Localized synaptic actions of neurotrophin-4.
Neurotrophins secreted by the postsynaptic target cell may participate in activity-dependent synaptic modification during development and in the mature brain. A fundamental question of how neurotrophins can sculpt synaptic connections is whether neurotrophin-induced synaptic changes are spatially restricted to the site of neurotrophin secretion or whether they can spread to neighboring synapses. Using a model system of nerve-muscle coculture in which neurotrophin-4 (NT-4) is overexpressed in a subpopulation of postsynaptic myocytes, we demonstrated that presynaptic potentiation is restricted to synapses on myocytes overexpressing NT-4 without affecting nearby synapses formed by the same neuron on control myocytes. Likewise, postsynaptic modulation of acetylcholine channels by secreted NT-4 is spatially restricted to <60 micron from the site of NT-4 secretion. Therefore, activity-dependent secretion of neurotrophins can result in highly localized modification of neuronal connections.
Wang
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Department of Biology, University of California at San Diego, La Jolla, California 92093-0357, USA.
Berninger
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B
Poo
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M
D000818:Animals; D019898:Autocrine Communication / Q000502:physiology; D002478:Cells, Cultured; D004594:Electrophysiology; D007074:Immunoglobulin G / Q000494:pharmacology; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000294:innervation; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000737:chemistry / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism*; D012333:RNA, Messenger / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D020801:Receptor, Ciliary Neurotrophic Factor; D011950:Receptors, Cholinergic / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D014981:Xenopus
D007074:Immunoglobulin G; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D011950:Receptors, Cholinergic; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; C073922:neurotrophin 4