Automated screening of baseline behaviors in the home cage
Importance of long-term screening in the home cage
Figure 1: Model of the reinforcement vs. avoidance relation in C57BL/6 substrains based on the Yerkes-Dodson law. The avoidance (performance or ‘cognition’) as a function of reinforcement (arousal or ‘stress’) is shown here in relative dimensions for the two C57BL/6 substrains (from Hager, 2015).
Irrespective of the type of study involving the assessment of behavioral performance, individual performance significantly depends on individual susceptibility to ‘stress’ (i.e., unspecific, external and/or uncontrollable factors that lead to arousal). While substrains show significant differences in performance in an inter-substrain comparison, also within isogentic substrains significantly different performances of sub-populations are obvious (Figure 1; Hager 2015). Conventional behavioral screening, which (amongst other unspecific factors) often involve handling of the animals and exposure to novel environments, introduce coercion (Hager et al., 2014), which is a confounding factor not only in the context of emotionality-based performance.
Thus, home cage-based approaches, which allow to assess behavioral performance in the home cage on extended time-scales that actually match the underlying physiological processes, reducing the amount of unspecific ‘stressors’, provide for scientific interpretations of increased validity by minimizing the unspecific effect of individual susceptibility to ‘stress’.
Consequently, screening pipelines and test batteries must take these effects into account, as well as challenges due to small sample size, the rare event nature (Karp et al., 2017) and the multiple testing problem (i.e., contrasting carry-over effects [Priya et al., 2018]).
Baseline behaviors in the home cage
Figure 2: The CageGuard system on top of a type II and a type III home cage.
Baseline behaviors such as drinking, feeding, and locomotor activity, especially under controlled and ethological valid conditions in habituated environments, allow for the assessment of essential parameters in the context of valid phenotyping (Bonasera et al. 2017). While the advantages of automated long-term scoring of these behaviors in the home cage are evident, individually compiled setups of instruments might lack reliability and reduce reproducibility. The Cage Guard (Figure 2) offers a reliable and economically reasonable system to reproducibly monitor baseline behaviors and is easily placed on any of your home cages.
Novel feature: automated body weight measurement
Figure 3: Example relationship between body weight and phenotypic trait of interest. The relationship between body weight and selected phenotypes observed for B6N mice from a high-throughput phenotyping project (modified from Ingvorsen et al., 2017).
Ingvorsen and colleagues recently described the effects of body weight and sex on metabolic parameters and demonstrated the value of body size as a covariate to assess metabolic phenotypes of increased validity (Ingvorsen et al., 2017). Obviously, increasing the validity of body weight screening in behavioral pipelines (aiming at the assessment of baseline parameters as well as for example involving motor skills), is imperative for unambiguous scientific interpretations.
Consequently, we proudly introduce a novel feature to our Cage Guard (Figure 2), which allows for the fully automated monitoring of body weight in the home cage. This novel feature constantly monitors body weight of rodents in their home cage, as soon and as often as they approach the feeding zone. Alike the assessment of the previously described baseline parameters, also the assessment of body weight is based on deliberate choice of the animal and does not introduce additional unspecific ‘stressors’.
Perspective: group housed capability
Whether or not to house rodent animal models in groups or separately during certain phases of behavioral studies, is a matter of debate, and in the end often subject to individual decisions in the context of experimental paradigms. While the ethological validity of social housing is obvious (as for example recommended by the Guide for the Care and Use of Laboratory Animals, ILAR, NAS, Eighth Edition, 2011), Nagy and colleagues on the other hand suggested already in 2002, that mice housed singly may be more representative of genotypic effects on body composition than group-housed mice (Nagy et al., 2002).
Therefore, we are currently integrating our approved RFID technology in the Cage Guard system. This will allow for the fully automated assessment of all previously described parameters of group housed rodents individually.
Keep in touch to be the first to know, when this exciting new technology in the Cage Guard is ready to be installed in your lab!
Please do not hesitate to contact us regarding your next behavioral study!
References:
Bonasera SJ, Chaudoin TR, Goulding EH, Mittek M, Dunaevsky A (2017) Decreased home cage movement and oromotor impairments in adult Fmr1-KO mice. Genes Brain Behav. 16(5):564-573.
Ingvorsen C, Karp NA, Lelliott CJ (2017) The role of sex and body weight on the metabolic effects of high-fat diet in C57BL/6N mice. Nutr Diabetes. 7(4):e261.
Hager T, Jansen RF, Pieneman AW, Manivannan SN, Golani I, van der Sluis S, Smit AB, Verhage M, Stiedl O (2014) Display of individuality in avoidance behavior and risk assessment of inbred mice. Front Behav Neurosci. 16;8:314.
Hager T (2015) Advanced autonomic and behavioral phenotyping of emotional behaviour of mice. PhD-thesis; VU Amsterdam.
Karp NA, Heller R, Yaacoby S, White JK, Benjamini Y (2017) Improving the Identification of Phenotypic Abnormalities and Sexual Dimorphism in Mice When Studying Rare Event Categorical Characteristics. Genetics. 205(2):491-501.
Nagy TR, Krzywanski D, Li J, Meleth S, Desmond R (2002) Effect of group vs. single housing on phenotypic variance in C57BL/6J mice. Obes Res. 10(5):412-5.
Priya V, Srikumar BN, Shankaranarayana Rao BS (2018) Contrasting effects of pre-training on acquisition of operant and radial arm maze tasks in rats. J Integr Neurosci.