A comparison of discrimination learning in touchscreen and 2-choice swim tank using an allelic series of Huntington’s disease mice.


BACKGROUND: Progressive cognitive impairments are a major, debilitating symptom of neurodegenerative disorders such as Alzheimer's disease (AD) and Huntington's disease (HD). Developing treatments to slow or prevent cognitive decline is a key challenge for these fields. Unfortunately, preclinical therapeutic testing has not kept pace with molecular advances, and the methods for systematic cognitive testing in mice remain largely unchanged. Although higher throughput semi-automated systems exist, the lack of a 'positive control' (i.e. a drug or treatment that works) makes it challenging to test their sensitivity and predict usefulness for preclinical drug testing. NEW METHOD: We used an allelic series of transgenic HD mice to test the sensitivity and flexibility of two cognitive testing systems; a semi-automated touchscreen system and a traditional water-based task, the 2-choice swim tank. RESULTS: We found significant differences in performance of HD mice with different CAG repeats, with timing and severity of deficits dependent on CAG repeat length. We also found deficits in long-term memory retention that have not been reported previously. COMPARISON WITH EXISTING METHOD(S): Both systems were useful for detecting deficits, and were sensitive enough to detect small changes (10-20%) in cognitive performance. CONCLUSIONS: While the touchscreen system is more sensitive and can identify deficits up to 10 weeks earlier than the 2-choice swim tank, both tests detected similar patterns of deficit progression in HD mice, regardless of CAG repeat length. Thus, although it has its limitations, the 2-choice swim tank remains a simple, cheap and accessible system for assessing cognitive function.