Spindle neurons in human cortex possess distinctive firing properties and transcriptomic signatures

Spindle neurons (SPNs), also known as von Economo neurons (VENs), are predominantly found in large-brained species including humans. SPNs in human neocortex are implicated in cognitive functions and affected in various brain disorders. Despite their unique morphology, whether SPNs possess distinctive electrophysiological properties and transcriptomic identities remains unclear. Here, we performed whole-cell patch clamp recording (134 cells) together with RNA-sequencing (patch-seq, 124 cells) on visually identified SPNs and pyramidal cells (PCs) in human cortical slices. Compared with putative extratelencephalic-projecting PCs, SPNs possess less complex proximal apical dendrites and emanate axons from the basal dendritic trunk. Additionally, they exhibit heightened excitability and characteristic firing properties, including robust bursting and persistent firing pattern. Patch-seq analysis revealed transcriptomic heterogeneity within SPNs, and identified their fingerprint genes. Collectively, our results indicate that SPNs form a molecularly and functionally distinctive neuronal population, which may serve as a specialized neural substrate for human cortical processing. Spindle neurons in the human cortex are morphologically distinct. Here, authors show that they also possess distinctive electrophysiological and transcriptomic features, establishing them as a functionally specialized cell type in the human brain.