An MCell model of calcium dynamics and frequency-dependence of calmodulin activation in dendritic spines

Abstract Pairing action potentials in synaptically coupled cortical pyramidal cells induces LTP in a frequency-dependent manner (H. Markram et al., Science 275 (1997) 213). Using MCell, which simulated the 3D geometry of the spine and the diffusion and binding of Ca 2+ , we show that pairing five EPSPs and back-propagating action potentials results in a Ca 2+ influx into a model dendritic spine that is largely frequency independent but leads to a frequency-dependent activation of postsynaptic calmodulin. Furthermore, we show how altering the availability of calmodulin and the calcium-binding capacity can alter the efficacy and potency of the frequency-response curve. The model shows how the cell can regulate its plasticity by buffering Ca 2+ signals.