Abstract
Epidemiological evidence suggests that Developmental Vitamin D (DVD) deficiency is associated with an increased risk of schizophrenia. DVD deficiency in mice is associated with altered behaviour, however there has been no detailed investigation of cognitive behaviours in DVD-deficient mice. The aim of this study was to determine the effect of DVD deficiency on a range of cognitive tasks assessing attentional processing in C57BL/6J mice. DVD deficiency was established by feeding female C57BL/6J mice a vitamin D-deficient diet from four weeks of age. After six weeks on the diet, vitamin D-deficient and control females were mated with vitamin D-normal males and upon birth of the pups, all dams were returned to a diet containing vitamin D. The adult offspring were tested on a range of cognitive behavioural tests, including the five-choice serial reaction task (5C-SRT) and five-choice continuous performance test (5C-CPT), as well as latent inhibition using a fear conditioning paradigm. DVD deficiency was not associated with altered attentional performance on the 5C-SRT. In the 5C-CPT DVD-deficient male mice exhibited an impairment in inhibiting repetitive responses by making more perseverative responses, with no changes in premature or false alarm responding. DVD deficiency did not affect the acquisition or retention of cued fear conditioning, nor did it affect the expression of latent inhibition using a fear conditioning paradigm. DVD-deficient mice exhibited no major impairments in any of the cognitive domains tested. However, impairments in perseverative responding in DVD-deficient mice may indicate that these animals have specific alterations in systems governing compulsive or reward-seeking behaviour.
Highlights
An increasing body of epidemiological evidence supports the hypothesis that maternal vitamin D deficiency is a risk-modifying factor for schizophrenia [1,2]
We have shown that developmental vitamin D (DVD) deficiency altered brain morphology in C57BL6/J, but not 129X1/SvJ mice, in which adult C57BL/6J male DVD-deficient mice had smaller lateral ventricles compared to controls, which may have been compressed by the enlarged striatum seen in these DVD-deficient mice [10]
This study presents the first characterization of the consequences of DVD deficiency on attentional processing in adult mice
Summary
An increasing body of epidemiological evidence supports the hypothesis that maternal vitamin D deficiency is a risk-modifying factor for schizophrenia [1,2]. There is convincing experimental evidence based on a model in Sprague-Dawley rats that developmental vitamin D (DVD) deficiency is associated with a range of schizophrenia-related neurochemical, neuroanatomical, and behavioural phenotypes [4,5]. As such, these data support the biological plausibility of the epidemiological link between DVD deficiency and schizophrenia. Another study found that DVD-deficient C57BL/6J mice have subtly impaired performance in an olfactory tubing maze, which is an operant conditioning paradigm requiring mice to learn the associations between a scent and reward [16] These findings support the hypothesis that there are DVD deficiency-induced effects on behaviourally-relevant neuronal systems. Little is known regarding how DVD deficiency affects cognitive behaviours that are relevant to schizophrenia
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