NMDA Receptor-Dependent Long-Term Potentiation in Mouse Hippocampal Interneurons Shows a Unique Dependence on Ca(2+)/calmodulin-dependent Kinases

J Physiol. 2007 Nov 1;584(Pt 3):885-94. doi: 10.1113/jphysiol.2007.137380. Epub 2007 Sep 20.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Electrophysiology
  • Gene Expression Regulation
  • Hippocampus / cytology*
  • Long-Term Potentiation / physiology*
  • Mice
  • Mutation
  • Neurons / metabolism*
  • Receptors, N-Methyl-D-Aspartate / physiology*

Substances

  • Receptors, N-Methyl-D-Aspartate
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Camk2a protein, mouse