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. 2005 Nov 16;25(46):10637–10647. doi: 10.1523/JNEUROSCI.3279-05.2005

Figure 8.

Figure 8.

rTg(tauP301L)4510 mice develop age-dependent memory deficits. Longitudinal studies of rTg(tauP301L)4510 mice [2.5-9.5 months; n = 26 control and n = 9 rTg(tauP301L)4510] in the Morris water maze revealed cognitive impairments in retention of spatial reference memory. An independent study examined behavioral performance in 1.3-month-old mice [n = 31 control and n = 10 rTg(tauP301L)4510]. A, Compared with control mice, the mean time spent swimming in the target quadrant during probe trials decreased in rTg(tauP301L)4510 mice with increasing age. RMANOVA data are as follows: transgene: F(1,33) = 80.1, p < 0.0001; age versus transgene: F(3,99) = 7.46, p < 0.001; age, rTg(tauP301L)4510 mice: F(3,24) = 5.82, p < 0.01. Individual quadrant occupancy shows search bias as the percentage of time spent in each of the four quadrants (mean off our probe trials). B, Differences between the percentage of time spent in the target and opposite quadrants compared with all other quadrants was determined using an ANOVA with Fisher's PLSD post hoc analysis. Parallel analyses indicate increasing impairment in spatial navigation in hidden (C) but not cued (D) platform phases of the water-maze protocol. C, RMANOVA data for hidden platform mean path length are as follows: transgene: F(1,33) = 96.17, p < 0.0001; age versus transgene: F(3,99) = 12.02, p < 0.0001; age, rTg(tauP301L)4510 mice: F(3,24) = 4.64, p = 0.01. During the first 2 d of cued training in the longitudinal study, both nontransgenic and rTg(tauP301L)4510 mice developed shorter path lengths with repeated testing (age versus transgene RMANOVA: F(3,99) = 2.58, p = 0.06). D, Although nontransgenic mice also improved with repeated testing during the final day of cued training (age RMANOVA: F(3,75) = 26.47, p < 0.0001), rTg(tauP301L)4510 mice exhibited stable performance (age RMANOVA: F(3,24) = 2.08, p = 0.13). Transgenic control mice aged 7 and 9.5 months shown here were part of a concurrent study and received doxycycline (200 mg/kg) in their chow starting at 5.5 months of age. Previous studies have shown no effect of doxycycline supplementation on spatial reference memory performance in nontransgenic mice (SantaCruz et al., 2005). #p < 0.05, ⋄p < 0.01, *p < 0.001, **p < 0.0001. neg, Negative; pos, positive; Opp, opposite.