Before testing the Thy1-hAPPLond/Swe+ and their control littermates, a validation experiment was conducted using C57BL/6J mice and scopolamine. Scopolamine, a competitive

antagonist for muscarinic acetylcholine receptors, specifically M1 receptors, is known to induce memory impairment. In this four-day experiment, scopolamine and vehicle (1 mg/kg ip) was injected daily 20 min prior to Inhibitors,research,lifescience,medical the first trial. A total of 20 mice, (n = 10) vehicle and (n = 10) scopolamine, were used for this experiment. Fear conditioning Coulbourn Instruments (Whitehall, PA) FC chambers were used for the assessment of conditional learning and memory. A trace FC protocol was used for the training day followed by tone-cued and contextual memory retrieval tests. On the first day (training day), mice were placed in the chamber for Inhibitors,research,lifescience,medical a 3-min baseline recording followed by five find more tone-shock pairings with ITIs of 100 sec. The shocks (0.5 mA, 2 sec) were delivered 18 sec following the tone

(70 dB, 2 kHz, 20 sec). On the second day, a novel context (new olfactory environment, different shape of the chamber, new texture of the floor, blue plastic inserts for walls, extra source of blue light, and visual cues) was used for tone-cued testing. After 3 min of baseline recording, three tones without shocks with ITIs of 100 sec were presented to the mice. On the third day of the experiment, mice were placed in the same context as the first Inhibitors,research,lifescience,medical day for 5 min with no shocks or tones to test contextual memory retrieval (modified from the method described by Saxe et al. [2006]). The chambers

were cleaned by 10% ethanol on days 1 and 3. On day 2, chambers were first cleaned by Alcide and then wiped with wet paper towels. Freezing was defined as the complete lack of motion for a minimum of 0.75 sec, as assessed by FreezeFrame Inhibitors,research,lifescience,medical software (Actimetrics, Evanston, IL). A total of 23 mice, control (n = 12) and Thy1-hAPPLond/Swe+ (n = 11), were used for Inhibitors,research,lifescience,medical this experiment. Hot plate test Each mouse was handled for 2 min and habituated to the testing environment 24 h before testing. The hot plate apparatus (IITC Inc., Woodland Hills, CA) was set to a temperature of 55 ± 0.1°C. On the testing day, mice were placed on the surface of the hot plate and covered with a transparent glass cylinder (height 25 cm, diameter 12 cm). A 30-sec cut-off time was assigned and a remote foot-switch pad was used to control the start/stop function. The latency to the first Cell press hind paw lick or jump was recorded. A total of 18 mice, control (n = 9) and Thy1-hAPPLond/Swe+ (n = 9), were used for this experiment. Statistical analysis All data were presented as mean ± SEM and P < 0.05 was considered statistically significant. Repeated measures two-way ANOVA was used for evaluation of the parameters in activity chamber, open field, water maze, DMP dry maze, training day of FC, and social tests. The Bonferroni test was used for post-hoc analysis. The Student’s t-test was used where appropriate.