Abstract
Maturation of presynaptic transmitter secretion machinery is a critical step in synaptogenesis. Here we report that a brief train of presynaptic action potentials rapidly converts early nonfunctional contacts between cultured hippocampal neurons into functional synapses by enhancing presynaptic glutamate release. The enhanced release was confirmed by a marked increase in the number of depolarization-induced FM4-64 puncta in the presynaptic axon. This rapid presynaptic maturation can be abolished by treatments that interfered with presynaptic BDNF and Cdc42 signaling or actin polymerization. Activation of Cdc42 by applying BDNF or bradykinin mimicked the effect of electrical activity in promoting synaptic maturation. Furthermore, activity-induced increase in presynaptic actin polymerization, as revealed by increased concentration of actin-YFP at axon boutons, was abolished by inhibiting BDNF and Cdc42 signaling. Thus, rapid presynaptic maturation induced by neuronal activity is mediated by presynaptic activation of the Cdc42 signaling pathway.
MeSH terms
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Actin Cytoskeleton / drug effects
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Actin Cytoskeleton / metabolism
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Actin Cytoskeleton / ultrastructure
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Action Potentials / physiology
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Animals
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Bacterial Proteins
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Bradykinin / metabolism
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Bradykinin / pharmacology
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Brain-Derived Neurotrophic Factor / antagonists & inhibitors
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Brain-Derived Neurotrophic Factor / metabolism
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Cell Differentiation / drug effects
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Cell Differentiation / physiology*
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Cells, Cultured
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Enzyme Inhibitors / pharmacology
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Glutamic Acid / metabolism
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Hippocampus / cytology
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Hippocampus / embryology*
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Hippocampus / metabolism
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Luminescent Proteins
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Neural Pathways / cytology
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Neural Pathways / embryology*
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Neural Pathways / metabolism
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / physiology
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Presynaptic Terminals / drug effects
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Presynaptic Terminals / metabolism*
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Pyridinium Compounds / metabolism
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Quaternary Ammonium Compounds / metabolism
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Rats
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Rats, Sprague-Dawley
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
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Time Factors
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Up-Regulation / drug effects
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Up-Regulation / physiology
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cdc42 GTP-Binding Protein / antagonists & inhibitors
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cdc42 GTP-Binding Protein / genetics
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cdc42 GTP-Binding Protein / metabolism*
Substances
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Bacterial Proteins
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Brain-Derived Neurotrophic Factor
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Enzyme Inhibitors
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FM 4-64
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Luminescent Proteins
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Pyridinium Compounds
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Quaternary Ammonium Compounds
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yellow fluorescent protein, Bacteria
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Glutamic Acid
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cdc42 GTP-Binding Protein
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Bradykinin