The power of automated behavioural homecage technologies in characterizing disease progression in laboratory mice: A review

Abstract

a b s t r a c tBehavioural changes that occur as animals become sick have been characterized in a number of species and include the less frequent occurrence of 'luxury behaviours' such as playing, grooming and socialization. 'Sickness behaviours' or behavioural changes following exposure to infectious agents, have been particularly well described; animals are typically less active, sleep more, exhibit postural changes and consume less food/water. Disease is frequently induced in laboratory mice to model pathophysiological processes and investigate potential therapies but despite what is known about behavioural changes as animals become sick, behavioural phenotyping of mice involved in disease studies is relatively rare. A detailed understanding of how behaviour changes as mice get sick could be applied to improve welfare of laboratory mice and support the underlying biomedical research. Specifically, characterizing behavioural changes in ill health could help those working with laboratory mice to recognize when refinements should be introduced, when severity limits are being approached and when humane endpoints should be implemented. Understanding how behaviour changes with illness may also help to identify compounds that have a clinical effect as well as when these agents act. There are an increasing number of automated systems to monitor the behaviour of laboratory mice in their homecages incorporating technologies such as the quantification of cage movement, automated video analysis and radiofrequency identification transponders/readers. Mouse models of neurodegenerative diseases particularly Huntington's disease have been well characterized using these systems and behavioural biomarkers of pathology, including changes in the animals' use of environmental enrichment, changes in food/water consumption and alterations in circadian rhythms, are now monitored by laboratories worldwide and used to refine studies and develop therapies. In contrast, automated behavioural technologies have not been used to characterize the behaviour of mice with systemic diseases such as cancer and liver disease. In this review, common behavioural changes that occur in animals with declining health will be discussed with an emphasis on progressive disease studies involving mice. Automated homecage behaviour recording technologies will then be summarized, studies in which these systems have been used to characterize the behaviour of mice with progressive diseases will be reviewed and the potential to apply automated technologies to refine disease studies involving mice will be discussed.

Animal models of chronic pain: Advances and challenges for clinical translation

“…Other non‐reflexive measurements of pain include weight bearing (in which the distribution between paws/gait is analyzed; Schött et al, ; Bove et al, ), home cage monitoring for abnormal behaviors (such as altered locomotor activity or grooming; Houghton et al, ; Goulding et al, ; Richardson, ), and open‐field tests (Bailey and Crawley, ; Parent et al, ). Animals can also be subjected to free‐choice tests (place conditioning, place‐escape tests; Sufka, ; Davoody et al, ; Fuchs and McNabb, ), which correlate ongoing pain with reward processes.…”

Update of neurotrophic factors in neurobiology of addiction and future directions

“…Therefore, development and validation of reliable tests for studying addictive behavior in mice is important. Number of applications (at least 10) has been developed during the last decade for testing mice in their home cage environment (reviewed in Spruijt and DeVisser, 2006; Richardson 2015). These methods can contain specific experimental modules, are fully automated and, importantly, the handling of animals by humans is limited to routine cage cleaning.…”

“…In addition, IntelliCage has been used as either enriched or stressful environment and combined with measurement of changes in the levels of BDNF and glucocorticoids (Alboni et al, 2015; Branchi et al, 2013; Kulesskaya et al, 2014) provides an excellent ethological surrounding for modeling stress and depression-like behavior in mice. Overall, considering the role of NTFs in neuropsychiatric and neurodegenerative conditions on one hand, and flexible task design and longitudinal monitoring in animal home-cage on the other hand, we argue that these systems will be invaluable for future research (Alexandrov et al, 2015; Gomez-Marin et al, 2014; Richardson, 2015). …”

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

“…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.).…”