Fig. 1: Functional connectivity and anatomical alterations in adult CDKL5 KO mice.
From: CDKL5 sculpts functional callosal connectivity to promote cognitive flexibility
a Schematic representation of the experimental procedure of functional imaging. b 3D anatomical representation of unbiased connectional alterations in the CDKL5 KO compared to its WT littermates. c (Top) 3D visual representation of seed-based analysis originating from the cingulate cortex. (Bottom) Connectivity coupling was measured using Z-scored normalized Pearson’s correlation coefficient (FSLNets; two-way Anova, region F4,70 = 182.1, p < 0.0001, genotype: F1,70 = 6.873, p = 0.0107*). d Cohen D’s effect size of interhemispheric functional connectivity evaluated in different brain regions between WT and KO mice. (n = 10/group, multiple t-test, Bonferonni corrected). e Fractional anisotropy (FA) brain maps in a representative WT (top) and KO (bottom) mouse. Images are color coded by the first eigenvector of the FA, red for the left-right, green for anterior-posterior and blue for top-bottom direction. f Quantification of FA in the anterior commissure, CC, dorsal hippocampus, and internal capsule as assessed with diffusion-weighted imaging. Intergroup comparisons showed preserved FA in KO mutant mice with respect to control littermates (multiple t-test FDR corrected, p > 0.05 all regions). CC Body, body of the CC; CC Fmi, forcep minor of the CC; CC Genu, genu of the CC; CC Spl, splenium of the CC. n = 10 mice/group. g (Top) Schematic of region of interest in the cingulate cortex, in layers 2–4 and deeper layers (L5–6). (Bottom) Schematic representation of VGlut1 staining labeling both callosal and intracortical synapses (red), while VGlut2 labels excitatory thalamo-cortical synapses (green, CC: Corpus Callosum, T: Thalamus). h Example images of glutamatergic transporter markers VGlut1 (red), VGlut 2 (green) and DAPI (blue) staining. Scale bar, 5 µm. i VGlut1 density in all layers (WT: 0.262 ± 0.007, n = 4 mice (24 sections), KO: 0.318 ± 0.011, n = 5mice (29 section), Mann-Whitney test p = 0.0079**) Mean ± SEM.
