Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Autocrine Communication / physiology
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Cells, Cultured
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Electrophysiology
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Immunoglobulin G / pharmacology
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Motor Neurons / cytology
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Motor Neurons / metabolism
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Muscle Fibers, Skeletal / cytology
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Muscle Fibers, Skeletal / metabolism
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Muscle, Skeletal / cytology
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Muscle, Skeletal / innervation
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Nerve Growth Factors / genetics
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Nerve Growth Factors / metabolism*
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Neuromuscular Junction / chemistry
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Neuromuscular Junction / metabolism*
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Neuroprotective Agents / metabolism*
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RNA, Messenger / pharmacology
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Receptor Protein-Tyrosine Kinases / genetics
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Receptor Protein-Tyrosine Kinases / metabolism
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Receptor, Ciliary Neurotrophic Factor
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Receptors, Cholinergic / metabolism
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Receptors, Nerve Growth Factor / genetics
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Receptors, Nerve Growth Factor / metabolism
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Synapses / metabolism*
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Synaptic Transmission / physiology*
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Xenopus
Substances
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Immunoglobulin G
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Nerve Growth Factors
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Neuroprotective Agents
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RNA, Messenger
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Receptor, Ciliary Neurotrophic Factor
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Receptors, Cholinergic
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Receptors, Nerve Growth Factor
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Receptor Protein-Tyrosine Kinases
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neurotrophin 4