We examined enhancement of synaptic transmission by neurotrophins at the pr
esynaptic level. In a synaptosomal preparation, brain-derived neurotrophic
factor (BDNF) increased mitogen-activated protein (MAP) kinase-dependent sy
napsin I phosphorylation and acutely facilitated evoked glutamate release.
PD98059, used to inhibit MAP kinase activity, markedly decreased synapsin I
phosphorylation and concomitantly reduced neurotransmitter release. The st
imulation of glutamate release by BDNF was strongly attenuated in mice lack
ing synapsin I and/or synapsin II. These results indicate at causal link of
synapsin phosphorylation via BDNF, TrkB receptors and MAP kinase with down
stream facilitation of neurotransmitter release.