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

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Article number372
JournalCommunications Biology
Volume5
Issue number1
DOIs
Accepted/In press14 Mar 2022
Published19 Apr 2022

Bibliographical note

Funding Information: This research did not receive any grant from funding agencies in the commercial or not-for-profit sectors. P.B.L. is in receipt of a PhD studentship funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. This research was funded in whole, or in part, by the Wellcome Trust [Sir Henry Dale Fellowship 202397/Z/16/Z to G.M.]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. G.M., A.C.V. and F.E.T. acknowledge funding supporting this work from the Medical Research Council UK Centre grant MR/N026063/1. D.M. and V.M. are supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust. The authors would like to extend special thanks to colleagues from the Neurobiology Research Unit at Copenhagen University Hospital for making their data publicly available, as well as Dr Samuel Cooke for his advice on the interpretation of the results. Funding Information: This research did not receive any grant from funding agencies in the commercial or not-for-profit sectors. P.B.L.?is in receipt of a PhD studentship funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King?s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. This research was funded in whole, or in part, by the Wellcome Trust [Sir Henry Dale Fellowship 202397/Z/16/Z to?G.M.]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. G.M., A.C.V. and F.E.T.?acknowledge funding supporting this work from the Medical Research Council UK Centre grant MR/N026063/1. D.M. and V.M. are supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust. The authors would like to extend special thanks to colleagues from the Neurobiology Research Unit at Copenhagen University Hospital for making their data publicly available, as well as Dr Samuel Cooke for his advice on the interpretation of the results. Publisher Copyright: © 2022, The Author(s).

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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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