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Significance First recordings from awake walking symptomatic-stage amyotrophic lateral sclerosis (ALS) and control mice were made simultaneously from spinal cord motor pools and corresponding hindlimb flexor and extensor muscles. Spinal recordings revealed loss of high-frequency firing in ALS mice, and EMG showed an abnormal fractionated character with step-to-step variability and flexor/extensor coactivation, associated with step-to-step variability in kinematics and likely compensatory mechanisms that allow continued ability to walk in the face of motor neuron loss.

Reduced high-frequency motor neuron firing, EMG fractionation, and gait variability in awake walking ALS mice