Spatial learning and flexibility in 129S2/SvHsd and C57BL/6J mouse strains using different variants of the Barnes maze.

Behavioural flexibility is the ability to switch between tasks and strategies following a change in rules, and involves intact functioning of the medial prefrontal cortex. Impairments of behavioural flexibility have frequently been reported in patients with schizophrenia and rodents with disruption/dysfunction of the prefrontal cortex. The discovery of a mutation in the disrupted in schizophrenia 1 (DISC1) gene in the 129 mouse strain suggests that these mice may be exploited as a 'naturally occurring' model of schizophrenia. The aim of this present study was to assess cognition and behavioural flexibility of 129S2/SvHsd mice in comparison with C57BL/6J mice in the Barnes maze, using three different maze variations that consisted of either 8, 16 or 32 holes. Whereas C57BL/6J mice were able to perform both acquisition and reversal learning in all three mazes, 129S2/SvHsd mice displayed impairments dependent on the complexity of the test. Intact acquisition and reversal occurred in the 8-hole maze; intact acquisition, but impaired reversal, was evident in the 16-hole maze and impaired acquisition was evident in the most difficult 32-hole test. Furthermore, analysis of search strategies confirmed strain differences in the adoption of spatial searches across both acquisition and reversal trials. 129S2/SvHsd mice displayed fewer spatial-type trials than C57BL/6J mice and instead employed more random or serial/chaining search behaviours. The deficits observed in both cognition and behavioural flexibility support the notion of the 129 mouse strain as a potential model of schizophrenia.