Nov 7, 2018

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

BioRxiv : the Preprint Server for Biology
William PlumblyAdrian J Harwood

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 GABergic signalling shapes network behaviour into a synchronous regular pattern of burst firing activity and low activity periods. 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 ...Continue Reading

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Mentioned in this Paper

Neuron Differentiation
Voltage gated calcium channel
MEA Protocol
Study
Biological Neural Networks
Patterns
Genes
Schizophrenia
Regulation of Biological Process
Mea1 protein, mouse

About this Paper

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