Cellular and molecular signatures of in vivo imaging measures of GABAergic neurotransmission in the human brain

Paulina Barbara Lukow; Daniel Martins; Mattia Veronese; Anthony Christopher Vernon; Philip McGuire; Federico Edoardo Turkheimer; Gemma Modinos

doi:10.1038/s42003-022-03268-1

Cellular and molecular signatures of in vivo imaging measures of GABAergic neurotransmission in the human brain

Paulina Barbara Lukow, Daniel Martins, Mattia Veronese, Anthony Christopher Vernon, Philip McGuire, Federico Edoardo Turkheimer, Gemma Modinos

Research output: Contribution to journal › Article › peer-review

Abstract

Diverse GABAergic interneuron networks orchestrate information processing in the brain. Understanding the principles underlying the organisation of this system in the human brain, and whether these principles are reflected by available non-invasive in vivo neuroimaging methods, is crucial for the study of GABAergic neurotransmission. Here, we use human gene expression data and state-of-the-art imaging transcriptomics to uncover co-expression patterns between genes encoding GABAA receptor subunits and inhibitory interneuron subtype-specific markers, and their association with binding patterns of the gold-standard GABA PET radiotracers [11C]Ro15-4513 and [11C]flumazenil. We found that the inhibitory interneuron marker somatostatin covaries with GABAA receptor-subunit genes GABRA5 and GABRA2, and that their distribution followed [11C]Ro15-4513 binding. In contrast, the inhibitory interneuron marker parvalbumin covaried with GABAA receptor-subunit genes GABRA1, GABRB2 and GABRG2, and their distribution tracked [11C]flumazenil binding. Our findings indicate that existing PET radiotracers may provide complementary information about key components of the GABAergic system.

Original language	English
Pages (from-to)	372
Journal	Communications Biology
Volume	5
Issue number	1
DOIs	https://doi.org/10.1038/s42003-022-03268-1
Publication status	Published - 19 Apr 2022

Keywords

Brain/diagnostic imaging
Flumazenil/metabolism
Humans
Neuroimaging
Receptors, GABA-A/genetics
Synaptic Transmission

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10.1038/s42003-022-03268-1

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title = "Cellular and molecular signatures of in vivo imaging measures of GABAergic neurotransmission in the human brain",

abstract = "Diverse GABAergic interneuron networks orchestrate information processing in the brain. Understanding the principles underlying the organisation of this system in the human brain, and whether these principles are reflected by available non-invasive in vivo neuroimaging methods, is crucial for the study of GABAergic neurotransmission. Here, we use human gene expression data and state-of-the-art imaging transcriptomics to uncover co-expression patterns between genes encoding GABAA receptor subunits and inhibitory interneuron subtype-specific markers, and their association with binding patterns of the gold-standard GABA PET radiotracers [11C]Ro15-4513 and [11C]flumazenil. We found that the inhibitory interneuron marker somatostatin covaries with GABAA receptor-subunit genes GABRA5 and GABRA2, and that their distribution followed [11C]Ro15-4513 binding. In contrast, the inhibitory interneuron marker parvalbumin covaried with GABAA receptor-subunit genes GABRA1, GABRB2 and GABRG2, and their distribution tracked [11C]flumazenil binding. Our findings indicate that existing PET radiotracers may provide complementary information about key components of the GABAergic system.",

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AU - McGuire, Philip

AU - Turkheimer, Federico Edoardo

AU - Modinos, Gemma

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N2 - Diverse GABAergic interneuron networks orchestrate information processing in the brain. Understanding the principles underlying the organisation of this system in the human brain, and whether these principles are reflected by available non-invasive in vivo neuroimaging methods, is crucial for the study of GABAergic neurotransmission. Here, we use human gene expression data and state-of-the-art imaging transcriptomics to uncover co-expression patterns between genes encoding GABAA receptor subunits and inhibitory interneuron subtype-specific markers, and their association with binding patterns of the gold-standard GABA PET radiotracers [11C]Ro15-4513 and [11C]flumazenil. We found that the inhibitory interneuron marker somatostatin covaries with GABAA receptor-subunit genes GABRA5 and GABRA2, and that their distribution followed [11C]Ro15-4513 binding. In contrast, the inhibitory interneuron marker parvalbumin covaried with GABAA receptor-subunit genes GABRA1, GABRB2 and GABRG2, and their distribution tracked [11C]flumazenil binding. Our findings indicate that existing PET radiotracers may provide complementary information about key components of the GABAergic system.

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Cellular and molecular signatures of in vivo imaging measures of GABAergic neurotransmission in the human brain

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Keywords

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