An in vitro model of neuronal ensembles.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
09 06 2022
09 06 2022
Historique:
received:
07
03
2022
accepted:
01
06
2022
entrez:
10
6
2022
pubmed:
11
6
2022
medline:
14
6
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35680927
doi: 10.1038/s41467-022-31073-1
pii: 10.1038/s41467-022-31073-1
pmc: PMC9184643
doi:
Substances chimiques
Histone-Lysine N-Methyltransferase
EC 2.1.1.43
Setd1A protein, human
EC 2.1.1.43
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3340Subventions
Organisme : NIMH NIH HHS
ID : R01 MH097879
Pays : United States
Organisme : NIMH NIH HHS
ID : DP2 MH119423
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY011787
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH112860
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH115900
Pays : United States
Organisme : NCATS NIH HHS
ID : UG3 TR002151
Pays : United States
Informations de copyright
© 2022. The Author(s).
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