Transcriptomic evidence that von Economo neurons are regionally specialized extratelencephalic-projecting excitatory neurons

Rebecca D. Hodge; Jeremy A. Miller; Mark A. Novotny; Brian E. Kalmbach; Jonathan T. Ting; Trygve E. Bakken; Brian D. Aevermann; Eliza R. Barkan; Madeline L. Berkowitz-Cerasano; Charles Cobbs; Francisco Díez‐Fuertes; Song‐Lin Ding; Jamison McCorrison; Nicholas J. Schork; Soraya I. Shehata; Kimberly A. Smith; Susan M. Sunkin; Danny N. Tran; Pratap Venepally; Anna Marie Yanny; Frank J. Steemers; John W. Phillips; Amy Bernard; Christof Koch A; Roger S. Lasken; Richard H. Scheuermann; Ed S. Lein

doi:10.1038/s41467-020-14952-3

NeuroscienceNature CommunicationsMar 3, 2020

Peer-reviewed journal article

Transcriptomic evidence that von Economo neurons are regionally specialized extratelencephalic-projecting excitatory neurons

Rebecca D. Hodge iD, Jeremy A. Miller iD, Mark A. Novotny iD, Brian E. Kalmbach iD, Jonathan T. Ting iD, Trygve E. Bakken iD, Brian D. Aevermann iD, Eliza R. Barkan iD, Madeline L. Berkowitz-Cerasano, Charles Cobbs iD, Francisco Díez‐Fuertes iD, Song‐Lin Ding iD, Jamison McCorrison iD, Nicholas J. Schork iD, Soraya I. Shehata iD, Kimberly A. Smith iD, Susan M. Sunkin iD, Danny N. Tran, Pratap Venepally, Anna Marie Yanny iD, Frank J. Steemers, John W. Phillips iD, Amy Bernard iD, Christof Koch A iD, Roger S. Lasken, , Ed S. Lein iD

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Abstract

von Economo neurons (VENs) are bipolar, spindle-shaped neurons restricted to layer 5 of human frontoinsula and anterior cingulate cortex that appear to be selectively vulnerable to neuropsychiatric and neurodegenerative diseases, although little is known about other VEN cellular phenotypes. Single nucleus RNA-sequencing of frontoinsula layer 5 identified a transcriptomically-defined cell cluster that contained VENs, but also fork cells and a subset of pyramidal neurons. Cross-species alignment of this cell cluster with a well-annotated mouse classification shows strong homology to extratelencephalic (ET) excitatory neurons that project to subcerebral targets. This cluster also shows strong homology to a putative ET cluster in human temporal cortex, but with a strikingly specific regional signature. Together these results predict VENs are a regionally distinctive type of ET neuron, and we additionally describe the first patch clamp recordings of VENs from neurosurgically-resected tissue that show distinctive intrinsic membrane properties relative to neighboring pyramidal neurons.