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

Kevin Shen, Tommaso Zeppillo, Agenor Limon

    Research output: Contribution to journalArticlepeer-review

    3 Scopus citations

    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 GABAA 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 (tE/I) ratio. Then we refined the tE/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 tE/I ratio during the embryonic and early postnatal stages that ultimately lead to the tE/I balance in adults.

    Original languageEnglish (US)
    Article number11352
    JournalScientific reports
    Volume10
    Issue number1
    DOIs
    StatePublished - Dec 1 2020

    ASJC Scopus subject areas

    • General

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