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Spindle neurons in human cortex possess distinctive firing properties and transcriptomic signatures

  • Wei Ke
  • , Shuxuan Lyu
  • , Mengmeng Jin
  • , Shaoqing Jiao
  • , Liang Li
  • , Heyuan Zhang
  • , Kexin Ling
  • , Cuiping Tian
  • , Yiquan Song
  • , Liu Chen
  • , Quansheng He
  • , Yujie Xiao
  • , Suixin Deng
  • , Liu Fan
  • , Huawei Mu
  • , Hui Yang
  • , Hua Tai Xu
  • , Hao Wang
  • , Ai Hui Tang
  • , Jiajie Peng
  • Jie He, Hui Guo, Yousheng Shu
  • Fudan University
  • Chinese Academy of Sciences
  • Northwestern Polytechnical University Xian
  • ShanghaiTech University
  • University of Science and Technology of China
  • Central South University
  • Lingang Laboratory
  • Qingdao University

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Spindle neurons (SPNs), also known as von Economo neurons (VENs), are predominantly found in large-brained species including humans. SPNs in human neocortex are implicated in cognitive functions and affected in various brain disorders. Despite their unique morphology, whether SPNs possess distinctive electrophysiological properties and transcriptomic identities remains unclear. Here, we performed whole-cell patch clamp recording (134 cells) together with RNA-sequencing (patch-seq, 124 cells) on visually identified SPNs and pyramidal cells (PCs) in human cortical slices. Compared with putative extratelencephalic-projecting PCs, SPNs possess less complex proximal apical dendrites and emanate axons from the basal dendritic trunk. Additionally, they exhibit heightened excitability and characteristic firing properties, including robust bursting and persistent firing pattern. Patch-seq analysis revealed transcriptomic heterogeneity within SPNs, and identified their fingerprint genes. Collectively, our results indicate that SPNs form a molecularly and functionally distinctive neuronal population, which may serve as a specialized neural substrate for human cortical processing.

Original languageEnglish
Article number6330
JournalNature Communications
Volume17
Issue number1
DOIs
StatePublished - Dec 2026

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