| Summary: | 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 Ca2+ influx through postsynaptic N-methyl-d-aspartic acid (NMDA) receptors. Ca2+ influx triggers phosphorylation of several kinases, in particular Ca2+/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 αCaMKII T286A-mutant mice, where auto-phosphorylation of the α 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 αCaMKII has not been detected in interneurons. Here we show that pathway-specific NMDA receptor-dependent LTP is intact in hippocampal inhibitory interneurons of αCaMKII T286A-mutant mice, although in pyramidal cells it is blocked. However, LTP in interneurons is blocked by broad-spectrum pharmacological inhibition of Ca2+/calmodulin-dependent kinases. The results suggest that non-α Ca2+/calmodulin-dependent kinases substitute for the α isoform in NMDA receptor-dependent LTP in interneurons. © 2007 The Authors. Journal compilation © 2007 The Physiological Society.
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