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Publication : Deep brain stimulation-guided optogenetic rescue of parkinsonian symptoms.

First Author  Valverde S Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  2388
PubMed ID  32404907 Mgi Jnum  J:292280
Mgi Id  MGI:6447741 Doi  10.1038/s41467-020-16046-6
Citation  Valverde S, et al. (2020) Deep brain stimulation-guided optogenetic rescue of parkinsonian symptoms. Nat Commun 11(1):2388
abstractText  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.
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