Research report
Spontaneous alternation and spatial learning in Dab1scm (scrambler) mutant mice

https://doi.org/10.1016/j.brainresbull.2012.01.001Get rights and content

Abstract

Homozygous Dab1scm mutants with cell ectopias in cerebellar cortex, hippocampus, and neocortex were compared with non-ataxic heterozygous and wild-type controls in spontaneous alternation and Morris water maze tests. Although there were no group differences in alternation rates, wild-type and heterozygote groups alternated above chance levels, whereas homozygous Dab1scm mutants did not. In the Morris water maze, Dab1scm mutants were impaired in both hidden and visible platform subtests. The deficits in spontaneous alternation and water maze measures reproduce the phenotype previously described in Relnrl–Orl mutants, attributed to disturbance of the same molecular pathway involving reelin.

Highlights

Dab1scm mutants have ectopias in cerebellum and hippocampus. ► Dab1scm mutants were impaired in spontaneous alternation. ► Dab1scm mutants were impaired in water maze. ► Dab1scm phenotype resembles that of Relnrl–Orl mutants. ► Similar behavioral results are found for the same molecular pathways.

Section snippets

Mice

Dab1scm/+ breeders on the A/A (agouti) genetic background were purchased from Jackson Laboratory (Bar Harbor, Maine, USA) and crossed to obtain ataxic Dab1scm/Dab1scm mutants (n = 9, 4 males, 5 females), non-ataxic Dab1scm/+ heterozygotes (n = 6, 2 males, 4 females), and +/+ wild-type (n = 7, 3 males, 4 females), determined by genetic history. To facilitate survival of mutant homozygotes, food pellets were spread on the cage floor and the overhead bin. The mice were tested at about 10 months of age

Results

Although there were no intergroup differences in spontaneous alternation rates [Krusal–Wallis, p > 0.05], the more sensitive method of comparing each group to chance reached significance. Indeed, during the first 5 days of spontaneous alternation (Table 1), wild-type [U = 7, p < 0.05] and heterozygote [U = 5, p = 0.05] mice alternated above chance, whereas Dab1scm mutants did not [U = 36, p > 0.05]. This pattern held up for all 10 days of testing in heterozygotes [U = 3, p < 0.05] and Dab1scm mutants [U = 27, p > 

Discussion

The tendency of alternating arm choices in a T-maze was evaluated in Dab1scm mutant mice relative to two non-ataxic control groups. There was no intergroup difference in alternation rates, but significant results emerged with the more sensitive method of comparing each group to chance. Unlike either wild-type or heterozygotes, homozygous mutants did not alternate significantly above chance during the first 5 days of evaluation. When the test was prolonged to a maximum of 10 days, Dab1scm

Acknowledgment

This study was funded by a grant from the Natural Sciences and Engineering Research Council of Canada (NSERC) to RL.

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