Locomotor Recovery after Spinal Cord Lesions in the Lamprey Is Associated with Functional and Ultrastructural Changes below Lesion Sites

While axonal regeneration continues to be the major focus of research into spinal injury, there is growing evidence for changes in functional properties below lesion sites. In this study we have used the lamprey, a model system for studying axonal regeneration after spinal injury, to examine whether functional and ultrastructural changes below lesion sites might also contribute to the recovery of locomotor function in this system. In the current study, the majority of the animals showed good functional recovery 10 weeks after lesioning, even when there was no physiological evidence for regeneration across the lesion site (although animals that recovered poorly always lacked regeneration). Excitability was increased below, but not above, the lesion site, as shown by the significantly greater ventral root responses following electrical stimulation of the spinal cord, a depolarization of the resting membrane potential, and an increase in input resistance and excitability in spinal cord neurons. Synaptic properties were also affected: a slow postsynaptic depolarization developed during presynaptic spike trains, and there was an increase in the frequency and amplitude of tetrodotoxin (TTX)-resistant miniature excitatory postsynaptic potentials (mEPSPs). There were also changes in synaptic ultrastructure, including a reduction of the synaptic gap and an increase in synaptic vesicle pools at asymmetric (putative excitatory) synapses. These results provide the first evidence for functional changes below lesion sites in the lamprey, and suggest that locomotor recovery reflects an interaction between regenerated axons and altered networks below lesion sites. The lamprey offers a tractable model system in which to investigate how interactions between altered locomotor networks and regenerated axons are organized to promote locomotor recovery.