Contextual Fear Conditioning.

To assess contextual fear memory, a two-phase protocol was used, as described (15, 54) with minor modifications. In the training phase, mice were presented to the conditioning cage (40 × 25 × 30 cm), which they were allowed to freely explore for 2 minutes followed by application of a single foot shock (0.35 mA) for 2 s. Mice were kept for another 30 s in the cage and removed. On the next day, mice were presented to the same cage for 5 minutes without receiving a foot shock. Freezing behavior was recorded automatically using the Freezing software (Panlab) and was used as a memory index. For APPSwe/PS1ΔE9 mice, due to the extensive memory impairment in these mice, protocol included 2 min of free exploration, followed by two foot shocks (0.8 mA), 2 s each, spaced by 30 s. Mice were then kept for another 2 min in the cage and removed.