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

Abstract

Background and aimsAutomated recording of laboratory animal’s home cage behavior is receiving increasing attention since such non-intruding surveillance will aid in the unbiased understanding of animal cage behavior potentially improving animal experimental reproducibility.Material and methodsHere we investigate activity of group held female C57BL/6J mice (mus musculus) housed in standard Individually Ventilated Cages across three test-sites: Consiglio Nazionale delle Ricerche (CNR, Rome, Italy), The Jackson Laboratory (JAX, Bar Harbor, USA) and Karolinska Insititutet (KI, Stockholm, Sweden). Additionally, comparison of female and male C57BL/6J mice was done at KI. Activity was recorded using a capacitive-based sensor placed non-intrusively on the cage rack under the home cage collecting activity data every 250 msec, 24/7. The data collection was analyzed using non-parametric analysis of variance for longitudinal data comparing sites, weekdays and sex.ResultsThe system detected an increase in activity preceding and peaking around lights-on followed by a decrease to a rest pattern. At lights off, activity increased substantially displaying a distinct temporal variation across this period. We also documented impact on mouse activity that standard animal handling procedures have, e.g. cage-changes, and show that such procedures are stressors impacting in-cage activity.These key observations replicated across the three test-sites, however, it is also clear that, apparently minor local environmental differences generate significant behavioral variances between the sites and within sites across weeks. Comparison of gender revealed differences in activity in the response to cage-change lasting for days in male but not female mice; and apparently also impacting the response to other events such as lights-on in males. Females but not males showed a larger tendency for week-to-week variance in activity possibly reflecting estrous cycling.ConclusionsThese data demonstrate that home cage monitoring is scalable and run in real time, providing complementary information for animal welfare measures, experimental design and phenotype characterization.

A non-invasive digital biomarker for the detection of rest disturbances in the SOD1G93A mouse model of ALS

“…The DVC ® system monitored night and day time activity of mice 24/7 for about 4 months. As expected, mice are more active during the night period [14] and in particular are more active closer to light/dark transitions (Fig 1 and 2). along the experiment (from age 7 until 24 weeks of age).…”

“…As expected, day time activity on weekdays is higher than weekends ( Fig 7A; nparLD test, Day_type factor: Statistic=117.838, df=1, p<0.001). Day time activity is also strongly impacted by cage change procedures, as already observed in [14], and clearly visible in Fig 7A. For this reason, we remind that days of cage changing were excluded from all the previous analyses.…”

“…Since the same subjects were assessed over time, we performed non-parametric repeated measures analysis on most datasets with Genotype and Sex as between-subject factors and Age (weeks) as within-subject factor (see [14]). We used the rank-based analysis of variance-type statistic (ATS), as implemented in the nparLD R Software package [19].…”

“…To study activity and rest in the SOD1G93A mouse model during the pre-symptomatic and symptomatic stages of the disease we adopted a technology capable of monitoring animal activity directly in the home cage [12][13][14]. Such systems are generally designed with the aim of collecting animal activity data 24/7, without interfering with nor handling the animals.…”

“…Such systems are generally designed with the aim of collecting animal activity data 24/7, without interfering with nor handling the animals. This has the potential to unveil animal behaviors occurring at any time during the day [13] and over extended observation periods ranging from days to months and years [14]. The application of 24/7 long term home cage animal monitoring is particularly promising in the field of neurodegenerative diseases, especially the ones that potentially manifest complex modifications of the activity behaviors as the disease progresses over time, and that can be potentially hard to capture when observing animals outside the home cage as in conventional testing procedures (e.g., open field, rotarod, grid hanging ect.).…”