Cell type-specific expression of the molecular players in mouse prefrontal cortex during cocaine addiction

Abstract

Cocaine addiction is an issue that affects more than 5 million people in America per year. Although there has been much research into the genes and chemicals responsible for cocaine addiction, there are many specific questions left unanswered. Our experiment attempts to further previous research into certain molecular players. We follow up with their use of single-cell RNA sequencing on the prefrontal cortex cells of mice undergoing cocaine intravenous self-administration. Data of 12 samples from both saline and cocaine treated mice which are found on the Gene Expression Omnibus public database were retrieved. Using the Seurat function of RStudio, the data was merged into objects, normalized, clustered, and labeled into one of eight cell types. What resulted was a detailed UMAP plot displaying the clusters, their gene expression level, expression frequency, and their cell type. With this plot, we were able to determine the specific cell types that express the genes encoding the pre-established molecular players (∆FosB, MeCP2, and BDNF). When the analysis was expanded to a cell-type specific level, it was discovered some of these genes were selectively expressed in excitatory neurons and non-neuronal cells. Going further into the analysis, we determined the 6 genes with the most varied gene expression over the 3 stages of cocaine addiction for each of the 8 cell types. Overall, our computational analysis of publicly available transcriptome datasets from mouse addiction model provides new insights into the molecular basis of cocaine addiction.