@article{a240832a848a47e794c9be70646b9eee,
title = "Cell-type-specific synaptic imbalance and disrupted homeostatic plasticity in cortical circuits of ASD-associated Chd8 haploinsufficient mice",
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.",
author = "Ellingford, {Robert A} and Panasiuk, {Martyna J} and {de Meritens}, {Emilie Rabesahala} and Raghav Shaunak and Liam Naybour and Lorcan Browne and Basson, {M Albert} and Andreae, {Laura C}",
note = "Funding Information: Acknowledgements This work was funded by grants from the Simons Foundation (SFARI #344763 to MAB and #653443 to MAB and LCA), the BBSRC (BB/P000479/1 to LCA), and a KHP Challenge Fund Award (R160801 to LCA). LCA was supported by a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation. RAE was supported by the King{\textquoteright}s Bioscience Institute and the Guy{\textquoteright}s and St Thomas{\textquoteright} Charity Prize PhD program in Biomedical and Translational Science. MJP was supported by the UK Medical Research Council (#1934998). We acknowledge support from the Wellcome Trust (101529/Z/13/Z) for the Imaris imaging workstation and technical support by Dylan Herzog. The authors wish to thank Nathalie Higgs, Ruth Taylor, Carly Schott, and the BSU staff for their technical assistance during the study. We thank S. Anderson, S. Goebbels, and K. Nave for the Nkx2.1-Cre and NEX-Cre lines. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = jul,
doi = "10.1038/s41380-021-01070-9",
language = "English",
volume = "26",
pages = "3614--3624",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Springer Nature [academic journals on nature.com]",
number = "7",
}