Abstract
BACKGROUND: Spatial working memory is commonly assessed in rodents using delayed matching-to-position (DMTP) and delayed nonmatching-to-position (DNMTP) tasks. Although these tasks are widely used to examine memory function, particularly in relation to delay intervals and response requirements, strain differences in task performance remain underexplored. This study investigates spatial working memory in two widely used mouse strains, C57BL/6 and DBA/2, using these tasks. METHODS: Mice were trained and tested on the DNMTP task first, followed by the DMTP task. Both tasks were conducted with varying delay intervals and response requirements, allowing for the assessment of spatial working memory across different conditions. RESULTS: Both strains acquired the tasks. However, DBA/2 mice exhibited a smaller decline in accuracy with increasing delay intervals in the DNMTP task compared to C57BL/6 mice. DBA/2 mice also demonstrated more stable performance across both tasks, whereas C57BL/6 mice showed a more pronounced accuracy decline in the DNMTP task than in the DMTP task. In addition, enhancing response requirements during sample trials improved performance in DBA/2 mice for both tasks, a trend that was not observed in C57BL/6 mice. These findings suggest that task-specific variables, such as response modality (e.g., lever pressing vs. nose poking) and prior training history, can significantly influence strain performance. Overall, these results emphasize the need for considering strain-specific traits and experimental conditions when interpreting behavioral data, particularly for DBA/2 mice, frequently used as models for hippocampal dysfunction.