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Deep brain stimulation-guided optogenetic rescue of parkinsonian symptoms

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  • Sébastien Valverde

    (Dynamics and Pathophysiology of Neuronal Networks Team, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR7241/INSERM U1050, MemoLife Labex)

  • Marie Vandecasteele

    (Dynamics and Pathophysiology of Neuronal Networks Team, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR7241/INSERM U1050, MemoLife Labex)

  • Charlotte Piette

    (Dynamics and Pathophysiology of Neuronal Networks Team, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR7241/INSERM U1050, MemoLife Labex
    Brandeis University)

  • Willy Derousseaux

    (Dynamics and Pathophysiology of Neuronal Networks Team, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR7241/INSERM U1050, MemoLife Labex)

  • Giuseppe Gangarossa

    (Dynamics and Pathophysiology of Neuronal Networks Team, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR7241/INSERM U1050, MemoLife Labex)

  • Asier Aristieta Arbelaiz

    (Dynamics and Pathophysiology of Neuronal Networks Team, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR7241/INSERM U1050, MemoLife Labex)

  • Jonathan Touboul

    (Brandeis University)

  • Bertrand Degos

    (Dynamics and Pathophysiology of Neuronal Networks Team, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR7241/INSERM U1050, MemoLife Labex
    Sorbonne Paris Nord University)

  • Laurent Venance

    (Dynamics and Pathophysiology of Neuronal Networks Team, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR7241/INSERM U1050, MemoLife Labex)

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.

Suggested Citation

  • Sébastien Valverde & Marie Vandecasteele & Charlotte Piette & Willy Derousseaux & Giuseppe Gangarossa & Asier Aristieta Arbelaiz & Jonathan Touboul & Bertrand Degos & Laurent Venance, 2020. "Deep brain stimulation-guided optogenetic rescue of parkinsonian symptoms," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16046-6
    DOI: 10.1038/s41467-020-16046-6
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    Cited by:

    1. Bérénice Coutant & Jimena Laura Frontera & Elodie Perrin & Adèle Combes & Thibault Tarpin & Fabien Menardy & Caroline Mailhes-Hamon & Sylvie Perez & Bertrand Degos & Laurent Venance & Clément Léna & D, 2022. "Cerebellar stimulation prevents Levodopa-induced dyskinesia in mice and normalizes activity in a motor network," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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