Gait improvement by high-frequency stimulation of the subthalamic nucleus in Parkinsonian mice is not associated with changes of the cholinergic system in the pedunculopontine nucleus.

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Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is standard care for severe motor symptoms of Parkinson's disease (PD). However, a challenge of DBS remains improving gait. Gait has been associated with the cholinergic system in the pedunculopontine nucleus (PPN). In this study, we investigated the effects of long-term intermittent bilateral STN-DBS on PPN cholinergic neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Parkinsonian mouse model. Motor behavior, previously assessed by the automated Catwalk gait analysis, demonstrated a parkinsonian-like motor phenotype with static and dynamic gait impairments, which were reversed by STN-DBS. In this study, a subset of brains was further immunohistochemically processed for choline acetyltransferase (ChAT) and the neuronal activation marker c-Fos. MPTP treatment resulted in a significant reduction of PPN ChAT expressing neurons compared to saline treatment. STN-DBS did not alter the number of ChAT expressing neurons, nor the number of double-labelled PPN neurons for ChAT and c-Fos. Although STN-DBS improved gait in our model this was not associated with an altered expression or activation of PPN acetylcholine neurons. Motor and gait effects of STN-DBS are therefore less likely to be mediated by the STN-PPN connection and PPN cholinergic system.

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