Post-inhibitory rebound excitation drives extensor activity following spinal cord stimulation

Neural circuits throughout the CNS can exhibit rebound excitation following prolonged periods of inhibition. However, the potential to control this phenomenon and harness it for clinical applications remains largely unexplored.

We investigate rebound excitatory responses evoked by spinal cord stimulation (SCS) that can generate functional motor output, providing a testable model of circuit-level rebound excitation relevant to neuromodulation across the CNS.

Brief (5 s) electrical stimulation trains were delivered to the lumbar spinal cord in adult cats. We recorded intracellular neuronal activity in the cord and EMG and force output from hindlimb muscles.

SCS elicited a robust and long-lasting rebound excitation selectively targeting the ipsilateral ankle extensors-a response we term Long Extension Activated Post-stimulation (LEAP). The force output during LEAP can support weight-bearing in cats, underscoring its clinical potential. Intracellular recordings revealed that extensor motoneurons received strong inhibitory inputs during stimulation, driven by reciprocal inhibition via proprioceptive afferents. Upon cessation of stimulation, a shift to a rebound excitatory synaptic input occurred, resulting in sustained firing in extensor motoneurons during LEAP. We also observed concurrent dynamic changes in interneuron firing across spinal laminae, suggesting broad circuit engagement. We systematically mapped the parameter space required to reliably evoke LEAP, including stimulation location, amplitude, and frequency, providing a framework for controlled rebound activation.

LEAP represents a novel rebound response that can generate weight-supporting postural output. This mechanism not only expands the therapeutic potential of SCS in motor disorders but also serves as a model for modulating rebound excitation throughout the CNS.