra pars compacta (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.SIGNIFICANCE STATEMENTSome patients with Parkinson's disease are offered treatment through surgery, which consists of delivering electrical current to regions deep within the brain. This study shows that stimulation of an area located on the brain surface, known as the secondary motor cortex, can also reverse movement disorders in mice. Authors have used a brain stimulation technique called optogenetics, which allowed targeting a specific type of surface neuron that communicates with the deep part of the brain involved in movement control. The study also shows that a combination of this stimulation with drug treatment might be useful to treat memory impairment, a kind of cognitive problem in Parkinson's.