Transcriptomic evidence that von Economo neurons are regionally specialized extratelencephalic-projecting excitatory neurons
Rebecca D Hodge,
Jeremy A. Miller,
Brian E Kalmbach,
Jonathan T Ting,
Trygve E Bakken,
Brian D. Aevermann,
Eliza R Barkan,
Madeline L Berkowitz-Cerasano,
Nicholas J. Schork,
Soraya I Shehata,
Kimberly A Smith,
Danny N Tran,
Anna Marie Yanny,
Frank J Steemers,
John W. Phillips,
Roger S Lasken,
Richard H. Scheuermann,
Ed S Lein
Posted 07 May 2019
bioRxiv DOI: 10.1101/627505 (published DOI: 10.1038/s41467-020-14952-3)
Posted 07 May 2019
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.
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