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

Molecular origin of GABA receptor PET tracer signal is probed by performing correlation studies using regional PET signal and gene expression levels of GABA receptors and inhibitory interneuron markers. The results provide insight in the application and interpretation of these GABA receptor PET tracers in clinical populations. 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 [C-11]Ro15-4513 and [C-11]flumazenil. We found that the inhibitory interneuron marker somatostatin covaries with GABA(A) receptor-subunit genes GABRA5 and GABRA2, and that their distribution followed [C-11]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 [C-11]flumazenil binding. Our findings indicate that existing PET radiotracers may provide complementary information about key components of the GABAergic system.

Automated summary

Correlation studies between regional PET signal and gene expression levels of GABA receptors and inhibitory interneuron markers reveal insights into the molecular origin of GABA receptor PET tracer signal. This knowledge is crucial for understanding GABAergic neurotransmission and interpreting GABA receptor PET tracers in clinical populations.