@article{b6d07fc6d60849099794917feacf223f,
title = "A human in vitro neuronal model for studying homeostatic plasticity at the network level",
abstract = "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.",
keywords = "hiPSC, homeostatic plasticity, human neuronal networks",
author = "Xiuming Yuan and Sof{\'i}a Puvogel and {van Rhijn}, {Jon Ruben} and Ummi Ciptasari and Anna Esteve-Codina and Mandy Meijer and Simon Rouschop and {van Hugte}, {Eline J.H.} and Astrid Oudakker and Chantal Schoenmaker and Monica Frega and Dirk Schubert and Barbara Franke and {Nadif Kasri}, Nael",
note = "Funding Information: The work was supported by funding from the European Community's Horizon 2020 Programme (H2020/2014–2020) under grant agreement no. 728018 (Eat2beNICE) (to B.F.); ERA-NET NEURON-102 SYNSCHIZ grant (NWO) 013-17-003 4538 (to D.S.); China Scholarship Council 201906100038 (to X.Y.); ISCIII /MINECO (PT17/0009/0019) and FEDER (to A.E.C.); and M.M. was supported by an internal grant from the Donders Centre for Medical Neurosciences of the Radboud University Medical Center. X.Y. B.F. and N.N.K. conceived the hypothesis and designed the experiments. N.N.K. B.F. and D.S. supervised the study. X.Y. J.R.V.R. and U.C. performed the experiments. X.Y. S.P. J.R.V.R. U.C. and M.F. analyzed the data. A.E.C. M.M. S.R. and E.J.H.v.H. assisted in data analysis. A.O. and C.S. assisted in experiments. X.Y. S.P. and J.R.V.R drafted the manuscript. All authors reviewed and edited the draft manuscript. B.F. has received educational speaking fees from Medice. Funding Information: The work was supported by funding from the European Community{\textquoteright}s Horizon 2020 Programme ( H2020/2014–2020 ) under grant agreement no. 728018 ( Eat2beNICE ) (to B.F.); ERA-NET NEURON-102 SYNSCHIZ grant ( NWO ) 013-17-003 4538 (to D.S.); China Scholarship Council 201906100038 (to X.Y.); ISCIII /MINECO ( PT17/0009/0019 ) and FEDER (to A.E.C.); and M.M. was supported by an internal grant from the Donders Centre for Medical Neurosciences of the Radboud University Medical Center . Publisher Copyright: {\textcopyright} 2023 The Author(s)",
year = "2023",
month = nov,
day = "14",
doi = "10.1016/j.stemcr.2023.09.011",
language = "English",
volume = "18",
pages = "2222--2239",
journal = "Stem cell reports",
issn = "2213-6711",
publisher = "Cell Press",
number = "11",
}