Deep brain stimulation-guided optogenetic rescue of parkinsonian symptoms
Open Access
- 13 May 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 11 (1), 1-17
- https://doi.org/10.1038/s41467-020-16046-6
Abstract
Deep brain stimulation (DBS) of the subthalamic nucleus is a symptomatic treatment of Parkinson’s disease but benefits only to a minority of patients due to stringent eligibility criteria. To investigate new targets for less invasive therapies, we aimed at elucidating key mechanisms supporting deep brain stimulation efficiency. Here, using in vivo electrophysiology, optogenetics, behavioral tasks and mathematical modeling, we found that subthalamic stimulation normalizes pathological hyperactivity of motor cortex pyramidal cells, while concurrently activating somatostatin and inhibiting parvalbumin interneurons. In vivo opto-activation of cortical somatostatin interneurons alleviates motor symptoms in a parkinsonian mouse model. A computational model highlights that a decrease in pyramidal neuron activity induced by DBS or by a stimulation of cortical somatostatin interneurons can restore information processing capabilities. Overall, these results demonstrate that activation of cortical somatostatin interneurons may constitute a less invasive alternative than subthalamic stimulation.Keywords
Funding Information
- Fondation de France
- Association France Parkinson
- Centre National de la Recherche Scientifique
- Fondation Patrick Brou de Laurière Caisse de retraite et de prévoyance des clercs et employés de notaires
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