A single-cell genomic atlas for the effects of chronic ethanol exposure in the mouse dorsal striatum

In our study of AUD, we used single-nuclei RNA-sequencing (snRNA-seq; n = 86,715 cells) to examine the impact of chronic intermittent ethanol exposure on the dorsal striatum in C57BL/6 male and female mice. We detected 462 differentially expressed genes at FDR < 0.05, the majority of which were mapped to spiny projection neurons (SPNs), the most prominent cell type in the striatum. Gene co-expression network analysis and functional annotation of differentially expressed genes revealed down-regulation of postsynaptic intracellular signaling cascades specifically in canonical SPNs. Inflammation-related genes were down-regulated across many striatal cell types. Gene set enrichment analyses also pointed to altered states of rare cell types, including the induction of angiogenesis-related genes in vascular cells Overall design: Chronic Intermittent Ethanol: Mice were exposed to ethanol vapor or air 16 hours/day, 4 days a week for a total of 5 weeks. After 4 days in the inhalation chambers, mice underwent a 72-hour forced abstinence period from ethanol. pyrazole (1 mmol/kg, i.p.) was injected daily in weeks 4- 5 to stabilize blood ethanol concentrations. Male and female mice co-housed with littermates. Dorsal Striatal sections used for snRNAseq. In the discovery dataset, 16 animals total, with one male and one female pooled together. In both replication datasets, 8 animals total, with four males and four females pooled in each sample.