We used FISH to explore the anatomical distribution of MSN subtypes and archetypes. As expected, the majority of neurons expressed either DRD1 (325 ± 99 nuclei/mm2) or DRD2 (320 ± 99 nuclei/mm2; Figures 4A-4D). To investigate the relatively rare hybrid cell type (D1/2) that expresses both DRD1 and DRD2, we used probes against RXFP1, a highly specific marker gene for D1/2 cells (p = 2.47 x 10−135 , Wilcoxon). High resolution imaging confirmed that RXFP1 positive cells in the dorsal striatum co-labeled with DRD1 and DRD2 (Figure 4F). D1/2 cells were distributed uniformly throughout the DS (Figure 4G). Intestingly, D1/2 cells had the same amount of DRD1 expression as nearby D1-MSNs, but there was far less DRD2 expression when compared to nearby D2-MSNs (Figure 4H, p = 0.55 and p < 0.0001 respectively, unpaired t-tests). Co-clustering of the NHP data with striatum data from mouse indicates that the D1/2 shares important transcriptional characteristics with a subset of the recently described “D1H” (Figures S3A-S3C).15,17 These results confirm that a hybrid D1/2 cell type is also present in the NHP striatum.
