JNJ16259685 significantly decreased the internalization of PSD95 with lysosome marker CD68 in microglia (Iba1) in the rats injected with amyloid fibrils (a, n = 5 rats in each group, F3,16 = 73.0, P <0.0001, scale bar = 10 μm). Each dot represents the mean value of 4 brain sections of one animal. Microinjection of JNJ16259685 significantly recovered the amplitude (b, n = 13 rats in each group, Kruskal-Wallis Statistic KW = 18.2, P = 0.0004) and inter-event interval of mEPSCs (b, n = 13 rats in each group, F3,48 = 16.8, P<0.0001) in the hippocampal CA1 neurons in the rats injected with amyloid fibrils. Microinjection of JNJ16259685 also shortened the escape latency (c, n = 10 rats in each group, effect of group [F3,36 = 13.3, P<0.0001], effect of time [F4,36 = 135.5, P<0.0001], interaction between group and time [P = 0.47]) and increased the time spent in the target quadrant (d, n = 10 rats in each group, F4,36 = 6.57, P = 0.0012) in the amyloid-injected rats. (d) Representative path tracings in each quadrant during the probe trial on day 6 (T, target quadrant; R, right quadrant; O, opposite quadrant; L, left quadrant). Data represent mean ± s.e.m. For box-and-whiskers plots, the box extends from the 25th to 75th percentiles, a line within the box marks the median. Whiskers (error bars) above and below the box represent the minimum and maximum values. *P<0.05, **P<0.01, ***P<0.001.