Regional specificity of gene expression in dopaminoceptive neurons

Cell types are defined by their patterns of gene expression. Forebrain dopaminoceptive neurons play a key role in movement, action selection, and motivation, and are dysregulated in addiction, Parkinson’s disease, and many other medical conditions. To investigate similarities and differences between the main types of dopamine-sensitive neurons we compared the full ensemble of translated mRNAs in neurons expressing D1 or D2 dopamine receptors in the dorsal striatum and nucleus accumbens, and in D1 receptor-expressing neurons of the prefrontal cortex. We identified marked differences in mRNA profiles between these populations and distinct sets of genes that establish D1, D2, dorsal and ventral identities. Network analysis revealed transcription factors with known or putative role in these differences. Prostaglandin E2 appeared as a candidate upstream regulator of dorsal striatum and pharmacological experiments supported this hypothesis. Our study provides a powerful resource for the molecular studies of the striatum and new clues about its regional gene expression pattern. BAC (bacterial artificial chromosome) transgenic mice were generated, expressing eGFP fused to the N-terminus of the large subunit ribosomal protein L10a under the control of dopamine D1a or D2 receptor promoter. Brain tissue was punched from thick slices of prefrontal cortex, dorsal and ventral striatum. Each sample was generated by pooling together tissues from 3 mice, with at least one male and one female. 14 to 19 samples were created for each of the region/receptor combination.