Transcriptomic evidence that von Economo neurons are regionally specialized extratelencephalic-projecting excitatory neurons
Hodge RD, Miller JA, Novotny M, Kalmbach BE, Ting JT, Bakken TE, Aevermann BD, Barkan ER, Berkowitz-Cerasano ML, Cobbs C, Diez-Fuertes F, Ding SL, McCorrison J, Schork NJ, Shehata SI, Smith KA, Sunkin SM, Tran DN, Venepally P, Yanny AM, Steemers FJ, Phillips JW, Bernard A, Koch C, Lasken RS, Scheuermann RH, Lein ES
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.