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. 2021 Apr 9;26(7):3614–3624. doi: 10.1038/s41380-021-01070-9

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — A Schematic illustrating coronal ex vivo brain slice, blue shading indicates recording area in layers V/VI of the PFC. IL infralimbic cortex, PL prelimbic cortex. B, C Representative mEPSC (B) and mIPSC (C) recordings from pyramidal neurons from P19–21 WT (blue) and Chd8^+/– (red) animals alongside quantifications of mEPSC and mIPSC frequency (bottom left graphs) and amplitude (bottom right graphs). B Chd8^+/– neurons display significantly reduced mEPSC frequency (p = 0.0027) and amplitude (p < 0.0001) but C increased mIPSC frequency (p = 0.0009) and equivalent mIPSC amplitude. D Normal action potential (AP) firing frequency in Chd8^+/– neurons; left: representative voltage traces and current injection stimuli (below), right: f-I curves. E Sholl analysis of basal dendrites (P22) shows no significant difference in Chd8^+/– neurons. F Analysis of synapse densities at P20; left: representative reconstructions of secondary basal dendrites (green filament) with associated spines (blue) and inhibitory synapses (red dots) from WT (above) and Chd8^+/– (below) GFP+ pyramidal neurons immunolabeled for the inhibitory synapse marker VGAT (scale bar 10 µm), with quantifications of spine (middle) and VGAT (right) densities. Chd8^+/– neurons showed no difference in spine densities, nor in VGAT density on apical dendrites, but did show an increase in VGAT density on basal dendrites (p = 0.0002). G Representative PPR recordings (left) from WT and Chd8^+/– PFC neurons; quantification (right) shows elevated PPR in Chd8^+/– neurons. H Reduced spontaneous AP firing in Chd8^+/– neurons, representative traces (left) and quantification (right). For all figures, bars show mean, error bars SEM, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.