The utilisation of operant delayed matching and non-matching to position for probing cognitive flexibility and working memory in mouse models of Huntington's disease

BACKGROUND Operant behavioural testing provides a highly sensitive and automated method of exploring the behavioural deficits seen in rodent models of neurodegenerative diseases, including Huntington's disease (HD). The delayed matching to position (DMTP) and delayed non-matching to position (DNMTP) tasks probe spatial learning and working memory and when applied serially they can be used to measure reversal learning, which has been shown to be an early symptom of executive dysfunction in HD. NEW METHOD The DMTP and DNMTP tasks were conducted in two configurations of operant apparatus; the conventional 9-hole operant apparatus, and a Skinner-like operant apparatus, to compare, contrast and optimise the DMTP and DNMTP operant protocols for use in mice. The optimised tasks were then tested in the Hdh(Q111) mouse model of HD. RESULTS Optimisation of the operant apparatus demonstrated that the mice learned the DMTP and DNMTP tasks more rapidly and effectively in the Skinner-like apparatus configuration in comparison to the conventional 9-hole apparatus configuration. When tested in the Hdh(Q111) mouse model of HD, the DMTP and DNMTP tasks revealed significant deficits in reversal learning. COMPARISON WITH EXISTING METHOD We found that mice were capable of performing the DMTP and DNMTP tasks in both apparatus configurations, but in comparison to the 9-hole configuration, the Skinner-like configuration produced more efficient, robust and reliable results. CONCLUSIONS The results presented here suggest that DMTP and DNMTP tasks, incorporating a reversal learning manipulation, are valid and robust methods for probing selected cognitive deficits in mouse models of neurodegenerative diseases.