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.

Irregular behavior in an excitatory-inhibitory neuronal network

“…In animal models, however, it is known that the predominant class of striatal output cells have very low activity and may even be quiescent at rest while the striatal inhibition to GPe is strengthened in the absence of dopamine. 20 It is also reported that application of dopamine to STN reduces the effect of inhibitory synaptic inputs to the STN. 5 From these experimental results, we infer that the striatal input to GPe is less hyperpolarizing and STN response to inhibitory inputs from GPe is weak under normal condition.…”

Recurrent Collateral Connections of Striatal Medium Spiny Neurons Are Disrupted in Models of Parkinson's Disease

“…Anatomical studies of 6-OHDAlesioned rats revealed that striatal expression of GAD (glutamate decarboxylase), the synthetic enzyme for GABA, rises (Soghomonian and Laprade, 1997). Moreover, the terminals of striatopallidal D 2 MSNs in the GPe and the striatum are enlarged, in parallel with an increased expression of the releasable peptide enkephalin (Ingham et al, 1991(Ingham et al, , 1997. These changes have been assumed to reflect increased, rather than decreased, GABA release.…”

Striatal Information Signaling and Integration in Globus Pallidus: Timing Matters

“…Furthermore, tremor was observed in GABA A ␣ 1 subunit and GAT1 knockout mice [99,116] . An important feature of dopamine depletion is the dramatic enlargement in striatopallidal terminals (up to ϳ 90%) and the increased GABA synthesis in striatopallidal neurons at the GP level [124,[137][138][139][140] . Consistent with an enhanced release of GABA from striatopallidal terminals, the total number of GP GABA A receptors decreases after a nigrostriatal lesion [141][142][143][144][145] .…”