Home-cage monitoring of activity patterns of laboratory mice

The mouse, deriving from the house mouse, is the most common species used in biomedical research, and offers great advantages for researchers to study gene functions in a complex living organism. However, using animals as research models comes with a moral obligation to follow the 3Rs, (Refine, Reduce, Replace) and proved the best possible husbandry and welfare in order to secure scientific rigor. The problem with poor reproducibility, and contradicting results, has been discussed for many years and efforts have been made to reduce variability and to standardize experimental protocols. One approach has been to automate behavioral testing of mice, to move the test to the home cage, a familiar environment, instead of moving the mouse to the test arena. This has lead forward to the development of scalable systems with the possibility to monitor the animals 24/7 to ensure the welfare of the animals, and to collect unbiased data for research.

We have used a scalable home-cage monitoring system based on capacitive-sensing technology, to characterize un-disturbed activity patterns of C57BL/6 female and male mice, and to monitor changes in activity patterns due to aging as well as in adaptation to a modest (30%) caloric restriction.

In two studies using multi-center design, we conclude that the circadian rhythm of activity displays a very robust pattern across sites but despite efforts to harmonize protocols there are still un-elucidated differences between laboratories.

In long-term recordings of un-disturbed activity from cages of female or male mice (400-600 days of recording), we describe an overall decline in activity with age and on top of this decline, there are slow oscillations in activity levels, varying 1-2 standard deviations from the overall mean activity and a period of 2-4 months. The oscillations does not synchronize with seasons, or between cages, and has an unknown origin.

Mice on a modest caloric restriction spend more time in long periods of rest, have a lower body weight and lower body temperature during rest, than ad libitum fed controls. Our data support that mice on DR shift their metabolism to synthesize and burn fatty acids to produce energy. Daily energy expenditure is lowered and matches the extended time in long rest bouts with lowered body temperature and their smaller body size. In addition, when the mice are fed their daily food ration during the light phase, the food-entrained oscillator (FEO) will partially override the circadian rhythm of activity (which entrains to light) and the food anticipatory activity (FAA) will drive the pattern of activity and rest during daytime. These adaptations were present both in the short-term adjustment (2-3 months), after one year and after almost 2 years observations. Thus, the response to DR is remarkably stable over time and similar between sexes.

List of scientific papers

I. K. Pernold, F. Iannello, B.E. Low, M. Rigamonti, G. Rosati, F. Scavizzi, J. Wang, M. Raspa, M.V. Wiles, B. Ulfhake. Towards large scale automated cage monitoring – Diurnal rhythm and impact of interventions on in-cage activity of C57BL/6J mice recorded 24/7 with a non-disrupting capacitive-based technique. PLoS ONE. 2019; 14(2):e0211063 (lic).
https://doi.org/10.1371/journal.pone.0211063

II. B. Ulfhake, H. Lerat, J. Honetschlager, K. Pernold, M. Rynekrová, K. Escot, C. Recordati, R.V. Kuiper, G. Rosati, M. Rigamonti, S. Zordan, J.-B. Prins. A multicenter study on spontaneous in-cage activity and micro-environmental conditions of IVC housed C57BL/6J mice during consecutive cycles of bi-weekly cage-change. PLoS ONE. 2021; 17(5):e0267281.
https://doi.org/10.1371/journal.pone.0267281

III. K. Pernold, E. Rullman, B. Ulfhake. Bouts of rest and physical activity in C57BL/6J mice housed at different densities. [Submitted]

IV. K. Pernold, E. Rullman, B. Ulfhake. Major oscillations in spontaneous home-cage activity in C57BL/6J mice housed under constant conditions. Scientific Reports. 2021; (2021)11:4961.
https://doi.org/10.1038/s41598-021-84141-9

V. K. Pernold, E. Rullman, V. Arulampalam, M. Klein Hazebroek, S. Keipert, Å. Sjöling, B. Ulfhake. Adaptation to dietary restriction and changes in activity and rest during aging of C57BL/6 mice. [Manuscript]