Balancing Excitation and Inhibition in the Locomotor Spinal Circuits

Abstract

Presynaptic inhibition after spinal cord injury (SCI) has been hypothesised to disproportionately affect flexion reflex loops in locomotor spinal circuitry. Reducing gamma-aminobutyric acid (GABA) inhibitory activity increases the excitation of flexion circuits, restoring muscle activation, and stepping ability. Conversely, nociceptive sensitisation and muscular spasticity can emerge from insufficient GABAergic inhibition. To investigate the effects of neuromodulation and proprioceptive sensory afferents in the spinal cord, a biologically constrained spiking neural network (SNN) was developed. The network describes the flexor motoneuron (MN) reflex loop with inputs from ipsilateral Ia- and II-fibres and tonically firing interneurons. The model was tuned to a baseline level of locomotive activity before simulating an inhibitory-dominant and body-weight supported (BWS) SCI state. Electrical stimulation (ES) and serotonergic agonists were simulated by the excitation of dorsal fibres and reduced conductance in excitatory neurons. ES was applied across all afferent fibres without phase- or muscle-specific protocols. The present study describes, for the first time, the release of GABAergic inhibition on flexor MNs as a potential mechanism underlying BWS treadmill training. The results demonstrate the synaptic mechanisms by which neuromodulatory therapy tunes the excitation and inhibition of ankle flexor MNs during locomotion for smoother and more coordinated movement.