THE ROLE OF CALCIUM-CALMODULIN KINASE-II IN 3 FORMS OF SYNAPTIC PLASTICITY

Background: Calcium influx into postsynaptic dendritic spines can, dep ending on circumstances, activate three forms of synaptic plasticity: long-term potentiation (LTP), short-term potentiation (STP) and long-t erm depression (LTD). The increased postsynaptic calcium concentration s that trigger all three forms of plasticity should activate the a iso form of calcium-calmodulin kinase type II (alpha CaMKII), which is pre sent at high levels just below the postsynaptic membrane. Earlier expe riments have implicated alpha CaMKII in the regulation or induction of LTP, but no information is available on the possible role of this enz yme in the two other forms of synaptic plasticity, STP and LTD. Result s: We used mice that lack the gene for alpha CaMRII to investigate the role of this enzyme in synaptic plasticity. Field potential recording s from hippocampal slices taken from mutant mice show that STP and LTD are, like LTP, absent or markedly attenuated in the absence of alpha CaMKII. A brief form of synaptic modification - post-tetanic potentiat ion (PTP) - is, however, intact in the absence of this enzyme. Conclus ions: It appears likely that alpha CaMKII is involved in the productio n or global regulation of all three forms of synaptic plasticity. We p ropose that the activation of this enzyme is a common step in the indu ction of LTP and STP, and that alpha CaMKII activity is required for t he normal production of LTD.