title: High frequency stimulation of the subthalamic nucleus acutely rescues motor deficits and neocortical movement representations following 6-hydroxydopamine administration in rats.
abstract: Loss of frontal neocortical activation is one of the main neurophysiological abnormalities of Parkinson's disease (PD) and can be observed in rodent models of nigrostriatal degeneration. High-frequency deep brain stimulation (DBS) of the subthalamic nucleus improves motor deficits in PD. However, it is unknown whether this general therapeutic effect is associated with a restoration of frontal output function. To address this question, chronic stimulating electrodes were implanted bilaterally into the subthalamic nuclei of adult rats that received either bilateral intrastriatal 6-hydroxydopamine (6-OHDA) or vehicle infusion to induce nigrostriatal degeneration. Forelimb use and locomotor activity were assessed based on the cylinder and open field tests in intact, post-lesion+sham DBS, and post-lesion+DBS conditions. Intracortical microstimulation was then used to probe frontal output function of forelimb motor areas. DBS was found to improve motor deficits arising from 6-OHDA lesions, increase forelimb map area, and decrease movement thresholds relative to baseline. These effects were significantly greater in 6-OHDA lesion rats compared to vehicle controls. Results indicate that changes in motor map expression can take place during subthalamic DBS following dopamine depletion in a rodent model of PD.
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Alberta, Canada.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Brown
authors.forename: Michael C
authors.initials: MC
authors.lastname: Antle
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.forename: G Campbell
authors.initials: GC
authors.lastname: Teskey
mesh_terms: D000818:Animals; D046690:Deep Brain Stimulation / Q000379:methods*; D004567:Electrodes, Implanted; D008297:Male; D009069:Movement Disorders / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy*; D019579:Neocortex / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D009498:Neurotoxins / Q000633:toxicity; D016627:Oxidopamine / Q000633:toxicity*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000503:physiopathology* / Q000628:therapy*; D051381:Rats; D020318:Rats, Long-Evans; D020531:Subthalamic Nucleus / Q000187:drug effects / Q000473:pathology* / Q000502:physiology
chemical_list: D009498:Neurotoxins; D016627:Oxidopamine