FIGURE 1.

The nigrostriatal dopaminergic pathway and motor basal ganglia circuitry in Parkinson’s disease (PD) brain. (A) In the nigrostriatal pathway, the striatum, Str (caudate nucleus and putamen), receives dopaminergic innervation from the substantia nigra pars compacta (SNpc) in the midbrain. (B) A schematic showing normal motor basal ganglia circuitry (left side) and its irregularities in PD brain (right side), adapted from (Bjarkam and Sorensen, 2004). Normal brain (left): The dopaminergic afferent neurons from the SN synapse with GABAergic neurons which display either D1 or D2 dopaminergic receptors. These GABAergic populations project directly (red arrows) or indirectly (blue arrows; through globus pallidus externa, GPe, and subthalamic nucleus, STN) to globus pallidus interna (GPi). The output from the GPi (green arrows) to the thalamus is inhibitory and modulates normal motor function. PD brain (right): The loss of dopaminergic neurons in the SN and depletion of striatal dopamine leads to elevated inhibitory output from the GPi to the thalamus causing reduction in normal motor function. Inhibitory and excitatory inputs are marked as (–) and (+), respectively. The intensity of the inputs is marked with thickness of lines. Str, striatum; Th, thalamus.