Abstract
Neurotrophins (NTs) have recently been found to regulate synaptic transmission in the hippocampus. Whole-cell and single-channel recordings from cultured hippocampal neurons revealed a mechanism responsible for enhanced synaptic strength. Specifically, brain-derived neurotrophic factor augmented glutamate-evoked, but not acetylcholine-evoked, currents 3-fold and increased N-methyl-D-aspartic acid (NMDA) receptor open probability. Activation of trkB NT receptors was critical, as glutamate currents were not affected by nerve growth factor or NT-3, and increased open probability was prevented by the tyrosine kinase inhibitor K-252a. In addition, the NMDA receptor antagonist MK-801 blocked brain-derived neurotrophic factor enhancement of synaptic transmission, further suggesting that NTs modulate synaptic efficacy via changes in NMDA receptor function.
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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Acetylcholine / pharmacology
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Animals
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Brain-Derived Neurotrophic Factor / pharmacology*
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Brain-Derived Neurotrophic Factor / physiology
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Cells, Cultured
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Dizocilpine Maleate / pharmacology
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Glutamic Acid / pharmacology
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Hippocampus / cytology
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Hippocampus / drug effects*
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Hippocampus / physiology*
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N-Methylaspartate / pharmacology
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Nerve Growth Factors / pharmacology
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Neurotrophin 3
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Rats
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Receptors, N-Methyl-D-Aspartate / drug effects*
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Receptors, N-Methyl-D-Aspartate / physiology*
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Synaptic Transmission / drug effects*
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Synaptic Transmission / physiology*
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology
Substances
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Brain-Derived Neurotrophic Factor
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Nerve Growth Factors
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Neurotrophin 3
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Receptors, N-Methyl-D-Aspartate
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Glutamic Acid
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N-Methylaspartate
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Dizocilpine Maleate
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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Acetylcholine