Distinct mechanisms for neurotrophin-3-induced acute and long-term synaptic potentiation.
Although neurotrophins elicit both acute and long-term effects, it is unclear whether the two modes of action are mediated by the same or different mechanisms. Using neuromuscular junction (NMJ) as a model system, we identified three characteristic features required for long-term, but not acute, forms of synaptic modulation by neurotrophin-3 (NT-3): endocytosis of NT-3-receptor complex, activation of the PI3 kinase substrate Akt, and new protein synthesis. Long-term effects were eliminated when NT-3 was conjugated to a bead that was too large to be endocytosed or when dominant-negative dynamin was expressed in presynaptic neurons. Presynaptic inhibition of Akt also selectively prevented NT-3-mediated long-term effects. Blockade of protein translation by the mammalian target of rapamycin inhibitor rapamycin prevented the long-term structural and functional changes at the NMJ, without affecting the acute potentiation of synaptic transmission by NT-3. These results reveal fundamental differences between acute and long-term modulation by neurotrophins.
Je
Hyun-Soo
HS
Section on Neural Development and Plasticity, National Institute of Child Health and Human Development, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-3714, USA.
Zhou
Jianzheng
J
Yang
Feng
F
Lu
Bai
B
D000818:Animals; D005260:Female; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D020933:Neurotrophin 3 / Q000494:pharmacology* / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D014981:Xenopus; D029867:Xenopus Proteins / Q000502:physiology*
D020933:Neurotrophin 3; D029867:Xenopus Proteins