Research reportSpontaneous alternation and spatial learning in Dab1scm (scrambler) mutant mice
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.
References (47)
- et al.
Spatial and non-spatial spontaneous alternation and hippocampal mossy fibre distribution in nine inbred mouse strains
Behav. Brain Res.
(1991) - et al.
Reeler mutant mice fail to show spontaneous alternation
Brain Res.
(1977) - et al.
The effect of repeated rotarod training on motor skills and spatial learning ability in Lurcher mutant mice
Behav. Brain Res.
(2008) - et al.
The anatomy of the cerebellar nuclei in the normal and scrambler mouse as revealed by the expression of the microtubule-associated protein kinesin light chain 3
Brain Res.
(2007) Reelin mouse mutants as models of cortical development disorders
Epilepsy Behav.
(2006)- et al.
Excitotoxic lesions restricted to the dorsal CA1 field of the hippocampus impair spatial memory and extinction learning in C57BL/6 mice
Neurobiol. Learn. Mem.
(2008) - et al.
Cerebellar input to the posterior parietal cortex in the rat
Brain Res. Bull.
(2002) - et al.
Performance of normal and neurological mutant mice on radial arm maze and active avoidance tasks
Behav. Neural Biol.
(1986) - et al.
Dissociation of spatial navigation and visual guidance performance in Purkinje cell degeneration (pcd) mutant mice
Behav. Brain Res.
(1992) - et al.
Effects of dentate nucleus lesions on spatial and postural sensorimotor learning in rats
Behav. Brain Res.
(2001)
Functions of the frontal cortex of the rat: a comparative review
Brain Res. Rev.
The neurobiological basis of spontaneous alternation
Neurosci. Biobehav. Rev.
Sensorimotor learning in Dab1scm (scrambler) mutant mice
Behav. Brain Res.
Does the mutant mouse Lurcher have deficits in spatially oriented behaviours
Brain Res.
Neurobehavioral evaluation of Relnrl–orl mutant mice and correlations with cytochrome oxidase activity
Neurosci. Res.
Arousal and T-maze choice behavior in mice: a convergent paradign for neophobia constructs and optimal arousal startegy
Learn. Motiv.
A qualitative and quantitative light microscopic study of the inferior olivary complex of normal, reeler, and weaver mutant mice
J. Comp. Neurol.
Topographic and zonal organization of the olivocerebellar projection in the reeler mutant mouse
J. Comp. Neurol.
Reeler: new tales on an old mutant mouse
Bioessays
A protein related to extracellular matrix proteins deleted in the mouse mutant reeler
Nature
Spontaneous alternation in rats with lesions in the frontal lobe: extension of the frontal lobe syndrome
Physiol. Behav.
Cerebellar abnormalities in the disabled (mdab1-1) mouse
J. Comp. Neurol.
The embryonic development of the cerebellum in normal and reeler mutant mice
Anat. Embryol.
Cited by (8)
Meox2 haploinsufficiency increases neuronal cell loss in a mouse model of Alzheimer's disease
2016, Neurobiology of AgingCitation Excerpt :To test spatial working memory, spontaneous alternation behavior was assessed using the Y-maze test. Each group of mice was compared with the other experimental/control groups and also to chance levels (50%) as reported by others (Bertholet and Crusio, 1991; Hooper et al., 1996; Jacquelin et al., 2012). At the beginning of trials, mice were placed midway in the start arm and allowed to freely explore the 3 arms for 8 minutes.
Neurobehavioral performances and brain regional metabolism in Dab1<sup>scm</sup> (scrambler) mutant mice
2013, Behavioural Brain ResearchCitation Excerpt :Although cytoarchitectonic disorganization of hippocampus [65,66] may be the major cause of such functional alterations, the influence of cerebellar pathways cannot be dismissed [67], because correlations were also obtained between the medial vestibular nucleus and the two anxiety tests. A dysfunctional hippocampus [6,65] is likely responsible for the severe water maze impairments previously found in this mutant [33]. Because of the massive cytoarchitectonic disorders in the cerebellum, its circuitries should represent a key system underlying motor deficits in Dab1scm.
Association study between genes in Reelin signaling pathway and autism identifies DAB1 as a susceptibility gene in a Chinese Han population
2013, Progress in Neuro-Psychopharmacology and Biological PsychiatryCitation Excerpt :These results indicated that Dab1 interacts with most of the proteins in the Reelin signaling pathway, phosphorylation/activation and polyubiquitination/degradation by them during signal transmission and plays an essential central role in Reelin signaling. Furthermore, recent studies showed impairment of spontaneous alternation, spatial learning, and abnormal grooming activity in Dab1scm (scrambler) mutant mice (Jacquelin et al., 2012; Strazielle et al., 2012), which may mimic some clinical characteristics of autism patients. To date, there are no data concerning the association between DAB1 and autism.