Persistent calcium microdomains in dendritic spines

Calcium is a ubiquitous signaling molecule in the nervous system. Selective induction of a particular pathway may depend on activation of a sensor that reads highly local Ca2+ levels. However, if Ca2+ equilibration is rapid compared to the kinetics of the sensor the latter strategy would be precluded. To test whether Ca2+ gradients persist for sufficiently long to differentially activate calmodulin (CaM) we developed a Monte Carlo model of intracellular Ca2+ dynamics in a dendritic spine. The model quantitatively reproduced experimental measures of fluorescent Ca2+ transients, and suggests a large, rapid spike in free intracellular Ca2+ concentration ([Ca]i) not predicted by the fluorescent signal. Because of the differential distribution of different Ca2+ sources, excitatory postsynaptic potentials (EPSPs), but not action potentials, induced large gradients across the spine. This differential distribution of Ca2+ produced location-specific activation of CaM following an EPSP, but a largely location-insensitive activation of CaM following an action potential. These simulations suggest functional Ca2+ microdomains can exist in dendritic spines, that Ca2+ sensors in spines can be sensitive to the mode of Ca2+ entry, and that these can lead to specificity in activation of Ca2+-dependent signaling pathways. Franks et al, 2002. 2