Research articleSelective cholinergic depletion of pedunculopontine tegmental nucleus aggravates freezing of gait in parkinsonian rats

- Selective PPTg cholinergic lesion via injection of IgG immunotoxin-targeting choline acetyltransferase.
- SNc lesion and combined lesion led to significant changes in many gait parameters.
- Terminal dual stance increased higher in combined lesion rats than SNc lesion rats.
- The combined lesion group showed the most severe freezing among four groups.
- The cholinergic neurons of PPTg play a vital role in the occurrence of gait freezing in PD.

Many patients of advanced Parkinson's disease (PD) suffer from intractable axial symptoms (severe gait and postural impairments), which were recently speculated to be more relevant to cholinergic degeneration in the brainstem than dopaminergic degeneration in the substantia nigra compacta (SNc). To investigate the role of the cholinergic cells of the pedunculopontine tegmental nucleus (PPTg) on motor deficits, especially the axial motor impairments, we measured and analyzed the gait performance of sham lesion rats, SNc dopaminergic lesion rats, PPTg cholinergic lesion rats, and combined lesion rats by using the CatWalk system. Motor performance of PPTg cholinergic lesion rats was also tested on the rotarod. Independent loss of cholinergic neurons in the PPTg did not induce gait disturbance in CatWalk, but PPTg lesion rats showed motor impairments on the rotarod when the demands of the motor task increased. Both SNc lesion rats and combined lesion rats displayed significant changes in many gait parameters, but the terminal dual stance increased much higher in combined lesion group than SNc lesion group. Furthermore, combined lesion rats showed more severe freezing of gait (FOG) than SNc lesion rats during behavioral re-evaluations after lesion. These results suggest that the PPTg cholinergic neurons play a vital role in the occurrence of FOG in PD.