TY - JOUR T1 - A Novel Automated Home-Cage System to Assess Learning and Performance of a Skilled Motor Task in a Mouse Model of Huntington’s Disease JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0141-17.2017 SP - ENEURO.0141-17.2017 AU - Cameron L. Woodard AU - Federico Bolaños AU - James D. Boyd AU - Gergely Silasi AU - Timothy H. Murphy AU - Lynn A. Raymond Y1 - 2017/09/07 UR - http://www.eneuro.org/content/early/2017/09/07/ENEURO.0141-17.2017.abstract N2 - Behavioural testing is a critical step in assessing the validity of rodent models of neurodegenerative disease, as well as evaluating the efficacy of pharmacological interventions. In models of Huntington’s disease (HD), a gradual progression of impairments is observed across ages, increasing the need for sensitive, high-throughput and longitudinal assessments. Recently, a number of automated systems have been developed to perform behavioural profiling of animals within their own home-cage, allowing for 24-hour monitoring and minimizing experimenter interaction. However as of yet, few of these have had functionality for the assessment of skilled motor learning, a relevant behaviour for movement disorders such as HD. To address this, we assess a lever positioning task within the mouse home-cage. Animals first acquire a simple operant response, before moving to a second phase where they must learn to hold the lever for progressively longer in a rewarded position range. Testing with this paradigm has revealed the presence of distinct phenotypes in the YAC128 mouse model of HD at three early symptomatic time points. YAC128 mice at 2 months-old, but not older, had a motor learning deficit when required to adapt their response to changes in task requirements. In contrast, 6 month-old YAC128 mice exhibited circadian abnormalities and displayed kinematic abnormalities during performance of the task, suggesting an impairment in motor control. This system holds promise for facilitating high throughput behavioural assessment of HD mouse models for preclinical therapeutic screening.Significance Statement Difficulty with the learning and performance of skilled motor tasks is a common feature observed in many movement disorders, including Huntington’s Disease (HD) and Parkinson’s Disease (PD). Modeling these characteristics is an important goal in our ongoing effort to understand the mechanisms by which these diseases progress, as well as in the search for prospective therapies. In this paper, we use an automated behavioural testing system to assess learning and performance of a lever positioning task in a mouse model of HD, revealing several parallels with the human disease. We hope that this methodology will provide a more high-throughput platform for the behavioural screening of drugs that may help in the treatment of HD and similar diseases. ER -