NEUROTROPHINS PROMOTE MATURATION OF DEVELOPING NEUROMUSCULAR SYNAPSES

Although the effects of neurotrophins on survival and differentiation of various neuronal populations have been well studied, little is know n about their role in synaptic development and function. We have inves tigated the long-term effects of neurotrophins in the maturation of ne uromuscular synapses in Xenopus nerve-muscle cocultures. BDNF and NT-3 , but not NGF, elicited significant changes in several properties of s pontaneous synaptic currents (SSCs), indicative of more mature synapse s, Most synapses treated by the neurotrophins exhibited a bell-shaped distribution of SSC amplitudes, which reflects mature quantal secretio n. The neurotrophins also potentiated the efficacy and reliability of stimulus-induced synaptic transmission, Moreover, BDNF and NT-3 increa sed the levels of the synaptic vesicle proteins, synaptophysin, and sy napsin I in the spinal neurons, The number of varicosities per neuron also showed a significant increase after neurotrophin treatment. The e ffects of the neurotrophins appear to be mediated by the Trk family of receptor tyrosine kinases, primarily through a presynaptic mechanism. These results suggest that BDNF and NT-3 promote functional maturatio n of synapses.