IntelliCage: the development and perspectives of a mouse- and user-friendly automated behavioral test system.

IntelliCage for mice is a rodent home-cage equipped with four corner structures harboring symmetrical double panels for operant conditioning at each of the two sides, either by reward (access to water) or by aversion (non-painful stimuli: air-puffs, LED lights). Corner visits, nose-pokes and actual licks at bottle-nipples are recorded individually using subcutaneously implanted transponders for RFID identification of up to 16 adult mice housed in the same home-cage. This allows for recording individual in-cage activity of mice and applying reward/punishment operant conditioning schemes in corners using workflows designed on a versatile graphic user interface. IntelliCage development had four roots: (i) dissatisfaction with standard approaches for analyzing mouse behavior, including standardization and reproducibility issues, (ii) response to handling and housing animal welfare issues, (iii) the increasing number of mouse models had produced a high work burden on classic manual behavioral phenotyping of single mice. and (iv), studies of transponder-chipped mice in outdoor settings revealed clear genetic behavioral differences in mouse models corresponding to those observed by classic testing in the laboratory. The latter observations were important for the development of home-cage testing in social groups, because they contradicted the traditional belief that animals must be tested under social isolation to prevent disturbance by other group members. The use of IntelliCages reduced indeed the amount of classic testing remarkably, while its flexibility was proved in a wide range of applications worldwide including transcontinental parallel testing. Essentially, two lines of testing emerged: sophisticated analysis of spontaneous behavior in the IntelliCage for screening of new genetic models, and hypothesis testing in many fields of behavioral neuroscience. Upcoming developments of the IntelliCage aim at improved stimulus presentation in the learning corners and videotracking of social interactions within the IntelliCage. Its main advantages are (i) that mice live in social context and are not stressfully handled for experiments, (ii) that studies are not restricted in time and can run in absence of humans, (iii) that it increases reproducibility of behavioral phenotyping worldwide, and (iv) that the industrial standardization of the cage permits retrospective data analysis with new statistical tools even after many years.