These authors contributed equally to this work.
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Original Article
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High-throughput phenotyping of avoidance learning in mice discriminates different genotypes and identifies a novel gene†
Article first published online: 2 AUG 2012
DOI: 10.1111/j.1601-183X.2012.00820.x
© 2012 Vrije Universiteit Amsterdam. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society
Additional Information
How to Cite
Maroteaux, G., Loos, M., van der Sluis, S., Koopmans, B., Aarts, E., van Gassen, K., Geurts, A., The NeuroBSIK Mouse Phenomics Consortium, Largaespada, D. A., Spruijt, B. M., Stiedl, O., Smit, A. B. and Verhage, M. (2012), High-throughput phenotyping of avoidance learning in mice discriminates different genotypes and identifies a novel gene. Genes, Brain and Behavior, 11: 772–784. doi: 10.1111/j.1601-183X.2012.00820.x
- †
M.L., B.M.S., A.B.S., M.V. and The NeuroBSIK consortium designed research; G.M., M.L., and B.K. performed experiments; K.v.G. generated and genotyped transposon mice, S.v.d.S and B.K. generated analytical tools; A.G. and D.A.L. contributed transposon seeder and transposase mice and advice; G.M., M.L., S.v.d.S., B.K. and E.A. performed data analyses; G.M., M.L., S.v.d.S., O.S., A.B.S. and M.V. wrote the article.
Publication History
- Issue published online: 8 OCT 2012
- Article first published online: 2 AUG 2012
- Accepted manuscript online: 30 JUL 2012 12:00AM EST
- Manuscript Revised: 3 JUL 2012
- Manuscript Accepted: 3 JUL 2012
- Manuscript Revised: 2 JUL 2012
- Manuscript Revised: 8 JUN 2012
- Manuscript Revised: 27 APR 2012
- Manuscript Received: 30 JAN 2012
Funded by
- Agentschap NL. Grant Number: BSIK03053
- Netherlands Organization for Scientific Research
- European Union Seventh Framework Program. Grant Number: HEALTH-F2-2009-241498, HEALTH-F2-2009-242167
Keywords:
- Avoidance learning;
- behavioral flexibility;
- common inbred;
- high-throughput behavioral screening;
- home cage;
- SPECC1
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.
