Effects of brain-derived neurotrophic factor on optic axon branching and remodelling in vivo.

Neurotrophins are thought to be important for the survival and differentiation of vertebrate neurons. Roles have been suggested for target-derived neurotrophins, based both on their expression in target tissues at the time of neuron innervation, and on their effects on axonal sprouting. However, direct in vivo evidence of their involvement in axon arborization has remained elusive. We have used in vivo microscopy to follow individual optic axons over time, and have examined the role of the neurotrophin brain-derived neurotrophic factor (BDNF) in their development. Here we show that injection of BDNF into the optic tectum of live Xenopus laevis tadpoles increased the branching and complexity of optic axon terminal arbors. In contrast, injection of specific neutralizing antibodies to BDNF reduced axon arborization and complexity. The onset of these effects was rapid (within 2 hours) and persisted throughout the 24-hour observation period. Other neurotrophins had little or no significant effects. These results demonstrate the involvement of neurotrophins in the dynamic elaboration of axon terminals, and suggest a direct role for target-derived BDNF during synaptic patterning in the developing central nervous system.