Figure 4

Tau ^RDΔ expression causes morphological changes of the DG - CA3 postsynapse in hippocampal organotypic slice cultures at DIV 10. (a) A DiI crystal was placed on the dentate gyrus of fixed hippocampal organotypic slices from pro-aggregant mice or control littermates. DiI labeled mossy fibers and CA3 pyramidal neurons were imaged 10 days later. (b) Nuclear counterstaining with TO-PRO was used to visualize hippocampal sub- regions. Arrows indicate DiI labeled mossy fibers. (c) Higher magnification of a single CA3 pyramidal neuron displays thorny excrescences (th.ex.) in the stratum lucidum and stratum oriens as well as projecting mossy fibers (mf) from the dentate gyrus granule cells with large boutons. (d) Examples of thorny excrescences dendritic spines from CA3 pyramidal neurons taken from control (Ctrl), pro-aggregant (Pro) and pro-aggregant slices treated with Tau aggregation inhibitor bb14 (Pro + bb14). (e) Dendritic spine density of CA3 neurons was reduced by ~20% in pro-aggregant (Pro) vs. control littermate slice cultures (Ctrl) (10 slices prepared from 5 different animals per group). This effect is abolished when pro-aggregant slice cultures are treated with the aggregation inhibitor bb14 (Pro + bb14) (One way ANOVA followed by Tukey’s post-hoc test ** p-value < 0.01; * p-value < 0.05). Error bars represent SEM.