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.