RT Journal Article SR Electronic T1 Transcriptomic evidence that von Economo neurons are regionally specialized extratelencephalic-projecting excitatory neurons JF bioRxiv FD Cold Spring Harbor Laboratory SP 627505 DO 10.1101/627505 A1 Rebecca D Hodge A1 Jeremy A Miller A1 Mark Novotny A1 Brian E Kalmbach A1 Jonathan T Ting A1 Trygve E Bakken A1 Brian D Aevermann A1 Eliza R Barkan A1 Madeline L Berkowitz-Cerasano A1 Charles Cobbs A1 Francisco Diez-Fuertes A1 Song-Lin Ding A1 Jamison McCorrison A1 Nicholas J Schork A1 Soraya I Shehata A1 Kimberly A Smith A1 Susan M Sunkin A1 Danny N Tran A1 Pratap Venepally A1 Anna Marie Yanny A1 Frank J Steemers A1 John W Phillips A1 Amy Bernard A1 Christof Koch A1 Roger S Lasken A1 Richard H Scheuermann A1 Ed S Lein YR 2019 UL http://biorxiv.org/content/early/2019/05/07/627505.abstract AB 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.