Potentiation of developing synapses by postsynaptic release of neurotrophin-4.
The hypothesis that synaptic functions can be regulated by neurotrophins secreted from the postsynaptic cell was examined in Xenopus nerve-muscle cultures. Neuromuscular synapses formed on myocytes overexpressing neurotrophin-4 (M+ synapses) exhibited a higher level of spontaneous synaptic activity and enhanced evoked synaptic transmission as compared to those formed on normal control myocytes (M- synapses). The NT-4 effects involve a potentiation of presynaptic transmitter secretion as well as a lengthening of the mean burst duration of postsynaptic low conductance acetylcholine channels. Repetitive stimulation of either the presynaptic neuron or the postsynaptic myocyte led to a potentiation of synaptic transmission at M+ synapses. All potentiation effects of NT-4 overexpression were abolished by the extracellular presence of TrkB-IgG but not by the presence of TrkA-IgG, indicating that postsynaptic secretion of NT-4 was responsible for the synaptic modification.
Wang
X H
XH
Department of Biology, University of California at San Diego, La Jolla 92093-0357, USA.
Poo
M M
MM
D000818:Animals; D002478:Cells, Cultured; D004558:Electric Stimulation; D004625:Embryo, Nonmammalian / Q000502:physiology; D005071:Evoked Potentials; D005260:Female; D005307:Fertilization in Vitro; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000096:biosynthesis; D008297:Male; D009132:Muscles / Q000502:physiology*; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000502:physiology*; D009469:Neuromuscular Junction / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011518:Proto-Oncogene Proteins / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D020801:Receptor, Ciliary Neurotrophic Factor; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission; D014158:Transcription, Genetic; D014981:Xenopus
D008164:Luminescent Proteins; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; C073922:neurotrophin 4