An in vitro model of neuronal ensembles.

Autor: 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.; Department of Biomedical Engineering, Columbia University, New York, NY, USA., Gong C; Department of Biological Sciences, Columbia University, New York, NY, USA.; Department of Biomedical Engineering, Columbia University, New York, NY, USA., Crabtree G; Mortimer B. Zuckerman Mind Brain and Behavior Institute, Columbia University, New York, NY, USA., Xu B; Department of Psychiatry, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA., Markx S; Department of Psychiatry, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA., Gogos JA; Mortimer B. Zuckerman Mind Brain and Behavior Institute, Columbia University, New York, NY, USA.; Department of Physiology, Columbia University, New York, NY, USA.; Department of Neuroscience, Columbia University, New York, NY, USA.; Department of Psychiatry, Columbia University, New York, NY, USA., Yuste R; Department of Biological Sciences, Columbia University, New York, NY, USA.; NeuroTechnology Center, Columbia University, New York, NY, USA., Tomer R; Department of Biological Sciences, Columbia University, New York, NY, USA. raju.tomer@columbia.edu.; Mortimer B. Zuckerman Mind Brain and Behavior Institute, Columbia University, New York, NY, USA. raju.tomer@columbia.edu.; Department of Biomedical Engineering, Columbia University, New York, NY, USA. raju.tomer@columbia.edu.; NeuroTechnology Center, Columbia University, New York, NY, USA. raju.tomer@columbia.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Jun 09; Vol. 13 (1), pp. 3340. Date of Electronic Publication: 2022 Jun 09.
DOI: 10.1038/s41467-022-31073-1
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
Externí odkaz: