GABAergic inhibitory interneurons comprise many subtypes that differ in their molecular, anatomical, and functional properties. In mouse visual cortex, they also differ in their modulation with an animal’s behavioral state, and this state modulation can be predicted from the first principal component (PC) of the gene expression matrix. Here, we ask whether this link between transcriptome and state-dependent processing generalizes across species. To this end, we analysed seven single-cell and single-nucleus RNA sequencing datasets from mouse, human, songbird, and turtle forebrains. Despite homology at the level of cell types, we found clear differences between transcriptomic PCs, with greater dissimilarities between evolutionarily distant species. These dissimilarities arise from two factors: divergence in gene expression within homologous cell types and divergence in cell-type abundance. We also compare the expression of cholinergic receptors, which are thought to causally link transcriptome and state modulation. Several cholinergic receptors predictive of state modulation in mouse interneurons are differentially expressed between species. Circuit modelling and mathematical analyses suggest conditions under which these expression differences could translate into functional differences.

GABA 能抑制性中间神经元包括许多亚型，这些亚型在分子、解剖和功能特性上有所不同。在小鼠视觉皮层中，它们与动物行为状态的调节也不同，这种状态调节可以从基因表达矩阵的第一主成分 （PC） 预测。在这里，我们询问转录组和状态依赖性加工之间的这种联系是否在物种之间泛化。为此，我们分析了来自小鼠、人类、鸣禽和前脑的 7 个单细胞和单核 RNA 测序数据集。尽管在细胞类型水平上具有同源性，但我们发现转录组 PC 之间存在明显差异，进化上相距遥远的物种之间存在更大的差异。这些差异源于两个因素：同源细胞类型内基因表达的差异和细胞类型丰度的差异。我们还比较了胆碱能受体的表达，胆碱能受体被认为与转录组和状态调节之间存在因果关系。几种预测小鼠中间神经元状态调节的胆碱能受体在物种间差异表达。电路建模和数学分析表明，这些表达差异可以转化为功能差异的条件。