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 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 (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.

Transcriptional profiling from whole embryos to single neuroblast lineages in Drosophila

“…Single cell RNA-sequencing (scRNA-seq) is a powerful method for determining the transcriptional profile of complex tissues such as the central nervous system (CNS), including mammalian cortical excitatory and inhibitory neurons (Shen et al, 2020), hippocampal neurons (Hodge et al, 2019), zebrafish embryonic neurons (Tambalo et al, 2020), and Drosophila larval, pupal and adult neurons (Brunet Avalos and Sprecher, 2021;Davie et al, 2018;McLaughlin et al, 2021;Nguyen et al, 2021;Vicidomini et al, 2021;Xie et al, 2021) (Velten et al, 2022). Surprisingly, there has yet to be a sc-RNAseq study of Drosophila embryonic neurogenesis; the only embryonic sc-RNAseq study was tightly focused study on pre-gastrula embryos (Karaiskos et al, 2017).…”

Characteristic DNA methylation profiles of chorionic villi in recurrent miscarriage

“…Of these, 13,451 and 5816 probes showed different β-values between RM and AA (DMPs) in the chorionic villi and decidua, respectively (Supplementary Tables S3 , S4 ). Because there were multiple probes were designed within each gene, one representative probe showing the highest CpG score was selected 19 . This yielded a final count of 9073 DMPs and 4412 DMPs in chorionic villi and decidua, respectively, which were used for cluster analysis.…”

GluR2Q and GluR2R AMPA Subunits are not Targets of lypd2 Interaction

“…Here, we explored an alternative approach towards identifying potential new ionotropic receptor targets of Ly6 regulation. We focused on AMPA receptors as a possible target due to their role in mediating neuronal communication, the well-established precedence for regulation of AMPA receptor function via small regulatory proteins, and their highly dense expression in particular regions of the brain (including the hippocampus) where lypd2 is also expressed [ 34 , 35 , 37 , 38 , 54 ].…”

“…In mammalian systems, the majority of excitatory neurotransmission is mediated by ionotropic glutamate receptors. Specifically, AMPA receptors (AMPARs) are highly expressed in the brain, particularly in the hippocampal region [34]. AMPARs are synthesized, folded, and assembled in the endoplasmic reticulum, where they must undergo stringent quality control prior to export to the Golgi and ultimately to the cell surface [35][36][37].…”