title: Optogenetic Inhibition of the Subthalamic Nucleus Reduces Levodopa-Induced Dyskinesias in a Rat Model of Parkinson's Disease.
abstract: BACKGROUND
  The inhibition of neuronal activity by electrical deep brain stimulation is one of the mechanisms explaining the amelioration of levodopa-induced dyskinesia. However, electrical deep brain stimulation cannot specifically activate or inactivate selected types of neurons.
  
  
  OBJECTIVE
  We applied optogenetics as an alternative treatment to deep brain stimulation for levodopa-induced dyskinesia, and also to confirm that the mechanism of levodopa-induced dyskinesia amelioration by subthalamic nucleus deep brain stimulation is mediated through neuronal inhibition.
  
  
  METHODS
  6-hydroxydopamine-induced hemiparkinsonian rats received injections of hSynapsin1-NpHR-YFP adeno-associated virus (AAV) or hSynapsin1-YFP AAV. Two weeks after viral injections, all rats were treated with daily injections of levodopa. Then, the optic fiber was implanted into the ipsilateral subthalamic nucleus. We performed various behavioral tests to evaluate the changes in levodopa-induced dyskinesias after optogenetic expression and illumination in the subthalamic nucleus.
  
  
  RESULTS
  The behavioral tests revealed that optical inhibition of the subthalamic nucleus significantly ameliorated levodopa-induced dyskinesia by reducing the duration of the dyskinesias as well as the severity of axial dyskinesia.
  
  
  CONCLUSIONS
  These findings will provide a useful foundation for the future development of optogenetic modulation systems that could be considered as an approach to dyskinesia therapy.
authors.affiliation: Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyung Ho
authors.initials: HH
authors.lastname: Yoon
authors.forename: Joongkee
authors.initials: J
authors.lastname: Min
authors.forename: Eunmi
authors.initials: E
authors.lastname: Hwang
authors.forename: C Justin
authors.initials: CJ
authors.lastname: Lee
authors.forename: Jun-Kyo Francis
authors.initials: JK
authors.lastname: Suh
authors.forename: Onyou
authors.initials: O
authors.lastname: Hwang
authors.forename: Sang Ryong
authors.initials: SR
authors.lastname: Jeon
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology / Q000628:therapy*; D007980:Levodopa; D062308:Optogenetics; D010300:Parkinson Disease / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D020531:Subthalamic Nucleus / Q000503:physiopathology*
chemical_list: D007980:Levodopa