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

Frontiers in Neuroanatomy

Neuroanatomy

Ariadna Sancha-Velasco¹  Miguel Ángel García-Cabezas²  Alicia Uceda-Heras³ 

[1] Department of Anatomy, Histology and Neuroscience, School of Medicine, Autonomous University of Madrid, Madrid, Spain;Master Program in Neuroscience, Autonomous University of Madrid, Madrid, Spain;Department of Anatomy, Histology and Neuroscience, School of Medicine, Autonomous University of Madrid, Madrid, Spain;Master Program in Neuroscience, Autonomous University of Madrid, Madrid, Spain;Ph.D. Program in Neuroscience UAM-Cajal, Autonomous University of Madrid, Madrid, Spain;Neural Systems Laboratory, Department of Health Sciences, Boston University, Boston, MA, United States;Master Program in Neuroscience, Autonomous University of Madrid, Madrid, Spain;Ph.D. Program in Neuroscience UAM-Cajal, Autonomous University of Madrid, Madrid, Spain;

关键词: human neuroanatomy;    biological significance;    cerebral cortex;    excitation;    inhibition;    epigenetic regulation;    mesocortex;    eulaminate;   

DOI  :  10.3389/fnana.2023.1187280

 received in 2023-03-15, accepted in 2023-05-31,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Sancha-Velasco, Uceda-Heras and García-Cabezas.