Two Coordinates for Dopamine in the Basal Ganglia

Abstract

The striatum is the principal input structure of the basal ganglia, central to selecting behaviour and learning from its consequences. Its output is conventionally described through D1-associated direct and D2-associated indirect pathways. Striosome–matrix organisation provides a second, intersecting division. Together, these two divisions define four principal striatal output populations: matrix D1, matrix D2, striosomal D1 and striosomal D2. Mouse studies identify striosomal pathways that regulate dopamine neurons alongside the canonical pathways controlling basal ganglia output. We propose that these populations perform complementary functions: matrix routes predominantly support behavioural selection, while striosomal routes shape the dopamine signal that influences selection and learning. The key principle is that a receptor’s functional significance depends on its circuit position. Inhibiting a basal ganglia output neuron and inhibiting a dopamine neuron have different consequences, even when the cells defining each route express the same dopamine receptor. This distinction connects pathway anatomy with parallel basal ganglia loops, dopamine coding and a proposed relative weighting of content and value across compartments. The two coordinates describe preferential circuit organisation within a broader diversity of cell types, overlapping connections and regional specialisations. Parkinson’s disease and schizophrenia illustrate how neuronal degeneration and circuit dysregulation affect different parts of this organisation, while systemic treatments act beyond the circuits requiring correction. The framework yields specific predictions about pathway connectivity, compartmental information processing and dopamine feedback, providing an experimentally testable link between cellular organisation, behaviour and clinical function.