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.
Highlights
We studied the dyskinetic and anti-akinetic effects of subthalamic nucleus (STN) HFS and their relations to electrode location in the rat 6-OHDA model of Parkinson’s disease (PD) to further refine select methodological issues
We found that dyskinetic effects could be graded live during test stimulations with gradually increasing stimulation currents
Grading dyskinesias in this fashion can provide for greater fidelity than in the commonly used method of reporting threshold where dyskinesia appears [9]. This can be used to choose lower or higher stimulation currents to provide for both modest and considerable improvements in akinesia on individual bases. This is important since we observed considerable individual variation in the currents that induced the desired levels of dyskinesias and anti-akinetic effect, the range was within what has been previously used for stainless steel electrodes [9,10,14]
Summary
Given these considerable variations in the methodological details of rodent STN HFS, the aim of this study was: A) to further refine the method of grading STN HFS-–induced dyskinesias, as well as B) their use in choosing individual stimulation currents; C) to refine cylinder test behavioral analyses; D) to clarify the dose response of STN HFS in the reversal of forelimb use asymmetry; and E) to further explore the use of stimulation-induced dyskinesias as a marker of successful electrode placement in the STN
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