Functional recovery of a simple spinal locomotor circuit following injury during early development

Centre for Neuroregeneration, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 4SB

Spinal cord injury is detrimental in the adult mammalian system due to the inability of neurons to regenerate their axons and reconnect to their targets below the injury site. Spinal neural networks that control rhythmic locomotion, such as walking or swimming, are called central pattern generators (CPGs)(1). Once injured, CPG networks in mammals are difficult to restore, whereas some simple animals, such as the Xenopus laevis tadpoles, exhibit high regenerative capacity(2). Using young Xenopus tadpoles, we are trying to reveal how the CPG network repairs following injury and how neuronal activity affects axon regeneration. The CPG network of Xenopus embryos at the time of hatching (2 days old) is simple and well characterised (3,4), providing an excellent model for this study. A complete spinal cord transection is performed on 2-day old Xenopus embryos and the recovery is assessed one day later. High-speed video recordings of tadpole free swimming behaviour and ventral root recordings, just one day post lesion, have revealed that the CPG network below the lesion site regains its function. To explore the relationships between axon regeneration and individual neuron property and activity, simultaneous ventral root and single neuron whole-cell current-clamp recordings have been applied. Neurobiotin-DAB staining following intracellular recordings allows us to view the neuronal morphology and evaluate the extend of axonal regeneration. Our results reveal that individual neurons around the lesion site still generate similar action potentials upon depolarising pulses and during fictive swimming. Excitatory and inhibitory post-synaptic inputs are currently being tested, together with axon regeneration and other cellular properties. Understanding the basic mechanisms of motor circuit repair following spinal injury may reveal common mechanisms that could promote further studies in the mammalian spinal cord.

References

1. Kiehn, O. & Dougherty, K. Locomotion: circuits and physiology. Neuroscience in the 21st Century (2013). doi:10.1007/978-1-4614-1997-6_42
2. Lee-Liu, D., Méndez-Olivos, E. E., Muñoz, R. & Larraín, J. The African clawed frog Xenopus laevis: a model organism to study regeneration of the Central Nervous System. Neurosci. Lett. (2016). doi:10.1016/j.neulet.2016.09.054
3. Roberts, A., Li, W.-C. & Soffe, S. R. A functional scaffold of CNS neurons for the vertebrates: The developing Xenopus laevis spinal cord. Devel Neurobio 72, 575–584 (2012).
4. autois, B., Soffe, S. R., Li, W.-C. & Roberts, A. Role of type-specific neuron properties in a spinal cord motor network. J Comput Neurosci 23, 59–77 (2007).

Funded by: BBSRC and Wellcome Trust

* entered into the PhD student poster competition