Maturation of AMPAR Composition and the GABAAR Reversal Potential in hPSC-Derived Cortical Neurons

Matthew R. Livesey, Bilada Bilican, Jing Qiu, Nina Marie Rzechorzek, Ghazal Haghi, Karen Burr, Giles E. Hardingham, Siddharthan Chandran*, David J. A. Wyllie

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Rodent-based studies have shown that neurons undergo major developmental changes to ion channel expression and ionic gradients that determine their excitation-inhibition balance. Neurons derived from human pluripotent stem cells theoretically offer the potential to study classical developmental processes in a human-relevant system, although this is currently not well explored. Here, we show that excitatory cortical-patterned neurons derived from multiple human pluripotent stem cell lines exhibit native-like maturation changes in AMPAR composition such that there is an increase in the expression of GluA2(R) subunits. Moreover, we observe a dynamic shift in intracellular Cl(-) levels, which determines the reversal potential of GABAAR-mediated currents and is influenced by neurotrophic factors. The shift is concomitant with changes in KCC2 and NKCC1 expression. Because some human diseases are thought to involve perturbations to AMPAR GluA2 content and others in the chloride reversal potential, human stem-cell-derived neurons represent a valuable tool for studying these fundamental properties.
Original languageEnglish
Pages (from-to)4070-4075
Number of pages6
JournalJournal of Neuroscience
Volume34
Issue number11
DOIs
Publication statusPublished - 12 Mar 2014

Keywords

  • GABA
  • glutamate
  • neurotransmitter
  • patch clamp
  • qRT-PCR
  • stem cells
  • PLURIPOTENT STEM-CELLS
  • RECEPTOR SUBUNIT EXPRESSION
  • RAT HIPPOCAMPAL-NEURONS
  • CEREBRAL WHITE-MATTER
  • DEVELOPMENTAL REGULATION
  • REGIONAL SUSCEPTIBILITY
  • HYPOXIC/ISCHEMIC INJURY
  • CORTEX
  • FOREBRAIN
  • BRAIN

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