Axon,Axotomy,Growth cone

Injured axons of the adult mammalian central nervous system (CNS) do not regenerate yet those in peripheral nerves do. This difference, and the hope of finding a treatment for the huge number of people disabled by CNS damage has motivated scientists to identify the obstacles that prevent axonal regeneration. This has led to many important discoveries including growth-inhibiting molecules. However, before a cut axon can attempt to grow it first has to assemble a new growth cone (GC) at its tip. It is now becoming clear that many axons in the mammalian CNS fail to complete this critical step.

In this project we focused on the mechanisms that underlie the regenerative reassembly of a GC after axotomy, and on the reasons why this process may fail. After injury, CNS axons that have failed to regenerate are often tipped with dystrophic end-bulbs (retraction-bulbs), hallmarks of degenerating axons. Using cultured Aplysia neurons in combination with confocal imaging, molecular tools and electrophysiological methods we analyzed the cellular and molecular mechanisms that underlie the formation of competent GCs, the formation of retraction bulbs (rather than GCs), the mechanisms by which a regenerating neuron “economically” allocate cell resources in support of growth processes on the one hand and on the other to the assembly of functional presynaptic boutons. Finally, we studied the mechanisms by which transected axon “know” how to “allocate” cell resources to injured branches and not to intact branches, and how do cells know when to stop the regenerative processes to prevent over-growth.