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Biochem Biophys Res Commun. 2019 Apr 4. pii: S0006-291X(19)30561-3. doi: 10.1016/j.bbrc.2019.03.161. [Epub ahead of print]

Synchronous spike patterns in differently mixed cultures of human iPSC-derived glutamatergic and GABAergic neurons.

Author information

1
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-0033, Japan; Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan. Electronic address: tsasaki@mol.f.u-tokyo.ac.jp.
2
Department of Electronics, Graduate School of Engineering, Tohoku Institute of Technology, 35-1 Yagiyama Kasumicho, Taihaku-ku, Sendai, Miyagi, 982-8577, Japan; iPS-non-Clinical Experiments for Nervous System (iNCENS) Project, Kanagawa, Japan; Consortium for Safety Assessment using Human iPS Cells (CSAHi), Kanagawa, Japan. Electronic address: i-suzuki@tohtech.ac.jp.
3
Department of Electronics, Graduate School of Engineering, Tohoku Institute of Technology, 35-1 Yagiyama Kasumicho, Taihaku-ku, Sendai, Miyagi, 982-8577, Japan.
4
iPS-non-Clinical Experiments for Nervous System (iNCENS) Project, Kanagawa, Japan; Consortium for Safety Assessment using Human iPS Cells (CSAHi), Kanagawa, Japan; Laboratory of Neuropharmacology, Division of Pharmacology, Laboratory of Neuropharmacology, National Institute of Health Sciences, Tokyo, Japan.
5
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-0033, Japan; Center for Information and Neural Networks, Suita City, Osaka, 565-0871, Japan.

Abstract

Human induced-pluripotent stem cell (hiPSC)-derived neurons develop organized neuronal networks under in vitro cultivation conditions. Here, using a multielectrode array system, we examined whether the spike patterns of hiPSC-derived neuronal populations differed in a manner that depended on the proportions of glutamatergic and gamma-aminobutyric acid (GABA)ergic neurons in the cultures. Synchronous burst firing events spanning multiple electrodes became more frequent as the number of days in culture increased. However, at all developmental stages, the event rates of synchronous burst firing, the repertoires of synchronous burst firing, and the frequencies of sporadic spikes did not differ in cultures with different glutamatergic-to-GABAergic ratios. Pharmacological blockade of GABAergic synaptic transmission increased the frequencies of spike patterns specifically in cultures with lower glutamatergic-to-GABAergic ratios. These results demonstrate that a robust homeostatic property of developing hiPSC-derived neuronal networks in culture counteracts chronically imbalanced glutamatergic and GABAergic signaling.

KEYWORDS:

Cell type; Human induced-pluripotent stem cell-derived neurons; Multielectrode array; Synchronization

PMID:
30954214
DOI:
10.1016/j.bbrc.2019.03.161

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