Rat subthalamic stimulation: Evaluating stimulation-induced dyskinesias, choosing stimulation currents and evaluating the anti-akinetic effect in the cylinder test

Abstract

In experimental deep brain stimulation of the subthalamic nucleus (STN HFS), stimulation currents just below the appearance threshold of stimulation-induced dyskinesias has often been used. The behavioral effect of STN HFS can be measured by the reversal of forelimb use asymmetry produced by hemiparkinsonism can be measured with the cylinder test among other tests. We used 18 Wistar rats with 6-hydroxydopamine induced hemiparkinsonism to test a customized scale to rate the severity of stimulation-induced dyskinesia; we then used these ratings to choose low and high stimulation currents. Subsequent cylinder tests showed that stimulation at the higher current, inducing mild and short-lived dyskinesias, was required for robust improvement in forelimb use, contradicting the use of currents below stimulation-induced dyskinesia threshold. It was also beneficial to separately count both all touches and first touches with the cylinder wall; this provided additional sensitivity and robustness to our results. • Scoring stimulation-induced dyskinesias can be used as a quantitative measure of dyskinesias and to choose stimulation currents. • Cylinder test scoring separately for both first and all touches can improve both sensitivity and reliability. • STN HFS at a current producing short-lived dyskinesias was required for robust improvement in forelimb use asymmetry. Method name: Subthalamic high frequency stimulation, cylinder test, Keywords: STN DBS, STN HFS, 6-OHDA, Parkinson’s disease, Cylinder test, Dyskinesia