The locomotor central pattern generator of the rat spinal cord in vitro is optimally activated by noisy dorsal root waveforms

Abstract

The spinal cord contains an intrinsic locomotor program driven by a central pattern generator that rhythmically activates flexor and extensor limb motor pools. Although long-lasting locomotor activity can be generated pharmacologically, trains of afferent stimuli trigger only few locomotor cycles. The present study investigated whether a new electrical stimulation protocol (termed FListim) could elicit long-lasting fictive locomotion (FL) in the rat spinal cord in vitro. Thus, after first inducing FL by bath application of N-methyl-d-aspartate and serotonin, the recorded waveform obtained from a lumbar ventral root was digitized and then applied to either a lumbar dorsal root or the cauda equina following washout of pharmacological agents. Two FListim cycles were the threshold input to evoke an episode of FL from ventral roots. Longer cycles (up to 1 min) induced sustained FL (up to 1 min) with stereotyped periodicity (2.2 ± 0.5 s), despite changing frequency (2-4 s) or cycle amplitude of FListim. Gradual filtering out of the noise from FListim trace concomitantly decreased the efficiency of FL so that stimulation with equivalent pure sinusoids produced asynchronous, irregular discharges only that could not be converted to FL by adding spontaneous basal activity. This study is the first demonstration that epochs of rhythmic locomotor-like oscillations applied to a dorsal root represent an efficient stimulus to evoke FL as long as they contain the electrophysiological noise produced within FL cycles. These observations suggest novel strategies to improve the efficiency of electrical stimulation delivered by clinical devices for neurorehabilitation after spinal injury.