Kinematic and electromyographic tools for characterizing movement disorders in mice

Abstract

Increasing interest in rodent models for movement disorders has led to an increasing need for more accurate and precise methods for both delineating the nature of abnormal movements and measuring their severity. These studies describe application of simultaneous high-speed video kinematics with multichannel electromyography (EMG) to characterize the movement disorder exhibited by tottering mutant mice. These mice provide a uniquely valuable model, because they exhibit paroxysmal dystonia superimposed on mild baseline ataxia, permitting the examination of these two different problems within the same animals. At baseline with mild ataxia, the mutants exhibited poorly coordinated movements with increased variation of stance and swing times, and slower spontaneous walking velocities. The corresponding EMG showed reduced mean amplitudes of biceps femoris and vastus lateralis, and poorly modulated EMG activities during the step cycle. Attacks of paroxysmal dystonia were preceded by trains of EMG bursts with doublets and triplets simultaneously in the biceps femoris and vastus lateralis followed by more sustained coactivation. These EMG characteristics are consistent with the clinical phenomenology of the motor phenotype of tottering mice as a baseline of mild ataxia with intermittent attacks of paroxysmal dystonia. The EMG characteristics of ataxia and dystonia in the tottering mice also are consistent with EMG studies of other ataxic or dystonic animals and humans. These studies provide insights into how these methods can be used for delineating movement disorders in mice and for how they may be compared with similar disorders of humans.

Figure 1

Step cycle in a mutant tottering mouse during treadmill locomotion. The sequence for one step cycle (a–g) begins with foot-down (f-d1, then stance (st1), and foot-up (f-u). The subsequent swing phase (sw) is divided into 4 phases (sw1-1 to sw 1–4). The next step cycle begins again with foot-down (f-d2) and stance (st2). Vertical hip displacements (v.h.d.) can also be seen.

Figure 2

EMG for two step cycles of a tottering mouse during treadmill locomotion. Abbreviations for step cycle follow those used in Figure 1. Four monopolar (m) recordings are shown each for biceps femoris (BF) and vastus lateralus (VL) muscle. Bipolar (b) recordings reflect the difference between the monopolar leads indicated. For example the signal difference between monopolar leads 1 and 2 is designated b1,2. Comparisons of the first stance phase (st1) to the second stance phase (st2) shows abnormal variation of EMG amplitudes for a similar movement.

Figure 3

Time course of EMG amplitudes in 11 controls (a) and 4 individual tottering mutants (b–e). Results show bipolar mean amplitudes (RMS) ±SD. The biceps femoris (BF) is shown as a dotted line, while the vastus lateralis (VL) is shown as a solid line. Steps were time-normalized according to prior studies, with foot-down at abscissa (0) and foot-up at 1.

Figure 4

High resolution EMG recordings during a paroxysmal dystonic attack. The early phase (a) shows simultaneous EMG activities in BF and VL with high-amplitude bursts in VL partly appearing as doublets (D) and triplets (T). The late phase (b) shows simultaneous EMG activities in VL and BF, partly with interposed sequences of alternating short discharges (AD).

Figure 5

EMG recordings during the peak of an attack of paroxysmal dystonia in a tottering mutant, showing simultaneous prolonged semi-rhythmic EMG discharges of VL and BF associated with lengthy co-contraction of these normally antagonistic muscles.