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.

Department of Animal Science Biotechnical Faculty University of Ljubljana Ljubljana Slovenia

Department of Experimental Medicine University of Copenhagen Copenhagen Denmark

Department of Veterinary Medicine Faculty of Agriculture University of East Sarajevo East Sarajevo Bosnia and Herzegovina

Div Clinical Physiology Department of Laboratory Medicine Karolinska Institutet Stockholm Sweden

Faculty of Veterinary Medicine Spiru Haret University Bucharest Romania

German Federal Institute for Risk Assessment Berlin Germany

Helmholtz Zentrum München German Research Centre for Environmental Health Munich Germany

iNOVA4Health NOVA Medical School Faculdade de Ciências Médicas NMS FCM Universidade Nova de Lisboa Lisbon Portugal

Institute of Animal Welfare Animal Behavior and Laboratory Animal Science Department of Veterinary Medicine Freie Universität Berlin Berlin Germany

Institute of Biochemistry and Cell Biology National Research Council CNR Rome Italy

Institute of Medical Physiology Richard Burian Faculty of Medicine University of Belgrade Belgrade Serbia

International Clinical Research Center St Anne's University Hospital Brno Brno Czech Republic

Istituto Superiore Di Sanità Research Coordination and Support Service Rome Italy

Laboratory of Preclinical Testing of Higher Standard Neurobiology Center Nencki Institute of Experimental Biology Polish Academy of Science Warsaw Poland

Lithuanian University of Health Sciences Medical Academy Institute of Physiology and Pharmacology Kaunas Lithuania

Neuroscience Center Helsinki Institute of Life Science University of Helsinki Helsinki Finland

Preclinical Phenotyping Facility Vienna Biocenter Core Facilities Vienna Austria

Research Institute for Experimental Medicine and NeuroCure Cluster of Excellence Animal Behaviour Phenotyping Facility Charité Universitätsmedizin Berlin Berlin Germany

Science of Intelligence Research Cluster of Excellence Marchstr 23 10587 Berlin Germany

Université de Strasbourg CNRS Inserm IGBMC Institut Clinique de la Souris CELPHEDIA PHENOMIN UMR 7104 UMR S 1258 Illkirch 67400 France

Université de Strasbourg CNRS INSERM Institut Clinique de La Souris CELPHEDIA PHENOMIN 1 Rue Laurent Fries Illkirch 67404 France

Université de Strasbourg CNRS Inserm Institut de Génétique et de Biologie Moléculaire et Cellulaire UMR 7104 UMR S 1258 Illkirch 67400 France

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