Primates and rodents, which descended from a common ancestor around 90 million years ago 1 , exhibit profound differences in behaviour and cognitive capacity; the cellular basis for these differences is unknown. Here we use single-nucleus RNA sequencing to profile RNA expression in 188,776 individual interneurons across homologous brain regions from three primates (human, macaque and marmoset), a rodent (mouse) and a weasel (ferret). Homologous interneuron types—which were readily identified by their RNA-expression patterns—varied in abundance and RNA expression among ferrets, mice and primates, but varied less among primates. Only a modest fraction of the genes identified as ‘markers’ of specific interneuron subtypes in any one species had this property in another species. In the primate neocortex, dozens of genes showed spatial expression gradients among interneurons of the same type, which suggests that regional variation in cortical contexts shapes the RNA expression patterns of adult neocortical interneurons. We found that an interneuron type that was previously associated with the mouse hippocampus—the ‘ivy cell’, which has neurogliaform characteristics—has become abundant across the neocortex of humans, macaques and marmosets but not mice or ferrets. We also found a notable subcortical innovation: an abundant striatal interneuron type in primates that had no molecularly homologous counterpart in mice or ferrets. These interneurons expressed a unique combination of genes that encode transcription factors, receptors and neuropeptides and constituted around 30% of striatal interneurons in marmosets and humans. Single-nucleus RNA-sequencing analyses of brain from humans, macaques, marmosets, mice and ferrets reveal diverse ways that interneuron populations have changed during evolution.

中文翻译：

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灵长类中间神经元库中的创新

大约 9000 万年前，灵长类动物和啮齿类动物起源于一个共同的祖先 1 ，它们在行为和认知能力方面表现出深刻的差异；这些差异的细胞基础尚不清楚。在这里，我们使用单核 RNA 测序来分析来自三种灵长类动物（人类、猕猴和狨猴）、一只啮齿动物（小鼠）和一只鼬鼠（雪貂）的同源脑区的 188,776 个个体中间神经元的 RNA 表达。同源中间神经元类型——很容易通过它们的 RNA 表达模式识别——在雪貂、小鼠和灵长类动物中的丰度和 RNA 表达存在差异，但在灵长类动物中差异较小。在任何一个物种中，只有一小部分被确定为特定中间神经元亚型“标记”的基因在另一个物种中具有这种特性。在灵长类动物的新皮质中，数十个基因在同一类型的中间神经元之间显示出空间表达梯度，这表明皮质环境中的区域差异塑造了成人新皮质中间神经元的 RNA 表达模式。我们发现以前与小鼠海马体相关的一种中间神经元类型——具有神经胶质细胞特征的“常春藤细胞”——在人类、猕猴和狨猴的新皮质中变得丰富，但在小鼠或雪貂中则不然。我们还发现了一个显着的皮层下创新：灵长类动物中丰富的纹状体中间神经元类型在小鼠或雪貂中没有分子同源对应物。这些中间神经元表达了编码转录因子、受体和神经肽的独特基因组合，占狨猴和人类纹状体中间神经元的 30% 左右。