We propose to extend our investigation of the role of natural and artificially imposed electrical current in initiating, guiding, and enhancing nerve regeneration. We propose an integrated investigation in two major areas: 1) We wish to extend ou preliminary studies into the endogenous electrical fields and currents generated within the lesioned lamprey spinal cord in vivo and in organ culture. We wish to further characterize these injury currents by determining their ionic composition and by establishing ways to modify, reduce, or eliminate them by various techniques. In this way we hope to identify the possible ways these endogenous currents influence the responses of neurons to axotomy and their subsequent regeneration. To do this we will analyze neurons using a variety of different morphological techniques (E.M. and L.M.) and coventional electrophysiological technique coupled with the use of the "Ultrasensitive vibrating probe". We also propose to extend our earlier success in enhancing the linear regeneration of identifiable axons within the lesioned lamprey spinal cord by the application of steady electric fields. We wish to optomize these responses, and more fully characterize the nature of the response by a variety of morphological techniques; wholemount preparation of horseradish peroxidase filled axons; fluorescent dye iontophoresis; and high resolution light microscope and electron microscope technique. We will functionally characterize the responses by simultaneous extracellular (whole cord) and intracellular recording of action potentials across the original lesions. Overall, we hope to establish a linkage between endogenous currents of injury and the mechanisms of action of artificially applied fields in nerve regeneration. Moverover, we ultimately wish to produce an effective means of enhancing nerve regenerations in the CNS of higher vertebrates.