Development and Application of Home Cage Monitoring in Laboratory Mice and Rats: a Systematic Review

Abstract

Traditionally, in biomedical animal research, laboratory rodents are individually examined in test apparatuses outside their home cages at selected time points. However, the outcome of such tests can be influenced by the novel environment, the time of day, separation from the social group, or the presence of an experimenter. Moreover, valuable information may be missed when the animals are only monitored in short periods. These issues can be overcome by longitudinal 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. Both the absolute (~ x26) and relative (~ x7) number of HCM-related publications increased from 1974 to 2020. In both mice and rats, 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. More than 70% of the studies did not involve a disease model, but the percentage of studies using disease models increased since the 2000s. In most studies, animals were kept for short (up to 4 weeks) length periods in the HCM systems; intermediate length 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 hours, while 24-hour measurements have been more frequently since the 2000s. The systematic review demonstrated that manual monitoring is decreasing 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 publication year, 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 could be investigated in the home cage in recent times. Over the period covered in this study, techniques for HCM of mice and rats has improved considerably. This development is ongoing and further progress and 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.

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

“…Given the high number of divergent IntelliCage papers and topics, we will refrain from discussing them further and we will focus on selected studies showing interesting directions. Readers interested in how the IntelliCage compares to the increasing number of home-cage-based testing systems can find tabulated comparisons ( Kiryk et al, 2020 ; Mingrone et al, 2020 ; Voikar and Gaburro, 2020 ; Iman et al, 2021a ; Coulibaly, 2022 ; Kahnau et al, 2023b ).…”

“…Because IntelliCage was not suited for presenting auditory cues, the consortium developed an audiobox which uses an IntelliCage corner placed at some distance in a sound-attenuated box and permits the use of IntelliCage software for self-paced auditory conditioning, resulting in publications that appeared even in particularly high-ranking journals ( de Hoz and Nelken, 2014 ; Atlan et al, 2018 ; de Hoz et al, 2018 ; Chen et al, 2019 ; Chen and de Hoz, 2023 ). One may note that Kahnau et al (2023a , b) used a reverse approach by keeping the mice in a home-cage connected to an empty IntelliCage from where the mice had temporary access to solitary auditory conditioning as controlled by an animal gate. Most of the add-ons are available from TSE-Systems, while another add-on is a floor plate made of RFID antennae described later under “Tracking of mice on the floor of IntelliCage” (Section 2.10.2).…”

“…The first compartment contains the RFID reader. For a figure showing an outside home cage connected to the IntelliCage for auditory testing, see Kahnau et al (2023a , b) . The add-on most successfully used up-to-now is the audiobox.…”

Development of an IntelliCage-based cognitive bias test for mice

“…Nevertheless, even with the best handling and habituation, a possibly negative influence of the separation from the home-cage and/or the group ( Krohn et al , 2006 ; Manouze et al , 2019 ) as well as the experimenter's immediate influence on the mice, and thereby the test results, must be taken into account. Home-cage based experiments are a good way to address this shortcoming and are becoming increasingly common (see https://www.cost-teatime.org/ for more on home-based cage-based systems + ( Kahnau et al , 2023 )).…”

Challenges and advanced concepts for the assessment of learning and memory function in mice

“…The use of such home cage systems has increased in the past ( Kahnau et al, 2023c ). This development spawned movements such as the COST Action initiative “Improving biomedical research by automated behavior monitoring in the animal home-cage”, 1 which was established in 2021.…”