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

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 i...

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Detalles Bibliográficos
Autores: 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/59060
Acceso en línea:http://hdl.handle.net/10230/59060
http://dx.doi.org/10.1016/j.stemcr.2023.09.011
Access Level:acceso abierto
Palabra clave:hiPSC
Homeostatic plasticity
Human neuronal networks
Descripción
Sumario: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.