Cortical type: a conceptual tool for meaningful biological interpretation of high-throughput gene expression data in the human cerebral cortex

Abstract

The interpretation of massive high-throughput gene expression data requires computational and biological analyses to identify statistically and biologically significant differences, respectively. There are abundant sources that describe computational tools for statistical analysis of massive gene expression data but few address data analysis for biological significance. In the present article we exemplify the importance of selecting the proper biological context in the human brain for gene expression data analysis and interpretation. For this purpose, we use cortical type as conceptual tool to make predictions about gene expression in areas of the human temporal cortex. We predict that the expression of genes related to glutamatergic transmission would be higher in areas of simpler cortical type, the expression of genes related to GABAergic transmission would be higher in areas of more complex cortical type, and the expression of genes related to epigenetic regulation would be higher in areas of simpler cortical type. Then, we test these predictions with gene expression data from several regions of the human temporal cortex obtained from the Allen Human Brain Atlas. We find that the expression of several genes shows statistically significant differences in agreement with the predicted gradual expression along the laminar complexity gradient of the human cortex, suggesting that simpler cortical types may have greater glutamatergic excitability and epigenetic turnover compared to more complex types; on the other hand, complex cortical types seem to have greater GABAergic inhibitory control compared to simpler types. Our results show that cortical type is a good predictor of synaptic plasticity, epigenetic turnover, and selective vulnerability in human cortical areas. Thus, cortical type can provide a meaningful context for interpreting high-throughput gene expression data in the human cerebral cortex.