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An in vitro model of neuronal ensembles.
Rabadan, M Angeles; De La Cruz, Estanislao Daniel; Rao, Sneha B; Chen, Yannan; Gong, Cheng; Crabtree, Gregg; Xu, Bin; Markx, Sander; Gogos, Joseph A; Yuste, Rafael; Tomer, Raju.
Afiliación
  • Rabadan MA; Department of Biological Sciences, Columbia University, New York, NY, USA.
  • De La Cruz ED; Department of Biological Sciences, Columbia University, New York, NY, USA.
  • Rao SB; Mortimer B. Zuckerman Mind Brain and Behavior Institute, Columbia University, New York, NY, USA.
  • Chen Y; Department of Biological Sciences, Columbia University, New York, NY, USA.
  • Gong C; Department of Biomedical Engineering, Columbia University, New York, NY, USA.
  • Crabtree G; Department of Biological Sciences, Columbia University, New York, NY, USA.
  • Xu B; Department of Biomedical Engineering, Columbia University, New York, NY, USA.
  • Markx S; Mortimer B. Zuckerman Mind Brain and Behavior Institute, Columbia University, New York, NY, USA.
  • Gogos JA; Department of Psychiatry, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.
  • Yuste R; Department of Psychiatry, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.
  • Tomer R; Mortimer B. Zuckerman Mind Brain and Behavior Institute, Columbia University, New York, NY, USA.
Nat Commun ; 13(1): 3340, 2022 06 09.
Article en En | MEDLINE | ID: mdl-35680927
Advances in 3D neuronal cultures, such as brain spheroids and organoids, are allowing unprecedented in vitro access to some of the molecular, cellular and developmental mechanisms underlying brain diseases. However, their efficacy in recapitulating brain network properties that encode brain function remains limited, thereby precluding development of effective in vitro models of complex brain disorders like schizophrenia. Here, we develop and characterize a Modular Neuronal Network (MoNNet) approach that recapitulates specific features of neuronal ensemble dynamics, segregated local-global network activities and a hierarchical modular organization. We utilized MoNNets for quantitative in vitro modelling of schizophrenia-related network dysfunctions caused by highly penetrant mutations in SETD1A and 22q11.2 risk loci. Furthermore, we demonstrate its utility for drug discovery by performing pharmacological rescue of alterations in neuronal ensembles stability and global network synchrony. MoNNets allow in vitro modelling of brain diseases for investigating the underlying neuronal network mechanisms and systematic drug discovery.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esquizofrenia / Encefalopatías Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esquizofrenia / Encefalopatías Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido