Comprehensive Behavioral Phenotyping in Female Mice

By application of our IntelliCage-based behavioral phenotyping design, we assessed multiple facets of cognition as well as sucrose preference, as measure of anhedonia, in female mice only, at age 6 months as described (Dere et al., 2014 (link)). One day after subcutaneous implantation of transponders (see above), mice were group-housed, separated by genotype, and remained in the IntelliCages for 6 days. Place learning was acquired within the first 24 hr (day 1), in which an individual mouse learned that only one out of four corners was rewarded with water, while the other corners remained blocked. The number of mice assigned to each corner was balanced and semi-randomly determined. On day 2, reversal learning was assessed to measure cognitive flexibility as well as perseveration. Mice had to learn that the previously rewarded corner was now blocked, and instead the diametrically opposed corner now rewarded. Sucrose preference was assessed on day 3 by comparing preference for a corner rewarded with a 2% sucrose solution over another corner rewarded with tap water. During these 24 hr, the two previously blocked corners were now rewarded with either sucrose solution or tap water, whereas the remaining corners were blocked. The visits to the respective target corners during place and reversal learning as well as sucrose preference testing were used for statistical analysis. On days 4–5 mice had again access to two rewarding corners providing either a sucrose solution or tap water. However, these corners were now again the diametrically opposed corners to day 3 and access to the corners was only provided for a limited time, namely during the first 2 hr of the active phase of the mice (6–8 PM). Hence, mice were required to form a multimodal association containing the information on the type of reward provided (what) as well as their locations (where) and the time at which to expect the reward (when), rendering this approach an experimental model for the assessment of episodic memory comparably to humans. Visits to rewarded corners during acquisition (day 4) and retrieval (day 5) of episodic-like memory were recorded and the delta between visits to the corner providing sucrose solution and the corner providing tap water was calculated.