High frequency stimulation of the subthalamic nucleus acutely rescues motor deficits and neocortical movement representations following 6-hydroxydopamine administration in rats |
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Authors: | Brown Andrew R Antle Michael C Hu Bin Teskey G Campbell |
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Institution: | aHotchkiss Brain Institute, University of Calgary, Alberta, Canada;bDepartment of Psychology, University of Calgary, Alberta, Canada;cDepartment of Physiology and Pharmacology, University of Calgary, Alberta, Canada;dDepartment of Clinical Neurosciences, University of Calgary, Alberta, Canada;eDepartment of Cell Biology and Anatomy, University of Calgary, Alberta, Canada |
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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. |
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Keywords: | Deep brain stimulation Motor map Dopamine 6-Hydroxydopamine Behaviour Subthalamic nucleus Parkinson's disease |
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