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

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 GABA(A) receptor subunits and inhibitory interneuron subtype-specific markers, and their association with binding patterns of the gold-standard GABA PET radiotracers [(11)C]Ro15-4513 and [(11)C]flumazenil. We found that the inhibitory interneuron marker somatostatin covaries with GABA(A) receptor-subunit genes GABRA5 and GABRA2, and that their distribution followed [(11)C]Ro15-4513 binding. In contrast, the inhibitory interneuron marker parvalbumin covaried with GABA(A) receptor-subunit genes GABRA1, GABRB2 and GABRG2, and their distribution tracked [(11)C]flumazenil binding. Our findings indicate that existing PET radiotracers may provide complementary information about key components of the GABAergic system.