Normal basal ganglia circuit

Cortical information passes via the direct and indirect pathways to the output nuclei of the basal ganglia. In the direct pathway, striatal inhibitory GABAergic neurons (containing dynorphin and expressing D1 dopamine receptors) project monosynaptically to the SNr and GPi. Activation of the direct pathway causes inhibition of GABAergic neurons of the output nuclei. This results in disinhibition of thalamic nuclei, thereby promoting motor activation. The cortex inhibits competing motor programs through the hyperdirect and the indirect pathways. The hyperdirect pathway consists of frontal cortical projections to the subthalamic nucleus, which, via relatively divergent glutamatergic projections, exerts a powerful excitatory influence on cells of the GPe, GPi, and SNpr to suppress the thalamus and inhibit thalamocortical circuits. The indirect pathway contains a subset of GABAergic neurons (containing enkephalin and expressing D2 receptors) and runs from striatum to the globus pallidus externa (GPe) and then to the subthalamic nucleus. (DeLong MR and Wichmann MD. Circuits and circuit disorders of the basal ganglia. Arch Neurol 2007; 64: 20-24).