NMDA receptor-dependent long-term potentiation in mouse hippocampal interneurons shows a unique dependence on Ca(2+)/calmodulin-dependent kinases.
Long-term potentiation (LTP) of excitatory synaptic transmission plays a major role in memory encoding in the cerebral cortex. It can be elicited at many synapses on principal cells, where it depends on Ca(2+) influx through postsynaptic N-methyl-D-aspartic acid (NMDA) receptors. Ca(2+) influx triggers phosphorylation of several kinases, in particular Ca(2+)/calmodulin-dependent kinase type II (CaMKII). Auto-phosphorylation of CaMKII is a key step in the LTP induction cascade, as revealed by the absence of LTP in hippocampal pyramidal neurons of alphaCaMKII T286A-mutant mice, where auto-phosphorylation of the alpha isoform at residue T286 is prevented. A subset of hippocampal interneurons mediating feed-forward inhibition also exhibit NMDA receptor-dependent LTP, which shows all the cardinal features of Hebbian LTP in pyramidal neurons. This is unexpected, because alphaCaMKII has not been detected in interneurons. Here we show that pathway-specific NMDA receptor-dependent LTP is intact in hippocampal inhibitory interneurons of alphaCaMKII T286A-mutant mice, although in pyramidal cells it is blocked. However, LTP in interneurons is blocked by broad-spectrum pharmacological inhibition of Ca(2+)/calmodulin-dependent kinases. The results suggest that non-alpha Ca(2+)/calmodulin-dependent kinases substitute for the alpha isoform in NMDA receptor-dependent LTP in interneurons.
Lamsa
Karri
K
Institute of Neurology, University College London, Queen Square, London, UK.
Irvine
Elaine E
EE
Giese
K Peter
KP
Kullmann
Dimitri M
DM
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics* / Q000378:metabolism; D004594:Electrophysiology; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology*; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
D016194:Receptors, N-Methyl-D-Aspartate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C517671:Camk2a protein, mouse