The detection and measurement of locomotor deficits in a transgenic mouse model of Huntington's disease are task- and protocol-dependent: Influence of non-motor factors on locomotor function

Abstract

Locomotor performance of transgenic R6/2 mice carrying the Huntington's disease (HD) mutation was assessed using four different tasks, fixed speed rotarod, accelerating rotarod, Digigait and footprint test. The tasks were compared directly in age- and CAG repeat-matched R6/2 mice. Accelerating rotarod was more sensitive than fixed speed rotarod for detecting early motor deficits in R6/2 mice. The sensitivity of accelerating rotarod increased with the acceleration rate and/or the start speed from which the rod accelerated. Differences between tasks were not due to inability of R6/2 mice to maintain balance at high speeds or increased fatigue on accelerating rotarod, but to difficulties in coordinating gait changes required by the constant change in speed on accelerating rotarod. The footprint test was sensitive to gait disturbances. However, surprisingly, R6/2 mice did not show major gait abnormalities on an automated treadmill task (Digigait), even though they showed overt gait deficits in the home cage. The fact that the sensitivity for detecting motor deficits depended strongly on the individual task, and on the protocol used, suggests that non-motor factors were differentially engaged in the different paradigms. We thus recommend that more than one task should be used for detecting and tracking different aspects of motor decay in animal models of HD. Since deficits in non-motor factors such as executive function and motivation may differentially influence motor outcome in each task, our results call for a more thorough investigation of the importance of higher level control of locomotion in animal models of HD.