The Rodent Big Brother project: we CRACKed IT

A new paper, published today in PLOS ONE describes an automated home cage monitoring system for rats developed through the NC3Rs CRACK IT open innovation platform. The system allows, for the first time, the recording and analysis of the behaviour of individual rats whilst socially housed in their familiar home cage.

Monitoring changes in behaviour is key to many animal studies including phenotyping genetically altered rodents and safety pharmacology tests focusing on central nervous system endpoints. In most cases, behavioural analyses involve removing animals from their home cage and cage mates and putting them in novel and unfamiliar environments where they undergo a variety of tests for various lengths of time. The tests are often subjective, there can be significant data variability due to factors such as the presence of the experimenter and different laboratory conditions, and manual observations are usually limited to ‘snapshots’ during the light phase when rodents are naturally less active.

Rats are social animals. Single housing, disruption to their social hierarchy and a change in environment can be highly stressful leading to behavioural and physiological changes. A system that allows automated monitoring of the behaviour of group housed rats in their home cage offers major animal welfare as well as scientific benefits.

In 2011, Dr Will Redfern from AstraZeneca set the Rodent Big Brother CRACK IT Challenge to develop a home cage monitoring system that could be used in safety pharmacology and other studies involving the analysis of rat behaviour. The specific requirements of the system included:  

  • Minimally invasive monitoring of group-housed rats in their home cage.
     
  • Automated monitoring of temperature and ambulatory activity over 24 hours or longer.
     
  • Ability to detect convulsions and other abnormal behaviours.
     
  • Compatibility with standard Individually Ventilated Cage (IVC) racks, without having to modify the home cage.
     
  • A portable, rack-based system.

Professor Douglas Armstrong and his colleagues from Actual Analytics Ltd, a spin-out company from the University of Edinburgh, were awarded a £0.5 million contract from the NC3Rs to deliver a product to address the Challenge. They developed the Home Cage Analyser system (ActualHCATM).

This system is able to longitudinally and non-invasively track individual rats in group housed environments. The system is compatible with IVC home caging and is able to distinguish and capture basal motor activity. An RFID reader baseplate with antennae in specific positions beneath the home cage provides spatial monitoring of location and activity. An infrared camera positioned to the side of the cage records HD video footage for validation of the system and the further development of automated behaviour recognition using a machine learning algorithm. The system is currently able to identify ambulatory and vertical activity, with recognition of other behaviours such as eating and drinking being developed.

AstraZeneca has conducted proof-of-principle studies of the system in group-housed rats.  These began with optimisation work, progressing to data validation/verification and pharmacological validation. The optimal implantation site for the subcutaneous RFID transponder was found to be a ventral abdominal midline location. Using this implantation site, good correlations were achieved between baseplate-derived ambulatory activity and manually verified ambulatory activity (using a vertically mounted video camera).  Similarly, when compared over a longer time period (7-28 days) with whole-cage activity (detected as pixel movement from the side-view HD video camera), there was a good correlation between baseplate-derived ambulatory activity and overall movement within the cage. 

The technology has wide application in safety pharmacology and toxicology as well as for neurological and other disease models, circadian biology studies and drug dependence and withdrawal syndromes and phenotyping.

"Making animal welfare your starting point when developing a new technology inevitably leads to better quality data.  Being able to monitor individual animals when they are undisturbed in their familiar home cage, with their familiar cage mates, 24/7 opens up new possibilities in biomedical research.  Using conventional techniques, you would either have to house rats singly or use invasive surgery to implant radiotelemetry devices, neither of which is desirable.  Also, with this new technology we are able to acquire data we simply couldn't collect before, plus we can greatly increase the information content of existing study types.  During this CRACK IT funded project we focused on its application to the preclinical safety evaluation of candidate drugs, but if the technology becomes more widely used in both the commercial and academic sectors its potential applications are widespread."
Dr Will Redfern, AstraZeneca

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