Paraplegic patients dream to be able to walk again after spinal cord injuries. A practical issue concerns the feasibility to reactivate the spared spinal neural circuitry to control some of the lost locomotor functions. It is critical to understand the properties of interneurons and their interactions within the spinal circuitry in order to unlock this potential. This study thus focuses on the control of walking by interneurons within the recently identified flexor and extensor centers of the mudpuppy (Necturus Maculatus).
The specific aims are to identified interneurons in these specialized regions that are candidate pacemaker or transitional cells for the generation of walking, to determine the membrane properties of these cells, to determine the role of electrical and metabolic coupling through gap junction channels in the generation of locomotor-like activity, and to determine the pattern of synaptic projections from sensory afferent pathways to these interneurons. Intracellular recording will be performed in the in vitro mudpuppy spinal cord-forelimb preparation during walking-like movement of the limbs induced by bath application of glutamate or its agonist NMDA. Four classes of interneurons will be identified by a combination of criteria and based on their firing pattern in relation to the phasic activity of the elbow flexor and extensor muscles. Each type of cells will be examined electrophysiologically and histologically. The goals are to unravel common principles that govern the organization and operation of the neural circuitry for walking. What will emerge from this study is a detailed picture of differential sensory projections to each type of identified interneurons associated with the generation of walking. It will also be determined whether there is a population of interneurons that function as pacemaker cells in the spinal cord locomotor circuitry. Although this investigation focuses on the basic neuroscience of the locomotor circuitry, this information is essential before considering how one can utilize clinically whatever human central pattern generator remains after spinal cord injury.
