Cell-type-specific synaptic imbalance and disrupted homeostatic plasticity in cortical circuits of ASD-associated Chd8 haploinsufficient mice.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
27
04
2020
accepted:
19
03
2021
revised:
28
02
2021
pubmed:
11
4
2021
medline:
27
1
2022
entrez:
10
4
2021
Statut:
ppublish
Résumé
Heterozygous mutation of chromodomain helicase DNA binding protein 8 (CHD8) is strongly associated with autism spectrum disorder (ASD) and results in dysregulated expression of neurodevelopmental and synaptic genes during brain development. To reveal how these changes affect ASD-associated cortical circuits, we studied synaptic transmission in the prefrontal cortex of a haploinsufficient Chd8 mouse model. We report profound alterations to both excitatory and inhibitory synaptic transmission onto deep layer projection neurons, resulting in a reduced excitatory:inhibitory balance, which were found to vary dynamically across neurodevelopment and result from distinct effects of reduced Chd8 expression within individual neuronal subtypes. These changes were associated with disrupted regulation of homeostatic plasticity mechanisms operating via spontaneous neurotransmission. These findings therefore directly implicate CHD8 mutation in the disruption of ASD-relevant circuits in the cortex.
Identifiants
pubmed: 33837267
doi: 10.1038/s41380-021-01070-9
pii: 10.1038/s41380-021-01070-9
pmc: PMC8505247
mid: EMS120345
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3614-3624Subventions
Organisme : Wellcome Trust (Wellcome)
ID : 101529/Z/13/Z
Organisme : Medical Research Council
ID : MR/K022377/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N026063/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : 1934998
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/P000479/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
© 2021. The Author(s).
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