Aberrant information transfer interferes with functional axon regeneration

Abstract

Functional axon regeneration requires regenerating neurons to restore appropriate synaptic connectivity and circuit function. To model this process, we developed an assay in Caenorhabditis elegans that links axon and synapse regeneration of a single neuron to recovery of behavior. After axon injury and regeneration of the DA9 neuron, synapses reform at their pre-injury location. However, these regenerated synapses often lack key molecular components. Further, synaptic vesicles accumulate in the dendrite in response to axon injury. Dendritic vesicle release results in information misrouting that suppresses behavioral recovery. Dendritic synapse formation depends on dynein and jnk-1. But even when information transfer is corrected, axonal synapses fail to adequately transmit information. Our study reveals unexpected plasticity during functional regeneration. Regeneration of the axon is not sufficient for the reformation of correct neuronal circuits after injury. Rather, synapse reformation and function are also key variables, and manipulation of circuit reformation improves behavioral recovery.