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L-type voltage-gated calcium channel regulation of in vitro human cortical neuronal networks

Plumbly, William, Brandon, Nick, Deeb, Tarek Z, Hall, Jeremy and Harwood, Adrian J 2019. L-type voltage-gated calcium channel regulation of in vitro human cortical neuronal networks. Scientific Reports 9 , 13810. 10.1038/s41598-019-50226-9

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Abstract

The combination of in vitro multi-electrode arrays (MEAs) and the neuronal differentiation of stem cells offers the capability to study human neuronal networks from patient or engineered human cell lines. Here, we use MEA-based assays to probe synaptic function and network interactions of hiPSC-derived neurons. Neuronal network behaviour first emerges at approximately 30 days of culture and is driven by glutamate neurotransmission. Over a further 30 days, inhibitory GABAergic signalling shapes network behaviour into a synchronous regular pattern of burst firing activity and low activity periods. Gene mutations in L-type voltage gated calcium channel subunit genes are strongly implicated as genetic risk factors for the development of schizophrenia and bipolar disorder. We find that, although basal neuronal firing rate is unaffected, there is a dose-dependent effect of L-type voltage gated calcium channel inhibitors on synchronous firing patterns of our hiPSC-derived neural networks. This demonstrates that MEA assays have sufficient sensitivity to detect changes in patterns of neuronal interaction that may arise from hypo-function of psychiatric risk genes. Our study highlights the utility of in vitro MEA based platforms for the study of hiPSC neural network activity and their potential use in novel compound screening.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Biosciences
Neuroscience and Mental Health Research Institute (NMHRI)
Publisher: Nature Publishing Group
ISSN: 2045-2322
Funders: Wellcome Trust
Date of First Compliant Deposit: 10 September 2019
Date of Acceptance: 2 September 2019
Last Modified: 25 Sep 2019 11:34
URI: http://orca.cf.ac.uk/id/eprint/125380

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