The role of calcium–calmodulin kinase II in three forms of synaptic plasticity

Abstract

Background Calcium influx into postsynaptic dendritic spines can, depending on circumstances, activate three forms of synaptic plasticity: long-term potentiation (LTP), short-term potentiation (STP) and long-term depression (LTD). The increased postsynaptic calcium concentrations that trigger all three forms of plasticity should activate the α isoform of calcium–calmodulin kinase type II (αCaMK II), which is present at high levels just below the postsynaptic membrane. Earlier experiments have implicated αCaMK II in the regulation or induction of LTP, but no information is available on the possible role of this enzyme in the two other forms of synaptic plasticity, STP and LTD.Results We used mice that lack the gene for αCaMK II to investigate the role of this enzyme in synaptic plasticity. Field potential recordings from hippocampal slices taken from mutant mice show that STP and LTD are, like LTP, absent or markedly attenuated in the absence of αCaMK II. A brief form of synaptic modification — post-tetanic potentiation (PTP) — is, however, intact in the absence of this enzyme.Conclusion It appears likely that αCaMK II is involved in the production or global regulation of all three forms of synaptic plasticity. We propose that the activation of this enzyme is a common step in the induction of LTP and STP, and that αCaMK II activity is required for the normal production of LTD.