Signature morpho-electric, transcriptomic, and dendritic properties of human layer 5 neocortical pyramidal neurons

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. [Display omitted] •Species differences in the relative density of L5 ET neurons: mouse > macaque > human•Correspondence between physiological and transcriptomic definition of L5 classes•Human L5 ET dendrites display electrogenesis during direct electrical recordings•Many conserved and divergent properties of human and rodent L5 ET neurons Transcriptomics identifies a human L5 neuron corresponding to extratelencephalic projecting neurons in mouse neocortex. Patch-seq recordings from this cell type reveal many conserved and divergent morpho-electric features of L5 ET neurons in human cortex.