Abstract
The repetitive activation of synaptic glutamate receptors can induce a lasting change in the number or subunit composition of synaptic AMPA receptors (AMPARs). However, NMDA receptors that are present extrasynaptically can also be activated by a burst of presynaptic activity, and thus may be involved in the induction of synaptic plasticity. Here we show that the physiological-like activation of extrasynaptic NMDARs induces a lasting change in the synaptic current, by changing the subunit composition of AMPARs at the parallel fibre-to-cerebellar stellate cell synapse. This extrasynaptic NMDAR-induced switch in synaptic AMPARs from GluR2-lacking (Ca(2+)-permeable) to GluR2-containing (Ca(2+)-impermeable) receptors requires the activation of protein kinase C (PKC). These results indicate that the activation of extrasynaptic NMDARs by glutamate spillover is an important mechanism that detects the pattern of afferent activity and subsequently exerts a remote regulation of AMPAR subtypes at the synapse via a PKC-dependent pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Benzodiazepines / pharmacology
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Calcium / metabolism
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Carrier Proteins / metabolism
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Cell Cycle Proteins
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Cerebellum / cytology
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Cerebellum / drug effects
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Cerebellum / enzymology
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Cerebellum / metabolism*
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Electric Stimulation
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Excitatory Amino Acid Antagonists / pharmacology
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Excitatory Postsynaptic Potentials
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Glutamic Acid / metabolism
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Mice
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Mice, Inbred C57BL
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N-Methylaspartate / metabolism
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Neuronal Plasticity* / drug effects
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Nuclear Proteins / metabolism
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Organophosphonates / pharmacology
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Peptide Fragments / pharmacology
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Piperazines / pharmacology
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / metabolism*
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Protein Kinase C / pharmacology
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Protein Kinase Inhibitors / pharmacology
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Receptors, AMPA / antagonists & inhibitors
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Receptors, AMPA / metabolism*
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Receptors, N-Methyl-D-Aspartate / metabolism*
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Synapses / drug effects
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Synapses / enzymology
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Synapses / metabolism*
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Synaptic Transmission* / drug effects
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Time Factors
Substances
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Carrier Proteins
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Cell Cycle Proteins
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Excitatory Amino Acid Antagonists
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Nuclear Proteins
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Organophosphonates
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Peptide Fragments
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Piperazines
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Prkcabp protein, mouse
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Protein Kinase Inhibitors
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Receptors, AMPA
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Receptors, N-Methyl-D-Aspartate
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carboxypiperazinyl propylphosphonic acid
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protein kinase C (19-36)
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GYKI 52466
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Benzodiazepines
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Glutamic Acid
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N-Methylaspartate
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Protein Kinase C
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glutamate receptor ionotropic, AMPA 2
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Calcium