Gladstone Institute of Neurological Disease, University of California, San Francisco, USA.
Department of Life Sciences, B.R.A.I.N., Centre for Neuroscience, University of Trieste, Trieste, Italy.
Sci Rep. 2020 Jul 9;10(1):11352. doi: 10.1038/s41598-020-68165-1.
Theoretical and experimental work has demonstrated that excitatory (E) and inhibitory (I) currents within cortical circuits stabilize to a balanced state. This E/I balance, observed from single neuron to network levels, has a fundamental role in proper brain function and its impairment has been linked to numerous brain disorders. Over recent years, large amount of microarray and RNA-Sequencing datasets have been collected, however few studies have made use of these resources for exploring the balance of global gene expression levels between excitatory AMPA receptors (AMPARs) and inhibitory GABA receptors. Here, we analyzed the relative relationships between these receptors to generate a basic transcriptional marker of E/I ratio. Using publicly available data from the Allen Brain Institute, we generated whole brain and regional signatures of AMPAR subunit gene expression in healthy human brains as well as the transcriptional E/I (tE/I) ratio. Then we refined the tE/I ratio to cell-type signatures in the mouse brain using data from the Gene Expression Omnibus. Lastly, we applied our workflow to developmental data from the Allen Brain Institute and revealed spatially and temporally controlled changes in the tE/I ratio during the embryonic and early postnatal stages that ultimately lead to the tE/I balance in adults.
理论和实验工作表明，皮质电路中的兴奋性 (E) 和抑制性 (I) 电流会稳定到平衡状态。这种从单个神经元到网络水平的 E/I 平衡，在大脑的正常功能中起着至关重要的作用，其功能障碍与许多大脑疾病有关。近年来，已经收集了大量的微阵列和 RNA 测序数据集，但很少有研究利用这些资源来探索兴奋性 AMPA 受体 (AMPAR) 和抑制性 GABA 受体之间的整体基因表达水平的平衡。在这里，我们分析了这些受体之间的相对关系，以生成 E/I 比率的基本转录标志物。我们使用艾伦脑研究所的公开数据，生成了健康人脑的整个大脑和区域 AMPAR 亚基基因表达图谱以及转录 E/I（tE/I）比率。然后，我们使用来自基因表达综合数据库的数据，将 tE/I 比率细化为小鼠大脑中的细胞类型图谱。最后，我们将我们的工作流程应用于艾伦脑研究所的发育数据，并揭示了胚胎和新生儿阶段 tE/I 比率的时空控制变化，这些变化最终导致成年期的 tE/I 平衡。
