Major oscillations in spontaneous home-cage activity in C57BL/6 mice housed under constant conditions

Abstract

The mouse is the most important mammalian model in life science research and the behavior of the mouse is a key read-out of experimental interventions and genetic manipulations. To serve this purpose a solid understanding of the mouse normal behavior is a prerequisite. Using 14–19 months of cumulative 24/7 home-cage activity recorded with a non-intrusive technique, evidence is here provided for a highly significant circannual oscillation in spontaneous activity (1–2 SD of the mean, on average 65% higher during peak of highs than lows; P = 7E−50) of male and female C57BL/6 mice held under constant conditions. The periodicity of this hitherto not recognized oscillation is in the range of 2–4 months (average estimate was 97 days across cohorts of cages). It off-sets responses to environmental stimuli and co-varies with the feeding behavior but does not significantly alter the preference for being active during the dark hours. The absence of coordination of this rhythmicity between cages with mice or seasons of the year suggest that the oscillation of physical activity is generated by a free-running intrinsic oscillator devoid of external timer. Due to the magnitude of this rhythmic variation it may be a serious confounder in experiments on mice if left unrecognized.

A multicentre study on spontaneous in-cage activity and micro-environmental conditions of IVC housed C57BL/6J mice during consecutive cycles of bi-weekly cage-change

“…We recently published cumulative records of the spontaneous in-cage activity of female C57BL/6J subjected to a weekly cage-change, including the impact of cage-change and other husbandry routines [ 2 ]. Although the cage change results in a decrease of the in-cage load of mould and bacteria, hence NH 3 concentration (ppm), and an increase of soil-free cage floor space [ 43 , 44 ], the animals react with altered behaviours and responses, increased hart rate and mean arterial blood pressure, disrupted sleep patterns, and increased levels of stress hormones [ 1 , 2 , 9 , 45 – 51 ].…”

Emerging Role of Translational Digital Biomarkers Within Home Cage Monitoring Technologies in Preclinical Drug Discovery and Development

“…Furthermore, true baseline information can be difficult to obtain because of both the novelty of entering a testing apparatus and the physiological changes that result from handling stress. These factors can obscure the behavioral phenotype one seeks to understand ( Chesler et al, 2002 ; de Visser et al, 2006 ; Pernold et al, 2021 ). In fact, even in a home cage, handling mice for routine husbandry procedures (e.g., weighing or cage change) can increase the hormone corticosterone and daytime activity for at least 24 h ( Rasmussen et al, 2011 ; Pernold et al, 2019 ).…”

Advances in Animal Models and Cutting-Edge Research in Alternatives: Proceedings of the Second International Conference on 3Rs Research and Progress, Hyderabad, 2021

“…Also, he highlighted that better experimental design leads to maximum quality of data from the animals that need to be used, and ensures that they are not wasted due to insufficient 'experimental power'. [36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54] Designing your in vivo studies while supporting the 3Rs…”