A human in vitro neuronal model for studying homeostatic plasticity at the network level

Yuan, Xiuming; Puvogel, Sofía; van Rhijn, Jon-Ruben; Ciptasari, Ummi; Esteve-Codina, Anna; Meijer, Mandy; Rouschop, Simon; van Hugte, Eline J. H.; Oudakker, Astrid; Schoenmaker, Chantal; Frega, Monica; Schubert, Dirk; Franke, Barbara; Nadif Kasri, Nael

doi:http://dx.doi.org/10.1016/j.stemcr.2023.09.011

A human in vitro neuronal model for studying homeostatic plasticity at the network level

Llicència

Citació

Yuan X, Puvogel S, van Rhijn JR, Ciptasari U, Esteve-Codina A, Meijer M, Rouschop S, van Hugte EJH, Oudakker A, Schoenmaker C, Frega M, Schubert D, Franke B, Nadif Kasri N. A human in vitro neuronal model for studying homeostatic plasticity at the network level. Stem Cell Reports. 2023 Nov 14;18(11):2222-39. DOI: 10.1016/j.stemcr.2023.09.011

Resum

Mechanisms that underlie homeostatic plasticity have been extensively investigated at single-cell levels in animal models, but are less well understood at the network level. Here, we used microelectrode arrays to characterize neuronal networks following induction of homeostatic plasticity in human induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons co-cultured with rat astrocytes. Chronic suppression of neuronal activity through tetrodotoxin (TTX) elicited a time-dependent network re-arrangement. Increased expression of AMPA receptors and the elongation of axon initial segments were associated with increased network excitability following TTX treatment. Transcriptomic profiling of TTX-treated neurons revealed up-regulated genes related to extracellular matrix organization, while down-regulated genes related to cell communication; also astrocytic gene expression was found altered. Overall, our study shows that hiPSC-derived neuronal networks provide a reliable in vitro platform to measure and characterize homeostatic plasticity at network and single-cell levels; this platform can be extended to investigate altered homeostatic plasticity in brain disorders.