Consistent behavioral phenotype differences between inbred mouse strains in the IntelliCage

Abstract

The between-laboratory effects on behavioral phenotypes and spatial learning performance of three strains of laboratory mice known for divergent behavioral phenotypes were evaluated in a fully balanced and synchronized study using a completely automated behavioral phenotyping device (IntelliCage). Activity pattern and spatial conditioning performance differed consistently between strains, i.e. exhibited no interaction with the between-laboratory factor, whereas the gross laboratory effect showed up significantly in the majority of measures. It is argued that overall differences between laboratories may not realistically be preventable, as subtle differences in animal housing and treatment will not be controllable, in practice. However, consistency of strain (or treatment) effects appears to be far more important in behavioral and brain sciences than the absolute overall level of such measures. In this respect, basic behavioral and learning measures proved to be highly consistent in the IntelliCage, therefore providing a valid basis for meaningful research hypothesis testing. Also, potential heterogeneity of behavioral status because of environmental and social enrichment has no detectable negative effect on the consistency of strain effects. We suggest that the absence of human interference during behavioral testing is the most prominent advantage of the IntelliCage and suspect that this is likely responsible for the between-laboratory consistency of findings, although we are aware that this ultimately needs direct testing.

Effects of Spatial and Cognitive Enrichment on Activity Pattern and Learning Performance in Three Strains of Mice in the IntelliMaze

“…Parallel analysis of mouse behavior in the IntelliCage and IntelliMaze set-ups offers such an opportunity. Strain by laboratory interactions did not have a significant impact on behavioral data obtained using the IntelliCages (Krackow et al 2010), however results obtained in isolated IntelliMaze systems bear the risk of low generalizability (i.e., external validity), since behaviors in add-on connected IntelliCages might be affected significantly and in a strain dependent manner. Therefore, in the current study we focused on the effects of added complexity on trait variability in the IntelliCage, as well as inter-laboratory replicability of results from IntelliCage and IntelliMaze systems.…”

“…Automated equipment for behavioral phenotyping is intended to increase replicability of studies on laboratory mice (De Visser et al 2006;Krackow et al 2010). Other approaches include the use of standardized animal care and test conditions Wahlsten et al 2003;Gates et al 2011), improved measurement technology and data analysis techniques (Kafkafi et al 2003(Kafkafi et al , 2005, or the use of ethologically relevant behavioral endpoints and ethologically inspired tests (Benjamini et al 2001;Meyerson et al 2006;Deacon 2009).…”

“…4 Boxplots of trials (visits with nosepokes) to criterion, i.e., until the preference for the previously rewarded corner became extinct, for three strains of mice (B6, D2, F1) during Place Learning Reversal. Note that the data were log transformed We focused the analysis on measures of activity and learning in the IntelliCage, which have differentiated strains of mice consistently across laboratories (Krackow et al 2010). In brief, we have previously found that in the IntelliCage B6 mice are more active (visit frequency) during the Free and Nosepoke Adaptation phases.…”

“…The IntelliCage system was developed as an automated behavioural phenotyping equipment for group housed laboratory mice, aimed to maximize throughput while minimizing animal handling (Galsworthy et al 2005). Low inter-laboratory replicability of behavioral data (Crabbe et al 1999) can be avoided using the IntelliCages, as strain differences in activity and cognitive measures proved replicable between four European laboratories (Krackow et al 2010).…”

Nucleus accumbens dopamine D2-receptor expressing neurons control behavioral flexibility in a place discrimination task in the IntelliCage

“…More recently, IntelliCage place discrimination tasks have been used to investigate higher-order cognitive functions in both normal and disease model mice. Acquisition and reversal of place discrimination was found to differ between various commonly used inbred mouse strains (Krackow et al 2010;Endo et al 2011), and valproatetreated C57BL/6 mice, used as a model of autism, displayed impairments in place learning associated with perseverative responding (Puscian et al 2014). However, little is known about the neural circuitry that mediates performance on this task.…”