We observed a small cluster of MSNs expressing both D1 and D2 dopamine receptor genes, variously described as eccentric MSNs, D1H, and D1/D2 hybrid MSNs33,56, which have been observed in mice56,57, primates33, and humans58. These neurons, which showed strong enrichment of the marker RXFP1, showed a markedly different gene expression profile than that of in silico-created doublets of D1 and D2 cells. These neurons have been shown in a recent study in mice to be morphologically distinct from D1- and D2-type MSNs, with a smaller cell body, less expansive dendrite structure, and fewer spines, and were differently affected by treatment with a denervating agent57. The pattern of gene expression changes and pathways in these neurons differed from those of the other MSN types, suggesting that D1/D2 hybrid MSNs play a distinct role in the caudate of those with AUD.
