Abstract View HIGH SPATIAL AND TEMPORAL RESOLUTION ESTIMATES OF CALCIUM DYNAMICS IN DENDRITIC SPINES USING MCELL SIMULATIONS
Calcium plays a critical signaling role in many biological systems. For example, in the postsynaptic neuron, increases in Ca2+ concentration are believed to be essential for the induction of long-term potentiation and long-term depression, changes in synaptic efficacy thought to be the cellular mechanisms underlying learning and memory. Measurements of intracellular Ca2+ have typically relied on the use of fluorescent imaging where the sensors used buffer the Ca2+, obscuring concentration measurements, and have limited spatial and temporal resolution. In postsynaptic spines, the spatial localization of Ca2+-dependent effectors such as calmodulin, CaMKII and calcineurin make the measurement of Ca2+ concentration in the entire spine less than ideal. Using MCell, a Monte Carlo simulator, to monitor both the influx of Ca2+ into a spine and dendrite and its reactions with intracellular molecules, we have reproduced fluorescent transients measured in neocortical and hippocampal neurons. This has allowed determination of the unperturbed Ca2+ dynamics and suggests kinetics and concentrations of endogenous Ca2+ binding proteins. We have measured Ca2+ concentrations in microdomains throughout the spine showing highly heterogenous concentrations of free intracellular Ca2+. Furthermore, we show the spatial and temporal activation of different Ca2+-dependent effectors resulting from asynchronous pairing of preand postsynaptic action potentials. To complement experimental studies, we show how computer simulations can offer an alternate and complementary method of assaying intracellular Ca2+ dynamics and reactions. Supported by: NSF, HHMI, NIH & HFSP.