The muscarinic long-term enhancement of NMDA and AMPA receptor-mediated transmission at Schaffer collateral synapses develop through different intracellular mechanisms.
We had described a muscarinic-mediated long-term synaptic enhancement at Schaffer collateral synapses caused by the insertion of AMPARs in spines of rat hippocampal CA1 pyramidal neurons that requires Ca(2+) release from IP3-sensitive stores (Fernández de Sevilla et al., 2008). We now show that this AMPA-mediated LTP(IP3) is precisely matched by an amplification of NMDAR-mediated transmission. The enhanced AMPAR transmission involves SNARE protein activity and CaMKII activation. The amplification of NMDA transmission requires combined CaMKII, PKC, and SRC kinase activity without detectable surface incorporation of NMDARs, suggesting that changes in receptor properties mediate this process. The enhanced AMPAR- and NMDAR-mediated transmission markedly reduce the induction threshold of "Hebbian" LTP. We conclude that both modes of glutamatergic synaptic potentiation may play a critical functional role in the regulation of the learning machinery of the brain by adding flexibility to the demands of the hippocampal network.
Fernández de Sevilla
David
D
Instituto Cajal, Consejo Superior de Investigaciones Científicas, 28002-Madrid, Spain. david.fernandezdesevilla@uam.es
Buño
Washington
W
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D049229:Dendritic Spines / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D043643:Receptor, Muscarinic M1 / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D050600:SNARE Proteins / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D019061:src-Family Kinases / Q000378:metabolism
D053496:Inositol 1,4,5-Trisphosphate Receptors; D043643:Receptor, Muscarinic M1; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D050600:SNARE Proteins; D018698:Glutamic Acid; D019061:src-Family Kinases; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium