5-HT2 receptors mediate functional modulation of GABAa receptors and inhibitory synaptic transmissions in human iPS-derived neurons

Scientific Reports
Haitao WangJufang He

Abstract

Neural progenitors differentiated from induced pluripotent stem cells (iPS) hold potentials for treating neurological diseases. Serotonin has potent effects on neuronal functions through multiple receptors, underlying a variety of neural disorders. Glutamate and GABA receptors have been proven functional in neurons differentiated from iPS, however, little is known about 5-HT receptor-mediated modulation in such neuronal networks. In the present study, human iPS were differentiated into cells possessing featured physiological properties of cortical neurons. Whole-cell patch-clamp recording was used to examine the involvement of 5-HT2 receptors in functional modulation of GABAergic synaptic transmission. We found that serotonin and DOI (a selective agonist of 5-HT2A/C receptor) reversibly reduced GABA-activated currents, and this 5-HT2A/C receptor mediated inhibition required G protein, PLC, PKC, and Ca(2+) signaling. Serotonin increased the frequency of miniature inhibitory postsynaptic currents (mIPSCs), which could be mimicked by α-methylserotonin, a 5-HT2 receptor agonist. In contrast, DOI reduced both frequency and amplitude of mIPSCs. These findings suggested that in iPS-derived human neurons serotonin postsynaptically redu...Continue Reading

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Citations

Mar 12, 2017·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Stefano AringhieriMarco Scarselli
Jan 22, 2019·Expert Opinion on Therapeutic Targets·Nina K Popova, Vladimir S Naumenko
Apr 7, 2016·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Xixi DongJiang Chang
Aug 28, 2021·International Journal of Molecular Sciences·Parthena MartinBradley S Galer

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