A detailed comparative analysis of human, chimpanzee and macaque brains reveals elements that make the human brain unique, including cortical circuits underlying production of the neurotransmitter dopamine. To pinpoint differences among primate brains, André M. M. Sousa et al. evaluated brain tissue samples from six humans, five chimpanzees, and five macaques. They generated transcriptional profiles of 247 tissue samples in total, representing several different brain regions (hippocampus, amygdala, striatum, mediodorsal nucleus of thalamus, cerebellar cortex, and neocortex). The researchers found that 11.9% of messenger RNAs and 13.6% of microRNAs exhibited human-specific up-regulation or down-regulation of genes in at least one brain region. Of particular note, the authors found that human brains exhibited significant up-regulation of two genes that encode enzymes involved in dopamine biosynthesis: tyrosine hydroxylase (TH) and dopa (3,4-dihydroxyphenylalanine) decarboxylase (DDC). Dopamine is known to play a role in aspects of cognition and behavior, such as working memory, reasoning, reflective exploratory behavior, and overall intelligence. This up-regulation of dopamine-related gene expression prompted the researchers to quantify and compare TH+ interneurons in 45 adult brains of nine primate species. The authors confirmed that humans, indeed, have a higher number of TH+ interneurons in both the dorsal caudate nucleus and putamen (striatum) when compared with the nonhuman primates analyzed in this study. The authors discuss possible explanations for the differences in TH+ neurons for these brain regions, for example, differences related to neuron migration and/or differentiation.