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Cell-type-specific synaptic imbalance and disrupted homeostatic plasticity in cortical circuits of ASD-associated Chd8 haploinsufficient mice
- Source :
- Molecular Psychiatry
- Publication Year :
- 2021
- Publisher :
- Nature Publishing Group UK, 2021.
-
Abstract
- 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.
- Subjects :
- Heterozygote
Autism Spectrum Disorder
Haploinsufficiency
Neurotransmission
Biology
medicine.disease_cause
Inhibitory postsynaptic potential
Article
Chromodomain
03 medical and health sciences
Cellular and Molecular Neuroscience
Mice
0302 clinical medicine
Homeostatic plasticity
medicine
Animals
Prefrontal cortex
Molecular Biology
030304 developmental biology
Neurons
0303 health sciences
Mutation
Autism spectrum disorders
Cortex (botany)
Psychiatry and Mental health
Excitatory postsynaptic potential
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 14765578 and 13594184
- Volume :
- 26
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Molecular Psychiatry
- Accession number :
- edsair.doi.dedup.....8645773e241754c75ab3056ff731bc68