C7 The bachd rat model of huntington’s disease shows signs of fronto-striatal dysfunction in two skinner box-based tests of short-term memory

Background The BACHD rat is a recently established animal model of Huntington’s disease (HD), which expresses the full-length HD-causing gene. The rats are currently being characterised in order to investigate to what extent they model HD pathology. Aims To assess BACHD rats’ performance in Skinner box-based delayed alternation and delayed non-matching to position tests. Methods Both tests evaluate short-term memory. During test sessions, levers are available during discrete trials and rats are trained to respond to them in either an alternating or a non-matching to position-based fashion. Delays are then introduced to investigate how long the rats remember which lever to push. Two separate cohorts of male rats were used, one for each test. Rats were initially trained at 2–4 months of age and then retested at 7–9, 12–14 and 17–19 months of age. Performance baselines for wild type (WT) rats were established for two different food restriction protocols at each age, to evaluate if any parameters were affected by motivational changes. Results The BACHD rats had problems learning the alternation task, but not the non-matching to position task. During baseline performance BACHD rats still performed worse than WT rats in both tests. Specifically, BACHD rats showed generally lower success rates compared to WT rats, but showed similar drops in success rate with delay duration. Both genotypes appeared to use specific and identical behaviours during the delays to guide their lever choices. Still, BACHD rats showed a higher frequency of performing these mediating behaviours. The phenotypes did not appear to change with age or be affected by motivational factors. Conclusions The results indicate that BACHD rats have general problems with performing both tests, while not showing an impaired short-term memory function. Similar phenotypes have been found in other transgenic HD models, in animals with lesions to fronto-striatal circuits, and in HD patients. The BACHD rats’ frequent use of mediating behaviours might indicate that they are more dependent on these compared to WT rats, but it could also indicate a change in inhibitory control.