Detection of early behavioral markers of Huntington's disease in R6/2 mice employing an automated social home cage

Abstract

Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder, for which no known cure or effective treatment exists. To facilitate the search for new potential treatments of HD, an automated system for analyzing the behavior of transgenic HD mice is urgently needed. A recently developed behavior screening system, the IntelliCage, allows automated testing of mouse behavior in the home cage employing individual recognition of animals living in social groups. The present study validates the ability of the IntelliCage system to detect behavioral and cognitive dysfunction in R6/2 mice, an established transgenic model of HD. The results indicate that the IntelliCage is a reliable system for recording exploratory activity, drinking behavior, circadian rhythm, spatial preference, and cognition in mice during prolonged periods of assessment. The system detected early dysfunctional behaviors in R6/2 mice, such as decrease in exploratory activity, sleep disturbances, increased drinking, and repetitive behavior. Additionally, the use of various learning tasks, such as spatial avoidance and spatial patrolling, revealed early cognitive changes in R6/2 mice. The simple learning tasks may be used at both early and late stages of the disease.