PT  - JOURNAL ARTICLE
AU  - Silvia Ronchi
AU  - Alessio Paolo Buccino
AU  - Gustavo Prack
AU  - Sreedhar Saseendran Kumar
AU  - Manuel Schröter
AU  - Michele Fiscella
AU  - Andreas Hierlemann
TI  - Electrophysiological Phenotype Characterization of Human iPSC-Derived Neuronal Cell Lines by Means of High-Density Microelectrode Arrays
AID  - 10.1101/2020.09.02.271403
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.09.02.271403
4099  - http://biorxiv.org/content/early/2020/09/02/2020.09.02.271403.short
4100  - http://biorxiv.org/content/early/2020/09/02/2020.09.02.271403.full
AB  - Recent advances in the field of cellular reprogramming have opened a route to study the fundamental mechanisms underlying common neurological disorders. High-density microelectrode-arrays (HD-MEAs) provide unprecedented means to study neuronal physiology at different scales, ranging from network through single-neuron to subcellular features. In this work, we used HD-MEAs in vitro to characterize and compare human induced-pluripotent-stem-cell (iPSC)-derived dopaminergic and motor neurons, including isogenic neuronal lines modeling Parkinson’s disease and amyotrophic lateral sclerosis. We established reproducible electrophysiological network, single-cell and subcellular metrics, which were used for phenotype characterization and drug testing. Metrics such as burst shapes and axonal velocity enabled the distinction of healthy and diseased neurons. The HD-MEA metrics could also be used to detect the effects of dosing the drug retigabine to human motor neurons. Finally, we showed that the ability to detect drug effects and the observed culture-to-culture variability critically depend on the number of available recording electrodes.Competing Interest StatementM.F. is co-founder of MaxWell Biosystems AG, which commercializes HD-MEA technology.