Effect of deep brain stimulation in the pedunculopontine nucleus on motor function in the rat 6-hydroxydopamine Parkinson model

Abstract

The pedunculopontine nucleus (PPN) has been introduced only recently as a new target for deep brain stimulation (DBS) to treat gait disorders and postural instability in Parkinson's disease (PD). We here tested whether the 6-hydroxydopamine (6-OHDA) PD rat model can be used to study the pathophysiological mechanisms of DBS of the pedunculopontine tegmental nucleus (PPTg), the equivalent to the human PPN. In male Sprague-Dawley rats with unilateral 6-OHDA-induced nigrostriatal lesions and an electrode implanted into the ipsilateral PPTg the individual threshold for stimulation-induced side effects was higher for 25 than for 130Hz, and lower for lesioned compared to sham-lesioned controls. Rats were thus divided into four groups, (1) sham-stimulation, (2,3) 130Hz and 25Hz stimulation with the individual threshold determined for 130Hz, and (4) 25Hz stimulation at 20% below threshold (25Hz high). After 24h stimulation the rats were tested for limb use contralateral to the lesion (cylinder test and adhesive removal test), for locomotor activity (open field), and for postural instability (pole test). In lesioned rats 130Hz and 25Hz high stimulation improved postural instability in the pole test, but deteriorated limb use during adhesive removal. Additionally, 25Hz high deteriorated motor activity in the cylinder test and open field, while 25Hz stimulation marginally improved activity. Sham-lesioned rats were not affected by stimulation. Stimulation with different frequencies and intensities had complex effects on behavioral function tested. The present data provide foundation for future investigations on DBS of the PPTg in sensorimotor functions.