Modulation of Striatal Projection Systems by Dopamine

The basal ganglia are a chain of subcortical nuclei that facilitate action selection. Two striatal projection systems-so-called direct and indirect pathways-form the functional backbone of the basal ganglia circuit. Twenty years ago, investigators proposed that the striatum's ability to use dopamine (DA) rise and fall to control action selection was due to the segregation of D-1 and D-2 DA receptors in direct- and indirect-pathway spiny projection neurons. Although this hypothesis sparked a debate, the evidence that has accumulated since then clearly supports this model. Recent advances in the means of marking neural circuits with optical or molecular reporters have revealed a clear-cut dichotomy between these two cell types at the molecular, anatomical, and physiological levels. The contrast provided by these studies has provided new insights into how the striatum responds to fluctuations in DA signaling and how diseases that alter this signaling change striatal function.