Date Published: September 6, 2017
Publisher: Public Library of Science
Author(s): William S. Redfern, Karen Tse, Claire Grant, Amy Keerie, David J. Simpson, John C. Pedersen, Victoria Rimmer, Lauren Leslie, Stephanie K. Klein, Natasha A. Karp, Rowland Sillito, Agis Chartsias, Tim Lukins, James Heward, Catherine Vickers, Kathryn Chapman, J. Douglas Armstrong, Judith Homberg.
Measuring the activity and temperature of rats is commonly required in biomedical research. Conventional approaches necessitate single housing, which affects their behavior and wellbeing. We have used a subcutaneous radiofrequency identification (RFID) transponder to measure ambulatory activity and temperature of individual rats when group-housed in conventional, rack-mounted home cages. The transponder location and temperature is detected by a matrix of antennae in a baseplate under the cage. An infrared high-definition camera acquires side-view video of the cage and also enables automated detection of vertical activity. Validation studies showed that baseplate-derived ambulatory activity correlated well with manual tracking and with side-view whole-cage video pixel movement. This technology enables individual behavioral and temperature data to be acquired continuously from group-housed rats in their familiar, home cage environment. We demonstrate its ability to reliably detect naturally occurring behavioral effects, extending beyond the capabilities of routine observational tests and conventional monitoring equipment. It has numerous potential applications including safety pharmacology, toxicology, circadian biology, disease models and drug discovery.
Behavioral studies in academic research and drug discovery are commonly conducted on rats, which are also the preferred rodent species for toxicology and safety pharmacology studies [1;2;3]. In drug discovery, such studies are used to inform critical decisions; in preclinical safety assessment they are required by regulatory authorities prior to human exposure . Conventional approaches to recording the behavior of laboratory rats are limited to ‘snapshot’ assessments, whether for academic research or in the pharmaceutical industry. Typical examples include manual observations by a trained observer using multi-parameter assessments of global neurobehavioral effects (e.g., the Irwin test or Functional Observational Battery (FOB) [2;5;6;7;8;9;10], or a scoring scale for abnormal behaviors (e.g., stereotypies [11;12;13]; seizures ). For convenience, behavioral assessments are usually performed during the daytime, when these nocturnal animals are generally less active. Ambulatory activity measurements can be automated using photobeam arrays [15;16;17;18;19;20], a passive infrared sensor [21;22], a stabilimeter (‘rocking cage’/’jiggle box’) [15;23] or birds-eye videotracking [24;25;26;27]. A wider set of behaviors can be detected using pressure sensors beneath the cage [28;29;30] or by videoanalysis software . These automated methods necessitate the rats, which are social animals [32;33], to be singly housed, typically in bespoke cages, and generally on bench tops rather than cage racks, requiring dedicated space. In mice, methods have been described using radiofrequency identity (RFID) transponders or differently colored fur dyes for recording ambulatory activity of individuals when group-housed [34;35;36;37;38;39]; with a recent exception , these required the use of bespoke cages. This presents a significantly greater challenge for rats, which are ~10 times larger in size, therefore with their RFID transponder potentially at a greater distance from the baseplate RFID reader (located beneath the cage floor) than with mice.