Nigral dopaminergic contact patterns related to striatal regions and cell types in male mice

Dopaminergic (DA) neurons of the substantia nigra pars compacta (SNc) form widespread projections to the dorsal striatum, yet whether these axons exhibit region or cell-type-specific structural organization remains unclear. Using AAV1-assisted anterograde trans-neuronal labeling combined with confocal three-dimensional reconstruction, we examined putative appositions between SNc-derived DA axons and three striatal neuron types-parvalbumin-positive interneurons (PV-INs), cholinergic interneurons (CINs), and preproenkephalin-positive indirect-pathway medium spiny neurons (PPE-iMSNs)-in the dorsomedial (DMS) and dorsolateral striatum (DLS). DA varicosities formed close appositions on both somata and dendrites of all neuron types. Quantitative analyses revealed significantly greater somatic appositions and a greater number of axons forming contacts in CINs of the DMS than in the DLS, whereas dendritic appositions exhibited modest variability depending on region and cell type. These findings indicate that DA axons form distinct region-specific contact patterns, particularly enhancing somatic appositions on cholinergic interneurons in the DMS. This anatomical specialization may contribute to differential DA modulation underlying goal-directed versus habitual behaviors mediated by DMS and DLS circuits.