Deep brain stimulation-guided optogenetic rescue of parkinsonian symptoms

• Published in: Nature communications 2020-05, Vol.11 (1), p.2388-17, Article 2388
• Main Authors: Valverde, Sébastien, Vandecasteele, Marie, Piette, Charlotte, Derousseaux, Willy, Gangarossa, Giuseppe, Aristieta Arbelaiz, Asier, Touboul, Jonathan, Degos, Bertrand, Venance, Laurent
• Format: Article
• Language: English
• Subjects: 13; 631/114/116/2394; 631/378/1689/1718; 631/378/2632/1663; 9/30; 9/74; Activation; Algorithms; Animals; Antiparkinson Agents - therapeutic use; Basal ganglia; Brain; Central nervous system diseases; Computational neuroscience; Cortex (motor); Data processing; Deep brain stimulation; Deep Brain Stimulation - methods; Disease Models, Animal; Electrical stimuli; Electrophysiological Phenomena - drug effects; Electrophysiology; Female; Genetics; Humanities and Social Sciences; Humans; Hyperactivity; Information processing; Interneurons; Levodopa - therapeutic use; Life Sciences; Male; Mathematical models; Medical treatment; Mice, Inbred C57BL; Mice, Transgenic; Motor Cortex - drug effects; Motor Cortex - metabolism; Motor Cortex - physiopathology; Mouse devices; Movement disorders; multidisciplinary; Neurobiology; Neurodegenerative diseases; Neurons and Cognition; Optics; Optogenetics - methods; Oxidopamine; Parkinson's disease; Parkinsonian Disorders - chemically induced; Parkinsonian Disorders - physiopathology; Parkinsonian Disorders - therapy; Parvalbumin; Pyramidal cells; Pyramidal Cells - drug effects; Pyramidal Cells - metabolism; Pyramidal Cells - physiology; Science; Science (multidisciplinary); Signs and symptoms; Somatostatin; Somatostatin - metabolism; Stimulation; Subthalamic nucleus; Subthalamic Nucleus - drug effects; Subthalamic Nucleus - metabolism; Subthalamic Nucleus - physiopathology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-16046-6

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. Deep brain stimulation (DBS) is a symptomatic treatment of Parkinson’s disease (PD) that benefits only a minority of patients. Here, the authors show that activation of cortical somatostatin interneurons alleviates motor symptoms in a mouse model of PD and may constitute a less invasive alternative than DBS.