PROJECT SUMMARY Axon regeneration is a fundamental and conserved property of nervous systems. But axon regeneration often fails to restore function after nerve injury. Thus, a key question in the field is to discover what determines the capacity of injured neurons to rebuild functional circuits. This proposal investigates new mechanisms that function in the injured neuron and that help determine whether or not effective regeneration occurs. The long-term goal is to gain a comprehensive understanding of the cellular functions that link neuronal injury to successful functional regeneration. The specific goal of this project is to analyze the process of synapse regeneration. The project uses a combination of in vivo approaches aimed at understanding how synapse regeneration works, why it fails to restore normal function, and how it can be improved. Completion of these Aims will describe fundamental cellular mechanisms that mediate functional axon regeneration after nerve injury.