Morris water maze

The Morris water maze was performed as previously described^{46, 47} with the following modifications. Mice received two practice trials per day for 7 days with probe trials on day 5 and day 7. Each mouse had to learn to find a hidden platform under the water surface of a pool filled with opaque water. The starting position was randomly altered for every trial. To assess how accurately animals had learned the platform position during training, we analysed the time the mice spent in the target quadrant during the probe trials and compared this to the time spent in the other quadrants (quadrant occupancy). Furthermore, we analysed, for probe trials, the average distance the mouse kept from the position that contained the platform during training and compared this to the distance to equivalent positions in the other three quadrants (proximity).

For reversal learning, the hidden platform was placed in the centre of the opposite quadrant of the pool (i.e., the one opposite to the previous target quadrant) and mice were trained for 3 more days (2 trials per day) to learn the new location of the platform. On day 10, an additional probe trial was performed (during which the platform was removed from the pool). The time the mouse spent searching for the platform in the new target quadrant was measured and compared to the time spent searching in the other quadrants. We also analysed velocity and distance to the target position during probe trials as well as escape latencies during all training trials via an automated system (Ethovision XT, Noldus). Cumulative heat maps for each group were created for all training days and probe trials in Ethovision XT (Noldus).