Mechanisms and regulation of dopamine release

•Striatal dopamine release is mediated by vesicular exocytosis.•Active zone-like sites are required for rapid and efficient dopamine secretion.•Localized dopamine release generates signaling hotspots and is powerfully regulated.•Some striatal dopamine release is independent of ascending action potentials.•Future work should assess triggering and sensing mechanisms for fast dopamine coding. Dopamine controls motor functions, motivation, and reward-related learning through G-protein coupled receptor signaling. The current working model is that upon release, dopamine diffuses to influence many target cells via wide-spread receptors. Recent studies, however, suggest that dopamine release is fast and generates small signaling hotspots. In this review, we summarize progress on the understanding of the dopamine release apparatus and evaluate how its properties may shape dopamine signaling during firing. We discuss how mechanisms of regulation may act through this machinery and propose that striatal architecture for dopamine signaling may have evolved to support rapid dopamine coding.