(A1-6) Representative coronal sections from diffusion-weighted tractography at different time points during epileptogenesis (before injection = pre; 1d, 4d, 7d, 14d and 31d following SE). (B1-6) Enlarged images of the ipsilateral hippocampus at different levels along the rostro-caudal axis. The orientation of computed streamlines is color-coded [dorsoventral (DV), turquoise; mediolateral (ML), red; rostrocaudal (RC), blue]. (C–D) Representative tractography image and a Nissl-stained section (modified from Paxinos and Franklin, The Mouse Brain in Stereotaxic Coordinates, 2001) of corresponding brain regions for anatomical comparison. Computed fibers relate to major axonal pathways and brain regions exhibiting highly oriented dendrites (cc, corpus callosum; cp, cerebral peduncle; Cx, cortex; Dlg, dorsal lateral geniculate nucleus; ec, external capsule; eml, external medullary lamina; Hc, hippocampus; HyTh, hypothalamus; ic, internal capsule; ml, medial lemniscus; opt, optic nerve; Th, thalamus). (E, G) Enlarged tractography images demonstrating the distinct orientation of streamlines in different hippocampal layer (dashed lines; cc, corpus callosum; so, stratum oriens; py, pyramidal layer; sr, stratum radiatum; slm, stratum lacunosum moleculare; ml, molecular layer; gcl, granule cell layer; asterisks denote the region of pyramidal cell loss). (F, H) Corresponding DAPI-stained sections. Scale bars in A, 2 mm; B-D, 500 µm; H (left), 100 µm. (I, K, M, O) Quantitative analysis of DWI metrics [mean- (MD), radial (RD), axial diffusivity (AD) and fractional anisotropy (FA)] in the DG, plotted for individual mice (left panel; controls, black, n = 5; kainate-injected animals color-coded) and for groups (right panel; epileptic, dark grey; non-epileptic, light grey) during epileptogenesis. Source data is provided in ‘Figure 5—source data 1'. Two-way ANOVA, Bonferroni’s post-test, **p<0.01; ***p<0.001; nnon-epi = 6, nepi = 7. Values are presented as the mean ± SEM. (J, L, N, P) Corresponding linear regression analysis of DWI metrics at distinct time points during epileptogenesis with the total GCL volume in epileptic and non-epileptic mice (n = 13; Pearson’s correlation, corrected for multiple comparison; *p<0.05, **p<0.01, ***p<0.001). Refer to ‘Figure 5—figure supplement 1' for DWI metrics acquired in CA1.