Striosomes: Small Circuits With a Large Role in Locomotion

The striosome compartment is a distinct anatomical structure embedded in a labyrinth-like fashion within the mammalian striatum, first identified nearly half a century ago. Although the striosome is a small structure comprising only about 10% to 20% of the total striatal volume, its unique developmental, neurochemical, and projectional characteristics have long suggested specialized and significant functional roles. Furthermore, while clinical evidence has implicated striosomal dysfunction in movement disorders including dystonia and Huntington’s disease, their specific involvement in locomotor control has remained a mystery for decades. However, the functional properties of striosomes have begun to become unveiled through the development of genetically modified mouse lines that target striosome-enriched molecules. Accumulating evidence has indicated that striosomes play distinctive roles that differ fundamentally from the canonical direct and indirect pathway models. The striosome inhibits striatal dopamine release and locomotion vigor, potentially biasing subsequent context-dependent action selection. Consequently, the striosome compartment is an indispensable part of the functional anatomy of striatal projection neurons. We hereby describe the anatomy of the striosome compartment and the neuroscience methodologies used for its assessment, emphasizing the emerging roles of the striosome compartment in locomotor control and dopamine regulation.