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 identifies 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 suggest that VENs are a regionally distinctive type of ET neuron. Additionally, we describe the first patch clamp recordings of VENs from neurosurgically-resected tissue that show distinctive intrinsic membrane properties relative to neighboring pyramidal neurons.
Neurosciences (Brain & Spine)
Hodge, Rebecca D; Miller, Jeremy A; Novotny, Mark; Kalmbach, Brian E; Ting, Jonathan T; Bakken, Trygve E; Aevermann, Brian D; Barkan, Eliza R; Berkowitz-Cerasano, Madeline L; Cobbs, Charles; Diez-Fuertes, Francisco; Ding, Song-Lin; McCorrison, Jamison; Schork, Nicholas J; Shehata, Soraya I; Smith, Kimberly A; Sunkin, Susan M; Tran, Danny N; Venepally, Pratap; Yanny, Anna Marie; Steemers, Frank J; Phillips, John W; Bernard, Amy; Koch, Christof; Lasken, Roger S; Scheuermann, Richard H; and Lein, Ed S, "Transcriptomic evidence that von Economo neurons are regionally specialized extratelencephalic-projecting excitatory neurons." (2020). Articles, Abstracts, and Reports. 2892.