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Journal of Neuroscience, Vol 15, 4796-4805, Copyright © 1995 by Society for Neuroscience
Neurotrophins promote maturation of developing neuromuscular synapses
T Wang, K Xie and B Lu
Roche Institute of Molecular Biology, Nutley, New Jersey 07110, USA.
Although the effects of neurotrophins on survival and differentiation of
various neuronal populations have been well studied, little is known about
their role in synaptic development and function. We have investigated the
long-term effects of neurotrophins in the maturation of neuromuscular
synapses in Xenopus nerve-muscle cocultures. BDNF and NT-3, but not NGF,
elicited significant changes in several properties of spontaneous synaptic
currents (SSCs), indicative of more mature synapses. Most synapses treated
by the neurotrophins exhibited a bell- shaped distribution of SSC
amplitudes, which reflects mature quantal secretion. The neurotrophins also
potentiated the efficacy and reliability of stimulus-induced synaptic
transmission. Moreover, BDNF and NT-3 increased the levels of the synaptic
vesicle proteins, synaptophysin, and synapsin 1 in the spinal neurons. The
number of varicosities per neuron also showed a significant increase after
neurotrophin treatment. The effects 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 maturation of synapses.
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