Leonie de Visser, Raymond C. de Heer and Berry M. Spruijt

Department of Animals, Science and Society, Utrecht University and Rudolf Magnus Institute of Neuroscience, UMC Utrecht, Utrecht, The Netherlands 

In search for genes underlying complex CNS processes, behavioral phenotyping of inbred and genetically modified mice deserves full attention. Maybe trivial, but it is also one of the most challenging tasks in behavioral genetics as behavior is highly dynamic and complex and at the same time unpredictable and sensitive to confounding environmental factors that are either unaccounted for or practically unavoidable. Current behavioral assays have the advantage of an extensive literature backup and pharmacological validation, but are limited in the ability to study long-term effects on behavior, circadian rhythms and address multiple interacting motivational systems in a single test setup. Moreover, factors like handling and transport have considerable, but not well quantified impact on experimental outcomes in short-lasting tests. To tackle these problems, we developed a system that allows continuous registration of mouse locomotor behavior in a home cage environment (PhenoTyper^®, Noldus Information Technology, Wageningen, The Netherlands). Testing animals in their home cage environment yields several advantages; it allows observations of habituation to the new home cage over consecutive days and the evaluation of both challenge-induced and baseline behaviors. Home cage testing also minimizes human intervention [1]. Apart from detailed analysis of baseline activity and circadian rhythmicity, this set-up could be used to study approach-avoidance behavior.

We deliberately choose the approach of first thoroughly defining and describing the various elements of home cage behavior, how they interrelate and how they can be manipulated [2]. Challenging the animals by exposing them to different stimuli and problems allows us to study approach-avoidance and learning behavior within the home cage environment. One of the major challenges resides in the pharmacological validation of the new home cage paradigms. First attempts in this direction have been undertaken to determine the anxiogenic influence of an aversive light stimulus. Administration of an anxiolytic compound (diazepam) indeed decreased the observed avoidance behavior when mice were exposed to the light stimulus. Improving our understanding of the longitudinal aspects and dynamics of behavior displayed in the stimulus-rich home cage environment will contribute to the ultimate goal of behavioral genetics: a functional interpretation of the gene effect on behavior.

[1] Spruijt, BM; Visser, L. de (2006). Advanced behavioural screening: automated home cage ethology. Drug Discovery Today: Technologies. 3(2), 231-237.

[2] Visser, L. de (2006). Novel approach to the behavioural characterization of inbred mice: automated home cage observations. Genes Brain and Behavior. 5(6), 458-66.