EFFECTS OF BRAIN-DERIVED NEUROTROPHIC FACTOR ON OPTIC AXON BRANCHING AND REMODELING IN-VIVO

NEUROTROPHINS are thought to be important for the survival and differe ntiation of vertebrate neurons(1). Roles have been suggested for targe t-derived neurotrophins, based both on their expression in target tiss ues at the time of neuron innervation(2,3), and on their effects on ax onal sprouting(4-6). However, direct in vivo evidence of their involve ment in axon arborization has remained elusive. We have used in vivo m icroscopy to follow individual optic axons over time, and have examine d the role of the neurotrophin brain-derived neurotrophic factor (BDNF ) in their development. Here we show that injection of BDNF into the o ptic tectum of live Xenopus laevis tadpoles increased the branching an d 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 neurotroph ins had little or no significant effects. These results demonstrate th e involvement of neurotrophins in the dynamic elaboration of axon term inals, and suggest a direct role for target-derived BDNF during synapt ic patterning in the developing central nervous system.