Regional transcriptome analysis of AMPA and GABAA receptor subunit expression generates E/I signatures of the human brain

• Published in: Scientific reports Vol. 10; no. 1; p. 11352
• Main Authors: Shen, Kevin, Zeppillo, Tommaso, Limon, Agenor
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 09.07.2020; Nature Publishing Group UK; Nature Portfolio
• Subjects: Brain; DNA microarrays; Embryos; Gene expression; Ribonucleic acid; RNA; Transcription; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors; γ-Aminobutyric acid A receptors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-68165-1

Abstract Theoretical and experimental work has demonstrated that excitatory (E) and inhibitory (I) currents within cortical circuits stabilize to a balanced state. This E/I balance, observed from single neuron to network levels, has a fundamental role in proper brain function and its impairment has been linked to numerous brain disorders. Over recent years, large amount of microarray and RNA-Sequencing datasets have been collected, however few studies have made use of these resources for exploring the balance of global gene expression levels between excitatory AMPA receptors (AMPARs) and inhibitory GABA A receptors. Here, we analyzed the relative relationships between these receptors to generate a basic transcriptional marker of E/I ratio. Using publicly available data from the Allen Brain Institute, we generated whole brain and regional signatures of AMPAR subunit gene expression in healthy human brains as well as the transcriptional E/I ( t E/I) ratio. Then we refined the t E/I ratio to cell-type signatures in the mouse brain using data from the Gene Expression Omnibus. Lastly, we applied our workflow to developmental data from the Allen Brain Institute and revealed spatially and temporally controlled changes in the t E/I ratio during the embryonic and early postnatal stages that ultimately lead to the t E/I balance in adults.