Evidence for asymmetric intra substantia nigra functional connectivity-application to basal ganglia processing.

The growing uses of deep brain stimulation for various basal ganglia (BG) abnormalities have reinforced the need to better understand its functional circuitry and organization. Here we focus on cortico-basal-ganglia pathways to test the "parallel, segregated" versus "funneling, integrated" theories. Using manganese-enhanced MRI (MEMRI) together with principal component spatiotemporal analysis, we previously described two patterns of caudomedial striatum efferent connectivity to the substantia nigra pars reticulata (SNr) that were hypothesized to represent the coexistence of integrated and segregated processes. These patterns corresponded to a direct mono-synaptic projection to the dorsolateral core of the SN and to a di-synaptic projection covering the entire nucleus. In the current study, MEMRI of the rostrolateral striatum was carried out to test whether this coexistence remains in the mirror pathway, by measuring rostrolateral striatum efferent connectivity that is known to connect to the ventromedial SNr. Only one spatiotemporal pattern of manganese accumulation, corresponding to projections from the striatum, was observed. It corresponds to a mono-synaptic projection to the ventromedial SNr covering SNr laminas, but no manganese was observed at the dorsolateral SNr core. Together with our previous findings, this suggests functional asymmetry along the SNr which is consistent with the known anatomical organization of dendrite and axonal 3D arborization. Consequently, the polarized connectivity along the dorsolateral-ventromedial axis implies that funneling and integration occur in the core (dorsolateral SNr) to the lamina (ventromedial SNr) direction, whereas in the other direction, and within other parts of the SNr, segregation predominates.