Striatonigrostriatal Pathways in Primates Form an Ascending Spiral from the Shell to the Dorsolateral Striatum

TLDR

Dopamine system disorders manifest deficits in emotional, cognitive, and motor function, yet how dopamine integrates across parallel corticostriatal circuits remains poorly understood. The study aimed to elucidate how the striatonigrostriatal (SNS) subcircuit channels information among ventromedial, central, and dorsolateral striatal regions. Researchers compiled retrograde and anterograde tracing data to map SNS projections and identify an ascending spiral of dopamine cell interactions linking these striatal domains. The analysis revealed that ventromedial striatum projects broadly to dopamine cells but receives limited input, dorsolateral striatum receives extensive dopamine input yet projects narrowly to the substantia nigra, central striatum has reciprocal wide connections, and the SNS pathway contains dorsal, central, and ventral nigral components that together form a hierarchical spiral from shell to core to central to dorsolateral, providing an anatomical basis for limbic‑cognitive‑motor integration.

Abstract

Clinical manifestations in diseases affecting the dopamine system include deficits in emotional, cognitive, and motor function. Although the parallel organization of specific corticostriatal pathways is well documented, mechanisms by which dopamine might integrate information across different cortical/basal ganglia circuits are less well understood. We analyzed a collection of retrograde and anterograde tracing studies to understand how the striatonigrostriatal (SNS) subcircuit directs information flow between ventromedial (limbic), central (associative), and dorsolateral (motor) striatal regions. When viewed as a whole, the ventromedial striatum projects to a wide range of the dopamine cells and receives a relatively small dopamine input. In contrast, the dorsolateral striatum (DLS) receives input from a broad expanse of dopamine cells and has a confined input to the substantia nigra (SN). The central striatum (CS) receives input from and projects to a relatively wide range of the SN. The SNS projection from each striatal region contains three substantia nigra components: a dorsal group of nigrostriatal projecting cells, a central region containing both nigrostriatal projecting cells and its reciprocal striatonigral terminal fields, and a ventral region that receives a specific striatonigral projection but does not contain its reciprocal nigrostriatal projection. Examination of results from multiple tracing experiments simultaneously demonstrates an interface between different striatal regions via the midbrain dopamine cells that forms an ascending spiral between regions. The shell influences the core, the core influences the central striatum, and the central striatum influences the dorsolateral striatum. This anatomical arrangement creates a hierarchy of information flow and provides an anatomical basis for the limbic/cognitive/motor interface via the ventral midbrain.