The large larval sea lamprey (4-5 years old) is a valuable model for the reparative potential of the vertebrate CNS. It recovers from spinal transection by a process which involves short distance axonal regeneration. By recording simultaneously from pairs of neurons above and below the transection scar, this laboratory has demonstrated for the first time the regeneration of functioning synaptic connections between individual identified neurons within the vertebrate CNS. We now propose to determine whether synaptic regeneration is specific by comparing the pattern of interconnections among several identified types of neurons across a healed transection with the pattern seen in nontransected animals. We have also found that the giant reticulospinal axons (RAs) of the Muller and Mauthner cells regenerate much better when they are cut high in the spinal cord than when they are cut at the level of the cloaca. Therefore, regeneration may be more effective the closer the site of injury is to the cell body. This hypothesis will be tested by comparing the distances of regeneration of RAs cut by spinal transection at four different levels. Regeneration will be measured in spinal cord wholemounts following intraaxonal injection of HRP at a point just above the scar. The test of this hypothesis will be extended to other neurons by retrograde labeling of their cell bodies with HRP injected below the scar. Labeled cells are clearly visible in brain wholemounts. The technique will first be validated by comparing the results on the labeling of the Muller and Mauthner cells with those obtained by direct injection of HRP into their axons. Thus, we have an opportunity to critically evaluate a powerful technique which is in common use in mammalian regeneration research and which may allow more rapid testing of the effects of pharmacological and surgical manipulations on axonal regeneration.
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