A Longitudinal Operant Assessment of Cognitive and Behavioural Changes in the Hdh(Q111) Mouse Model of Huntington’s Disease

Huntington’s disease (HD) is characterised by motor symptoms which are often preceded by cognitive and behavioural changes, that can significantly contribute to disease burden for people living with HD. Numerous knock-in mouse models of HD are currently available for scientific research. However, before their use, they must be behaviourally characterised to determine their suitability in recapitulating the symptoms of the human condition. Thus, we sought to longitudinally characterise the nature, severity and time course of cognitive and behavioural changes observed in Hdh(Q111) heterozygous knock-in mice.To determine changes in cognition and behaviour an extensive battery of operant tests including: fixed ratio, progressive ratio, the five choice serial reaction time task and the serial implicit learning task, were applied longitudinally to Hdh(Q111) and wild type mice. The operant test battery was conducted at 6, 12 and 18 months of age. Significant deficits were observed in Hdh(Q111) animals in comparison to wild type animals in all operant tests indicating altered cognition (attentional and executive function) and motivation. However, the cognitive and behavioural deficits observed were not shown to be progressive over time in the longitudinal testing paradigm that was utilised. The results therefore demonstrate that the Hdh(Q111) mouse model of HD reflects some features of the cognitive and behavioural changes shown in the human condition of HD. Although, the cognitive and behavioural deficits demonstrated were not shown to be progressive over time.