In the neocortex, subcerebral axonal projections originate largely from layer 5 (L5) extratelencephalic-projecting (ET) neurons. The unique morpho-electric properties of these neurons have been mainly described in rodents, where retrograde tracers or transgenic lines can label them. Similar labeling strategies are infeasible in the human neocortex, rendering the translational relevance of findings in rodents unclear. We leveraged the recent discovery of a transcriptomically defined L5 ET neuron type to study the properties of human L5 ET neurons in neocortical brain slices derived from neurosurgeries. Patch-seq recordings, where transcriptome, physiology, and morphology were assayed from the same cell, revealed many conserved morpho-electric properties of human and rodent L5 ET neurons. Divergent properties were often subtler than differences between L5 cell types within these two species. These data suggest a conserved function of L5 ET neurons in the neocortical hierarchy but also highlight phenotypic divergence possibly related to functional specialization of human neocortex.

在新皮质中，大脑下轴突投射主要源自第 5 层 (L5) 端脑外投射 (ET) 神经元。这些神经元独特的形态电特性主要在啮齿类动物中得到描述，逆行示踪剂或转基因系可以标记它们。类似的标记策略在人类新皮质中是不可行的，这使得啮齿类动物研究结果的转化相关性尚不清楚。我们利用最近发现的转录组定义的 L5 ET 神经元类型来研究来自神经外科的新皮质脑切片中人类 L5 ET 神经元的特性。Patch-seq 记录对同一细胞进行转录组、生理学和形态学分析，揭示了人类和啮齿动物 L5 ET 神经元的许多保守的形态电特性。不同的特性通常比这两个物种内 L5 细胞类型之间的差异更微妙。这些数据表明新皮质层次结构中 L5 ET 神经元的功能保守，但也强调了可能与人类新皮质功能特化相关的表型差异。