Activation of extrasynaptic NMDA receptors induces a PKC-dependent switch in AMPA receptor subtypes in mouse cerebellar stellate cells.
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.
Sun
Lu
L
Department of Biology, 208 Mueller lab, Penn State University, State College, PA 16802, USA.
June Liu
Siqiong
S
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials; D018698:Glutamic Acid / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016202:N-Methylaspartate / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects; D009687:Nuclear Proteins / Q000378:metabolism; D063065:Organophosphonates / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D018691:Excitatory Amino Acid Antagonists; D009687:Nuclear Proteins; D063065:Organophosphonates; D010446:Peptide Fragments; D010879:Piperazines; C091822:Prkcabp protein, mouse; D047428:Protein Kinase Inhibitors; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C493869:carboxypiperazinyl propylphosphonic acid; C072093:protein kinase C (19-36); C061950:GYKI 52466; D001569:Benzodiazepines; D018698:Glutamic Acid; D016202:N-Methylaspartate; D011493:Protein Kinase C; C104722:glutamate receptor ionotropic, AMPA 2; D002118:Calcium