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

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  • dc.contributor.author Yuan, Xiuming
  • dc.contributor.author Puvogel, Sofía
  • dc.contributor.author van Rhijn, Jon-Ruben
  • dc.contributor.author Ciptasari, Ummi
  • dc.contributor.author Esteve-Codina, Anna
  • dc.contributor.author Meijer, Mandy
  • dc.contributor.author Rouschop, Simon
  • dc.contributor.author van Hugte, Eline J. H.
  • dc.contributor.author Oudakker, Astrid
  • dc.contributor.author Schoenmaker, Chantal
  • dc.contributor.author Frega, Monica
  • dc.contributor.author Schubert, Dirk
  • dc.contributor.author Franke, Barbara
  • dc.contributor.author Nadif Kasri, Nael
  • dc.date.accessioned 2024-02-12T06:36:45Z
  • dc.date.available 2024-02-12T06:36:45Z
  • dc.date.issued 2023
  • dc.description.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.
  • dc.description.sponsorship 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.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation 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
  • dc.identifier.doi http://dx.doi.org/10.1016/j.stemcr.2023.09.011
  • dc.identifier.issn 2213-6711
  • dc.identifier.uri http://hdl.handle.net/10230/59060
  • dc.language.iso eng
  • dc.publisher Elsevier
  • dc.relation.ispartof Stem Cell Reports. 2023 Nov 14;18(11):2222-39
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/728018
  • dc.rights © 2023 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
  • dc.subject.keyword hiPSC
  • dc.subject.keyword Homeostatic plasticity
  • dc.subject.keyword Human neuronal networks
  • dc.title A human in vitro neuronal model for studying homeostatic plasticity at the network level
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion