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

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 Ca2+, we show that pairing five EPSPs and bac k-propagating action potentials results in a Ca2+ influx into a model dendr itic spine that is largely frequency independent but leads to a frequency-d ependent activation of postsynaptic calmodulin. Furthermore, we show how al tering the availability of calmodulin and the calcium-binding capacity can alter the efficacy and potency of the frequency-response curve. The model s hows how the cell can regulate its plasticity by buffering Ca2+ signals. (C ) 2001 Elsevier Science B.V. All rights reserved.