A systematic review of the development and application of home cage monitoring in laboratory mice and rats.

BACKGROUND: Traditionally, in biomedical animal research, laboratory rodents are individually examined in test apparatuses outside of their home cages at selected time points. However, the outcome of such tests can be influenced by various factors and valuable information may be missed when the animals are only monitored for short periods. These issues can be overcome by longitudinally monitoring mice and rats in their home cages. To shed light on the development of home cage monitoring (HCM) and the current state-of-the-art, a systematic review was carried out on 521 publications retrieved through PubMed and Web of Science. RESULTS: Both the absolute (~ × 26) and relative (~ × 7) number of HCM-related publications increased from 1974 to 2020. There was a clear bias towards males and individually housed animals, but during the past decade (2011-2020), an increasing number of studies used both sexes and group housing. In most studies, animals were kept for short (up to 4 weeks) time periods in the HCM systems; intermediate time periods (4-12 weeks) increased in frequency in the years between 2011 and 2020. Before the 2000s, HCM techniques were predominantly applied for less than 12 h, while 24-h measurements have been more frequent since the 2000s. The systematic review demonstrated that manual monitoring is decreasing in relation to automatic techniques but still relevant. Until (and including) the 1990s, most techniques were applied manually but have been progressively replaced by automation since the 2000s. Independent of the year of publication, the main behavioral parameters measured were locomotor activity, feeding, and social behaviors; the main physiological parameters were heart rate and electrocardiography. External appearance-related parameters were rarely examined in the home cages. Due to technological progress and application of artificial intelligence, more refined and detailed behavioral parameters have been investigated in the home cage more recently. CONCLUSIONS: Over the period covered in this study, techniques for HCM of mice and rats have improved considerably. This development is ongoing and further progress as well as validation of HCM systems will extend the applications to allow for continuous, longitudinal, non-invasive monitoring of an increasing range of parameters in group-housed small rodents in their home cages.

Rating enrichment items by female group-housed laboratory mice in multiple binary choice tests using an RFID-based tracking system.

Laboratory mice spend most of their lives in cages, not experiments, so improving housing conditions is a first-choice approach to improving their welfare. Despite the increasing popularity of enrichment, little is known about the benefits from an animal perspective. For a detailed analysis, we categorized enrichment items according to their prospective use into the categories 'structural', 'housing', and 'foraging'. In homecage-based multiple binary choice tests 12 female C57BL/6J mice chose between enrichment items within the respective categories over a 46-hour period. A new analyzing method combined the binary decisions and ranked the enrichment items within each category by calculating worth values and consensus errors. Although there was no unequivocal ranking that was true in its entire rank order for all individual mice, certain elements (e.g. lattice ball, second plane) were always among the top positions. Overall, a high consensus error in ranking positions reflects strong individual differences in preferences which could not be resolved due to the relatively small sample size. However, individual differences in the preference for enrichment items highlights the importance of a varied enrichment approach, as there does not seem to be one item that satisfies the wants and needs of all individuals to the same degree. An enrichment concept, in which the needs of the animals are central, contributes to a more specific refinement of housing conditions.

Determining the value of preferred goods based on consumer demand in a home-cage based test for mice.

From the preference of one good over another, the strength of the preference cannot automatically be inferred. While money is the common denominator to assess the value of goods in humans, it appears difficult at first glance to put a price tag on the decisions of laboratory animals. Here we used consumer demand tests to measure how much work female mice expend to obtain access to different liquids. The mice could each choose between two liquids, one of which was free. The amount of work required to access the other liquid, by contrast, increased daily. In this way, the value of the liquid can be determined from a mouse's microeconomic perspective. The unique feature is that our test was carried out in a home-cage based setup. The mice lived in a group but could individually access the test-cage, which was connected to the home-cage via a gate. Thereby the mice were able to perform their task undisturbed by group members and on a self-chosen schedule with minimal influence by the experimenter. Our results show that the maximum number of nosepokes depends on the liquids presented. Mice worked incredibly hard for access to water while a bitter-tasting solution was offered for free whereas they made less nosepokes for sweetened liquids while water was offered for free. The results demonstrate that it is possible to perform automated and home-cage based consumer demand tests in order to ask the mice not only what they like best but also how strong their preference is.

Development of an IntelliCage-based cognitive bias test for mice.

The cognitive bias test is used to measure the emotional state of animals with regard to future expectations. Thus, the test offers a unique possibility to assess animal welfare with regard to housing and testing conditions of laboratory animals. So far, however, performing such a test is time-consuming and requires the presence of an experimenter. Therefore, we developed an automated and home-cage based cognitive bias test based on the IntelliCage system. We present several developmental steps to improve the experimental design leading to a successful measurement of cognitive bias in group-housed female C57BL/6J mice. The automated and home-cage based test design allows to obtain individual data from group-housed mice, to test the mice in their familiar environment, and during their active phase. By connecting the test-cage to the home-cage via a gating system, the mice participated in the test on a self-chosen schedule, indicating high motivation to actively participate in the experiment. We propose that this should have a positive effect on the animals themselves as well as on the data. Unexpectedly, the mice showed an optimistic cognitive bias after enrichment was removed and additional restraining. An optimistic expectation of the future as a consequence of worsening environmental conditions, however, can also be interpreted as an active coping strategy in which a potential profit is sought to be maximized through a higher willingness to take risks.