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In vitro generated neurons form functional networks

In vitro generated neurons form functional networks - Milou Dingemans; co-authored by Martje de Groot and Remco Westerink

The growing number of (suspected) developmentally toxic chemicals strongly argues forthedevelopment of in vitro assays to identify and prioritize cellular and molecular mechanisms of action of chemicals on the development of structure and function of the neuronal networks that form the basis for human cognition. In vitro cell-based models reduce the complexity of the nervous system, making it easier to detect small but significant changes in specific neurodevelopmental processes. Many efforts are currently undertaken in the field of developmental neurotoxicology to assess the predictivity of in vitro strategies. It is encouraging that a recent study by Weick and co-workers from the University of Wisconsin-Madison has demonstrated that human embryonic stem cell (hESC)-derived neurons develop functional characteristics and can participate in and modulate neural network activity, both in vitro and in vivo.

hESC-derived neurons were co-cultured with mouse cortical neurons or transplanted in the brain of mice. The transfection of hESC-derived neurons with light-sensitive ion channels allowed the researchers to evoke the influx of ions by hitting the neurons with a light beam. By using these optogenetics techniques, they were thus able to selectively depolarize individual neurons, thereby controlling the activity of the cells.

The investigators used patch-clamping on cortical neurons and hESC-derived neurons in co-culture and revealed that the hESC-derived neurons adapted the activity pattern of the neural network of mouse cortical neurons and that the hESC-derived neurons, when stimulated by light, could regulate the activity of the neuronal network. In hippocampal slices from mice in which hESC-derived neurons were transplanted 4 months earlier in the CA3-region, the hESC-derived neurons could be seen migrating through hippocampal CA3, CA1 and dentate gyrus. The investigators also demonstrated that upon light-stimulation of hESC-derived neurons, signals could be measured in nearby mouse hippocampal neurons.

In summary, this research by Weick and co-workers demonstrates that functional neuronal networks can be derived from embryonic stem cell-derived neurons, thereby also supporting the applicability of stem/progenitor cells-based in vitro assays for developmental neurotoxicity.