Abstract
The mechanisms of induction and the site of expression of long-term depression (LTD) at the hippocampal mossy fiber-CA3 synapses are not clear. Here, we show that a brief bath application of insulin induces a novel form of mossy fiber LTD. This insulin-LTD is (1) induced and expressed postsynaptically, (2) entirely independent of synaptic stimulation during insulin application, (3) involving a rise in postsynaptic [Ca(2+)](i) and L-type voltage-activated Ca(2+) channel activation, (4) mechanistically distinct from low-frequency stimulation-induced LTD, (5) dependent on phosphatidylinositol 3-kinase signaling, and (6) associated with a clathrin-mediated endocytotic removal of surface 3-hydroxy-5-methylisoxazole-4-propionic acid receptors from the postsynaptic neurons. Moreover, insulin-LTD is specific to mossy fibers to CA3 pyramidal cell synapses, and is not present at associational commissural synapses. These findings not only support a postsynaptic locus of mossy fiber LTD, but also provide a further link between the AMPA receptor trafficking and the bidirectional expression of long-term synaptic plasticity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calcium / metabolism
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Calcium Channels, L-Type / drug effects
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Calcium Channels, L-Type / metabolism
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Calcium Signaling / drug effects
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Calcium Signaling / physiology
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Clathrin-Coated Vesicles / drug effects
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Clathrin-Coated Vesicles / metabolism
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Endocytosis / drug effects
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Endocytosis / physiology
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Glucose / metabolism
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Insulin / metabolism*
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Insulin / pharmacology
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Long-Term Synaptic Depression / drug effects
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Long-Term Synaptic Depression / physiology*
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Mice
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Mice, Inbred ICR
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Mossy Fibers, Hippocampal / drug effects
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Mossy Fibers, Hippocampal / metabolism*
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Organ Culture Techniques
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Phosphatidylinositol 3-Kinases / drug effects
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Phosphatidylinositol 3-Kinases / metabolism
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Protein Transport / drug effects
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Protein Transport / physiology
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Pyramidal Cells / drug effects
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Pyramidal Cells / metabolism
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Receptor, Insulin / drug effects
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Receptor, Insulin / metabolism
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Receptors, AMPA / drug effects
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Receptors, AMPA / metabolism*
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Synapses / drug effects
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Synapses / metabolism*
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
Substances
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Calcium Channels, L-Type
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Insulin
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Receptors, AMPA
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Phosphatidylinositol 3-Kinases
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Receptor, Insulin
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Glucose
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Calcium