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Session: Poster session II
Session starts: Thursday 24 January, 16:00

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Areti Sfakianou ()
Femke de Vrij ()
Steven Kushner ()
Virgilio Valente ()

Abstract:
The pathophysiology of many neurological and psychiatric diseases remains undiscovered, due to our limited understanding of the biological mechanisms underlying these disorders. Induced pluripotent stem cell (iPSC) technology provides the unique opportunity to study neural cell cultures of individual patients in-vitro [1], thus enabling to assess the physiology of psychiatric disorders. Several protocols used to obtain iPSCs-derived neuron subtypes, networks or whole brain organoids, expose low efficiency, often resulting into immature neuronal cultures. In addition, the conventional adoption of co-cultures, especially with exogenous mouse astrocytes, increases variability. Growing human iPSCs-derived neural cultures from a common neural progenitor cell (NPC), has shown to improve the differentiation efficiency [1]. NPCs are differentiated into functional neural network cultures of neurons and astrocytes in a controlled ratio, without the need of exogenous astrocyte co-culture [2]. Monitoring of the differentiation process is conventionally performed by patch clamp recordings. Single-cell patch clamp measurements, however, do not reveal network behaviour during the differentiation process, which is a critical aspect in potentially assessing the biological mechanisms of psychiatric disorders [1]. In this work, we combine the simplified neural differentiation protocol with the use of microelectrode arrays to record and stimulate neural activity at the network level during differentiation period using a MEA system (Multi Channel Systems) . Measured cell culture data is analysed using a commercial analysis software (Multiwell-Analyzer), to assess spontaneous and stimulated network activity, synchronicity and bursting activity during a developmental phase. Long-term characterisation of human iPSC-derived neural network cultures using MEA recordings helps us gain more detailed knowledge for the biological mechanisms that underlie neuropsychiatric disorders, for phenotype screening and for the development of personalized treatment and drugs with medium-throughput capacity. References [1] N Gunhanlar, G Shpak, M van der Kroeg, LA Gouty-Colomer, ST Munshi, B Lendemeijer, M Ghazvini, C Dupont, WJG Hoogendijk, J Gribnau, FMS de Vrij and SA Kushner. A simplified protocol for differentiation of electrophysiologically mature neuronal networks from human induced pluripotent stem cells. Molecular Psychiatry, 23, 1336-1344. doi:10.1038/mp.2017.56 (2018). [2] Frega, M., van Gestel, S. H., Linda, K., van der Raadt, J., Keller, J., Van Rhijn, J. R., Schubert, D., Albers, C. A., Nadif Kasri, N. Rapid Neuronal Differentiation of Induced Pluripotent Stem Cells for Measuring Network Activity on Micro-electrode Arrays. J. Vis. Exp. (119), e54900, doi:10.3791/54900 (2017).