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- Title
Maturation of AMPAR Composition and the GABA<sub>A</sub>R Reversal Potential in hPSC-Derived Cortical Neurons.
- Authors
Livesey, Matthew R.; Bilican, Bilada; Jing Qiu; Rzechorzek, Nina M.; Haghi, Ghazal; Burr, Karen; Hardingham, Giles E.; Chandran, Siddharthan; Wyllie, David J. A.
- 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 inAMPARcomposition 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 ofGABAAR-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,humanstem-cell-derived neurons represent a valuable tool for studying these fundamental properties.
- Subjects
NEURONS; EXCITATION (Physiology); PLURIPOTENT stem cells; HUMAN stem cells; NEUROTROPHINS
- Publication
Journal of Neuroscience, 2014, Vol 34, Issue 11, p4070
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.5410-13.2014