Exploring the mechanisms underlying excitation/inhibition imbalance in human iPSC-derived models of ASD

Mol Autism. 2020 May 11;11(1):32. doi: 10.1186/s13229-020-00339-0.


Autism spectrum disorder (ASD) is a range of neurodevelopmental disorders characterized by impaired social interaction and communication, and repetitive or restricted behaviors. ASD subjects exhibit complex genetic and clinical heterogeneity, thus hindering the discovery of pathophysiological mechanisms. Considering that several ASD-risk genes encode proteins involved in the regulation of synaptic plasticity, neuronal excitability, and neuronal connectivity, one hypothesis that has emerged is that ASD arises from a disruption of the neuronal network activity due to perturbation of the synaptic excitation and inhibition (E/I) balance. The development of induced pluripotent stem cell (iPSC) technology and recent advances in neuronal differentiation techniques provide a unique opportunity to model complex neuronal connectivity and to test the E/I hypothesis of ASD in human-based models. Here, we aim to review the latest advances in studying the different cellular and molecular mechanisms contributing to E/I balance using iPSC-based in vitro models of ASD.

Keywords: Autism spectrum disorder; Excitation/inhibition balance; Induced pluripotent stem cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Autism Spectrum Disorder / diagnosis
  • Autism Spectrum Disorder / etiology*
  • Autism Spectrum Disorder / metabolism*
  • Biomarkers
  • Cell Differentiation
  • Disease Susceptibility*
  • Electrophysiological Phenomena*
  • Genetic Predisposition to Disease
  • Humans
  • Induced Pluripotent Stem Cells / metabolism*
  • Interneurons / metabolism
  • Models, Biological
  • Multigene Family
  • Neuronal Plasticity
  • Neurons / metabolism*
  • Phenotype


  • Biomarkers