I propose to study the polarity of axonal regeneration in a primitive vertebrate, the sea lamprey, Petromyzon marinus. My goal is to understand how neurons maintain their normal polarity following axotomy; i.e., how they regenerate their axons at the axon stump, by-passing other sites within the cell. The lamprey is ideal for addressing this question, as it permits direct access to and visualization of mature identified neurons in a vertebrate CNS in situ. Furthermore, the site of axotomy of certain identified neurons (ABCs) determines whether axonal regeneration occurs from the axon stump (following axotomy distant from the soma) or from ectopic sites in the dendrites (following axotomy close to the soma). I will therefore compare the effects of close .and distant axotomy on factors that preliminary experiments suggest may be important in maintaining normal polarity (i.e., the distribution and phosphorylation of neurofilaments, the stability of microtubules and the influx of Ca++ at the site of axotomy). The importance of each of these factors in maintaining normal polarity following axotomy will be assessed by (1) comparing post lesion changes in these factors that correlate with the occurrence and distribution of sprouts, and (2) perturbing neurofilament transport and phosphorylation, microtubule stability and the intracellular free Ca++ level with specifically acting drugs, and then examining the response of treated ABCs to axotomy. The results of this work should illuminate the cellular mechanisms that maintain axonal and dendritic identity following injury. They should also be relevant to the important health related problems of CNS axonal regeneration and the loss of aspects of dendritic and axonal identity that occur in Alzheimer's disease.
| Pijak, D S; Hall, G F; Tenicki, P J et al. (1996) Neurofilament spacing, phosphorylation, and axon diameter in regenerating and uninjured lamprey axons. J Comp Neurol 368:569-81 |
| Hall, G F; Kosik, K S (1993) Axotomy-induced neurofilament phosphorylation is inhibited in situ by microinjection of PKA and PKC inhibitors into identified lamprey neurons. Neuron 10:613-25 |
