Rodent Big Brother

Background

Measurement of the activity of individual rats or mice in their home cage provides useful information in studies from basic research through to drug discovery and development. This includes:

• Detecting and assessing toxicological effects (for example effects on the central nervous system) of candidate drugs, including physical dependence.
• Characterization of agents targeting disorders of the CNS.
• Behavioural phenotyping of genetically altered animals.
• Studies of circadian rhythms.

Measurement of body temperature in rodents may also be used in each of the research applications above; particularly for some toxicology studies and the assessment of physical dependence. Activity and temperature can currently only be measured separately, unless surgically implanted telemetry devices are used; however the surgery required places an additional welfare burden on the animals. Activity can be measured non-invasively using transparent cages and photocell beams or infrared movement sensors, or by placing the cages on mechanical sensor platforms. However, this requires animals to be singly housed, which is not ideal for social species such as rats and mice which live in groups.

Video tracking systems, with individuals marked with different colours, can be used for group-housed rodents but these methods are not readily incorporated into standard caging with wire mesh lids, especially when measuring simultaneously from multiple cages; also, video tracking in darkness requires infrared lighting, which would not enable discrimination between individuals marked with different colours. The aim of this challenge is to develop an integrated system which combines measurement of activity and temperature in rodents that can be used with group housing and without surgery.ID microchip transponders which measure temperature already exist and may potentially be utilised for this challenge. These chips are about 14 mm x 2 mm, and are injected subcutaneously in the nape of the neck. Examples include the IPTT-300 (PLEXX, Netherlands; BioMedic Data Systems Inc., USA). Accelerometers have been used to record and characterise behavioural movements in rodents, but so far only when worn externally.

3Rs benefits

The development of a non-surgical, automated approach to measure activity and temperature in animals supports reduction and refinement by avoiding the need for surgery or single housing. It would enable incorporation of these additional measurements into existing study types, thereby reducing the number of separate standalone studies. It could potentially impact on the welfare of thousands of animals. More broadly, this technology could also be used to provide additional information for other studies where early identification of animals with subdued activity or changes in body temperature could be used to improve humane endpoints.

Challenge Winner

Project team led by:

• Professor Douglas Armstrong, Actual Analytics, £500,000.

Full Challenge information

Actual Analytics Ltd in collaboration with Challenge Sponsors AstraZeneca has developed the innovative rodent home cage behavioural monitoring system, the Home Cage Analyser (HCA). The system provides minimally-invasive, 24/7 automated monitoring of individual rat’s behavior (ambulatory activity, eating, drinking and rearing) and temperature while group-housed in a standard unmodified home cage. When used in safety pharmacology studies, the system avoids the need for surgery or single housing, reduces the number of animals needed, delivers welfare benefits to the animals used and, through the incorporation of additional measurements into existing study types, reduces the number of studies needed overall.

The HCA system fits into two rack spaces of standard IVC racks without modifying the home cage (Figure 1). Each animal is tagged subcutaneously in the ventral midline with a radiofrequency identification (RFID) chip to record temperature, location and identity using a 2D array of RFID readers that sit underneath each cage. The cage is illuminated by infrared LED lighting and a side-view HD camera captures recordings of rat behaviour. The video and baseplate data is processed using a small computer, and trained software detects specific behaviours.  

Figure 1. An illustration of the Home Cage Analysis system with the key components highlighted.

AstraZeneca conduced proof-of-principle studies of the HCA system using three reference drugs (chlorpromazine and clonidine (sedatives), and amphetamine (stimulant)) and demonstrated that the HCA could detect changes in ambulatory activity, vertical activity and subcutaneous temperature in group housed animals consistent with effects seen in the conventional modified Irwin test (mIT), but extending into the 24 hour profile (Tse et al., 2018). The HCA also detected effects that were missed by the mIT, highlighting the benefits of continuous monitoring.

Although the system was developed initially for use by the pharmaceutical industry to support safety studies, the system also has broad applicability across a wide range of research areas including phenotyping and pharmacological profiling of new disease models.

Actual Analytics was awarded the contract for the CRACK IT Challenge Rodent Little Brother and has developed a system for mice. 

Actual Analytics was been awarded funding through the NC3Rs technology partnering hub CRACK IT Solutions to expand the scope of the system. Actual Analytics worked with researchers from Queen Mary, University of London to validate the system for longitudinal monitoring of home cage behavior and welfare in animals undergoing spinal cord or brain injury procedures https://www.nc3rs.org.uk/rodent-big-brother.

The NC3Rs in collaboration with Actual Analytics and AstraZeneca held a one day workshop to showcase the rodent HCA system to potential industry users. Further information can be found here.

The HCA system for rats and mice is commercially available to purchase and has been implemented by a number of CROs, research institutes and pharmaceutical companies. For more information about the HCA system, please visit the Actual Analytics website or alternatively contact Actual Analytics at getintouch@actualanalytics.com.