Experiment name: High-throughput phenotyping of avoidance learning in mice discriminates different genotypes and identifies a novel gene. (Maroteaux 2012)
LSID: http://syli.cz/urn:lsid:public.sylics.com:experiment:DEA2-G453-987B

TreatmentAmountAdministration routeAdministration time

Treatment info:
Order of behavioural testing
PhenoTyper Spontaneous Behaviour
PhenoTyper Appetitive Conditioning
PhenoTyper Avoidance Learning

Published in Genes Brain and Behavior 2012:

High-throughput phenotyping of avoidance learning in mice discriminates different genotypes and identifies a novel gene
Grégoire Maroteaux* (1), Maarten Loos* (2,4), Sophie van der Sluis (3), Bastijn Koopmans (4), Emmeke Aarts (1), Koen van Gassen (1), Aron Geurts (5), The NeuroBSIK Mouse Phenomics Consortium (6), David A. Largaespada (5), Berry M. Spruijt (7), Oliver Stiedl (1,2), August B. Smit* (2) and Matthijs Verhage* (1,3)
1) Department of Functional Genomics, 2) Department of Molecular and Cellular Neurobiology and 3) Department of Clinical Genetics; Center for Neurogenomics and Cognitive Research (CNCR), Neuroscience Campus Amsterdam; VU University Amsterdam and VU Medical Center, 1081 HV, Amsterdam, The Netherlands, 4) Sylics (Synaptologics BV), Amsterdam, The Netherlands, 5) Department of Genetics, Cell Biology and Development, The Cancer Center, Minnesota, University of Minnesota, USA, 6) The NeuroBSIK Mouse Phenomics consortium collaborators are: Brussaard AB, Borst JGG, Elgersma Y, Galjart N, van der Horst GT, Levelt CN, Pennartz CMA, Smit AB, Spruijt BM, Verhage M, de Zeeuw CI.
7) Department of Biology, Faculty of Beta Sciences, University Utrecht, Utrecht, The Netherlands.
*these authors made equal contributions

Recognizing and avoiding aversive situations are central aspects of mammalian cognition. These abilities are essential for health and survival and are expected to have a prominent genetic basis. We modeled these abilities in eight common mouse inbred strains covering ~75% of the species' natural variation and in gene-trap mice (>2000 mice), using an unsupervised, automated assay with an instrumented home cage (PhenoTyper) containing a shelter with two entrances. Mice visited this shelter for 20-1200 times/24 h and 71% of all mice developed a significant and often strong preference for one entrance. Subsequently, a mild aversive stimulus (shelter illumination) was automatically delivered when mice used their preferred entrance. Different genotypes developed different coping strategies. Firstly, the number of entries via the preferred entrance decreased in DBA/2J, C57BL/6J and 129S1/SvImJ, indicating that these genotypes associated one specific entrance with the aversive stimulus. Secondly, mice started sleeping outside (C57BL/6J, DBA/2J), indicating they associated the shelter, in general, with the aversive stimulus. Some mice showed no evidence for an association between the entrance and the aversive light, but did show markedly shorter shelter residence times in response to illumination, indicating they did perceive illumination as aversive. Finally, using this assay, we screened 43 different mutants, which yielded a novel gene, specc1/cytospinB. This mutant showed profound and specific delay in avoidance learning. Together, these data suggest that different genotypes express distinct learning and/or memory of associations between shelter entrance and aversive stimuli, and that specc1/cytospinB is involved in this aspect of cognition.

In this manuscript: The effect of the aversive stimulus on shelter entrances (Fig 3)
The PhenoTyper is equipped with a shelter compartment, with two entrances, in which mice typically spend 80% of their time (resting/sleeping). During the first 4 days, mice develop a preference to enter the shelter through one of the two entrances. The preference index is calculated by : [(number of entries through the preferred entrance) - (number of entries through non-preferred entrance)]/(total number of entries).
Avoidance learning is studied by automatically applying a mild aversive stimulus (shelter illumination with bright light) during days 5 and 6 each time mice entered the shelter using their preferred entrance, but not when using the other entrance. A reduction in the preference index indicates that a mouse is establishing a specific association between its preferred entrance and the aversive stimulus. During day 7 sanctioning (i.e. shelter illumination) is discontinued, and the stability of the change in preference can be determined.
The behavior during this task of 8 common inbred strains was visualized in the multi-day preference index curve (http://syli.cz/w) as well as the aversion index curve (http://syli.cz/x).

Mouse info:
Mouse ID Strain Coat color Genotype Ear tag Internal ID Sex Date of Birth Sub experiment 1 Sub experiment 2 Sub experiment 3