Artikel
Hyperactivity of the subthalamic nucleus in the rat 6-hydroxydopamine Parkinson model is reduced by deep brain stimulation of the pedunculopontine nucleus
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Veröffentlicht: | 28. April 2011 |
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Objective: The pedunculopontine nucleus (PPN) is used as a target for deep brain stimulation (DBS) to treat severe and pharmaceutical-resistant postural instability and freezing in Parkinson’s disease (PD). It has been shown that lesions of the PPN reverse the increased firing rate of neurons in the subthalamic nucleus (STN) in the rat 6-hydroxydopamine (6-OHDA) PD model. We tested the effects of 25 Hz DBS of the PPN on single unit activity in the STN in 6-OHDA lesioned rats.
Methods: Unilateral nigrostriatal lesions were induced by the injection of 6-OHDA into the medial forebrain bundle of male Sprague Dawley rats (n=6), controls received vehicle injection (sham-lesioned, n=6). Three weeks after surgery a bipolar stimulating electrode was implanted in the ipsilateral PPN. After one week of recovery individual thresholds for side effects were determined and rats were stimulated (25Hz, 100µs pulse width) or sham-stimulated for five days. Thereafter, in anesthetized rats, extracellular single-unit activity of the STN was recorded for 100 sec before and after stimulation of the PPN for 50 sec.
Results: In 6-OHDA lesioned rats, PPN DBS significantly reduced the enhanced firing rate of the STN (p<0.05), but did not affect the enhanced burst activity. Stimulation had no effect on the frequency rate of STN neurons in sham-lesioned controls, i.e. non-parkinsonian rats.
Conclusions: We showed an important modulatory influence of PPN DBS on the altered STN activity in the PD 6-OHDA rat model. Our observations are in line with previous studies on the effects of PPN lesions in this PD rat model.