The connections of The PPN, and the direct and indirect pathway of BG-thalamocortical circuits under normal (A) and PD (B) conditions. Red, green, and yellow lines denote glutamatergic, GABAergic and dopaminergic projections respectively, while blue lines indicate chemically amalgamated projections. Thickening lines show increased activity whereas thinning lines show decreased activity when alterations occur in the average activity rate of specific projection pathways in PD compared with the normal state. Dotted yellow lines indicate loss. The striatum and STN deliver input from incoming cortical information to the BG. The GPi and SNr deliver output information from the BG to the rest of the brain and apply robust inhibitory control on targets in the thalamus and the brainstem. This tonic inhibitory input must be disinhibited to permit normal movements to occur. The striatum applies opposite influences on the GPi and SNr via two distinct classes of efferent neurons, namely the D1-receptor-rich “direct pathway” positively modulated by DA and the D2-receptor-rich “indirect pathway” negatively modulated by DA. The loss of DA in PD's causes disequilibrium in the activity of these two striatofugal pathways and their corresponding cortical inputs.
