Treatment with rolofylline restores the dendritic spine level in proaggregant Tau transgenic slices and reverses spatial memory deficits and normalizes basal synaptic transmission in proaggregant Tau transgenic mice. (A and B) Quantification of dendritic spines of in rolofylline (A1 ant.) or sham-treated organotypic slices. Error bars indicate SEM. ***P < 0.001 (one-way ANOVA with Tukey’s test). (Scale bar in A: 2 µm.) (C–F) Outcome of behavior testing after 10–20 d of rolofylline treatment for the Y-maze test (C), novel object recognition test (NORT) (D), and fear conditioning test (E and F). Error bars indicate SEM. ****P < 0.0001, ***P < 0.001, **P < 0.01, and *P < 0.05. (G and H) Basal synaptic transmission (I/O curve) in acute slices from littermate control and proaggregant Tau transgenic. Representative traces of the I/O curves of proaggregants and littermate controls are displayed. Sham treated in G and rolofylline (A1 ant.) treated in H. Representative traces of the I/O curves are displayed. (I) The slope and maximum amplitude of the I/O curves of CA1 of rolofylline (A1 ant.) and sham-treated acute slices of proaggregant Tau transgenic and littermate controls. Error bars indicate SEM. ****P < 0.0001, *P < 0.05 (two-way ANOVA with Tukey’s test).