Plasticity of striatopallidal terminals following unilateral lesion of the dopaminergic nigrostriatal pathway: a morphological study.

ABSTRACT

In Parkinson's disease the dopaminergic nigrostriatal pathway degenerates, resulting in an imbalance in activity of two pathways of information flow through the basal ganglia. In animal models of the disease, the striatonigral pathway becomes underactive and the striatopallidal pathway becomes overactive. In the present study immunocytochemistry for enkephalin and GABA and anterograde labelling were used to investigate whether morphological plasticity occurs in striatopallidal terminals following unilateral removal of the nigrostriatal dopaminergic pathway. Pallidal terminals were immunostained to reveal enkephalin and examined in the electron microscope (n=399). Immunoreactive synaptic bouton profiles were on average 64% larger on the experimental side 26 days after the lesion. Analysis of their shape revealed that those on the dopamine-depleted side of the brain were more irregular in profile and that their synaptic specialisations were more complex in shape but not significantly different in length. Striatopallidal terminals were also identified by GABA immunocytochemistry combined with anterograde labelling (n=20). Double-labelled boutons were significantly larger in cross-sectional area on the experimental side (57%). Analysis of terminals that were simply labelled by the immunogold method to reveal GABA (n=278) showed no significant differences in size between terminals from the dopamine-depleted and control side. This suggests that a substantial number of GABAergic terminals in the globus pallidus do not belong to the striatopallidal population of terminals. These morphological changes correlate with previous studies suggesting striatopallidal boutons are more active after destruction of dopaminergic input to the neostriatum.