Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, 16 De Crespigny Park, SE5 8AF, London, UK.
Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, 16 De Crespigny Park, SE5 8AF, London, UK.
Commun Biol. 2022 Apr 19;5(1):372. doi: 10.1038/s42003-022-03268-1.
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 receptor subunits and inhibitory interneuron subtype-specific markers, and their association with binding patterns of the gold-standard GABA PET radiotracers [C]Ro15-4513 and [C]flumazenil. We found that the inhibitory interneuron marker somatostatin covaries with GABA receptor-subunit genes GABRA5 and GABRA2, and that their distribution followed [C]Ro15-4513 binding. In contrast, the inhibitory interneuron marker parvalbumin covaried with GABA receptor-subunit genes GABRA1, GABRB2 and GABRG2, and their distribution tracked [C]flumazenil binding. Our findings indicate that existing PET radiotracers may provide complementary information about key components of the GABAergic system.
不同的 GABA 能中间神经元网络协调大脑中的信息处理。了解人类大脑中该系统组织的基本原则，以及这些原则是否反映在现有的非侵入性体内神经影像学方法中，对于 GABA 能神经传递的研究至关重要。在这里，我们使用人类基因表达数据和最先进的成像转录组学，揭示编码 GABA 受体亚基和抑制性中间神经元亚型特异性标志物的基因之间的共表达模式，以及它们与金标准 GABA PET 放射性示踪剂 [C]Ro15-4513 和 [C]flumazenil 结合模式的关联。我们发现，抑制性中间神经元标志物生长抑素与 GABA 受体亚基基因 GABRA5 和 GABRA2 相关，其分布遵循 [C]Ro15-4513 结合。相比之下，抑制性中间神经元标志物钙蛋白与 GABA 受体亚基基因 GABRA1、GABRB2 和 GABRG2 相关，其分布与 [C]flumazenil 结合相关。我们的研究结果表明，现有的 PET 放射性示踪剂可能提供 GABA 能系统关键成分的互补信息。
