The VS is strongly implicated in reward processing.9 The NAc and OT complex comprises a major portion of the rostral VS, and this complex is traditionally recognized as a limbic-motor interface.46 The NAc is further divided into core and shell territories with distinct behavioral functions.47 We found several gene markers, including ARHGAP6, GREB1L, and GRIA4, that were upregulated in the VS samples (Figure 2). FISH labeling with these probes revealed that their upregulation traced the transition of the ventrally positioned, Calbindin-poor shell to the dorsally positioned, Calbindin-rich core (Figure S5C). Thus, these marker genes label D1- and D2-MSN subtypes that were specific to the NAc shell and OT. Within the D1Sh subtype, we detected an archetype that expresses the gene for Neurokinin-B (TAC3) (Figures 5C-5I). Previous tracing studies in rodents have shown that a small population Neurokinin B-positive D1-MSNs have direct projections to other basal forebrain structures, including notably the cholinergic substantia inomiata.39,48,49 Thus, this TAC3 MSN archetype could represent the genesis of an additional pathway, along with the direct and indirect pathways, for cortico-striatal signals to reach the cortex.
