Fig. 4: TauC3 induces region-specific dendritic atrophy in CA1 neurons of the hippocampus.

A Schematic representation of an organotypic hippocampal slice showing neurons in the Cornu Ammonis 1 (CA1) and Dentate Gyrus (DG) region that express mCherry-tagged tau after Sindbis virus infection. The segment was counterstained with DAPI to visualize cell bodies. B Representative high-magnification micrographs and corresponding image analysis of apical dendritic segments from CA1 neurons after expression of mCherry-tagged Tau or TauC3 to illustrate the algorithm-based detection of dendritic spines (colored protrusions). Scale bar, 5 µm. Quantification of spine density (left) and spine morphology (right) is shown below (mean ± SEM, n = 30 and 34 dendritic segments from 12 and 17 cells (Tau and TauC3, respectively); slices were prepared from 8 and 9 tau knockout animals, respectively). C Sholl analysis of apical and basal arbors of CA1 hippocampal pyramidal cells expressing mCherry-tagged Tau or TauC3 (mean ± SEM, n = 9–10 cells from 9–10 slices; slices were prepared from 5 and 6 tau knockout animals). Representative reconstructions of the basal (blue) and apical (red) CA1 dendritic arbors are shown below. D Quantification of total lengths of basal and apical dendritic arbor (mean ± SEM, n = 9–10 reconstructed neurons from 9–10 hippocampal slices per condition; slices were prepared from 5 and 6 tau knockout animals). All transduced tau constructs are based on the human tau sequence. Statistically significant differences determined by unpaired two-tailed t-tests are indicated. *p < 0.05.