Electrophysiological Maturation of Cerebral Organoids Correlates with Dynamic Morphological and Cellular Development

Stem Cell Reports. 2020 Oct 13;15(4):855-868. doi: 10.1016/j.stemcr.2020.08.017. Epub 2020 Sep 24.


Cerebral organoids (COs) are rapidly accelerating the rate of translational neuroscience based on their potential to model complex features of the developing human brain. Several studies have examined the electrophysiological and neural network features of COs; however, no study has comprehensively investigated the developmental trajectory of electrophysiological properties in whole-brain COs and correlated these properties with developmentally linked morphological and cellular features. Here, we profiled the neuroelectrical activities of COs over the span of 5 months with a multi-electrode array platform and observed the emergence and maturation of several electrophysiologic properties, including rapid firing rates and network bursting events. To complement these analyses, we characterized the complex molecular and cellular development that gives rise to these mature neuroelectrical properties with immunohistochemical and single-cell transcriptomic analyses. This integrated approach highlights the value of COs as an emerging model system of human brain development and neurological disease.

Keywords: MEA; brain organoids; cerebral cortex; cerebral organoids; electrophysiology; multi-electrode array; neural network; single cell RNA sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation*
  • Cell Line
  • Cerebrum / cytology*
  • Electrophysiological Phenomena*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Microelectrodes
  • Neuroglia / cytology
  • Neurons / cytology
  • Neurons / metabolism
  • Organoids / cytology*
  • Organoids / physiology*
  • Receptors, Nerve Growth Factor / metabolism
  • Signal Transduction
  • Single-Cell Analysis
  • Synapses / physiology


  • Receptors, Nerve Growth Factor