How to study our brain’s “thermostat” in a human neuronal model?

Homeostatic plasticity is natural ability of our brain to maintain balance and stability. It is like a built-in thermostat for our brain, ensuring that the connections between neurons stay at the right level of activity during learning and memory. Previous studies identified disrupted homeostatic plasticity in rodent models for different neurodevelopmental disorders (NDDs), such as Fragile X syndrome, Kleefstra syndrome, Rett syndrome, which suggests that altered or insufficient homeostatic plasticity during development contributes to cognitive and behavioural impairments that characterize NDDs. While mechanisms that underlie homeostatic plasticity have been extensively investigated at single-cell level in animal models, they are not well understood at cell population level in human models.

Researchers at the Department of Human Genetics of Radboudumc (Xiuming Yuan, Sofía Puvogel, Barbara Franke and Nael Nadif Kasri) recently established a new model of homeostatic plasticity in human induced pluripotent stem cell (hiPSC)-derived excitatory neurons on microelectrode arrays, which they have previously shown to facilitate non-invasive, reproducible, real-time, and multidimensional measurement of activity in hiPSC-derived neuronal networks (Mossink et al., 2021). 

They find that homeostatic plasticity in human neurons elicited a time-dependent re-arrangement of neuronal networks connectivity. This re-arrangement was accompanied by changes in gene expression, which may underlie the network re-arrangement. 

Overall, they showed that hiPSC-derived neuronal networks provide a reliable in vitro platform to measure and characterize homeostatic plasticity at population level. This platform is currently extended to investigate altered homeostatic plasticity in brain disorders in the lab.

Read the study here

Yuan, X., Puvogel, S., van Rhijn, J.R., Ciptasari, U., Esteve-Codina, A., Meijer, M., Rouschop, S., van Hugte, E.J.H., Oudakker, A., Schoenmaker, C., et al. (2023). A human in vitro neuronal model for studying homeostatic plasticity at the network level. Stem Cell Reports. 10.1016/j.stemcr.2023.09.011.