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

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...

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Autores principales:	Kevin Shen, Tommaso Zeppillo, Agenor Limon
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8bb5a3342ac040598e5e92620ab54c06
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spelling	oai:doaj.org-article:8bb5a3342ac040598e5e92620ab54c062021-12-02T16:24:49ZRegional transcriptome analysis of AMPA and GABAA receptor subunit expression generates E/I signatures of the human brain10.1038/s41598-020-68165-12045-2322https://doaj.org/article/8bb5a3342ac040598e5e92620ab54c062020-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-68165-1https://doaj.org/toc/2045-2322Abstract 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.Kevin ShenTommaso ZeppilloAgenor LimonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kevin Shen Tommaso Zeppillo Agenor Limon Regional transcriptome analysis of AMPA and GABAA receptor subunit expression generates E/I signatures of the human brain
description	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.
format	article
author	Kevin Shen Tommaso Zeppillo Agenor Limon
author_facet	Kevin Shen Tommaso Zeppillo Agenor Limon
author_sort	Kevin Shen
title	Regional transcriptome analysis of AMPA and GABAA receptor subunit expression generates E/I signatures of the human brain
title_short	Regional transcriptome analysis of AMPA and GABAA receptor subunit expression generates E/I signatures of the human brain
title_full	Regional transcriptome analysis of AMPA and GABAA receptor subunit expression generates E/I signatures of the human brain
title_fullStr	Regional transcriptome analysis of AMPA and GABAA receptor subunit expression generates E/I signatures of the human brain
title_full_unstemmed	Regional transcriptome analysis of AMPA and GABAA receptor subunit expression generates E/I signatures of the human brain
title_sort	regional transcriptome analysis of ampa and gabaa receptor subunit expression generates e/i signatures of the human brain
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/8bb5a3342ac040598e5e92620ab54c06
work_keys_str_mv	AT kevinshen regionaltranscriptomeanalysisofampaandgabaareceptorsubunitexpressiongenerateseisignaturesofthehumanbrain AT tommasozeppillo regionaltranscriptomeanalysisofampaandgabaareceptorsubunitexpressiongenerateseisignaturesofthehumanbrain AT agenorlimon regionaltranscriptomeanalysisofampaandgabaareceptorsubunitexpressiongenerateseisignaturesofthehumanbrain
_version_	1718384120285888512

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

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