C F Stevens1, S Tonegawa, Y Wang. 1. Howard Hughes Medical Institute, Salk Institute, La Jolla, California 92110.
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 alpha isoform of calcium-calmodulin kinase type II (alpha CaMKII), which is present at high levels just below the postsynaptic membrane. Earlier experiments have implicated alpha CaMKII 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 alpha CaMKII 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 alpha CaMKII. A brief form of synaptic modification--post-tetanic potentiation (PTP)--is, however, intact in the absence of this enzyme. CONCLUSIONS: It appears likely that alpha CaMKII 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 alpha CaMKII activity is required for the normal production of LTD.
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 alpha isoform of calcium-calmodulin kinase type II (alpha CaMKII), which is present at high levels just below the postsynaptic membrane. Earlier experiments have implicated alpha CaMKII 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 alpha CaMKII 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 alpha CaMKII. A brief form of synaptic modification--post-tetanic potentiation (PTP)--is, however, intact in the absence of this enzyme. CONCLUSIONS: It appears likely that alpha CaMKII 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 alpha CaMKII activity is required for the normal production of LTD.