• Muller, Kenneth J (PI)

Project: Research project

Project Details


Individual neurons in the leech can regenerate severed axons to reconnect
with particular neurons that are their normal synaptic targets. Repair
occurs in stages, from initial sprouting of the injured axon and growth
that may be along selected pathways to recognition of the target, synapse
formation, and cessation of growth. The proposed project addresses the
questions: (1) what cellular interactions and capabilities control
sprouting, (2) which cells and extracellular elements along the pathway
might stimulate or direct growth, (3) are inappropriate as well as
appropriate contacts made, (4) how do the new synapses compare with the old
in distribution and function, (5) why do axons stop growing, and (6) what
features of axon growth and synapse formation during development are
revived during regeneration? The methodology will include intracellular
and extracellular electrophysiological recording and intracellular
injection of markers for subsequent light and electron microscopic
examination. Growth of axons, filled with fluorescent markers, will be
tracked in living preparations, in some cases maintained in culture
medium. Properties of pathways and surfaces of particular cells will be
examined, using electron microscopy, with cell-specific ligands including
monoclonal antibodies and with freeze-fracture. Single cells can be killed
with intracellular injection of proteases or focally lesioned using dyes
that produce photodynamic damage. The morphology of certain cells and the
complex patterns of normal and regenerated synaptic contacts between them
will be reconstructed with a computer. Growth of individual neurons will
be studied during development and compared with regeneration. An
understanding of the mechanisms for accurate regeneration in the leech
central nervous system might suggest ways that nerve regeneration in higher
animals including humans could be made more reliable and precise.
Effective start/end date9/1/837/31/94


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $213,478.00
  • National Institutes of Health
  • National Institutes of Health


  • Medicine(all)
  • Neuroscience(all)


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