Force-plate quantification of progressive behavioral deficits in the R6/2 mouse model of Huntington’s disease

Abstract

The R6/2 mouse is a popular model of Huntington’s disease (HD) because of its rapid progression and measurable behavioral phenotype. Yet current behavioral phenotyping methods are usually univariate (e.g., latency to fall from a rotarod) and labor intensive. We used a force-plate actometer and specialized computer algorithms to partition the data into topographically specific behavioral categories that were sensitive to HD-like abnormalities. Seven R6/2 male mice and 7 wild type (WT) controls were placed in a 42 cm X 42 cm force-plate actometer for 20-min recording sessions at 6–7, 8–9, 10–11 and 12–13 weeks of age. Distance traveled, number of wall rears, and number of straight runs (traveling 175 mm or more in 1.5 s) were reduced in R6/2 relative to WT mice at all ages tested. Low mobility bouts (each defined as remaining continuously in a virtual circle of 15 mm radius for 5 s) were increased in R6/2 mice at 6–7 wk and beyond. Independent of body weight, force off-load during wall rears was reduced in R6/2 mice except at 6–7 wk. Power spectra of force variation during straight runs indicated an age-related progressive loss of rhythmicity in R6/2 compared to WT, suggesting gait dysrhythmia and dysmetria. Collectively, these data, which extend results obtained with other widely different behavioral phenotyping methods, document a multifaceted syndrome of motor abnormalities in R6/2 mice. We suggest, moreover, that the force-plate actometer offers a high-throughput tool for screening drugs that may affect symptom expression in R6/2 or other HD model mice.