We observed a small cluster of medium spiny neurons expressing both D1 and D2 dopamine receptor genes. This MSN type, variously described as eccentric MSNs, D1H, and D1/D2 hybrid MSNs,41,62 has been observed in mice,62,63 primates,41 and humans,64 but its association with AUD has thus far been unknown. The pattern of gene expression changes in these neurons was less correlated with the other MSN types and different biological pathways were enriched: ‘HDMs Demethylate Histones’ was the most highly enriched pathway in individuals with AUD, while many metabolic and translational control pathways had lower than expected expression in those with AUD. These differences from the classical D1 and D2 neurons suggest that D1/D2 hybrid MSNs play a distinct role in the caudate. 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 agent.63 Genes involved in collagen-containing extracellular matrix and vesicular pathways were upregulated in those with AUD. Collagen is
