A quantitative framework for whole-body coordination reveals specific deficits in freely walking ataxic mice

Abstract

The coordination of movement across the body is a fundamental, yet poorly understood aspect of motor control. Mutant mice with cerebellar circuit defects exhibit characteristic impairments in locomotor coordination; however, the fundamental features of this gait ataxia have not been effectively isolated. Here we describe a novel system (LocoMouse) for analyzing limb, head, and tail kinematics of freely walking mice. Analysis of visibly ataxic Purkinje cell degeneration (pcd) mice reveals that while differences in the forward motion of individual paws are fully accounted for by changes in walking speed and body size, more complex 3D trajectories and, especially, inter-limb and whole-body coordination are specifically impaired. Moreover, the coordination deficits in pcd are consistent with a failure to predict and compensate for the consequences of movement across the body. These results isolate specific impairments in whole-body coordination in mice and provide a quantitative framework for understanding cerebellar contributions to coordinated locomotion.DOI: http://dx.doi.org/10.7554/eLife.07892.001

Midbrain circuits that set locomotor speed and gait selection

“…1i, blue) and all gaits including the alternating gaits walk and trot and synchronous gaits like gallop and bound (Fig. 1e, j –upper panel) 1,17,18 . The onset of locomotion was in the range of 100–150 ms (Extended Data Fig.…”

A comparative approach to cerebellar function: insights from electrosensory systems

“…Finally, a possible role for the cerebellum in generating forward models and cancellation signals comes from a recent quantitative analysis of gait in mutant mice with selective degeneration of Purkinje cells[72]. The analysis suggested that gait ataxia in these animals can be understand in terms of a failure of forward model predictions.…”

Expansion coding and computation in the cerebellum: 50 years after the Marr–Albus codon theory

“…) and disorders of cerebellar development (Fogel & Perlman, ; Machado et al . ). Common clinical signs included under the heading of ‘cerebellar ataxia’ include poor coordination of multijoint movement (dyssynergia), intention tremor, inappropriate magnitude of movement (dysmetria), poor timing or rhythmicity (dysrhythmia), and inability to perform rapid alternating movements (dysdiadochokinesia) (Schmitz‐Hübsch et al .…”

“…; Machado et al . ). Recent clinical studies document cognitive findings that form the ‘cerebellar cognitive affective syndrome’, which includes deficits of executive function (including abstract reasoning, context‐shifting, sequencing and planning), language (including deficits of grammar as well as fluency), memory (particularly spatial memory) and affect (Schmahmann & Sherman, , ; Kraan, ).…”