Abstract
The dopamine-containing nigrostriatal system and its return striatonigral pathway form a loop–circuit crucial for the functions of dopamine in modulating movement and mood. Here we identify a specialized subsystem within this loop. With new mouse models and tissue expansion to allow nanoscale imaging, we demonstrate that striatonigral fibers originating in striosomes form bouquet-like arborizations innervating clusters of dopamine-containing neurons and their ventrally extending, tightly bundled dendrites. Within these formations (termed “striosome–dendron bouquets”), striosomal axons and dopamine-containing dendrites are intimately intertwined, as are other afferent and glial elements. The stunning selectivity of striosomal output to the bouquets suggests that the bouquets could exert powerful and focused control over elements of the dopamine system in normal and abnormal states.
The dopamine systems of the brain powerfully influence movement and motivation. We demonstrate that striatonigral fibers originating in striosomes form highly unusual bouquet-like arborizations that target bundles of ventrally extending dopamine-containing dendrites and clusters of their parent nigral cell bodies. Retrograde tracing showed that these clustered cell bodies in turn project to the striatum as part of the classic nigrostriatal pathway. Thus, these striosome–dendron formations, here termed “striosome–dendron bouquets,” likely represent subsystems with the nigro–striato–nigral loop that are affected in human disorders including Parkinson’s disease. Within the bouquets, expansion microscopy resolved many individual striosomal fibers tightly intertwined with the dopamine-containing dendrites and also with afferents labeled by glutamatergic, GABAergic, and cholinergic markers and markers for astrocytic cells and fibers and connexin 43 puncta. We suggest that the striosome–dendron bouquets form specialized integrative units within the dopamine-containing nigral system. Given evidence that striosomes receive input from cortical regions related to the control of mood and motivation and that they link functionally to reinforcement and decision-making, the striosome–dendron bouquets could be critical to dopamine-related function in health and disease.